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@@ -13,8 +13,8 @@ PPR664019,https://doi.org/10.21203/rs.3.rs-2789162/v1,Association between antibo
 PPR706917,https://doi.org/10.1101/2023.08.07.23293778,"Diabetes following SARS-CoV-2 infection: Incidence, persistence, and implications of COVID-19 vaccination. A cohort study of fifteen million people","Taylor K, Eastwood S, Walker V, Cezard G, Knight R, Al Arab M, Wei Y, Horne EMF, Teece L, Forbes H, Walker A, Fisher L, Massey J, Hopcroft LEM, Palmer T, Cuitun Coronado J, Ip S, Davy S, Dillingham I, Morton C, Greaves F, Macleod J, Goldacre B, Wood A, Chaturvedi N, Sterne JAC, Denholm R, CONVALESCENCE study, The OpenSAFELY collaborative.",,No Journal Info,2023,2023-08-09,N,,,,"<h4>Background</h4> Type 2 diabetes (T2DM) incidence is increased after diagnosis of COVID-19. The impact of vaccination on this increase, for how long it persists, and the effect of COVID-19 on other types of diabetes remain unclear. <h4>Methods</h4> With NHS England approval, we studied diabetes incidence following COVID-19 diagnosis in pre-vaccination (N=15,211,471, January 2020-December 2021), vaccinated (N =11,822,640), and unvaccinated (N=2,851,183) cohorts (June-December 2021), using linked electronic health records. We estimated adjusted hazard ratios (aHRs) comparing diabetes incidence post-COVID-19 diagnosis with incidence before or without diagnosis up to 102 weeks post-diagnosis. Results were stratified by COVID-19 severity (hospitalised/non-hospitalised) and diabetes type. <h4>Findings</h4> In the pre-vaccination cohort, aHRS for T2DM incidence after COVID-19 (compared to before or without diagnosis) declined from 3.01 (95% CI: 2.76,3.28) in weeks 1-4 to 1.24 (1.12,1.38) in weeks 53-102. aHRS were higher in unvaccinated than vaccinated people (4.86 (3.69,6.41)) versus 1.42 (1.24,1.62) in weeks 1-4) and for hospitalised COVID-19 (pre-vaccination cohort 21.1 (18.8,23.7) in weeks 1-4 declining to 2.04 (1.65,2.51) in weeks 52-102), than non-hospitalised COVID-19 (1.45 (1.27,1.64) in weeks 1-4, 1.10 (0.98,1.23) in weeks 52-102). T2DM persisted for 4 months after COVID-19 for ∼73% of those diagnosed. Patterns were similar for Type 1 diabetes, though excess incidence did not persist beyond a year post-COVID-19. <h4>Interpretation</h4> Elevated T2DM incidence after COVID-19 is greater, and persists longer, in hospitalised than non-hospitalised people. It is markedly less apparent post-vaccination. Testing for T2DM after severe COVID-19 and promotion of vaccination are important tools in addressing this public health problem. <h4>Research in context</h4> <h4>Evidence before this study</h4> We searched PubMed for population-based observational studies published between December 1st 2019 and July 12th 2023 examining associations between SARS-CoV-2 infection or COVID-19 diagnosis (search string: SARS-CoV-2 or COVID* or coronavirus*) and subsequent incident diabetes (search term: diabetes). Of nineteen relevant studies; eight had a composite outcome of diabetes types, six stratified by diabetes type and five pertained to type-1-diabetes (T1DM) only. We did not identify any studies relating to gestational or other types of diabetes. Eleven studies were from the US, three from the UK, two from Germany, one from Canada, one from Denmark and one from South Korea. Most studies described cumulative relative risks (for infection versus no infection) one to two years post-SARS-CoV-2 infection of 1.2 to 2.6, though four studies found no associations with T1DM after the post-acute period. All studies lacked the power to compare diabetes relative risk by type, severity, and vaccination status in population subgroups. One study examined relative risks by vaccination status, but this used a composite outcome of diabetes and hyperlipidaemia and was conducted in a predominantly white male population. Two studies of T1DM found no evidence of elevated risk beyond 30 days after COVID-19 diagnosis, whilst two reported elevated risks at six months. Two studies of type 2 diabetes (T2DM) examined relative risks by time period post-infection: one study of US insurance claims reported a persistent association six months post-infection, whereas a large UK population-based study reported no associations after 12 weeks. However, the latter study used only primary care data, therefore COVID-19 cases were likely to have been under-ascertained. No large studies have investigated the persistence of diabetes diagnosed following COVID-19; key to elucidating the role of stress/steroid-induced hyperglycaemia. <h4>Added value of this study</h4> This study, which is the largest to address the question to date, analysed linked primary and secondary care health records with SARS-CoV-2 testing and COVID-19 vaccination data for 15 million people living in England. This enabled us to compare the elevation in diabetes incidence after COVID-19 diagnosis by diabetes type, COVID-19 severity and vaccination status, overall and in population subgroups. Importantly, excess diabetes incidence by time period since infection could also be quantified. Since healthcare in the UK is universal and free-at-the-point-of-delivery, almost the entire population is registered with primary care. Therefore the findings are likely to be generalisable. We found that, before availability of COVID-19 vaccination, a COVID-19 diagnosis (vs. no diagnosis) was associated with increased T2DM incidence which remained elevated by approximately 30% beyond one year after diagnosis. Though still present (with around 30% excess incidence at eight weeks), these associations were substantially attenuated in unvaccinated compared with vaccinated people. Excess incidence was greater in people hospitalised with COVID-19 than those who were not hospitalised after diagnosis. T1DM incidence was elevated up to, but not beyond, a year post COVID-19. Around 73% of people diagnosed with incident T2DM after COVID-19 still had evidence of diabetes four months after infection. <h4>Implications of all the available evidence</h4> There is a 30-50% elevated T2DM incidence post-COVID-19, but we report the novel finding that there is elevated incidence beyond one-year post-diagnosis. Elevated T1DM incidence did not appear to persist beyond a year, which may explain why previous studies disagree. For the first time in a general-population dataset, we demonstrate that COVID-19 vaccination reduces, but does not entirely ameliorate, excess diabetes incidence after COVID-19. This supports a policy of universal vaccination and suggests that other public health activities, such as enhanced diabetes screening after severe COVID-19, may be warranted, particularly in unvaccinated people.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/08/09/2023.08.07.23293778.full.pdf; doi:https://doi.org/10.1101/2023.08.07.23293778; html:https://europepmc.org/article/PPR/PPR706917; doi:https://doi.org/10.1101/2023.08.07.23293778
 PPR503749,https://doi.org/10.1101/2022.06.08.22276154,Validity of self-testing at home with rapid SARS-CoV-2 antibody detection by lateral flow immunoassay,"Atchison CJ, Moshe M, Brown JC, Whitaker M, Wong NCK, Bharath AA, McKendry RA, Darzi A, Ashby D, Donnelly CA, Riley S, Elliott P, Barclay WS, Cooke GS, Ward H.",,No Journal Info,2022,2022-06-09,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow immunoassays (LFIA) can be carried out in the home and have been used as an affordable and practical approach to large-scale antibody prevalence studies. However, assay performance differs from that of high-throughput laboratory-based assays which can be highly sensitive. We explore LFIA performance under field conditions compared to laboratory-based ELISA and assess the potential of LFIAs to identify people who lack functional antibodies following infection or vaccination. <h4>Methods</h4> Field evaluation of a self-administered LFIA test (Fortress, NI) among 3758 participants from the REal-time Assessment of Community Transmission-2 (REACT-2) study in England selected based on vaccination history and previous LFIA result to ensure a range of antibody titres. In July 2021, participants performed, at home, a self-administered LFIA on finger-prick blood, reported and submitted a photograph of the result, and provided a self-collected capillary blood sample (Tasso-SST) for serological assessment of IgG antibodies to the spike protein using the Roche Elecsys® Anti-SARS-CoV-2 assay. We compared the self-administered and reported LFIA result to the quantitative Roche assay and checked the reading of the LFIA result with an automated image analysis (ALFA). In a subsample of 250 participants, we compared the results to live virus neutralisation. <h4>Results</h4> Almost all participants (3593/3758, 95.6%) had been vaccinated or reported prior infection, with most having received one (862, 22.9%) or two (2430, 64.7%) COVID-19 vaccine doses. Overall, 2777/3758 (73.9%) were positive on self-reported LFIA, 2811/3457 (81.3%) positive by LFIA when ALFA-reported, and 3622/3758 (96.4%) positive on Roche anti-S (using the manufacturer reference standard threshold for positivity of 0.8 U ml -1 ). Live virus neutralisation was detected in 169 of 250 randomly selected samples (67.6%); 133/169 were positive with self-reported LFIA (sensitivity 78.7%; 95% CI 71.8, 84.6), 142/155 (91.6%; 86.1, 95.5) with ALFA, and 169 (100%; 97.8, 100.0) with Roche anti-S. There were 81 samples with no detectable virus neutralisation; 47/81 were negative with self-reported LFIA (specificity 58.0%; 95% CI 46.5, 68.9), 34/75 (45.3%; 33.8, 57.3) with ALFA, and 0/81 (0%; 0.0, 4.5) with Roche anti-S. All 250 samples remained positive with Roche anti-S when the threshold was increased to 1000U ml -1 . <h4>Conclusions</h4> Self-administered LFIA can provide insights into population patterns of infection and vaccine response, and sensitivity can be improved with automated reading of the result. The LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ELISA with virus neutralisation.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/98622/18/ciac629.pdf; doi:https://doi.org/10.1101/2022.06.08.22276154; html:https://europepmc.org/article/PPR/PPR503749; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR503749&type=FILE&fileName=EMS145889-pdf.pdf&mimeType=application/pdf
 PPR687749,https://doi.org/10.1101/2023.07.06.23292296,Long-term symptom profiles after COVID-19<i>vs</i>other acute respiratory infections: a population-based observational study (COVIDENCE UK),"Vivaldi G, Pfeffer PE, Talaei M, Basera J, Shaheen SO, Martineau AR.",,No Journal Info,2023,2023-07-07,Y,,,,"<h4>Summary</h4> <h4>Background</h4> Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms. <h4>Methods</h4> COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data on 16 potential long COVID symptoms and health-related quality of life (HRQoL), reported in January, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (≥4 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). <h4>Findings</h4> We included 10,203 participants (1343 [13.2%] with SARS-CoV-2 infection, 472 [4.6%] with non-COVID-19 ARI). Both types of infection were associated with increased prevalence/severity of most symptoms and decreased HRQoL compared with no infection. Participants with SARS-CoV-2 infection had increased odds of taste/smell problems and hair loss compared with participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. In the most severe groups (including 23% of participants with SARS-CoV-2, and 21% with non-COVID-19 ARI), SARS-CoV-2 infection presented with a higher probability of memory problems, difficulty concentrating, hair loss, and taste/smell problems than non-COVID-19 ARI. <h4>Interpretation</h4> Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of long-term symptoms. Research on post-acute sequelae of ARIs should extend from SARS-CoV-2 to include other pathogens. <h4>Funding</h4> Barts Charity. <h4>Research in context</h4> <h4>Evidence before this study</h4> We searched PubMed and Google Scholar for studies on post-acute sequelae of COVID-19 and other acute respiratory infections (ARIs), published up to May 24, 2023. We used search terms relating to COVID-19 and other ARIs (“COVID-19”, “SARS”, “severe acute respiratory syndrome”, “Middle East respiratory”, “MERS”, “respiratory infection”, “influenza”, “flu”) and post-acute symptoms (“long COVID”, “post-acute”, “PACS”, “sequelae”, “long-term”). Previous studies have shown a wide range of post-acute sequelae for COVID-19, affecting people with all severities of the acute disease. The few studies that have compared long-term symptoms between people with COVID-19 and non-COVID-19 ARIs have generally found a higher symptom burden among people with COVID-19; however, these studies have been restricted to hospitalised patients or electronic health record data, and thus do not capture the full picture in the community. Research into long COVID phenotypes has been inconclusive, with some analyses classifying people with long COVID according to the types of symptoms experienced, and others classifying them according to the overall severity of their symptoms. <h4>Added value of this study</h4> In this population-based study of ARIs in the community, we observed high symptom burden among people with previous SARS-CoV-2 infection when compared with controls, highlighting the extensive reach of long COVID. Our finding of a similar symptom burden among people with non-COVID-19 ARIs suggests that post-acute sequelae of other ARIs may be going unrecognised, particularly given that the vast majority did not experience a severe acute infection. Latent class analyses of symptoms identified groupings based on overall symptom severity, rather than symptom types, for both SARS-CoV-2 infections and non-COVID-19 ARIs, suggesting that overall symptom burden may best characterise the experience of people with post-acute sequelae. Notably, among participants with the most severe symptoms, only half of those with previous SARS-CoV-2 infection attributed their symptoms to long COVID, suggesting they either did not believe the infection was the cause, or they did not consider their symptoms severe enough to qualify as long COVID. <h4>Implications of all the available evidence</h4> The long-term symptoms experienced by some people with previous ARIs, including SARS-CoV-2, highlights the need for improved understanding, diagnosis, and treatment of post-acute infection syndromes. As much-needed research into long COVID continues, we must take the opportunity to investigate and consider the post-acute burden of ARIs due to other pathogens.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/07/07/2023.07.06.23292296.full.pdf; doi:https://doi.org/10.1101/2023.07.06.23292296; html:https://europepmc.org/article/PPR/PPR687749; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR687749&type=FILE&fileName=EMS178685-pdf.pdf&mimeType=application/pdf
-PPR674309,https://doi.org/10.1101/2023.06.07.23291077,Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease,"Liew F, Efstathiou C, Fontanella S, Richardson M, Saunders R, Swieboda D, Sidhu JK, Ascough S, Moore SC, Mohamed N, Nunag J, King C, Leavy OC, Elneima O, McAuley HJ, Shikotra A, Singapuri A, Sereno M, Harris VC, Houchen-Wolloff L, Greening NJ, Lone NI, Thorpe M, Roger Thompson AA, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho L, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard L, Wootton DG, Quint JK, de Silva TI, Ho A, Chiu C, Harrison EM, Greenhalf W, Kenneth Baillie J, Semple MG, Evans RA, Wain LV, Brightling C, Turtle L, Thwaites RS, Openshaw PJ, ISARIC4C Investigators and the PHOSP-COVID collaborative group.",,No Journal Info,2023,2023-06-12,Y,,,,"One in ten SARS-CoV-2 infections result in prolonged symptoms termed ‘long COVID’, yet disease phenotypes and mechanisms are poorly understood. We studied the blood proteome of 719 adults, grouped by long COVID symptoms. Elevated markers of monocytic inflammation and complement activation were associated with increased likelihood of all symptoms. Elevated IL1R2, MATN2 and COLEC12 associated with cardiorespiratory symptoms, fatigue, and anxiety/depression, while elevated MATN2 and DPP10 associated with gastrointestinal (GI) symptoms, and elevated C1QA was associated with cognitive impairment (the proteome of those with cognitive impairment and GI symptoms being most distinct). Markers of neuroinflammation distinguished cognitive impairment whilst elevated SCG3, indicative of brain-gut axis disturbance, distinguished those with GI symptoms. Women had a higher incidence of long COVID and higher inflammatory markers. Symptoms did not associate with respiratory inflammation or persistent virus in sputum. Thus, persistent inflammation is evident in long COVID, distinct profiles being associated with specific symptoms.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/06/12/2023.06.07.23291077.full.pdf; doi:https://doi.org/10.1101/2023.06.07.23291077; html:https://europepmc.org/article/PPR/PPR674309; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR674309&type=FILE&fileName=EMS177314-pdf.pdf&mimeType=application/pdf
 PPR508282,https://doi.org/10.1101/2022.06.20.22276205,Cohort Profile: Longitudinal population-based study of COVID-19 in UK adults (COVIDENCE UK),"Holt H, Relton C, Talaei M, Symons J, Davies MR, Jolliffe DA, Vivaldi G, Tydeman F, Williamson AE, Pfeffer PE, Orton C, Ford DV, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Breen G, Shaheen SO, Martineau AR.",,No Journal Info,2022,2022-06-20,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is estimated to have caused more than 18 million deaths worldwide as of end-May 2022. <h4>Methods</h4> COVIDENCE UK is a longitudinal population-based study that investigates risk factors for, and impacts of, COVID-19 in UK residents aged ≥16 years. A unique feature is the capacity to support trial-within-cohort studies to evaluate interventions for prevention of COVID-19 and other acute respiratory illnesses. Participants complete a detailed online baseline questionnaire capturing self-reported information relating to their socio-demographic characteristics, occupation, lifestyle, quality of life, weight, height, longstanding medical conditions, medication use, vaccination status, diet and supplemental micronutrient intake. Follow-up on-line questionnaires capturing incident symptoms of COVID-19 and other acute respiratory infections, incident swab test-confirmed COVID-19, doses of SARS-CoV-2 vaccine received, and quality of life are completed at monthly intervals. <h4>Results</h4> The study was launched on 1 st May 2020 and closed to recruitment on 6 th October 2021. A total of 19,981 participants enrolled and consented to 5-year follow-up with medical record linkage. Their mean age was 59.1 years (range 16.0 to 94.4 years), 70.2% were female, and 93.7% identified their ethnic origin as White. Analyses conducted to date have provided key insights into risk factors for SARS-CoV-2 infection and COVID-19 disease, determinants of SARS-CoV-2 vaccine immunogenicity and efficacy, and impacts of COVID-19 on health economic outcomes. The cohort has also supported conduct of a Phase 3 randomised trial-within-cohort study (CORONAVIT) evaluating implementation of a test-and-treat approach to correcting sub-optimal vitamin D status on incidence and severity of acute respiratory infections, including COVID-19. <h4>Conclusions</h4> The COVIDENCE UK dataset represents a valuable resource containing granular information on factors influencing susceptibility to, and impacts of, COVID-19 in UK adults. Researchers wishing to access anonymised participant-level data should contacting the corresponding author for further information.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/06/24/2022.06.20.22276205.full.pdf; doi:https://doi.org/10.1101/2022.06.20.22276205; html:https://europepmc.org/article/PPR/PPR508282; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR508282&type=FILE&fileName=EMS149878-pdf.pdf&mimeType=application/pdf
+PPR674309,https://doi.org/10.1101/2023.06.07.23291077,Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease,"Liew F, Efstathiou C, Fontanella S, Richardson M, Saunders R, Swieboda D, Sidhu JK, Ascough S, Moore SC, Mohamed N, Nunag J, King C, Leavy OC, Elneima O, McAuley HJ, Shikotra A, Singapuri A, Sereno M, Harris VC, Houchen-Wolloff L, Greening NJ, Lone NI, Thorpe M, Roger Thompson AA, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho L, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard L, Wootton DG, Quint JK, de Silva TI, Ho A, Chiu C, Harrison EM, Greenhalf W, Kenneth Baillie J, Semple MG, Evans RA, Wain LV, Brightling C, Turtle L, Thwaites RS, Openshaw PJ, ISARIC4C Investigators and the PHOSP-COVID collaborative group.",,No Journal Info,2023,2023-06-12,Y,,,,"One in ten SARS-CoV-2 infections result in prolonged symptoms termed ‘long COVID’, yet disease phenotypes and mechanisms are poorly understood. We studied the blood proteome of 719 adults, grouped by long COVID symptoms. Elevated markers of monocytic inflammation and complement activation were associated with increased likelihood of all symptoms. Elevated IL1R2, MATN2 and COLEC12 associated with cardiorespiratory symptoms, fatigue, and anxiety/depression, while elevated MATN2 and DPP10 associated with gastrointestinal (GI) symptoms, and elevated C1QA was associated with cognitive impairment (the proteome of those with cognitive impairment and GI symptoms being most distinct). Markers of neuroinflammation distinguished cognitive impairment whilst elevated SCG3, indicative of brain-gut axis disturbance, distinguished those with GI symptoms. Women had a higher incidence of long COVID and higher inflammatory markers. Symptoms did not associate with respiratory inflammation or persistent virus in sputum. Thus, persistent inflammation is evident in long COVID, distinct profiles being associated with specific symptoms.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/06/12/2023.06.07.23291077.full.pdf; doi:https://doi.org/10.1101/2023.06.07.23291077; html:https://europepmc.org/article/PPR/PPR674309; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR674309&type=FILE&fileName=EMS177314-pdf.pdf&mimeType=application/pdf
 PPR625484,https://doi.org/10.2139/ssrn.4343760,Association between Antibody Responses Post-Vaccination and Severe COVID-19 Outcomes: National Population-Based Cohort Study in Scotland,"Macdonald C, Palmateer N, McAuley A, Lindsay L, Hasan T, Hameed SS, Hall E, Jeffrey K, Grange Z, Gousias P, Marvin S, Jarvis L, Cameron JC, Daines L, Tibble H, Fagbamigbe AF, Simpson C, McCowan C, Katikireddi SV, Rudan I, Fagbamigbe AF, Ritchie LD, Swallow B, Robertson C, Sheikh A, Murray J.",,No Journal Info,2023,2023-02-07,N,,,,"Background: Immune responses to COVID-19 vaccines differ between individuals. Identifying characteristics associated with insufficient post-vaccination IgG antibody responses and describing the association between post-vaccination IgG and subsequent SARS-CoV-2 infection and severe COVID-19 outcomes could inform future vaccination strategies.    <br><br>Methods: We linked population-based SARS-CoV-2 seroprevalence surveillance data to national cohort data from Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II), comprising primary care, RT-PCR testing, vaccination, hospitalisation, and mortality data. We used logistic regression to examine risk factors for an insufficient response (defined as only negative SARS-CoV-2 IgG tests ≥14 days post-vaccination) and Cox regression to investigate the association between IgG titres and subsequent severe COVID-19 outcomes. <br><br>Findings: Among 23,607 vaccinated individuals with seroprevalence data, 2,633 (11·2%) had an insufficient response. Individuals with multimorbidity had increased adjusted odds (1·94 [95% CI 1·45-2·60]) of generating an insufficient response compared to those without COVID-19 risk factors, as did those with certain single conditions: haematological cancer (1·85 [1·21-2·83]); rare neurological conditions (1·94 [1·18-3·19]); respiratory cancer (2·32 [1·13-4.78]); and sickle cell disease (2·55 [1·16-5·59]). Antibody titres showed a dose-dependent association with severe COVID-19: those with undetectable IgG were at greatest risk of COVID-19 hospitalisation or death (HR 8·25 [4·39-15·49]) compared to those with average levels.  <br><br>Interpretation: We have identified predictors of insufficient antibody response post-vaccination and found a direct dose-dependent association between insufficient antibody levels and severe COVID-19 outcomes. Identification of people at risk of insufficient vaccine responses and prioritising them for COVID-19 therapeutics may be warranted.<br><br>Funding: This study is part of the EAVE II project. EAVE II is funded by the MRC (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional funding for this work was received by National Core Studies Immunity. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). Additional support has been provided through Public Health Scotland, the Scottish Government Director General Health and Social Care and the University of Edinburgh. The original EAVE project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (11/46/23). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the UK government.<br><br>Declaration of Interests: AS and CR are members of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and AS its Standing Committee on Pandemics. AS is also a member of the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) Risk Stratification Subgroup. AS was a member of AstraZeneca’s Thrombotic Thrombocytopenic Taskforce. All AS’ roles are unremunerated. CR is a member of SPI-M. JM was a member of the National Incident Management Team COVID-19, and lead of Enhanced Surveillance of COVID-19 in Scotland during this project. IR is a member of the Scientific Council on COVID-19 pandemic of the Government of the Republic of Croatia and the co-Editor-in-Chief of the Journal of Global Health. <br><br>The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.",,doi:https://doi.org/10.2139/ssrn.4343760; html:https://europepmc.org/article/PPR/PPR625484; doi:https://doi.org/10.2139/ssrn.4343760
 PPR438858,https://doi.org/10.1101/2022.01.03.21268111,"The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism","Willett BJ, Grove J, MacLean OA, Wilkie C, Logan N, Lorenzo GD, Furnon W, Scott S, Manali M, Szemiel A, Ashraf S, Vink E, Harvey WT, Davis C, Orton R, Hughes J, Holland P, Silva V, Pascall D, Puxty K, da Silva Filipe A, Yebra G, Shaaban S, Holden MTG, Pinto RM, Gunson R, Templeton K, Murcia PR, Patel AH, Haughney J, Robertson DL, Palmarini M, Ray S, Thomson EC, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2022,2022-01-03,Y,,,,"Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron, the fifth VOC to be described, harbours 30 amino acid mutations in spike including 15 in the receptor-binding domain. Here, we demonstrate substantial evasion of neutralisation by Omicron in vitro using sera from vaccinated individuals. Importantly, these data are mirrored by a substantial reduction in real-world vaccine effectiveness that is partially restored by booster vaccination. We also demonstrate that Omicron does not induce cell syncytia and favours a TMPRSS2-independent endosomal entry pathway. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/26/2022.01.03.21268111.full.pdf; doi:https://doi.org/10.1101/2022.01.03.21268111; html:https://europepmc.org/article/PPR/PPR438858; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR438858&type=FILE&fileName=EMS142114-pdf.pdf&mimeType=application/pdf
 PPR704142,https://doi.org/10.2139/ssrn.4544777,Use of Sodium Valproate and Other Anti-Seizure Medications in England and Wales During the COVID-19 Pandemic: A Population-Level Analysis of 60 Million Individuals,"Dale C, Takhar R, Fan YY, Torabi F, Kim S, Lambarth A, Shankar R, Tomlinson C, Wilkinson T, Mueller T, Kurdi A, Ashworth M, Mamas M, Khunti K, Akbari A, Morris A, Pirmohamed M, Marson A, Williams D, Sudlow C, Sofat R, CVD-COVID-UK Consortium.",,No Journal Info,2023,2023-08-23,N,,,,"Background: Key policy statements in 2018 on the use of sodium valproate (SV), an evidence-based treatment for idiopathic generalised epilepsy (IGE), which also has teratogenic effects, were followed by the onset of the COVID-19 pandemic. We investigated the use of SV in England and Wales, the impact of policy implementation and the pandemic. <br><br>Methods: Prevalent (current) and incident (new) uses of SV and other anti-seizure medications (ASMs) before and during the COVID-19 pandemic (2019-2021) were identified in England and Wales (n=60 million), stratifying use by age-bands, sex, geography, ethnic group, deprivation and disease indication. We assessed pregnancy rates and examine the timing and dose of ASMs dispensed during pregnancy. Using multivariate logistic regression we investigated factors associated with SV use during pregnancy and trends in epilepsy-related deaths between 2015 to 2021 using time series analysis. <br><br>Findings: Use of SV in women of CBP  decreased whilst use of other ASMs increased between 2019 and 2021. New initiation of SV per 100,000 women fell from 13 to 8 in women aged 30-39, 10 to 6 in women aged 20-29 and 7 to 5 in women aged 15-19 between 2019 and 2021, while pregnancy rates fell from 5.9 to 5.1 per 1000 women of CBP dispensed SV. The number of pregnant women with evidence of a SV dispense during the pregnancy period fell from 112 in 2019 to 67 in 2021. Epilepsy was the most common indication, followed by bipolar disorder (678 and 190 per 1,000 women of CBP dispensed SV respectively). There was no clear evidence that epilepsy-related deaths increased in women and men aged 15-49 during the period 2018-2021.<br><br>Interpretation: Rates of use of SV by women, including during pregnancy, fell before and continued to decline during the COVID-19 pandemic. Further research using linked health data is needed to investigate how policy changes impact on seizure control and mortality in men and women of CBP and on harms to children exposed in utero. Our approach could be used to investigate medicines safety more broadly in pregnancy and demonstrate how linked routinely-collected electronic health record data can be used to inform policy.<br><br>Funding: This work was carried out with the support of the BHF Data Science Centre led by HDR UK (BHF Grant no. SP/19/3/34678).<br><br>Declaration of Interest: The views represented in this manuscript are entirely those of the authors, and do not represent the views of any organisations they represent. MP has received partnership funding for the following: MRC Clinical Pharmacology Training Scheme (co- funded by MRC and Roche, UCB, Eli Lilly and Novartis). He has developed an HLA genotyping panel with MC Diagnostics, but does not benefit financially from this. He is part of the IMI Consortium ARDAT (www.ardat.org) and Chair of the Commission on Human Medicines (CHM). RS is a member of the Pharmacovigilance Expert Advisory Group, a sub-committee of the CHM. CT has received funding paid to University College London from GlaxoSmithKline (GSK), outside of the scope of the submitted work. AGM has received funding paid to University of Liverpool from UCB Pharma, Sanofi, Eiasi and GSK. He is a member of the MHRA valproate implementation group, chief investigator of the SANAD trials and senior author of the Cochrane reviews assessing the teratogenic effects of anti-seizure medications.<br><br>Ethical Approval: The North East - Newcastle and North Tyneside 2 research ethics committee provided ethical approval for the CVD-COVID-UK/COVID-IMPACT research programme (REC No 20/NE/0161) to access, within secure trusted research environments, unconsented, whole-population, de-identified data from electronic health records collected as part of patients’ routine healthcare.",,doi:https://doi.org/10.2139/ssrn.4544777; html:https://europepmc.org/article/PPR/PPR704142; doi:https://doi.org/10.2139/ssrn.4544777
@@ -32,8 +32,8 @@ PPR302793,https://doi.org/10.2139/ssrn.3803364,"A Common
 <i>TMPRSS2</i> Variant Protects Against Severe COVID-19","David A, Parkinson N, Peacock TP, Pairo-Castineira E, Khanna T, Cobat A, Tenesa A, Sancho-Shimizu V, Group II, Group GI, Casanova J, Abel L, Barclay WS, Baillie JK, Sternberg M.",,No Journal Info,2021,2021-03-12,N,,,,"Background: The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus’ spike protein, facilitating entry into target cells. We hypothesized that naturally-occurring <i>TMPRSS2</i> human genetic variants affecting the structure and function of the TMPRSS2 protein may modulate the severity of SARS-CoV-2 infection.<br><br>Methods: We focused on the only common <i>TMPRSS2</i> non-synonymous variant predicted to be damaging (rs12329760 T to C, p.V160M), which has a minor allele frequency of ~25% in the population. We analysed the association between the rs12329760 and COVID19 severity in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units recruited as part of the GenOMICC (Genetics Of Mortality In Critical Care) study. Logistic regression analyses were adjusted for sex, age and deprivation index. For in vitro studies, HEK293 cells were co-transfected with ACE2 and either TMPRSS2 wild type or mutant (TMPRSS2<sub>V160M</sub>). A SARS-CoV-2 pseudovirus entry assay was used to investigate TMPRSS2<sub>V160M</sub> ability to promote viral entry.<br><br>Findings: We show that the T allele of rs12329760 is associated with a reduced likelihood of developing severe COVID19 (OR 0.87, 95%CI:0.79-0.97, p=0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p=1.3×10<sup>-3</sup>). We demonstrate <i>in vitro</i> that this variant, which causes the amino acid substitution valine to methionine, impacts the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells.<br><br>Interpretation: <i>TMPRSS2</i> rs12329760 is a common variant associated with a significantly decreased risk of severe COVID19. Further studies are needed to assess the expression of the <i>TMPRSS2</i> across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID19. Clinical trials are needed to confirm this.<br><br>Funding: Wellcome Trust, BBSRC, UKRI Future Leader’s Fellowship, Health Data Research UK<br><br>Declaration of Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest.<br><br>Ethics Approval Statement: Research ethics committees (Scotland 15/SS/0110, England, Wales and Northern Ireland: 19/WM/0247).",,doi:https://doi.org/10.2139/ssrn.3803364; html:https://europepmc.org/article/PPR/PPR302793; doi:https://doi.org/10.2139/ssrn.3803364
 PPR661573,https://doi.org/10.21203/rs.3.rs-2846109/v1,Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses,"Michael B, Dunai C, Needham E, Tharmaratnam K, Williams R, Huang Y, Boardman S, Clark J, Sharma P, Subramaniam K, Wood G, Collie C, Digby R, Ren A, Norton E, Leibowitz M, Ebrahimi S, Fower A, Fox H, Tato E, Ellul M, Sunderland G, Held M, Hetherington C, Egbe F, Palmos A, Stirrups K, Grundmann A, Stewart J, Griffiths M, Solomon T, Breen G, Coles A, Cavanagh J, Irani S, Vincent A, Baillie J, Openshaw P, Semple M, corsortium C, Taams L, Menon D, ISARIC-4C Investigators.",,No Journal Info,2023,2023-05-17,Y,,,,"Neurological complications occur in a significant proportion of COVID-19 cases. In order to identify key biomarkers, we measured brain injury markers, inflammatory mediators, and autoantibodies in 203 participants admitted to hospital for management of COVID-19; 111 provided acute sera (1-11 days post admission) and 56 with COVID-19-associated neurological diagnoses provided convalescent sera (up to76 weeks post admission). Compared to 60 controls, brain injury biomarkers (total-Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in participants with altered consciousness. Total-Tau (tTau) and NfL remained elevated in convalescent sera, particularly following cerebrovascular and neuroinflammatory disorders. Acutely, inflammatory mediators (including IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) were higher in participants with altered consciousness and correlated with brain injury biomarker levels. Inflammatory mediators were lower in convalescent sera than acute sera. Levels of CCL2, CCL7, IL-1RA, IL-2Rα, M-CSF, SCF, IL-16 and IL-18 in individual participants correlated with tTau levels even at later time points. When compared to acute COVID-19 patients with a normal Glasgow Coma Scale score (GCS), network analysis showed significantly altered immune responses in patients with acute alteration of consciousness, and in convalescent patients who had suffered an acute neurological complication. The frequency and range of autoantibodies did not associate with neurological disorders. However, autoantibodies against specific antigens were more frequent in patients with altered consciousness in the acute phase (including MYL7, UCH-L1, GRIN3B, and DDR2), and in patients with neurological complications in the convalescent phase (including MYL7, GNRHR, and HLA antigens). In a novel low-inoculum mouse model of SARS-CoV-2, while viral replication was only consistently seen in mouse lungs, inflammatory responses were seen in both brain and lungs, with significant increases in CCL4, IFNγ, IL-17A, and microglial reactivity in the brain. Neurological injury is common in the acute phase of COVID-19 and we found brain injury markers persist during convalescence and may be driven by a para-infectious process involving a dysregulated host response.",,pdf:https://www.researchsquare.com/article/rs-2846109/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-2846109/v1; html:https://europepmc.org/article/PPR/PPR661573; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR661573&type=FILE&fileName=EMS175982-pdf.pdf&mimeType=application/pdf
 PPR215604,https://doi.org/10.1101/2020.09.17.20196469,Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care,"Haroon S, Subramanian A, Cooper J, Anand A, Gokhale K, Byne N, Dhalla S, Acosta-Mena D, Taverner T, Okoth K, Wang J, Chandan JS, Sainsbury C, Zemedikun DT, Thomas GN, Parekh D, Marshall T, Sapey E, Adderley NJ, Nirantharakumar K.",,No Journal Info,2020,2020-09-18,Y,,,,"<h4>Introduction</h4> A significant proportion of patients with Coronavirus Disease-19 (COVID-19) have hypertension and are treated with renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme I inhibitors (ACE inhibitors) or angiotensin II type-1 receptor blockers (ARBs). These medications have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The objective of this study was to assess a possible association between prescription of RAS inhibitors and the incidence of COVID-19 and all-cause mortality. <h4>Methods</h4> We conducted a propensity-score matched cohort study to assess the incidence of COVID-19 among patients with hypertension who were prescribed ACE inhibitors or ARBs compared to patients treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 among those prescribed ACE inhibitors, ARBs and CCBs. We used a Cox proportional hazards model to produce adjusted hazard ratios for COVID-19 comparing patients prescribed ACE inhibitors or ARBs to those prescribed CCBs. We further assessed all-cause mortality as a secondary outcome and a composite of accidents, trauma or fractures as a negative control outcome to assess for residual confounding. <h4>Results</h4> In the propensity score matched analysis, 83 of 18,895 users (0.44%) of ACE inhibitors developed COVID-19 over 8,923 person-years, an incidence rate of 9.3 per 1000 person-years. 85 of 18,895 (0.45%) users of CCBs developed COVID-19 over 8,932 person-years, an incidence rate of 9.5 per 1000 person-years. The adjusted hazard ratio for suspected/confirmed COVID-19 for users of ACE inhibitors compared to CCBs was 0.92 (95% CI 0.68 to 1.26). 79 out of 10,623 users (0.74%) of ARBs developed COVID-19 over 5010 person-years, an incidence rate of 15.8 per 1000 person-years, compared to 11.6 per 1000 person-years among users of CCBs. The adjusted hazard ratio for suspected/confirmed COVID-19 for users of ARBs compared to CCBs was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of ACE inhibitors or ARBs and all-cause mortality, compared to use of CCBs. We found no evidence of significant residual confounding with the negative control analysis. <h4>Conclusion</h4> Current use of ACE inhibitors was not associated with the risk of suspected or confirmed COVID-19 whereas use of ARBs was associated with a statistically non-significant 38% relative increase in risk compared to use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality during the peak of the pandemic.",,pdf:http://pure-oai.bham.ac.uk/ws/files/118117066/s12879_021_05951_w.pdf; doi:https://doi.org/10.1101/2020.09.17.20196469; html:https://europepmc.org/article/PPR/PPR215604; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR215604&type=FILE&fileName=EMS96164-pdf.pdf&mimeType=application/pdf
-PPR712319,https://doi.org/10.21203/rs.3.rs-3209706/v1,The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data,"Tufts J, Guan N, Zemedikun D, Subramanian A, Gokhale K, Myles P, Williams T, Marshall T, Calvert M, Matthews K, Nirantharakumar K, Jackson L, Haroon S.",,No Journal Info,2023,2023-08-14,Y,,,,"<h4>Background: </h4> The economic impact of managing long COVID in primary care is unknown. We estimated the costs of primary care consultations associated with long COVID and explored the relationship between risk factors and costs. Methods  Data were obtained on non-hospitalised adults from the Clinical Practice Research Datalink Aurum primary care database. We used propensity score matching with an incremental cost method to estimate additional primary care consultation costs associated with long COVID (12 weeks after COVID-19) at an individual and UK national level. We applied multivariable regression models to estimate the association between risk factors and consultations costs beyond 12 weeks from acute COVID-19. Results  Based on an analysis of 472,173 patients with Covid-19 and 472,173 unexposed individuals, the annual incremental cost of primary care consultations associated with long COVID was £2.44 per patient and £23,382,452 at the national level. Among patients with COVID-19, a long COVID diagnosis and longer-term reporting of symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age, female sex, obesity, being from a white ethnic group, comorbidities and prior consultation frequency were all associated with increased primary care consultation costs. Conclusions  The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities.",,doi:https://doi.org/10.21203/rs.3.rs-3209706/v1; html:https://europepmc.org/article/PPR/PPR712319; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR712319&type=FILE&fileName=EMS187055-pdf.pdf&mimeType=application/pdf
 PPR557473,https://doi.org/10.1101/2022.10.12.22281016,Quantifying changes in the IFR and IHR over 23 months of the SARS-CoV-2 pandemic in England,"Eales O, Haw D, Wang H, Atchison C, Ashby D, Cooke G, Barclay W, Ward H, Darzi A, Donnelly CA, Chadeau-Hyam M, Elliott P, Riley S.",,No Journal Info,2022,2022-10-13,Y,,,,"<h4>Background</h4> The relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity in England approximately monthly from May 2020 to 31 March 2022. This period covers widespread circulation of the original strain, the emergence of the Alpha, Delta and Omicron variants and the rollout of England’s mass vaccination campaign. <h4>Methods</h4> Here, we explore this changing relationship between prevalence of swab positivity and the infection fatality rate (IFR) and infection hospitalisation rate (IHR) over 23 months of the pandemic in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models and Bayesian P-spline models. We analyse data for all age groups together, as well as in two sub-groups: those aged 65 and over and those aged 64 and under. <h4>Results</h4> During 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late-2021/early-2022 the IFR and IHR had both decreased to 0.097% and 0.76% respectively. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta’s emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR of the virus decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late-2021/early-2022 these time-lags had decreased to 7 days for hospitalisations, and 18 days for deaths. <h4>Conclusion</h4> Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on IHR and IFR. As investments in community surveillance are scaled back, alternative methods should be developed to accurately track the ever changing relationship between infection, hospitalisation and death.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/10/13/2022.10.12.22281016.full.pdf; doi:https://doi.org/10.1101/2022.10.12.22281016; html:https://europepmc.org/article/PPR/PPR557473; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR557473&type=FILE&fileName=EMS155665-pdf.pdf&mimeType=application/pdf
+PPR712319,https://doi.org/10.21203/rs.3.rs-3209706/v1,The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data,"Tufts J, Guan N, Zemedikun D, Subramanian A, Gokhale K, Myles P, Williams T, Marshall T, Calvert M, Matthews K, Nirantharakumar K, Jackson L, Haroon S.",,No Journal Info,2023,2023-08-14,Y,,,,"<h4>Background: </h4> The economic impact of managing long COVID in primary care is unknown. We estimated the costs of primary care consultations associated with long COVID and explored the relationship between risk factors and costs. Methods  Data were obtained on non-hospitalised adults from the Clinical Practice Research Datalink Aurum primary care database. We used propensity score matching with an incremental cost method to estimate additional primary care consultation costs associated with long COVID (12 weeks after COVID-19) at an individual and UK national level. We applied multivariable regression models to estimate the association between risk factors and consultations costs beyond 12 weeks from acute COVID-19. Results  Based on an analysis of 472,173 patients with Covid-19 and 472,173 unexposed individuals, the annual incremental cost of primary care consultations associated with long COVID was £2.44 per patient and £23,382,452 at the national level. Among patients with COVID-19, a long COVID diagnosis and longer-term reporting of symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age, female sex, obesity, being from a white ethnic group, comorbidities and prior consultation frequency were all associated with increased primary care consultation costs. Conclusions  The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities.",,doi:https://doi.org/10.21203/rs.3.rs-3209706/v1; html:https://europepmc.org/article/PPR/PPR712319; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR712319&type=FILE&fileName=EMS187055-pdf.pdf&mimeType=application/pdf
 PPR697303,https://doi.org/10.21203/rs.3.rs-3168263/v1,Impact of vaccination on the association of COVID-19 with arterial and venous thrombotic diseases: an OpenSAFELY cohort study using linked electronic health records,"Cezard G, Denholm R, Knight R, Wei Y, Teece L, Toms R, Forbes H, Walker A, Fisher L, Massey J, Hopcroft L, Horne E, Taylor K, Palmer T, Arab MA, Coronado JC, Ip S, Davy S, Dillingham I, Bacon S, Mehrkar A, Morton C, Greaves F, Hyams C, Smith GD, MacLeod J, Chaturvedi N, Goldacre B, Whiteley W, Wood A, Sterne J, Walker V.",,No Journal Info,2023,2023-07-25,Y,,,,"With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a ‘pre-vaccination’ cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and ‘vaccinated’ and ‘unvaccinated’ cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). The incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalized than non-hospitalized COVID-19 and higher in the pre-vaccination and unvaccinated than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before being vaccinated are at higher risk of cardiovascular events for at least two years.",,doi:https://doi.org/10.21203/rs.3.rs-3168263/v1; html:https://europepmc.org/article/PPR/PPR697303; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR697303&type=FILE&fileName=EMS181970-pdf.pdf&mimeType=application/pdf
 PPR687720,https://doi.org/10.1101/2023.07.06.23292295,Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern: a retrospective analysis,"Cavallaro M, Dyson L, Tildesley MJ, Todkill D, Keeling MJ.",,No Journal Info,2023,2023-07-07,Y,,,,"The SARS-CoV-2 pandemic has been characterized by the repeated emergence of genetically distinct virus variants of increased transmissibility and immune evasion compared to pre-existing lineages. In many countries, their containment required the intervention of public health authorities and the imposition of control measures. While the primary role of testing is to identify infection, target treatment, and limit spread (through isolation and contact tracing), a secondary benefit is in terms of surveillance and the early detection of new variants. Here we study the spatial invasion and early spread of the Alpha, Delta, and Omicron (BA.1 and BA.2) variants in England from September 2020 to February 2022 using the random neighbourhood covering (RaNCover) method. This is a statistical technique for the detection of aberrations in spatial point processes, which we tailored here to community PCR (polymerase-chain-reaction) test data where the TaqPath kit provides a proxy measure of the switch between variants. Retrospectively, RaNCover detected the earliest signals associated with the four novel variants that led to large infection waves in England. With suitable data our method therefore has the potential to rapidly detect outbreaks of future SARS-CoV-2 variants, thus helping to inform targeted public health interventions.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/07/07/2023.07.06.23292295.full.pdf; doi:https://doi.org/10.1101/2023.07.06.23292295; html:https://europepmc.org/article/PPR/PPR687720; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR687720&type=FILE&fileName=EMS178687-pdf.pdf&mimeType=application/pdf
 PPR625471,https://doi.org/10.2139/ssrn.4376992,Identifying Long Covid Using Electronic Health Records: A National Observational Cohort Study in Scotland,"Jeffrey K, Woolford L, Maini R, Basetti S, Batchelor A, Weatherill D, White C, Hammersley V, Millington T, Macdonald C, Quint J, Kerr R, Kerr S, Shah SA, Fagbamigbe AF, Simpson C, Katikireddi SV, Robertson C, Ritchie LD, Sheikh A, Daines L.",,No Journal Info,2023,2023-03-07,N,,,,"Background: Long COVID is a debilitating multisystem condition. To estimate prevalence and identify risk factors, we analysed routinely collected data from almost the entire adult population of Scotland.<br><br>Methods: A cohort of adults (≥18 years) resident in Scotland between March 1, 2020, and October 20, 2022, was created by linking data from primary care, secondary care, laboratory testing and prescribing. Four outcome measures were used to identify long COVID: clinical codes, free text in primary care records, free text on sick notes, and a novel operational definition. The latter was developed using Poisson regression to identify clinical encounters indicative of long COVID from a sample of negative and positive COVID-19 cases matched on time-varying propensity to test positive for SARS-CoV-2.<br><br>Findings: Of 5,104,198 participants, 90,712 (1·8%) were identified as having long COVID by one or more outcome measures. Clinical codes were rarely recorded (n=1,092, 0·02%). More people were identified using free text (n= 8,368, 0·2%), sick notes (n=14,471, 0·3%) and the operational definition (n=73,767, 1·4%). Compared with the general population, a higher proportion of people with long COVID were female, middle-aged, overweight/obese, had at least two comorbidities, were immunosuppressed, shielding, or hospitalised within 28 days of testing positive, and had tested positive before Omicron became the dominant variant.<br><br>Interpretation: The prevalence of long COVID presenting in general practice was estimated to be 0·02 - 1·8%, depending on the measure used. Of the four outcome measures used, clinical codes identified the fewest cases. With limited use of long COVID clinical codes, we consider free text analysis to be the most promising approach should future surveillance of long COVID at a national level be required.<br><br>Funding: Chief Scientist Office (Scotland) and Medical Research Council.<br><br>Declaration of Interest: AS reports grants from HDRUK, grants from NIHR, grants from MRC, grants from ICSF, during the conduct of the study; and Member of Scottish Government's CMO COVID-19 Advisory Group and Standing Committee on Pandemics. CR reports support from PHS and MRC. CS reports grants from MBIE (New Zealand), Ministry of Health (New Zealand), and HRC (New Zealand). JKQ reports grants from MRC, HDR UK, GlaxoSmithKline, BI, Asthma+Lung UK, and AstraZeneca and consulting fees from GlaxoSmithKline, Evidera, AstraZeneca, Insmed. All other authors declare no competing interests.<br><br>Ethical Approval: The EAVE II study obtained approvals from the West of Scotland Research Ethics Committee (reference: 22/WS/0071), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279).",,doi:https://doi.org/10.2139/ssrn.4376992; html:https://europepmc.org/article/PPR/PPR625471; doi:https://doi.org/10.2139/ssrn.4376992
@@ -77,8 +77,8 @@ PPR501811,https://doi.org/10.1101/2022.06.02.22275900,"Trends in SARS-CoV-2 infe
 PPR558630,https://doi.org/10.1101/2022.10.17.22281085,COVID-19 among adults living with HIV: Correlates of mortality in a general population in a resource-limited setting,"Kassanjee R, Davies M, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.",,No Journal Info,2022,2022-10-17,Y,,,,"<h4>Introduction</h4> While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower income settings. We studied the association between mortality and characteristics of HIV severity and management, and vaccination, among adult PWH. <h4>Methods</h4> We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with CD4 cell count, viral load, evidence of ART, time since first HIV evidence, and vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. <h4>Results</h4> Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17 831 first diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load (among those with ART evidence), and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis, chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. <h4>Conclusions</h4> Mortality was strongly associated with suboptimal HIV control, and prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimised.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603837; doi:https://doi.org/10.1101/2022.10.17.22281085; html:https://europepmc.org/article/PPR/PPR558630; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR558630&type=FILE&fileName=EMS155815-pdf.pdf&mimeType=application/pdf
 PPR342270,https://doi.org/10.2139/ssrn.3839453,Profile of Humoral and Cellular Immune Responses to Single BNT162b2 or ChAdOx1 Vaccine in Residents and Staff Within Residential Care Homes (VIVALDI Study),"Tut G, Lancaster T, Krutikov M, Sylla P, Bone D, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Butler M, Ayodele M, Bruton R, Shrotri M, Azmi B, Fuller C, Irwin-Singer A, Hayward AC, Copas A, Shallcross L, Moss P.",,No Journal Info,2021,2021-05-04,N,,,,"Background: Residents of long-term care facilities (LTCF) have experienced high mortality rates from SARS-CoV-2 infection and as such have been prioritized for Covid-19 vaccination. Several countries have implemented an extended interval of up to 12 weeks between first and second vaccine doses to increase population coverage after single administration. <br><br>Methods: Spike-specific immune responses that were induced following single administration of BNT162b2 or ChAdOx1 were studied in 89 staff and 35 residents within LTCFs. Quantitative antibody and cellular responses were determined as well as antibody inhibition of spike protein-ACE2 binding from viral variants. <br><br>Results: 20% of staff and 34% of residents were found to have serological evidence of prior SARS-CoV-2 infection and all of these donors demonstrated strong antibody responses that were independent of age. Antibody responses were detectable within 99% and 79% of ‘infection-naive’ staff and residents respectively but were 8.2-fold lower within residents. This effect resulted from slower kinetics of antibody generation within residents which reached levels comparable to staff after only 42 days. In contrast spike-specific cellular responses were equivalent between both groups. Antibody inhibition activity against the B.1.351 and P.1 viral variants of concern was low using serum from ‘infection-naive’ older donors. Prior history of natural infection thus has a marked impact on the magnitude and quality of antibody response after a single Covid-19 vaccine in care home residents. <br><br>Interpretation: Residents who are infection-naive have delayed antibody responses to the first dose of vaccine and might be considered for an early second vaccine where possible.  <br><br>Funding: UK Government Department of Health and Social Care<br><br>Declaration of Interests: LS reports grants from the Department of Health and Social Care during the conduct of the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AH is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health.<br><br>Ethics Approval Statement: Ethical approval for this study was obtained from the South Central - Hampshire B Research Ethics Committee, REC Ref: 20/SC/023.",,doi:https://doi.org/10.2139/ssrn.3839453; html:https://europepmc.org/article/PPR/PPR342270; doi:https://doi.org/10.2139/ssrn.3839453
 PPR461923,https://doi.org/10.1101/2022.02.24.22271466,Risk of COVID-19 related deaths for SARS-CoV-2 Omicron (B.1.1.529) compared with Delta (B.1.617.2),"Ward IL, Bermingham C, Ayoubkhani D, Gethings OJ, Pouwels KB, Yates T, Khunti K, Hippisley-Cox J, Banerjee A, Walker AS, Nafilyan V.",,No Journal Info,2022,2022-02-25,Y,,,,"<h4>Objective</h4> To assess the risk of death involving COVID-19 following infection from Omicron (B.1.1.539/BA.1) relative to Delta (B.1.617.2). <h4>Design</h4> Retrospective cohort study. <h4>Setting</h4> England, UK, 1 December 2021 to 25 January 2022. <h4>Participants</h4> 1,035,163 people aged 18-100 years who tested positive for SARS-CoV-2 in the national surveillance programme, and had an infection identified as either Omicron- or Delta compatible. <h4>Main outcome measures</h4> Death involving COVID-19 as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause-specific Cox proportional hazard regression models were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, Index of Multiple Deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Additionally, we tested for interactions between variant and sex, age, vaccination status and comorbidities. <h4>Results</h4> The risk of death involving COVID-19 was 67% lower for Omicron compared to Delta and the reduction in the risk of death involving COVID-19 for Omicron compared to Delta was more pronounced in males than in females and in people under 70 years old than in people aged 70 years or over. Regardless of age, reduction of the risk of death from Omicron relative to Delta more was more pronounced in people who had received a booster than in those having received only two doses. <h4>Conclusions</h4> Our results support early work showing the relative reduction in severity of Omicron compared to Delta in terms of hospitalisation and extends this research to assess COVID-19 mortality. Our work also highlights the importance of the vaccination booster campaign, where the reduction in risk of death involving COVID-19 is most pronounced in individuals who had received a booster. <h4>What is already known on this topic</h4> The Omicron variant, which refers to the whole lineage (BA.1, BA.2, BA.3) had already been shown to be more transmissible than the Delta variant, but there is emerging evidence suggests that the risk of hospitalisation and risk of death within 28 days after a SARS-COV-2 test is lower. However, with a highly transmissible infection and high levels of population testing, definition of death within 28 days is more likely to be susceptible to misclassification bias due to asymptomatic or co-incidental infection. There is no study so far comparing the risk of COVID-19 death as identified from death certification records, with the cause of death assessed by the physician who attended the patient in the last illness. <h4>What this study adds</h4> Using data from a large cohort of COVID-19 infections that occurred in December 2021, we examined the difference in the risk COVID-19 death, as identified from death certification records, between the Delta and Omicron BA.1 variant. Our study shows that risk of death involving COVID-19 was reduced by 67% following infection with the Omicron BA.1 variant relative to the Delta variant after adjusting for a wide range of potential confounders, including vaccination status and comorbidities. Importantly, we found that the relative risk of COVID-19 mortality following Omicron versus Delta infection varied by age and sex, with lower relative risk in younger individuals and for males than females. The reduction in risk of death involving COVID-19 was also most pronounced in individuals who had received a booster.",,pdf:https://ora.ox.ac.uk/objects/uuid:f58b35e2-2a6a-44a4-ae5c-8c6df8eb041b/files/rf4752h39j; doi:https://doi.org/10.1101/2022.02.24.22271466; html:https://europepmc.org/article/PPR/PPR461923; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR461923&type=FILE&fileName=EMS148831-pdf.pdf&mimeType=application/pdf
-PPR673302,https://doi.org/10.1101/2023.06.08.544212,Towards Pandemic-Scale Ancestral Recombination Graphs of SARS-CoV-2,"Zhan SH, Ignatieva A, Wong Y, Eaton K, Jeffery B, Palmer DS, Murall CL, Otto SP, Kelleher J.",,No Journal Info,2023,2023-06-08,Y,,,,"Recombination is an ongoing and increasingly important feature of circulating lineages of SARS-CoV-2, challenging how we represent the evolutionary history of this virus and giving rise to new variants of potential public health concern by combining transmission and immune evasion properties of different lineages. Detection of new recombinant strains is challenging, with most methods looking for breaks between sets of mutations that characterise distinct lineages. In addition, many basic approaches fundamental to the study of viral evolution assume that recombination is negligible, in that a single phylogenetic tree can represent the genetic ancestry of the circulating strains. Here we present an initial version of sc2ts, a method to automatically detect recombinants in real time and to cohesively integrate them into a genealogy in the form of an ancestral recombination graph (ARG), which jointly records mutation, recombination and genetic inheritance. We infer two ARGs under different sampling strategies, and study their properties. One contains 1.27 million sequences sampled up to June 30, 2021, and the second is more sparsely sampled, consisting of 657K sequences sampled up to June 30, 2022. We find that both ARGs are highly consistent with known features of SARS-CoV-2 evolution, recovering the basic backbone phylogeny, mutational spectra, and recapitulating details on the majority of known recombinant lineages. Using the well-established and feature-rich tskit library, the ARGs can also be stored concisely and processed efficiently using standard Python tools. For example, the ARG for 1.27 million sequences—encoding the inferred reticulate ancestry, genetic variation, and extensive metadata—requires 58MB of storage, and loads in less than a second. The ability to fully integrate the effects of recombination into downstream analyses, to quickly and automatically detect new recombinants, and to utilise an efficient and convenient platform for computation based on well-engineered technologies makes sc2ts a promising approach.",,pdf:https://www.biorxiv.org/content/biorxiv/early/2023/06/08/2023.06.08.544212.full.pdf; doi:https://doi.org/10.1101/2023.06.08.544212; html:https://europepmc.org/article/PPR/PPR673302; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR673302&type=FILE&fileName=EMS177195-pdf.pdf&mimeType=application/pdf
 PPR433492,https://doi.org/10.1101/2021.12.17.21267925,SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2,"Eales O, Page AJ, de Oliveira Martins L, Wang H, Bodinier B, Haw D, Jonnerby J, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Chadeau-Hyam M, Donnelly CA, Elliott P, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-12-17,Y,,,,"Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Here we present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. From 9 to 27 September 2021 (round 14) and 19 October to 5 November 2021 (round 15), all lineages sequenced within REACT-1 were Delta or a Delta sub-lineage with 44 unique lineages identified. The proportion of the original Delta variant (B.1.617.2) was found to be increasing between September and November 2021, which may reflect an increasing number of sub-lineages which have yet to be identified. The proportion of B.1.617.2 was greatest in London, which was further identified as a region with an increased level of genetic diversity. The Delta sub-lineage AY.4.2 was found to be robustly increasing in proportion, with a reproduction number 15% (8%, 23%) greater than its parent and most prevalent lineage, AY.4. Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Though no difference in the viral load based on cycle threshold (Ct) values was identified, a lower proportion of those infected with AY.4.2 had symptoms for which testing is usually recommend (loss or change of sense of taste, loss or change of sense of smell, new persistent cough, fever), compared to AY.4 (p = 0.026). The evolutionary rate of SARS-CoV-2, as measured by the mutation rate, was found to be slowing down during the study period, with AY.4.2 further found to have a reduced mutation rate relative to AY.4. As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.",,doi:https://doi.org/10.1101/2021.12.17.21267925; html:https://europepmc.org/article/PPR/PPR433492; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR433492&type=FILE&fileName=EMS141788-pdf.pdf&mimeType=application/pdf; pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/98322/13/s12879-022-07628-4.pdf
+PPR673302,https://doi.org/10.1101/2023.06.08.544212,Towards Pandemic-Scale Ancestral Recombination Graphs of SARS-CoV-2,"Zhan SH, Ignatieva A, Wong Y, Eaton K, Jeffery B, Palmer DS, Murall CL, Otto SP, Kelleher J.",,No Journal Info,2023,2023-06-08,Y,,,,"Recombination is an ongoing and increasingly important feature of circulating lineages of SARS-CoV-2, challenging how we represent the evolutionary history of this virus and giving rise to new variants of potential public health concern by combining transmission and immune evasion properties of different lineages. Detection of new recombinant strains is challenging, with most methods looking for breaks between sets of mutations that characterise distinct lineages. In addition, many basic approaches fundamental to the study of viral evolution assume that recombination is negligible, in that a single phylogenetic tree can represent the genetic ancestry of the circulating strains. Here we present an initial version of sc2ts, a method to automatically detect recombinants in real time and to cohesively integrate them into a genealogy in the form of an ancestral recombination graph (ARG), which jointly records mutation, recombination and genetic inheritance. We infer two ARGs under different sampling strategies, and study their properties. One contains 1.27 million sequences sampled up to June 30, 2021, and the second is more sparsely sampled, consisting of 657K sequences sampled up to June 30, 2022. We find that both ARGs are highly consistent with known features of SARS-CoV-2 evolution, recovering the basic backbone phylogeny, mutational spectra, and recapitulating details on the majority of known recombinant lineages. Using the well-established and feature-rich tskit library, the ARGs can also be stored concisely and processed efficiently using standard Python tools. For example, the ARG for 1.27 million sequences—encoding the inferred reticulate ancestry, genetic variation, and extensive metadata—requires 58MB of storage, and loads in less than a second. The ability to fully integrate the effects of recombination into downstream analyses, to quickly and automatically detect new recombinants, and to utilise an efficient and convenient platform for computation based on well-engineered technologies makes sc2ts a promising approach.",,pdf:https://www.biorxiv.org/content/biorxiv/early/2023/06/08/2023.06.08.544212.full.pdf; doi:https://doi.org/10.1101/2023.06.08.544212; html:https://europepmc.org/article/PPR/PPR673302; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR673302&type=FILE&fileName=EMS177195-pdf.pdf&mimeType=application/pdf
 PPR599577,https://doi.org/10.21203/rs.3.rs-2349826/v1,"COVID-19 Vaccination in Pregnancy: The Impact of Multimorbidity and Smoking Status on Vaccine Hesitancy, a Cohort Study of 25,111 Women in Wales, UK","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Akbari A, Zuccolo L, Azcoaga-Lorenzo A, Davies A, Nirantharakumar K, Brophy S.",,No Journal Info,2023,2023-01-18,Y,,,,"<h4>Background: </h4> Multimorbidity and pregnancy are two risk factors for more severe outcomes after a SARS-CoV-2 infection, thus vaccination uptake is important for pregnant women living with multimorbidity. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage. Methods This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13 th April 2021 to 31 st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy by multimorbidity and smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. Variation in uptake by; multimorbidity, smoking status, and demographics was examined jointly and separately for the independent conditions using hazard ratios (HR) from the Cox regression model. Results Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.02). Women living with multimorbidity were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). Conclusion Younger women, living without multimorbidity, current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Women living with multimorbidity are slightly but significantly less likely to be hesitant about COVID-19 vaccination when pregnant.",,pdf:https://www.researchsquare.com/article/rs-2349826/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-2349826/v1; html:https://europepmc.org/article/PPR/PPR599577; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR599577&type=FILE&fileName=EMS163297-pdf.pdf&mimeType=application/pdf
 PPR486653,https://doi.org/10.1101/2022.04.21.22274152,"Health care use attributable to COVID-19: A propensity matched national electronic health records cohort study of 249,390 people in Wales, UK","Kennedy J, Parker M, Seaborne M, Mhereeg M, Walker A, Walker V, Denaxas S, Kennedy N, Katikireddi S, Brophy S.",,No Journal Info,2022,2022-04-27,Y,,,,"<h4>Background</h4> To determine the extent and nature of changes in infected patients healthcare utilization, we studied healthcare contact in the 1-4 weeks and 5-24 weeks following a COVID-19 diagnosis compared to propensity matched controls. <h4>Methods</h4> Survival analysis was used for time to death and first clinical outcomes including clinical terminology concepts for post-viral illness, fatigue, embolism, respiratory conditions, mental and developmental conditions, fit note, or hospital attendance. Increased instantaneous risk for the occurrence of an outcome for positive individuals was quantified using hazard ratios (HR) from Cox Regression and absolute risk was quantified using relative risk (RR) from life table analysis. <h4>Results</h4> Compared to matched individuals testing negative, surviving positive community-tested patients had a higher risk of post-viral illness (HR: 4.57, 95%CI: 1.77-11.80, p=0.002), fatigue (HR: 1.47, 95%CI: 1.24-1.75, p<0.001) and embolism (HR: 1.51, 95%CI: 1.13-2.02, p=0.005) at 5-24 weeks post-diagnosis. In the four weeks after COVID-19 higher rates of sick notes were being issued for community-tested (HR: 3.04, 95%CI: 0.88 to 10.50, p<0.079); the risk was reduced after four weeks, compared to controls. Overall healthcare attendance for anxiety, depression was less likely in those with COVID-19 in the first four weeks (HR: 0.83, 95%CI: 0.73-1.06, p=0.007). After four weeks, anxiety, depression is less likely to occur for the positive community-tested individuals (HR: 0.87, 95%CI: 0.77-1.00, p=0.048), but more likely for positive hospital-tested individuals (HR: 1.16, 95%CI: 1.00-1.45, p=0.053). Although statistical associations between positive infection and post-infection healthcare use are clear, the absolute use of healthcare is very. <h4>Conclusions</h4> Community COVID-19 disease is associated with increased risks of post-viral illness, fatigue, embolism, depression, anxiety and respiratory conditions. Despite these elevated risks, the absolute healthcare burden is low. Either very small proportions of people experience adverse outcomes following COVID-19 or they are not presenting to healthcare. <h4>Trial registration</h4> Data held in SAIL databank are anonymised and therefore, no ethical approval is required. All data in SAIL has the permission from the relevant Caldicott Guardian or Data Protection Officer and SAIL-related projects are required to obtain Information Governance Review Panel (IGRP) approval. The IGRP approval number for this study is 1259.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/04/27/2022.04.21.22274152.full.pdf; doi:https://doi.org/10.1101/2022.04.21.22274152; html:https://europepmc.org/article/PPR/PPR486653; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR486653&type=FILE&fileName=EMS144659-pdf.pdf&mimeType=application/pdf
 PPR432994,https://doi.org/10.1101/2021.12.14.21267806,"REACT-1 round 15 final report: Increased breakthrough SARS-CoV-2 infections among adults who had received two doses of vaccine, but booster doses and first doses in children are providing important protection","Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Walters CE, Jonnerby J, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,No Journal Info,2021,2021-12-16,Y,,,,"<h4>Background</h4> It has been nearly a year since the first vaccinations against SARS-CoV-2 were delivered in England. The third wave of COVID-19 in England began in May 2021 as the Delta variant began to outcompete and largely replace other strains. The REal-time Assessment of Community Transmission-1 (REACT-1) series of community surveys for SARS-CoV-2 infection has provided insights into transmission dynamics since May 2020. Round 15 of the REACT-1 study was carried out from 19 October to 5 November 2021. <h4>Methods</h4> We estimated prevalence of SARS-CoV2 infection and used multiple logistic regression to analyse associations between SARS-CoV-2 infection in England and demographic and other risk factors, based on RT-PCR results from self-administered throat and nose swabs in over 100,000 participants. We estimated (single-dose) vaccine effectiveness among children aged 12 to 17 years, and among adults compared swab-positivity in people who had received a third (booster) dose with those who had received two vaccine doses. We used splines to analyse time trends in swab-positivity. <h4>Results</h4> During mid-October to early-November 2021, weighted prevalence was 1.57% (1.48%, 1.66%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14). Weighted prevalence increased between rounds 14 and 15 across most age groups (including older ages, 65 years and over) and regions, with average reproduction number across rounds of R=1.09 (1.08, 1.11). During round 15, there was a fall in prevalence from a maximum around 20-21 October, with an R of 0.76 (0.70, 0.83), reflecting falls in prevalence at ages 17 years and below and 18 to 54 years. School-aged children had the highest weighted prevalence of infection: 4.95% (4.39%, 5.58%) in those aged 5 to 12 years and 5.21% (4.61%, 5.87%) in those aged 13 to 17 years. In multiple logistic regression, age, sex, key worker status and presence of one or more children in the home were associated with swab positivity. There was evidence of heterogeneity between rounds in swab positivity rates among vaccinated individuals at ages 18 to 64 years, and differences in key demographic and other variables between vaccinated and unvaccinated adults at these ages. Vaccine effectiveness against infection in children was estimated to be 56.2% (41.3%, 67.4%) in rounds 13, 14 and 15 combined, adjusted for demographic factors, with a similar estimate obtained for round 15 only. Among adults we found that those who received a third dose of vaccine were less likely to test positive compared to those who received only two vaccine doses, with adjusted odds ratio (OR) =0.38 (0.26, 0.55). <h4>Discussion</h4> Swab-positivity was very high at the start of round 15, reaching a maximum around 20 to 21 October 2021, and then falling through late October with an uncertain trend in the last few days of data collection. The observational nature of survey data and the relatively small proportion of unvaccinated adults call into question the comparability of vaccinated and unvaccinated groups at this relatively late stage in the vaccination programme. However, third vaccine doses for eligible adults and the vaccination of children aged 12 years and over are associated with lower infection risk and, thus, remain a high priority (with possible extension to children aged 5-12 years). These should help reduce SARS-CoV-2 transmission during the winter period when healthcare demands typically rise.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/12/16/2021.12.14.21267806.full.pdf; doi:https://doi.org/10.1101/2021.12.14.21267806; html:https://europepmc.org/article/PPR/PPR432994; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR432994&type=FILE&fileName=EMS141765-pdf.pdf&mimeType=application/pdf
@@ -149,8 +149,8 @@ PPR433539,https://doi.org/10.1101/2021.12.16.21267934,Predictors of SARS-CoV-2 i
 PPR365249,https://doi.org/10.1101/2021.06.28.21259452,"Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people","Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P.",,No Journal Info,2021,2021-07-03,Y,,,,"<h4>Summary</h4> <h4>Background</h4> Long COVID, describing the long-term sequelae after SARS-CoV-2 infection, remains a poorly defined syndrome. There is uncertainty about its predisposing factors and the extent of the resultant public health burden, with estimates of prevalence and duration varying widely. <h4>Methods</h4> Within rounds 3–5 of the REACT-2 study, 508,707 people in the community in England were asked about a prior history of COVID-19 and the presence and duration of 29 different symptoms. We used uni-and multivariable models to identify predictors of persistence of symptoms (12 weeks or more). We estimated the prevalence of symptom persistence at 12 weeks, and used unsupervised learning to cluster individuals by symptoms experienced. <h4>Findings</h4> Among the 508,707 participants, the weighted prevalence of self-reported COVID-19 was 19.2% (95% CI: 19.1,19.3). 37.7% of 76,155 symptomatic people post COVID-19 experienced at least one symptom, while 14.8% experienced three or more symptoms, lasting 12 weeks or more. This gives a weighted population prevalence of persistent symptoms of 5.75% (5.68, 5.81) for one and 2.22% (2.1, 2.26) for three or more symptoms. Almost a third of people (8,771/28,713 [30.5%]) with at least one symptom lasting 12 weeks or more reported having had severe COVID-19 symptoms (“significant effect on my daily life”) at the time of their illness, giving a weighted prevalence overall for this group of 1.72% (1.69,1.76). The prevalence of persistent symptoms was higher in women than men (OR: 1.51 [1.46,1.55]) and, conditional on reporting symptoms, risk of persistent symptoms increased linearly with age by 3.5 percentage points per decade of life. Obesity, smoking or vaping, hospitalisation, and deprivation were also associated with a higher probability of persistent symptoms, while Asian ethnicity was associated with a lower probability. Two stable clusters were identified based on symptoms that persisted for 12 weeks or more: in the largest cluster, tiredness predominated, while in the second there was a high prevalence of respiratory and related symptoms. <h4>Interpretation</h4> A substantial proportion of people with symptomatic COVID-19 go on to have persistent symptoms for 12 weeks or more, which is age-dependent. Clinicians need to be aware of the differing manifestations of Long COVID which may require tailored therapeutic approaches. Managing the long-term sequelae of SARS-CoV-2 infection in the population will remain a major challenge for health services in the next stage of the pandemic. <h4>Funding</h4> The study was funded by the Department of Health and Social Care in England. <h4>Research in context</h4> <h4>Evidence before this study</h4> Recent systematic reviews have documented the wide range of symptoms and reported prevalence of persistent symptoms following COVID-19. A dynamic review of Long COVID studies (NIHR Evidence) in March 2021 summarised the literature on the prevalence of persistent symptoms after acute COVID19, and reported that most studies (14) were of hospitalised patients, with higher prevalence of persistent symptoms compared with two community-based studies. There was limited evidence from community studies beyond 12 weeks. Another systematic review reported a median of over 70% of people with symptoms lasting at least 60 days. A review of risk factors for Long COVID found consistent evidence for an increased risk amongst women and those with high body mass index (BMI) but inconsistent findings on the role of age and little evidence concerning risks among different socioeconomic or ethnic groups which are often not well captured in routine healthcare records. Long COVID is increasingly recognised as heterogenous, likely underpinned by differing biological mechanisms, but there is not yet consensus on defining subtypes of the condition. <h4>Added value of this study</h4> This community-based study of over half a million people was designed to be representative of the adult population of England. A random sample of adults ages 18 years and above registered with a GP were invited irrespective of previous access to services for COVID-19, providing an estimate of population prevalence that was representative of the whole population. The findings show substantial declines in symptom prevalence over the first 12 weeks following Covid-19, reported by nearly one fifth of respondents, of whom over a third remained symptomatic at 12 weeks and beyond, with little evidence for decline thereafter. Risk factors identified for persistent symptoms (12 weeks or more) suggestive of Long COVID confirm some previous findings - an increased risk in women, obese and overweight individuals and those hospitalised for COVID-19, with strong evidence for an increasing risk with age. Additional evidence was found for an increased risk in those with lower income, smoking or vaping and healthcare or care home workers. A lower risk was found in those of Asian ethnicity. Clustering identified two distinct groups of individuals wit h different symptom profiles at 12 weeks, highlighting the heterogeneity of clinical presentation. The smaller cluster had higher prevalence of respiratory and related symptoms, while for those in the larger cluster tiredness was the dominant symptom, with lower prevalence of organ-specific symptoms. <h4>Implications of available evidence</h4> There is a high prevalence of persistent symptoms beyond 12 weeks after acute COVID-19, with little evidence of decline thereafter. This highlights the needs for greater support for patients, both through specialised services and, for those from low-income settings, financial support. The understanding that there are distinct clusters of persistent symptoms, the most common of which is dominated by fatigue, is important for the recognition and clinical management of the condition outside of specialised services.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/03/2021.06.28.21259452.full.pdf; doi:https://doi.org/10.1101/2021.06.28.21259452; html:https://europepmc.org/article/PPR/PPR365249; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR365249&type=FILE&fileName=EMS129876-pdf.pdf&mimeType=application/pdf
 PPR382446,https://doi.org/10.1101/2021.08.12.21261987,Characterising the persistence of RT-PCR positivity and incidence in a community survey of SARS-CoV-2,"Eales O, Walters CE, Wang H, Haw D, Ainslie KEC, Atchison C, Page AJ, Prosolek SJ, Trotter AJ, Le Viet T, Alikhan N, Jackson LM, Ludden C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley S, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-08-13,Y,,,,"<h4>Background</h4> Community surveys of SARS-CoV-2 RT-PCR swab-positivity provide prevalence estimates largely unaffected by biases from who presents for routine case testing. The REal-time Assessment of Community Transmission-1 (REACT-1) has estimated swab-positivity approximately monthly since May 2020 in England from RT-PCR testing of self-administered throat and nose swabs in random non-overlapping cross-sectional community samples. Estimating infection incidence from swab-positivity requires an understanding of the persistence of RT-PCR swab positivity in the community. <h4>Methods</h4> During round 8 of REACT-1 from 6 January to 22 January 2021, of the 2,282 participants who tested RT-PCR positive, we recruited 896 (39%) from whom we collected up to two additional swabs for RT-PCR approximately 6 and 9 days after the initial swab. We estimated sensitivity and duration of positivity using an exponential model of positivity decay, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. Estimates of infection incidence were obtained for the entire duration of the REACT-1 study using P-splines. <h4>Results</h4> We estimated the overall sensitivity of REACT-1 to detect virus on a single swab as 0.79 (0.77, 0.81) and median duration of positivity following a positive test as 9.7 (8.9, 10.6) days. We found greater median duration of positivity where there was a low N-gene Ct value, in those exhibiting symptoms, or for infection with the Alpha variant. The estimated proportion of positive individuals detected on first swab, P 0 , was found to be higher for those with an initially low N-gene Ct value and those who were pre-symptomatic. When compared to swab-positivity, estimates of infection incidence over the duration of REACT-1 included sharper features with evident transient increases around the time of key changes in social distancing measures. <h4>Discussion</h4> Home self-swabbing for RT-PCR based on a single swab, as implemented in REACT-1, has high overall sensitivity. However, participants’ time-since-infection, symptom status and viral lineage affect the probability of detection and the duration of positivity. These results validate previous efforts to estimate incidence of SARS-CoV-2 from swab-positivity data, and provide a reliable means to obtain community infection estimates to inform policy response.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/08/13/2021.08.12.21261987.full.pdf; doi:https://doi.org/10.1101/2021.08.12.21261987; html:https://europepmc.org/article/PPR/PPR382446; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR382446&type=FILE&fileName=EMS132863-pdf.pdf&mimeType=application/pdf
 PPR339757,https://doi.org/10.1101/2021.05.08.21256867,SARS-CoV-2 lineage dynamics in England from January to March 2021 inferred from representative community samples,"Eales O, Page AJ, Tang SN, Walters CE, Wang H, Haw D, Trotter AJ, Viet TL, Foster-Nyarko E, Prosolek S, Atchison C, Ashby D, Cooke G, Barclay W, Donnelly CA, O’Grady J, Volz E, Darzi A, Ward H, Elliott P, Riley S, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-05-14,Y,,,,"Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained from a variety of sources. Here, we describe lineage dynamics and phylogenetic relationships using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR during the first three months of 2021 as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the B.1.1.7 lineage (first identified in Kent) predominant, driven by a 0.3 unit higher reproduction number over the prior wild type. During January, positive samples were more likely B.1.1.7 in younger and middle-aged adults (aged 18 to 54) than in other age groups. Although individuals infected with the B.1.1.7 lineage were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild type, they were more likely to be antibody positive 6 weeks after infection. Viral load was higher in B.1.1.7 infection as measured by cycle threshold (Ct) values, but did not account for the increased rate of testing positive for antibodies. The presence of infections with non-imported B.1.351 lineage (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing and targeted public health interventions and does not immediately imply similar lineages could not become established in the future. Sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/05/14/2021.05.08.21256867.full.pdf; doi:https://doi.org/10.1101/2021.05.08.21256867; html:https://europepmc.org/article/PPR/PPR339757; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR339757&type=FILE&fileName=EMS127680-pdf.pdf&mimeType=application/pdf
-PPR408448,https://doi.org/10.1101/2021.10.13.21264937,Comparative effectiveness of ChAdOx1 versus BNT162b2 COVID-19 vaccines in Health and Social Care workers in England: a cohort study using OpenSAFELY,"Hulme WJ, Williamson EJ, Green A, Bhaskaran K, McDonald HI, Rentsch CT, Schultze A, Tazare J, Curtis HJ, Walker AJ, Tomlinson L, Palmer T, Horne E, MacKenna B, Morton CE, Mehrkar A, Fisher L, Bacon S, Evans D, Inglesby P, Hickman G, Davy S, Ward T, Croker R, Eggo RM, Wong AY, Mathur R, Wing K, Forbes H, Grint D, Douglas IJ, Evans SJ, Smeeth L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Sterne JA, Hernán M, Goldacre B.",,No Journal Info,2021,2021-10-18,Y,,,,"<h4>Objectives</h4> To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines against infection and COVID-19 disease in health and social care workers. <h4>Design</h4> Cohort study, emulating a comparative effectiveness trial. <h4>Setting</h4> Linked primary care, hospital, and COVID-19 surveillance records available within the OpenSAFELY-TPP research platform. <h4>Participants</h4> 317,341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a GP practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable. <h4>Interventions</h4> Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national COVID-19 vaccine roll-out. <h4>Main outcome measures</h4> Recorded SARS-CoV-2 positive test, or COVID-19 related Accident and Emergency attendance or hospital admission occurring within 20 weeks of vaccination. <h4>Results</h4> The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks post-vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 6 weeks after vaccination with BNT162b2 was 19.2 per 1000 people (95%CI 18.6 to 19.7) and with ChAdOx1 was 18.9 (95%CI 17.6 to 20.3), representing a difference of -0.24 per 1000 people (95%CI -1.71 to 1.22). The difference in the cumulative incidence per 1000 people of COVID-19 accident and emergency attendance at 6 weeks was 0.01 per 1000 people (95%CI -0.27 to 0.28). For COVID-19 hospital admission, this difference was 0.03 per 1000 people (95%CI -0.22 to 0.27). <h4>Conclusions</h4> In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or COVID-19 disease up to 20 weeks after vaccination. Incidence dropped sharply after 3-4 weeks and there were very few COVID-19 hospital attendance and admission events after this period. This is in line with expected onset of vaccine-induced immunity, and suggests strong protection against COVID-19 disease for both vaccines.",,pdf:https://research-information.bris.ac.uk/files/345986511/bmj_2021_068946.full.pdf; doi:https://doi.org/10.1101/2021.10.13.21264937; html:https://europepmc.org/article/PPR/PPR408448; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR408448&type=FILE&fileName=EMS137186-pdf.pdf&mimeType=application/pdf
 PPR278785,https://doi.org/10.1101/2021.02.03.21251004,Ethnic differences in COVID-19 mortality during the first two waves of the Coronavirus Pandemic: a nationwide cohort study of 29 million adults in England,"Nafilyan V, Islam N, Mathur R, Ayoubkhani D, Banerjee A, Glickman M, Humberstone B, Diamond I, Khunti K.",,No Journal Info,2021,2021-02-05,Y,,,,"<h4>Background</h4> Ethnic minorities have experienced disproportionate COVID-19 mortality rates in the UK and many other countries. We compared the differences in the risk of COVID-19 related death between ethnic groups in the first and second waves the of COVID-19 pandemic in England. We also investigated whether the factors explaining differences in COVID-19 death between ethnic groups changed between the two waves. <h4>Methods</h4> Using data from the Office for National Statistics Public Health Data Asset on individuals aged 30-100 years living in private households, we conducted an observational cohort study to examine differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24 th January 2020 until 31 st August 2020) and second wave (from 1 st September to 28 th December 2020). We estimated age-standardised mortality rates (ASMR) in the two waves stratified by ethnic groups and sex. We also estimated hazard ratios (HRs) for ethnic-minority groups compared with the White British population, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions. <h4>Results</h4> The study population included over 28.9 million individuals aged 30-100 years living in private households. In the first wave, all ethnic minority groups had a higher risk of COVID-19 related death compared to the White British population. In the second wave, the risk of COVID-19 death remained elevated for people from Pakistani (ASMR: 339.9 [95% CI: 303.7 – 376.2] and 166.8 [141.7 – 191.9] deaths per 100,000 population in men and women) and Bangladeshi (318.7 [247.4 – 390.1] and 127.1 [91.1 – 171.3] in men and women)background but not for people from Black ethnic groups. Adjustment for geographical factors explained a large proportion of the differences in COVID-19 mortality in the first wave but not in the second wave. Despite an attenuation of the elevated risk of COVID-19 mortality after adjusting for sociodemographic characteristics and health status, the risk was substantially higher in people from Bangladeshi and Pakistani background in both the first and the second waves. <h4>Conclusion</h4> Between the first and second waves of the pandemic, the reduction in the difference in COVID-19 mortality between people from Black ethnic background and people from the White British group shows that ethnic inequalities in COVID-19 mortality can be addressed. The continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy changes. *VN and NI contributed equally to this paper <h4>Research in context</h4> <h4>Evidence before this study</h4> A recent systematic review by Pan and colleagues demonstrated that people of ethnic minority background in the UK and the USA have been disproportionately affected by the Coronavirus (COVID-19) pandemic, compared to White populations. While several studies have investigated whether adjusting for socio-demographic and economic factors and medical history reduces the estimated difference in risk of mortality and hospitalisation, the reasons for the differences in the risk of experiencing harms from COVID-19 are still being explored during the course of the pandemic. Studies so far have analysed the ethnic differences in COVID-19 mortality in the first wave of the pandemic. The evidence on the temporal trend of ethnic inequalities in COVID-19 mortality, especially those from the second wave of the pandemic, is scarce. <h4>Added value of this study</h4> Using data from the Office for National Statistics (ONS) Public Health Data Asset on 29 million adults aged 30-100 years living in private households in England, we conducted an observational cohort study to examine the differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24 th January 2020 until 31 st August 2020) and second wave (from 1 st September to 28 th December 2020). We find that in the first wave all ethnic minority groups were at elevated risk of COVID-19 related death compared to the White British population. In the second wave, the differences in the risk of COVID-19 related death attenuated for Black African and Black Caribbean groups, remained substantially higher in people from Bangladeshi background, and worsened in people from Pakistani background. We also find that some of the factors explaining these differences in mortality have changed in the two waves. <h4>Implications of all the available evidence</h4> The risk of COVID-19 mortality during the first wave of the pandemic was elevated in people from ethnic minority background. An appreciable reduction in the difference in COVID-19 mortality in the second wave of the pandemic between people from Black ethnic background and people from the White British group is reassuring, but the continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy response. Focusing on treating underlying conditions, although important, may not be enough in reducing the inequalities in COVID-19 mortality. Focused public health policy as well as community mobilisation and participatory public health campaign involving community leaders may help reduce the existing and widening inequalities in COVID-19 mortality.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00765-1.pdf; doi:https://doi.org/10.1101/2021.02.03.21251004; html:https://europepmc.org/article/PPR/PPR278785; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR278785&type=FILE&fileName=EMS116038-pdf.pdf&mimeType=application/pdf
+PPR408448,https://doi.org/10.1101/2021.10.13.21264937,Comparative effectiveness of ChAdOx1 versus BNT162b2 COVID-19 vaccines in Health and Social Care workers in England: a cohort study using OpenSAFELY,"Hulme WJ, Williamson EJ, Green A, Bhaskaran K, McDonald HI, Rentsch CT, Schultze A, Tazare J, Curtis HJ, Walker AJ, Tomlinson L, Palmer T, Horne E, MacKenna B, Morton CE, Mehrkar A, Fisher L, Bacon S, Evans D, Inglesby P, Hickman G, Davy S, Ward T, Croker R, Eggo RM, Wong AY, Mathur R, Wing K, Forbes H, Grint D, Douglas IJ, Evans SJ, Smeeth L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Sterne JA, Hernán M, Goldacre B.",,No Journal Info,2021,2021-10-18,Y,,,,"<h4>Objectives</h4> To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines against infection and COVID-19 disease in health and social care workers. <h4>Design</h4> Cohort study, emulating a comparative effectiveness trial. <h4>Setting</h4> Linked primary care, hospital, and COVID-19 surveillance records available within the OpenSAFELY-TPP research platform. <h4>Participants</h4> 317,341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a GP practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable. <h4>Interventions</h4> Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national COVID-19 vaccine roll-out. <h4>Main outcome measures</h4> Recorded SARS-CoV-2 positive test, or COVID-19 related Accident and Emergency attendance or hospital admission occurring within 20 weeks of vaccination. <h4>Results</h4> The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks post-vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 6 weeks after vaccination with BNT162b2 was 19.2 per 1000 people (95%CI 18.6 to 19.7) and with ChAdOx1 was 18.9 (95%CI 17.6 to 20.3), representing a difference of -0.24 per 1000 people (95%CI -1.71 to 1.22). The difference in the cumulative incidence per 1000 people of COVID-19 accident and emergency attendance at 6 weeks was 0.01 per 1000 people (95%CI -0.27 to 0.28). For COVID-19 hospital admission, this difference was 0.03 per 1000 people (95%CI -0.22 to 0.27). <h4>Conclusions</h4> In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or COVID-19 disease up to 20 weeks after vaccination. Incidence dropped sharply after 3-4 weeks and there were very few COVID-19 hospital attendance and admission events after this period. This is in line with expected onset of vaccine-induced immunity, and suggests strong protection against COVID-19 disease for both vaccines.",,pdf:https://research-information.bris.ac.uk/files/345986511/bmj_2021_068946.full.pdf; doi:https://doi.org/10.1101/2021.10.13.21264937; html:https://europepmc.org/article/PPR/PPR408448; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR408448&type=FILE&fileName=EMS137186-pdf.pdf&mimeType=application/pdf
 PPR468085,https://doi.org/10.1101/2022.03.11.22272276,Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT1262b2 and after booster vaccination with BNT1262b2 or mRNA-1273: a population-based cohort study (COVIDENCE UK),"Vivaldi G, Jolliffe DA, Holt H, Tydeman F, Talaei M, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,No Journal Info,2022,2022-03-13,Y,,,,"<h4>Background</h4> Little is known about the relative influence of demographic, behavioural, and vaccine-related factors on risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations. <h4>Methods</h4> We undertook a prospective population-based study in UK adults (≥16 years) vaccinated against SARS-CoV-2, including data from Jan 12, 2021, to Feb 21, 2022. We modelled risk of post-vaccination SARS-CoV-2 infection separately for participants who had completed a primary course of vaccination (two-dose or, in the immunosuppressed, three-dose course of either ChAdOx1 nCoV-19 [ChAdOx1] or BNT1262b2) and for those who had additionally received a booster dose (BNT1262b2 or mRNA-1273). Cox regression models were used to explore associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and breakthrough infection, defined as a self-reported positive result on a lateral flow or reverse transcription PCR (RT-PCR) test for SARS-CoV-2. Models were further adjusted for weekly SARS-CoV-2 incidence at the local (lower tier local authority) level. <h4>Findings</h4> 14,713 participants were included in the post-primary analysis and 10,665 in the post-booster analysis, with a median follow-up of 203 days (IQR 195–216) in the post-primary cohort and 85 days (66–103) in the post-booster cohort. 1051 (7.1%) participants in the post-primary cohort and 1009 (9.4%) participants in the post-booster cohort reported a breakthrough SARS-CoV-2 infection. A primary course of ChAdOx1 ( vs BNT182b2) was associated with higher risk of infection, both in the post-primary cohort (adjusted hazard ratio 1.63, 95% CI 1.41–1.88) and in the post-booster cohort after boosting with mRNA-1273 (1.29 [1.03–1.61] vs BNT162b2 primary plus BNT162b2 booster). A lower risk of breakthrough infection was associated with older age (post-primary: 0.96 [0.96–0.97] per year; post-booster: 0.97 [0.96–0.98]), whereas a higher risk of breakthrough infection was associated with lower levels of education (post-primary: 1.66 [1.35–2.06] for primary or secondary vs postgraduate; post-booster: 1.36 [1.08–1.71]) and at least three weekly visits to indoor public places (post-primary: 1.38 [1.15–1.66] vs none; post-booster: 1.33 [1.10–1.60]). <h4>Conclusions</h4> Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough SARS-CoV-2 infection following a primary schedule and a booster dose. <h4>Research in context</h4> <h4>Evidence before this study</h4> We searched PubMed, medRxiv, and Google Scholar for papers published up to Feb 18, 2022, using the search terms (breakthrough OR post-vaccin*) AND (SARS-CoV-2 OR COVID) AND (disease OR infection) AND (determinant OR “risk factor” OR associat*), with no language restrictions. Existing studies on risk factors for breakthrough SARS-CoV-2 infection among vaccinated individuals have found associations with age, comorbidities, vaccine type, and previous infection; however, findings have been inconsistent across studies. Most studies have been limited to specific subgroups or have focused on severe outcomes, and very few have considered breakthrough infections after a booster dose or have adjusted for behaviours affecting exposure to other people. <h4>Added value of this study</h4> This study is among the first to provide a detailed analysis of a wide range of risk factors for breakthrough SARS-CoV-2 infection, both after the primary course of vaccination and after a booster dose. Our large study size and detailed data have allowed us to investigate associations with various sociodemographic, clinical, pharmacological, and nutritional factors. Monthly follow-up data have additionally given us the opportunity to consider the effects of behaviours that may have changed across the pandemic, while adjusting for local SARS-CoV-2 incidence. <h4>Implications of all the available evidence</h4> Our findings add to growing evidence that risk factors for SARS-CoV-2 infection after primary or booster vaccinations can differ to those in unvaccinated populations, with effects attenuated for previously observed risk factors such as body-mass index and Asian ethnicity. The clear difference we observed between the efficacies of ChAdOx1 and BNT162b2 as the primary course of vaccination appears to have been reduced by the use of BNT162b2 boosters, but not by mNRA-1273 boosters. As more countries introduce booster vaccinations, future population-based studies with longer follow-up will be needed to investigate our findings further.",,pdf:https://pureadmin.qub.ac.uk/ws/files/383171042/1_s2.0_S2666776222001971_main.pdf; doi:https://doi.org/10.1101/2022.03.11.22272276; html:https://europepmc.org/article/PPR/PPR468085; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR468085&type=FILE&fileName=EMS148998-pdf.pdf&mimeType=application/pdf
 PPR373640,https://doi.org/10.1101/2021.07.21.21260926,"Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults","Ward H, Atchison C, Whitaker M, Donnelly CA, Riley S, Ashby D, Darzi A, Barclay WS, Cooke G, Elliott P, for the REACT study team.",,No Journal Info,2021,2021-07-22,Y,,,,"<h4>Background</h4> REACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England. <h4>Methods</h4> We contacted a random sample of the population by sending a letter to named individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to perform the test at home and complete a questionnaire, including reporting of their test result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for IgG against SARS-CoV-2 between 27 October and 10 November 2020. <h4>Results</h4> The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9% (24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at 9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2% (4.0-4.3). <h4>Interpretation</h4> The second wave of infection in England is apparent in increasing antibody prevalence, particularly in younger people, students, and in the Northern Regions. By late October a large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first and early second wave.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/22/2021.07.21.21260926.full.pdf; doi:https://doi.org/10.1101/2021.07.21.21260926; html:https://europepmc.org/article/PPR/PPR373640; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR373640&type=FILE&fileName=EMS132216-pdf.pdf&mimeType=application/pdf
 PPR354056,https://doi.org/10.1101/2021.06.08.21258535,Altered neutrophil phenotype and function in non-ICU hospitalised COVID-19 patients correlated with disease severity,"Belchamber K, Thein O, Hazeldine J, Grudzinska F, Hughes M, Jasper A, Yip K, Sapey E, Parekh D, Thickett D, Scott A.",,No Journal Info,2021,2021-06-08,Y,,,,"<h4>Rational</h4> Infection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based predominantly on transcriptomics or single functional assays. Cell functions are interwoven pathways, and so understanding the effect of COVID-19 across the spectrum of neutrophil function may identify tractable therapeutic targets. <h4>Objectives</h4> Examine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC) <h4>Methods</h4> Isolated neutrophils from 41 hospitalised, non-ICU COVID-19 patients and 23 AMC underwent ex vivo analyses for migration, bacterial phagocytosis, ROS generation, NET formation (NETosis) and cell surface receptor expression. DNAse 1 activity was measured, alongside circulating levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3-5 post hospitalisation were also measured. <h4>Results</h4> Compared to AMC, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397) and NETosis (p=0.0366), but impaired phagocytosis (p=0.0236) associated with impaired ROS generation (p<0.0001). Surface expression of CD54 (p<0.0001) and CD11c (p=0.0008) was significantly increased and CD11b significantly decreased (p=0.0229) on COVID-19 patient neutrophils. COVID-19 patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001). MPO (p<0.0001), VEGF (p<0.0001), TNFRI (p<0.0001) and IL-6 (p=0.009) were elevated in COVID-19, which positively correlated with disease severity by 4C score. <h4>Conclusion</h4> COVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function may help modulate COVID-19 severity.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/06/08/2021.06.08.21258535.full.pdf; doi:https://doi.org/10.1101/2021.06.08.21258535; html:https://europepmc.org/article/PPR/PPR354056; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR354056&type=FILE&fileName=EMS127476-pdf.pdf&mimeType=application/pdf
@@ -160,17 +160,17 @@ PPR265251,https://doi.org/10.1101/2021.01.15.21249724,Development and evaluation
 PPR241057,https://doi.org/10.1101/2020.11.18.20233932,REACT-1 round 6 updated report: high prevalence of SARS-CoV-2 swab positivity with reduced rate of growth in England at the start of November 2020,"Riley S, Ainslie KEC, Eales O, Walters CE, Wang H, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2020,2020-11-20,Y,,,,"<h4>Background</h4> England is now in the midst of its second wave of the COVID-19 pandemic. Multiple regions of the country are at high infection prevalence and all areas experienced rapid recent growth of the epidemic during October 2020. <h4>Methods</h4> REACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England designed to monitor the spread of the epidemic and thus increase situational awareness. Round 6 of REACT-1 commenced swab-collection on 16th October. A prior interim report included data from 16th to 25th October for 85,971 participants. Here, we report data for the entire round on 160,175 participants with swab results obtained up to 2nd November 2020. <h4>Results</h4> Overall weighted prevalence of infection in the community in England was 1.3% or 130 people per 10,000 infected, up from 60 people per 10,000 in the round 5 report (18th September to 5th October 2020), doubling every 24 days on average since the prior round. The corresponding R number was estimated to be 1.2. Prevalence of infection was highest in North West (2.4%, up from 1.2%), followed by Yorkshire and The Humber (2.3% up from 0.84%), West Midlands (1.6% up from 0.60%), North East (1.5% up from 1.1%), East Midlands (1.3% up from 0.56%), London (0.97%, up from 0.54%), South West (0.80% up from 0.33%), South East (0.69% up from 0.29%), and East of England (0.69% up from 0.30%). Rapid growth in the South observed in the first half of round 6 was no longer apparent in the second half of round 6. We also observed a decline in prevalence in Yorkshire and The Humber during this period. Comparing the first and second halves of round 6, there was a suggestion of decline in weighted prevalence in participants aged 5 to 12 years and in those aged 25 to 44 years. While prevalence remained high, in the second half of round 6 there was suggestion of a slight fall then rise that was seen nationally and also separately in both the North and the South. <h4>Conclusion</h4> The impact of the second national lockdown in England is not yet known. We provide here a detailed description of swab-positivity patterns at national, regional and local scales for the period immediately preceding lockdown, against which future trends in prevalence can be evaluated.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/11/20/2020.11.18.20233932.full.pdf; doi:https://doi.org/10.1101/2020.11.18.20233932; html:https://europepmc.org/article/PPR/PPR241057; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR241057&type=FILE&fileName=EMS104966-pdf.pdf&mimeType=application/pdf
 PPR359256,https://doi.org/10.1101/2021.06.17.21259103,REACT-1 round 12 report: resurgence of SARS-CoV-2 infections in England associated with increased frequency of the Delta variant,"Riley S, Wang H, Eales O, Haw D, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Prosolek SJ, Trotter AJ, Le Viet T, Alikhan N, Jackson LM, Ludden C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-06-21,Y,,,,"<h4>Background</h4> England entered a third national lockdown from 6 January 2021 due to the COVID-19 pandemic. Despite a successful vaccine rollout during the first half of 2021, cases and hospitalisations have started to increase since the end of May as the SARS-CoV-2 Delta (B.1.617.2) variant increases in frequency. The final step of relaxation of COVID-19 restrictions in England has been delayed from 21 June to 19 July 2021. <h4>Methods</h4> The REal-time Assessment of Community Transmision-1 (REACT-1) study measures the prevalence of swab-positivity among random samples of the population of England. Round 12 of REACT-1 obtained self-administered swab collections from participants from 20 May 2021 to 7 June 2021; results are compared with those for round 11, in which swabs were collected from 15 April to 3 May 2021. <h4>Results</h4> Between rounds 11 and 12, national prevalence increased from 0.10% (0.08%, 0.13%) to 0.15% (0.12%, 0.18%). During round 12, we detected exponential growth with a doubling time of 11 (7.1, 23) days and an R number of 1.44 (1.20, 1.73). The highest prevalence was found in the North West at 0.26% (0.16%, 0.41%) compared to 0.05% (0.02%, 0.12%) in the South West. In the North West, the locations of positive samples suggested a cluster in Greater Manchester and the east Lancashire area. Prevalence in those aged 5-49 was 2.5 times higher at 0.20% (0.16%, 0.26%) compared with those aged 50 years and above at 0.08% (0.06%, 0.11%). At the beginning of February 2021, the link between infection rates and hospitalisations and deaths started to weaken, although in late April 2021, infection rates and hospital admissions started to reconverge. When split by age, the weakened link between infection rates and hospitalisations at ages 65 years and above was maintained, while the trends converged below the age of 65 years. The majority of the infections in the younger group occurred in the unvaccinated population or those without a stated vaccine history. We observed the rapid replacement of the Alpha (B.1.1.7) variant of SARS-CoV-2 with the Delta variant during the period covered by rounds 11 and 12 of the study. <h4>Discussion</h4> The extent to which exponential growth continues, or slows down as a consequence of the continued rapid roll-out of the vaccination programme, including to young adults, requires close monitoring. Data on community prevalence are vital to track the course of the epidemic and inform ongoing decisions about the timing of further lifting of restrictions in England.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/06/21/2021.06.17.21259103.full.pdf; doi:https://doi.org/10.1101/2021.06.17.21259103; html:https://europepmc.org/article/PPR/PPR359256; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR359256&type=FILE&fileName=EMS128173-pdf.pdf&mimeType=application/pdf
 PPR445654,https://doi.org/10.1101/2022.01.21.22269605,Outcomes of SARS-CoV-2 Omicron infection in residents of Long-Term Care,"Krutikov M, Stirrup O, Nacer-Laidi H, Azmi B, Fuller C, Tut G, Palmer T, Shrotri M, Irwin-Singer A, Baynton V, Hayward A, Moss P, Copas A, Shallcross L, The COVID-19 Genomics UK (COG-UK) consortium.",,No Journal Info,2022,2022-01-23,Y,,,,"<h4>Background</h4> Recently there has been a rapid, global increase in SARS-CoV-2 infections associated with the Omicron variant (B.1.1.529). Although severity of Omicron cases may be reduced, the scale of infection suggests hospital admissions and deaths may be substantial. Definitive conclusions about disease severity require evidence from populations with the greatest risk of severe outcomes, such as residents of Long-Term Care Facilities (LTCFs). <h4>Methods</h4> We used a cohort study to compare the risk of hospital admission or death in LTCF residents in England who had tested positive for SARS-CoV-2 in the period shortly before Omicron emerged (Delta dominant) and the Omicron-dominant period, adjusting for age, sex, vaccine type, and booster vaccination. Variants were confirmed by sequencing or spike-gene status in a subset. <h4>Results</h4> Risk of hospital admission was markedly lower in 1241 residents infected in the Omicron-period (4.01% hospitalised, 95% CI: 2.87-5.59) compared to 398 residents infected in the pre-Omicron period (10.8% hospitalised, 95% CI: 8.13-14.29, adjusted Hazard Ratio 0.50, 95% CI: 0.29-0.87, p=0.014); findings were similar in residents with confirmed variant. No residents with previous infection were hospitalised in either period. Mortality was lower in the Omicron versus the pre-Omicron period, (p<0.0001). <h4>Conclusions</h4> Risk of severe outcomes in LTCF residents with the SARS-CoV-2 Omicron variant was substantially lower than that seen for previous variants. This suggests the current wave of Omicron infections is unlikely to lead to a major surge in severe disease in LTCF populations with high levels of vaccine coverage and/or natural immunity. <h4>Trial Registration Number</h4> ISRCTN 14447421",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/27/2022.01.21.22269605.full.pdf; doi:https://doi.org/10.1101/2022.01.21.22269605; html:https://europepmc.org/article/PPR/PPR445654; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR445654&type=FILE&fileName=EMS142621-pdf.pdf&mimeType=application/pdf
-PPR496296,https://doi.org/10.1101/2022.05.09.22274769,"COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from the Born In Wales study","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Beeson S, Zuccolo L, Davies A, Brophy S.",,No Journal Info,2022,2022-05-11,N,,,,"<h4>Background</h4> Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. <h4>Objectives</h4> The aims of this study were to 1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health records (EHR) linkage, and 2) explore pregnant women’s views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born in Wales Cohort). <h4>Design</h4> A mixed methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) (Objective 1) and the Born In Wales Birth Cohort participants (Objective 2). SAIL combines data from general practice, hospital admissions, the national community child health dataset, maternal indicators dataset, and COVID-19 vaccination databases. <h4>Setting and participants</h4> <h4>Objective: </h4> 1) All women documented as being pregnant on or after 13 th April 2021, aged 18 years or older, and eligible for COVID-19 vaccination were identified in routine health care. They were linked to the vaccination data up to and including 31 st December 2021. Objective 2) Separately, a cross-section of pregnant women in Wales were invited to complete an online survey via social media advertising. The survey asked what their views were on having the COVID-19 vaccination during pregnancy, and if they had already received, or intended to receive, the COVID-19 vaccination during their pregnancies. They were also asked to give reasons for their decisions. <h4>Outcomes</h4> 1 (a). Rate of vaccination uptake per month during pregnancy among women eligible for vaccination. 1 (b). Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnicity, and deprivation area was examined using hazard ratios (HR) from Cox regression. 2.Expectant mothers’ views of the COVID-19 vaccination during pregnancy. <h4>Results</h4> <h4>Population-level data linkage (objective 1)</h4> Within the population cohort, 32.7% (n = 8,203) were vaccinated (at least one dose of the vaccine) during pregnancy, 34.1% (n = 8,572) remained unvaccinated throughout follow-up period, and 33.2% (n = 8,336) received the vaccine postpartum. Younger women (<30 years) were less likely to have the vaccine and those living in areas of high deprivation were also less likely to have the vaccine (HR=0.88, 95% CI 0.82 to 0.95). Asian and other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared to women of White ethnicity (HR=1.12, 95% CI 1.00 to 1.25) and (HR=1.18, 95% CI 1.03 to 1.37) respectively. <h4>Survey responses (objective 2)</h4> 69% of participants stated that they would be happy to have the vaccine during pregnancy (n = 207). The remainder, 31%, indicated that they would not have the vaccine during pregnancy (n = 94). Reasons for having the vaccine related to protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy. <h4>Conclusion</h4> Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and to decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation level areas.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/11/2022.05.09.22274769.full.pdf; doi:https://doi.org/10.1101/2022.05.09.22274769; html:https://europepmc.org/article/PPR/PPR496296; doi:https://doi.org/10.1101/2022.05.09.22274769
 PPR233362,https://doi.org/10.1101/2020.10.30.20223123,High prevalence of SARS-CoV-2 swab positivity and increasing R number in England during October 2020: REACT-1 round 6 interim report,"Riley S, Ainslie KEC, Eales O, Walters CE, Wang H, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2020,2020-11-03,Y,,,,"<h4>Background</h4> REACT-1 measures prevalence of SARS-CoV-2 infection in representative samples of the population in England using PCR testing from self-administered nose and throat swabs. Here we report interim results for round 6 of observations for swabs collected from the 16th to 25th October 2020 inclusive. <h4>Methods</h4> REACT-1 round 6 aims to collect data and swab results from 160,000 people aged 5 and above. Here we report results from the first 86,000 individuals. We estimate prevalence of PCR-confirmed SARS-CoV-2 infection, reproduction numbers (R) and temporal trends using exponential growth or decay models. Prevalence estimates are presented both unweighted and weighted to be representative of the population of England, accounting for response rate, region, deprivation and ethnicity. We compare these interim results with data from round 5, based on swabs collected from 18th September to 5th October 2020 inclusive. <h4>Results</h4> Overall prevalence of infection in the community in England was 1.28% or 128 people per 10,000, up from 60 per 10,000 in the previous round. Infections were doubling every 9.0 (6.1, 18) days with a national reproduction number (R) estimated at 1.56 (1.27, 1.88) compared to 1.16 (1.05, 1.27) in the previous round. Prevalence of infection was highest in Yorkshire and The Humber at 2.72% (2.12%, 3.50%), up from 0.84% (0.60%, 1.17%), and the North West at 2.27% (1.90%, 2.72%), up from 1.21% (1.01%, 1.46%), and lowest in South East at 0.55% (0.45%, 0.68%), up from 0.29% (0.23%, 0.37%). Clustering of cases was more prevalent in Lancashire, Manchester, Liverpool and West Yorkshire, West Midlands and East Midlands. Interim estimates of R were above 2 in the South East, East of England, London and South West, but with wide confidence intervals. Nationally, prevalence increased across all age groups with the greatest increase in those aged 55-64 at 1.20% (0.99%, 1.46%), up 3-fold from 0.37% (0.30%, 0.46%). In those aged over 65, prevalence was 0.81% (0.58%, 0.96%) up 2-fold from 0.35% (0.28%, 0.43%). Prevalence remained highest in 18 to 24-year olds at 2.25% (1.47%, 3.42%). <h4>Conclusion</h4> The co-occurrence of high prevalence and rapid growth means that the second wave of the epidemic in England has now reached a critical stage. Whether via regional or national measures, it is now time-critical to control the virus and turn R below one if further hospital admissions and deaths from COVID-19 are to be avoided.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/11/03/2020.10.30.20223123.full.pdf; doi:https://doi.org/10.1101/2020.10.30.20223123; html:https://europepmc.org/article/PPR/PPR233362; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR233362&type=FILE&fileName=EMS103475-pdf.pdf&mimeType=application/pdf
+PPR496296,https://doi.org/10.1101/2022.05.09.22274769,"COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from the Born In Wales study","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Beeson S, Zuccolo L, Davies A, Brophy S.",,No Journal Info,2022,2022-05-11,N,,,,"<h4>Background</h4> Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. <h4>Objectives</h4> The aims of this study were to 1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health records (EHR) linkage, and 2) explore pregnant women’s views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born in Wales Cohort). <h4>Design</h4> A mixed methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) (Objective 1) and the Born In Wales Birth Cohort participants (Objective 2). SAIL combines data from general practice, hospital admissions, the national community child health dataset, maternal indicators dataset, and COVID-19 vaccination databases. <h4>Setting and participants</h4> <h4>Objective: </h4> 1) All women documented as being pregnant on or after 13 th April 2021, aged 18 years or older, and eligible for COVID-19 vaccination were identified in routine health care. They were linked to the vaccination data up to and including 31 st December 2021. Objective 2) Separately, a cross-section of pregnant women in Wales were invited to complete an online survey via social media advertising. The survey asked what their views were on having the COVID-19 vaccination during pregnancy, and if they had already received, or intended to receive, the COVID-19 vaccination during their pregnancies. They were also asked to give reasons for their decisions. <h4>Outcomes</h4> 1 (a). Rate of vaccination uptake per month during pregnancy among women eligible for vaccination. 1 (b). Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnicity, and deprivation area was examined using hazard ratios (HR) from Cox regression. 2.Expectant mothers’ views of the COVID-19 vaccination during pregnancy. <h4>Results</h4> <h4>Population-level data linkage (objective 1)</h4> Within the population cohort, 32.7% (n = 8,203) were vaccinated (at least one dose of the vaccine) during pregnancy, 34.1% (n = 8,572) remained unvaccinated throughout follow-up period, and 33.2% (n = 8,336) received the vaccine postpartum. Younger women (<30 years) were less likely to have the vaccine and those living in areas of high deprivation were also less likely to have the vaccine (HR=0.88, 95% CI 0.82 to 0.95). Asian and other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared to women of White ethnicity (HR=1.12, 95% CI 1.00 to 1.25) and (HR=1.18, 95% CI 1.03 to 1.37) respectively. <h4>Survey responses (objective 2)</h4> 69% of participants stated that they would be happy to have the vaccine during pregnancy (n = 207). The remainder, 31%, indicated that they would not have the vaccine during pregnancy (n = 94). Reasons for having the vaccine related to protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy. <h4>Conclusion</h4> Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and to decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation level areas.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/11/2022.05.09.22274769.full.pdf; doi:https://doi.org/10.1101/2022.05.09.22274769; html:https://europepmc.org/article/PPR/PPR496296; doi:https://doi.org/10.1101/2022.05.09.22274769
 PPR417361,https://doi.org/10.1101/2021.11.08.21265312,"Understanding COVID-19 trajectories from a nationwide linked electronic health record cohort of 56 million people: phenotypes, severity, waves & vaccination","Thygesen JH, Tomlinson C, Hollings S, Mizani M, Handy A, Akbari A, Banerjee A, Cooper J, Lai A, Li K, Mateen B, Sattar N, Sofat R, Torralbo A, Wu H, Wood A, Sterne JAC, Pagel C, Whiteley W, Sudlow C, Hemingway H, Denaxas S.",,No Journal Info,2021,2021-11-09,Y,,,,"<h4>Background</h4> Updatable understanding of the onset and progression of individuals COVID-19 trajectories underpins pandemic mitigation efforts. In order to identify and characterize individual trajectories, we defined and validated ten COVID-19 phenotypes from linked electronic health records (EHR) on a nationwide scale using an extensible framework. <h4>Methods</h4> Cohort study of 56.6 million people in England alive on 23/01/2020, followed until 31/05/2021, using eight linked national datasets spanning COVID-19 testing, vaccination, primary & secondary care and death registrations data. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity using a combination of international clinical terminologies (e.g. SNOMED-CT, ICD-10) and bespoke data fields; positive test, primary care diagnosis, hospitalisation, critical care (four phenotypes), and death (three phenotypes). Using these phenotypes, we constructed patient trajectories illustrating the transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. <h4>Findings</h4> We identified 3,469,528 infected individuals (6.1%) with 8,825,738 recorded COVID-19 phenotypes. Of these, 364,260 (11%) were hospitalised and 140,908 (4%) died. Of those hospitalised, 38,072 (10%) were admitted to intensive care (ICU), 54,026 (15%) received non-invasive ventilation and 21,404 (6%) invasive ventilation. Amongst hospitalised patients, first wave mortality (30%) was higher than the second (23%) in non-ICU settings, but remained unchanged for ICU patients. The highest mortality was for patients receiving critical care outside of ICU in wave 1 (51%). 13,083 (9%) COVID-19 related deaths occurred without diagnoses on the death certificate, but within 30 days of a positive test while 10,403 (7%) of cases were identified from mortality data alone with no prior phenotypes recorded. We observed longer patient trajectories in the second pandemic wave compared to the first. <h4>Interpretation</h4> Our analyses illustrate the wide spectrum of severity that COVID-19 displays and significant differences in incidence, survival and pathways across pandemic waves. We provide an adaptable framework to answer questions of clinical and policy relevance; new variant impact, booster dose efficacy and a way of maximising existing data to understand individuals progression through disease states. <h4>Research in Context</h4> <h4>Evidence before the study</h4> We searched PubMed on October 14, 2021, for publications with the terms “COVID-19” or “SARS-CoV-2”, “severity”, and “electronic health records” or “EHR” without date or language restrictions. Multiple studies explore factors associated with severity of COVID-19 infection, and model predictions of outcome for hospitalised patients. However, most work to date focused on isolated facets of the healthcare system, such as primary or secondary care only, was conducted in subpopulations (e.g. hospitalised patients) of limited sample size, and often utilized dichotomised outcomes (e.g. mortality or hospitalisation) ignoring the full spectrum of disease. We identified no studies which comprehensively detailed severity of infections while describing disease severity across pandemic waves, vaccination status, and patient trajectories. <h4>Added value of this study</h4> To our knowledge, this is the first study providing a comprehensive view of COVID-19 across pandemic waves using national data and focusing on severity, vaccination, and patient trajectories. Drawing on linked electronic health record (EHR) data on a national scale (56.6 million people alive and registered with GP in England), we describe key demographic factors, frequency of comorbidities, impact of the two main waves in England, and effect of full vaccination on COVID-19 severities. Additionally, we identify and describe patient trajectory networks which illustrate the main transition pathways of COVID-19 patients in the healthcare system. Finally, we provide reproducible COVID-19 phenotyping algorithms reflecting clinically relevant stages of disease severity i.e. positive tests, primary care diagnoses, hospitalisation, critical care treatments (e.g. ventilatory support) and mortality. <h4>Implications of all the available evidence</h4> The COVID-19 phenotypes and trajectory analysis framework outlined produce a reproducible, extensible and repurposable means to generate national-scale data to support critical policy decision making. By modelling patient trajectories as a series of interactions with healthcare systems, and linking these to demographic and outcome data, we provide a means to identify and prioritise care pathways associated with adverse outcomes and highlight healthcare system ‘touch points’ which may act as tangible targets for intervention.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/11/09/2021.11.08.21265312.full.pdf; doi:https://doi.org/10.1101/2021.11.08.21265312; html:https://europepmc.org/article/PPR/PPR417361; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR417361&type=FILE&fileName=EMS138265-pdf.pdf&mimeType=application/pdf
 PPR403344,https://doi.org/10.1101/2021.10.01.21264408,Reduced amplification efficiency of the RNA-dependent-RNA-polymerase (RdRp) target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests,"Valley-Omar Z, Marais G, Iranzadeh A, Naidoo M, Korsman S, Maponga T, Hussey H, Davies M, Boulle A, Doolabh D, Laubscher M, Deetlefs J, Maritz J, Scott L, Msomi N, Tegally H, de Oliveira T, Bhiman J, Williamson C, Preiser W, Hardie D, Hsiao N.",,No Journal Info,2021,2021-10-01,Y,,,,"Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced PCR amplification efficiency of the RdRp gene target of the Seegene, Allplex 2019-nCoV diagnostic assay when detecting the Delta variant. We propose that this can be used as a surrogate for variant detection.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/01/2021.10.01.21264408.full.pdf; doi:https://doi.org/10.1101/2021.10.01.21264408; html:https://europepmc.org/article/PPR/PPR403344; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR403344&type=FILE&fileName=EMS136740-pdf.pdf&mimeType=application/pdf
 PPR211672,https://doi.org/10.1101/2020.09.07.20189621,COVID-19 in patients with hepatobiliary and pancreatic diseases: A single-centre cross-sectional study in East London,"Ullah AZMD, Sivapalan L, Kocher HM, Chelala C.",,No Journal Info,2020,2020-09-09,N,,,,"<h4>ABSTRACT</h4> <h4>Objective</h4> To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions. <h4>Design</h4> Cross-sectional study. <h4>Setting</h4> East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) study at Barts Health NHS Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥ 18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020. <h4>Participants</h4> EL-PaC-Epidem study participants, alive on 12 February 2020, and living in East London within the previous six months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background. <h4>Main outcome measure</h4> COVID-19 incidence and mortality. <h4>Results</h4> Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with an increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance mis-users were at more risk of infection, so were patients on Vitamin D treatment. The higher odds ratios in patients with chronic pancreatic or mild liver conditions, age>70, and history of smoking or obesity were due to co-existing comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19). <h4>Conclusions</h4> In this large population-based study of HPB patients, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multi-morbidities, substance mis-use, and a history of Vitamin D treatment independently posed higher odds of acquiring COVID-19 compared to their respective counterparts. The odds of death were significantly high for men and Black people. <h4>STRENGTHS AND LIMITATIONS OF THIS STUDY</h4> First multi-ethnic population-based study on COVID-19 in patients with hepato-pancreato-biliary group of diseases. Systematic identification of the effect, or the lack of it, of individual demographic and clinical factors on the infection and mortality of COVID-19 in a large cohort of over 15 000 patients, robustly controlling for potential confounders in their evaluation. Access to longitudinal data from linked primary and secondary care electronic health records, and use of rule-based phenotyping algorithms allowed for improved completeness and accuracy of the explored variables. Some observed increased odds of SARS-CoV-2 infection and related death could be plausibly explained by unmeasured confounding. The effects reported in the study could be influenced by the relatively smaller size of COVID-19 cases within this cohort.",,pdf:https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/75991/2/Kocher%20COVID-19%20in%20patients%20with%20hepatobiliary%20and%20pancreatic%20diseases%3a%20A%20single-centre%20cross-sectional%20study%20in%20East%20London%202021%20Published.pdf; doi:https://doi.org/10.1101/2020.09.07.20189621; html:https://europepmc.org/article/PPR/PPR211672; doi:https://doi.org/10.1101/2020.09.07.20189621
 PPR380903,https://doi.org/10.1101/2021.08.10.21261834,Immuno-proteomic profiling reveals abundant airway CD8 T cells and ongoing epithelial injury in prolonged post-COVID19 respiratory disease,"Vijayakumar B, Boustani K, Ogger PP, Papadaki A, Tonkin J, Orton CM, Ghai P, Suveizdyte K, Hewitt RJ, Snelgrove RJ, Molyneaux PL, Garner JL, Peters JE, Shah PL, Lloyd CM, Harker JA.",,No Journal Info,2021,2021-08-10,Y,,,,"<h4>Summary</h4> Some patients hospitalized with acute COVID19 suffer respiratory symptoms that persist for many months. To characterize the local and systemic immune responses associated with this form of ‘Long COVID’, we delineated the immune and proteomic landscape in the airway and peripheral blood of normal volunteers and patients from 3 to 6 months after hospital discharge. The bronchoalveolar lavage (but not peripheral blood) proteome was abnormal in patients with post-COVID19 lung disease with significantly elevated concentration of proteins associated with apoptosis, tissue repair and epithelial injury. This correlated with an increase in cytotoxic lymphocytes (especially tissue resident CD8 + T cells), lactate dehydrogenase and albumin (biomarkers of cell death and barrier integrity). Follow-up of a subset of these patients greater than 1-year post-COVID19 indicated these abnormalities resolved over time. Collectively, these data indicate that COVID-19 results in a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to ongoing activation of cytotoxic T cells. <h4>Highlights</h4> The post-COVID19 airway is characterized by increased cytotoxic lymphocytes. Distinct airway proteomes are associated with the airway immune cell landscape. The peripheral blood does not predict immune-proteome alterations in the airway post-COVID19. Persistent abnormalities in the airway immune-proteome post-COVID19 airways correlate with ongoing epithelial damage.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/08/11/2021.08.10.21261834.full.pdf; doi:https://doi.org/10.1101/2021.08.10.21261834; html:https://europepmc.org/article/PPR/PPR380903; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR380903&type=FILE&fileName=EMS132662-pdf.pdf&mimeType=application/pdf
 PPR447312,https://doi.org/10.1101/2022.01.26.22269885,SARS-CoV-2 anti-spike antibody levels following second dose of ChAdOx1 nCov-19 or BNT162b2 in residents of long-term care facilities in England (VIVALDI),"Stirrup O, Krutikov M, Tut G, Palmer T, Bone D, Bruton R, Fuller C, Azmi B, Lancaster T, Sylla P, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Giddings R, Nacer-Laidi H, Baynton V, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,No Journal Info,2022,2022-01-27,Y,,,,"<h4>Background</h4> General population studies have shown strong humoral response following SARS-CoV-2 vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations such as Long-Term Care Facility (LTCF) residents but published data are scarce. <h4>Methods</h4> VIVALDI is a prospective cohort study in England which links serial blood sampling in LTCF staff and residents to routine healthcare records. We measured quantitative titres of SARS-CoV-2 anti-spike antibodies in residents and staff following second vaccination dose with ChAdOx1 nCov-19 (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech). We investigated differences in peak antibody levels and rates of decline using linear mixed effects models. <h4>Results</h4> We report on 1317 samples from 402 residents (median age 86 years, IQR 78-91) and 632 staff (50 years, 37-58), ≤280 days from second vaccination dose. Peak antibody titres were 7.9-fold higher after Pfizer-BioNTech vaccine compared to Oxford-AstraZeneca (95%CI 3.6-17.0; P <0.01) but rate of decline was increased, and titres were similar at 6 months. Prior infection was associated with higher peak antibody levels in both Pfizer-BioNTech (2.8-fold, 1.9-4.1; P <0.01) and Oxford-AstraZeneca (4.8-fold, 3.2-7.1; P <0.01) recipients and slower rates of antibody decline. Increasing age was associated with a modest reduction in peak antibody levels for Oxford-AstraZeneca recipients. <h4>Conclusions</h4> Double-dose vaccination elicits robust and stable antibody responses in older LTCF residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.",,pdf:https://discovery.ucl.ac.uk/10147322/1/spike-waning-JID.pdf; doi:https://doi.org/10.1101/2022.01.26.22269885; html:https://europepmc.org/article/PPR/PPR447312; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR447312&type=FILE&fileName=EMS142768-pdf.pdf&mimeType=application/pdf
-PPR729805,https://doi.org/10.1101/2023.09.22.23295850,Group A streptococcal cases and treatments during the COVID-19 pandemic and 2022 outbreak: a retrospective cohort study in England using OpenSAFELY-TPP,"Cunningham C, Fisher L, Wood C, Speed V, Brown AD, Curtis HJ, Higgins R, Croker R, Butler-Cole BF, Evans D, Inglesby P, Dillingham I, Bacon SC, Beech E, Hand K, Davy S, Ward T, Hickman G, Bridges L, O’Dwyer T, Maude S, Smith RM, Mehrkar A, Hart LC, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-09-23,Y,,,,"<h4>Objective</h4> To investigate the impact of the COVID-19 pandemic on Group A streptococcal (GAS) cases and related antibiotic prescriptions. <h4>Design</h4> A retrospective cohort study with supporting dashboards with the approval of NHS England. <h4>Setting</h4> Primary care practices in England using TPP SystmOne software from January 2018 through March 2023. <h4>Participants</h4> Patients included were those registered at a TPP practice for each month of the study period. Patients with missing sex or age were excluded, resulting in a population of 23,816,470 in January 2018, increasing to 25,541,940 by March 2023. <h4>Main outcome measures</h4> We calculated monthly counts and crude rates of GAS cases (sore throat/tonsillitis, scarlet fever, invasive group A strep) and prescriptions linked with a GAS case, before (pre-April 2020), during and after (post-April 2021) COVID-19 restrictions. We calculated the maximum and minimum count and rate for each season (years running September-August), and the rate ratio (RR) of the 2022/23 season to the last comparably high season (2017/18). <h4>Results</h4> Recording of GAS cases and antibiotic prescription linked with a GAS case peaked in December 2022, higher than the 2017/2018 peak. The peak rate of monthly sore throat/tonsillitis (possible group A strep throat) recording was 5.33 per 1,000 (RR 2022/23 versus 2017/18 1.39 (CI: 1.38 to 1.40)). Scarlet fever recording peaked at 0.51 per 1,000 (RR 2.68 (CI: 2.59 to 2.77)), and invasive group A streptococcal infection (iGAS) at 0.01 per 1,000 (RR 4.37 (CI: 2.94 to 6.48)). First line antibiotics with a record of a GAS infection peaked at 2.80 per 1,000 (RR 1.37 (CI:1.35 to 1.38)), alternative antibiotics at 2.03 per 1,000 (RR 2.30 (CI:2.26 to 2.34)), and reserved antibiotics at 0.09 per 1,000 (RR 2.42 (CI:2.24 to 2.61)). For individual antibiotics, azithromycin with GAS indication showed the greatest relative increase (RR 7.37 (CI:6.22 to 8.74)).This followed a sharp drop in recording of cases and associated prescriptions during the period of COVID-19 restrictions where the maximum count and rates were lower than any pre COVID-19 minimum. More detailed demographic breakdowns can be found in our regularly updated dashboard report. <h4>Conclusions</h4> Rates of scarlet fever, sore throat/tonsillitis and iGAS recording and associated antibiotic prescribing peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed clinical and demographic subgroups. <h4>What is known</h4> During the COVID-19 pandemic there has been a substantial change to the pattern of circulating viruses and bacteria that cause illnesses. A spike in group A streptococcal infections in England starting December 2022 was associated with 426 deaths, including 48 children as of 7th May 2023. Increased demand for antibiotics in this period led to medicines shortages and the introduction of Serious Shortage Protocols (SSPs). Existing surveillance systems such as notifiable disease reports and GP in-hours surveillance bulletins describe clinical events, but they do not link to relevant prescribing data. <h4>What this study adds</h4> - This study supports the findings of routine surveillance reports which indicated a drop in GAS infections during the COVID-19 restrictions, followed by a spike in December 2022, demonstrating that the OpenSAFELY platform and primary care data can be used to rapidly describe not only clinical events but also relevant prescribing in the case of future outbreaks. - Antibiotic prescribing with a GAS indication, particularly for phenoxymethylpenicillin alternatives and reserved antibiotics, was higher in the December 2022 peak than in the 2017/2018 peak.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/23/2023.09.22.23295850.full.pdf; doi:https://doi.org/10.1101/2023.09.22.23295850; html:https://europepmc.org/article/PPR/PPR729805
 PPR401642,https://doi.org/10.1101/2021.09.27.21264166,Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibody in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study,"Krutikov M, Palmer T, Tut G, Fuller C, Azmi B, Giddings R, Shrotri M, Kaur N, Sylla P, Lancaster T, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,No Journal Info,2021,2021-09-29,Y,,,,"<h4>Background</h4> Long Term Care Facilities (LTCF) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion infected amongst survivors and duration of the antibody response to natural infection is unknown. We determined the prevalence and stability of nucleocapsid antibodies – the standard assay for detection of prior infection - in staff and residents from 201 LTCFs. <h4>Methods</h4> Prospective cohort study of residents aged >65 years and staff of LTCFs in England (11 June 2020-7 May 2021). Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein. Prevalence and cumulative incidence of antibody-positivity were weighted to the LTCF population. Cumulative incidence of sero-reversion was estimated from Kaplan-Meier curves. <h4>Results</h4> 9488 samples were included, 8636 (91%) of which could be individually-linked to 1434 residents or 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 35% (95% CI: 30-40%) in residents and 26% (95% CI: 23-30%) in staff over 11 months. The incidence rate of loss of antibodies (sero-reversion) was 2·1 per 1000 person-days at risk, and median time to reversion was around 8 months. <h4>Interpretation</h4> At least one-quarter of staff and one-third of surviving residents were infected during the first two pandemic waves. Nucleocapsid-specific antibodies often become undetectable within the first year following infection which is likely to lead to marked underestimation of the true proportion of those with prior infection. Since natural infection may act to boost vaccine responses, better assays to identify natural infection should be developed. <h4>Funding</h4> UK Government Department of Health and Social Care. <h4>Research in context</h4> <h4>Evidence before this study</h4> A search was conducted of Ovid MEDLINE and MedRxiv on 21 July 2021 to identify studies conducted in long term care facilities (LTCF) that described seroprevalence using the terms “COVID-19” or “SARS-CoV-2” and “nursing home” or “care home” or “residential” or “long term care facility” and “antibody” or “serology” without date or language restrictions. One meta-analysis was identified, published before the introduction of vaccination, that included 2 studies with a sample size of 291 which estimated seroprevalence as 59% in LTCF residents. There were 28 seroprevalence surveys of naturally-acquired SARS-CoV-2 antibodies in LTCFs; 16 were conducted in response to outbreaks and 12 conducted in care homes without known outbreaks. 16 studies included more than 1 LTCF and all were conducted in Autumn 2020 after the first wave of infection but prior to subsequent peaks. Seroprevalence studies conducted following a LTCF outbreak were biased towards positivity as the included population was known to have been previously infected. In the 12 studies that were conducted outside of known outbreaks, seroprevalence varied significantly according to local prevalence of infection. The largest of these was a cross-sectional study conducted in 9,000 residents and 10,000 staff from 362 LTCFs in Madrid, which estimated seroprevalence in staff as 31·5% and 55·4% in residents. However, as this study was performed in one city, it may not be generalisable to the whole of Spain and sequential sampling was not performed. Of the 28 studies, 9 undertook longitudinal sampling for a maximum of four months although three of these reported from the same cohort of LTCFs in London. None of the studies reported on antibody waning amongst the whole resident population. <h4>Added value of this study</h4> We estimated the proportion of care home staff and residents with evidence of SARS-CoV-2 natural infection using data from over 3,000 staff and 1,500 residents in 201 geographically dispersed LTCFs in England. Population selection was independent of outbreak history and the sample is therefore more reflective of the population who reside and work in LTCFs. Our estimates of the proportion of residents with prior natural infection are substantially higher than estimates based on population-wide PCR testing, due to limited testing coverage at the start of the pandemic. 1361 individuals had at least one positive antibody test and participants were followed for up to 11 months, which allowed modelling of the time to loss of antibody in over 600 individuals in whom the date of primary infection could be reliably estimated. This is the longest reported serological follow up in a population of LTCF residents, a group who are known to be most at risk of severe outcomes following infection with SARS-CoV-2 and provides important evidence on the duration that nucleocapsid antibodies remained detectable over the first and second waves of the pandemic. <h4>Implications of all available research</h4> A substantial proportion of the LTCF population will have some level of natural immunity to infection as a result of past infection. Immunological studies have highlighted greater antibody responses to vaccination in seropositive individuals, so vaccine efficacy in this population may be affected by this large pool of individuals who have survived past infection. In addition, although the presence of nucleocapsid-specific antibodies is generally considered as the standard marker for prior infection, we find that antibody waning is such that up to 50% of people will lose detectable antibody responses within eight months. Individual prior natural infection history is critical to assess the impact of factors such as vaccine response or protection against re-infection. These findings may have implications for duration of immunity following natural infection and indicate that alternative assays for prior infection should be developed.",,pdf:http://www.thelancet.com/article/S2666756821002828/pdf; doi:https://doi.org/10.1101/2021.09.27.21264166; html:https://europepmc.org/article/PPR/PPR401642; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR401642&type=FILE&fileName=EMS136680-pdf.pdf&mimeType=application/pdf
-PPR725396,https://doi.org/10.1101/2023.09.14.23295499,Mechanisms for Integrating Real Data into Search Game Simulations: An Application to Winter Health Service Pressures and Preventative Policies,"Chapman M, G-Medhin A, Daneshi K, Bramwell T, Durbaba S, Curcin V, Parmar D, Boulding H, Becares L, Morgan C, Molokhia M, McBurney P, Harding S, Wolfe I, Ashworth M, Poston L.",,No Journal Info,2023,2023-09-15,Y,,,,"While modelling and simulation are powerful techniques for exploring complex phenomena, if they are not coupled with suitable real-world data any results obtained are likely to require extensive validation. We consider this problem in the context of search game modelling, and suggest that both demographic and behaviour data are used to configure certain model parameters. We show this integration in practice by using a combined dataset of over 150,000 individuals to configure a specific search game model that captures the environment, population, interventions and individual behaviours relating to winter health service pressures. The presence of this data enables us to more accurately explore the potential impact of service pressure interventions, which we do across 33,000 simulations using a computational version of the model. We find government advice to be the best-performing intervention in simulation, in respect of improved health, reduced health inequalities, and thus reduced pressure on health service utilisation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/15/2023.09.14.23295499.full.pdf; doi:https://doi.org/10.1101/2023.09.14.23295499; html:https://europepmc.org/article/PPR/PPR725396
+PPR729805,https://doi.org/10.1101/2023.09.22.23295850,Group A streptococcal cases and treatments during the COVID-19 pandemic and 2022 outbreak: a retrospective cohort study in England using OpenSAFELY-TPP,"Cunningham C, Fisher L, Wood C, Speed V, Brown AD, Curtis HJ, Higgins R, Croker R, Butler-Cole BF, Evans D, Inglesby P, Dillingham I, Bacon SC, Beech E, Hand K, Davy S, Ward T, Hickman G, Bridges L, O’Dwyer T, Maude S, Smith RM, Mehrkar A, Hart LC, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-09-23,Y,,,,"<h4>Objective</h4> To investigate the impact of the COVID-19 pandemic on Group A streptococcal (GAS) cases and related antibiotic prescriptions. <h4>Design</h4> A retrospective cohort study with supporting dashboards with the approval of NHS England. <h4>Setting</h4> Primary care practices in England using TPP SystmOne software from January 2018 through March 2023. <h4>Participants</h4> Patients included were those registered at a TPP practice for each month of the study period. Patients with missing sex or age were excluded, resulting in a population of 23,816,470 in January 2018, increasing to 25,541,940 by March 2023. <h4>Main outcome measures</h4> We calculated monthly counts and crude rates of GAS cases (sore throat/tonsillitis, scarlet fever, invasive group A strep) and prescriptions linked with a GAS case, before (pre-April 2020), during and after (post-April 2021) COVID-19 restrictions. We calculated the maximum and minimum count and rate for each season (years running September-August), and the rate ratio (RR) of the 2022/23 season to the last comparably high season (2017/18). <h4>Results</h4> Recording of GAS cases and antibiotic prescription linked with a GAS case peaked in December 2022, higher than the 2017/2018 peak. The peak rate of monthly sore throat/tonsillitis (possible group A strep throat) recording was 5.33 per 1,000 (RR 2022/23 versus 2017/18 1.39 (CI: 1.38 to 1.40)). Scarlet fever recording peaked at 0.51 per 1,000 (RR 2.68 (CI: 2.59 to 2.77)), and invasive group A streptococcal infection (iGAS) at 0.01 per 1,000 (RR 4.37 (CI: 2.94 to 6.48)). First line antibiotics with a record of a GAS infection peaked at 2.80 per 1,000 (RR 1.37 (CI:1.35 to 1.38)), alternative antibiotics at 2.03 per 1,000 (RR 2.30 (CI:2.26 to 2.34)), and reserved antibiotics at 0.09 per 1,000 (RR 2.42 (CI:2.24 to 2.61)). For individual antibiotics, azithromycin with GAS indication showed the greatest relative increase (RR 7.37 (CI:6.22 to 8.74)).This followed a sharp drop in recording of cases and associated prescriptions during the period of COVID-19 restrictions where the maximum count and rates were lower than any pre COVID-19 minimum. More detailed demographic breakdowns can be found in our regularly updated dashboard report. <h4>Conclusions</h4> Rates of scarlet fever, sore throat/tonsillitis and iGAS recording and associated antibiotic prescribing peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed clinical and demographic subgroups. <h4>What is known</h4> During the COVID-19 pandemic there has been a substantial change to the pattern of circulating viruses and bacteria that cause illnesses. A spike in group A streptococcal infections in England starting December 2022 was associated with 426 deaths, including 48 children as of 7th May 2023. Increased demand for antibiotics in this period led to medicines shortages and the introduction of Serious Shortage Protocols (SSPs). Existing surveillance systems such as notifiable disease reports and GP in-hours surveillance bulletins describe clinical events, but they do not link to relevant prescribing data. <h4>What this study adds</h4> - This study supports the findings of routine surveillance reports which indicated a drop in GAS infections during the COVID-19 restrictions, followed by a spike in December 2022, demonstrating that the OpenSAFELY platform and primary care data can be used to rapidly describe not only clinical events but also relevant prescribing in the case of future outbreaks. - Antibiotic prescribing with a GAS indication, particularly for phenoxymethylpenicillin alternatives and reserved antibiotics, was higher in the December 2022 peak than in the 2017/2018 peak.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/23/2023.09.22.23295850.full.pdf; doi:https://doi.org/10.1101/2023.09.22.23295850; html:https://europepmc.org/article/PPR/PPR729805
 PPR371208,https://doi.org/10.1101/2021.07.14.21260488,SARS-CoV-2 Antibody Lateral Flow Assay for antibody prevalence studies following vaccine roll out: a Diagnostic Accuracy Study,"Cann A, Clarke C, Brown J, Thomson T, Prendecki M, Moshe M, Badhan A, Elliott P, Darzi A, Riley S, Ashby D, Willicombe M, Kelleher P, Randell P, Ward H, Barclay WS, Cooke G.",,No Journal Info,2021,2021-07-16,Y,,,,"<h4>Background</h4> Lateral flow immunoassays (LFIAs) have the potential to deliver affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of SARS-CoV-2 vaccine. <h4>Methods</h4> This is a prospective diagnostic accuracy study. <h4>Setting</h4> Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Laboratory analyses were performed across Imperial College London sites and university facilities. <h4>Participants</h4> Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following SARS-CoV-2 vaccine booster, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination, and 21 day follow up. A total of 186 paired samples were collected. <h4>Interventions</h4> During the participants visit, capillary blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG were detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. <h4>Main outcome measures</h4> The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay. <h4>Results</h4> Using the threshold value for positivity on serological testing of ≥7.10 BAU/ml, the overall performance of the test produces an estimate of sensitivity of 91.94% (95% CI 85.67% to 96.06%) and specificity of 93.55% (95% CI 84.30% to 98.21%) using the Abbott assay as reference standard. <h4>Conclusions</h4> Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveys, but does not meet criteria for individual testing.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/16/2021.07.14.21260488.full.pdf; doi:https://doi.org/10.1101/2021.07.14.21260488; html:https://europepmc.org/article/PPR/PPR371208; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR371208&type=FILE&fileName=EMS130798-pdf.pdf&mimeType=application/pdf
+PPR725396,https://doi.org/10.1101/2023.09.14.23295499,Mechanisms for Integrating Real Data into Search Game Simulations: An Application to Winter Health Service Pressures and Preventative Policies,"Chapman M, G-Medhin A, Daneshi K, Bramwell T, Durbaba S, Curcin V, Parmar D, Boulding H, Becares L, Morgan C, Molokhia M, McBurney P, Harding S, Wolfe I, Ashworth M, Poston L.",,No Journal Info,2023,2023-09-15,Y,,,,"While modelling and simulation are powerful techniques for exploring complex phenomena, if they are not coupled with suitable real-world data any results obtained are likely to require extensive validation. We consider this problem in the context of search game modelling, and suggest that both demographic and behaviour data are used to configure certain model parameters. We show this integration in practice by using a combined dataset of over 150,000 individuals to configure a specific search game model that captures the environment, population, interventions and individual behaviours relating to winter health service pressures. The presence of this data enables us to more accurately explore the potential impact of service pressure interventions, which we do across 33,000 simulations using a computational version of the model. We find government advice to be the best-performing intervention in simulation, in respect of improved health, reduced health inequalities, and thus reduced pressure on health service utilisation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/15/2023.09.14.23295499.full.pdf; doi:https://doi.org/10.1101/2023.09.14.23295499; html:https://europepmc.org/article/PPR/PPR725396
 PPR367549,https://doi.org/10.1101/2021.07.08.21260185,REACT-1 round 13 interim report: acceleration of SARS-CoV-2 Delta epidemic in the community in England during late June and early July 2021,"Riley S, Eales O, Haw D, Wang H, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Barclay W, Cooke G, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-07-08,Y,,,,"<h4>Background</h4> Despite high levels of vaccination in the adult population, cases of COVID-19 have risen exponentially in England since the start of May 2021 driven by the Delta variant. However, with far fewer hospitalisations and deaths per case during the recent growth in cases compared with 2020, it is intended that all remaining social distancing legislation in England will be removed from 19 July 2021. <h4>Methods</h4> We report interim results from round 13 of the REal-time Assessment of Community Transmission-1 (REACT-1) study in which a cross-sectional sample of the population of England was asked to provide a throat and nose swab for RT-PCR and to answer a questionnaire. Data collection for this report (round 13 interim) was from 24 June to 5 July 2021. <h4>Results</h4> In round 13 interim, we found 237 positives from 47,729 swabs giving a weighted prevalence of 0.59% (0.51%, 0.68%) which was approximately four-fold higher compared with round 12 at 0.15% (0.12%, 0.18%). This resulted from continued exponential growth in prevalence with an average doubling time of 15 (13, 17) days between round 12 and round 13. However, during the recent period of round 13 interim only, we observed a shorter doubling time of 6.1 (4.0, 12) days with a corresponding R number of 1.87 (1.40, 2.45). There were substantial increases in all age groups under the age of 75 years, and especially at younger ages, with the highest prevalence in 13 to 17 year olds at 1.33% (0.97%, 1.82%) and in 18 to 24 years olds at 1.40% (0.89%, 2.18%). Infections have increased in all regions with the largest increase in London where prevalence increased more than eight-fold from 0.13% (0.08%, 0.20%) in round 12 to 1.08% (0.79%, 1.47%) in round 13 interim. Overall, prevalence was over 3 times higher in the unvaccinated compared with those reporting two doses of vaccine in both round 12 and round 13 interim, although there was a similar proportional increase in prevalence in vaccinated and unvaccinated individuals between the two rounds. <h4>Discussion</h4> We are entering a critical period with a number of important competing processes: continued vaccination rollout to the whole adult population in England, increased natural immunity through infection, reduced social mixing of children during school holidays, increased proportion of mixing occurring outdoors during summer, the intended full opening of hospitality and entertainment and cessation of mandated social distancing and mask wearing. Surveillance programmes are essential during this next phase of the epidemic to provide clear evidence to the government and the public on the levels and trends in prevalence of infections and their relationship to vaccine coverage, hospitalisations, deaths and Long COVID.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/08/2021.07.08.21260185.full.pdf; doi:https://doi.org/10.1101/2021.07.08.21260185; html:https://europepmc.org/article/PPR/PPR367549; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR367549&type=FILE&fileName=EMS130294-pdf.pdf&mimeType=application/pdf
 PPR592262,https://doi.org/10.1101/2023.01.04.23284174,Ethnic differences in the indirect impacts of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: An observational cohort study using OpenSAFELY,"Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EP, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AY, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, the longitudinal health and wellbeing collaborative and the OpenSAFELYcollaborative.",,No Journal Info,2023,2023-01-05,Y,,,,"<h4>Background</h4> The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. <h4>Methods</h4> We conducted a cohort study using OpenSAFELY (2018-2022). We grouped ethnicity (exposure), into five categories: White, South Asian, Black, Other, Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (e.g., blood pressure measurements) before and after 23rd March 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to: diabetes, cardiovascular disease, respiratory disease, and mental health before and after 23rd March 2020. <h4>Findings</h4> Of 14,930,356 adults in 2020 with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to White. There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in White ethnicity. Relatively, ethnic differences narrowed for heart failure admission in those of Asian and Black ethnicity compared to White. For other outcomes the pandemic had minimal impact on ethnic differences. <h4>Interpretation</h4> Our study suggests ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. <h4>Funding</h4> LSHTM COVID-19 Response Grant (DONAT15912). <h4>Research in context</h4> <h4>Evidence before this study</h4> We searched MEDLINE from inception to 7th September 2022, for articles published in English, including the title/abstract search terms (healthcare disruption OR indirect impact OR miss* diagnos* OR delayed diagnos* OR service disruption) AND (sars-cov-2 OR covid-19 OR pandemic OR lockdown) AND (ethnic*). Of the seven studies identified, two broadly investigated the indirect impacts of the pandemic on non-COVID outcomes and reported ethnic differences. However, these two only included data until January 2021 at the latest. Other studies investigated just one disease area such as dementia or diabetes and frequently did not have the power to investigate specific ethnic groups. <h4>Added value of this study</h4> This is one of the largest studies to describe how the pandemic impacted ethnic differences in clinical monitoring at primary care and hospital admissions for non-COVID conditions (across four disease areas: cardiovascular disease, diabetes mellitus, respiratory disease and mental health) in England. A study population of nearly 15 million people, allowed the examination of five ethnic groups, and data until April 2022 allowed the evaluation of impacts for a longer period than previous studies.We showed that clinical monitoring had still not returned to pre-pandemic levels even by April 2022. Ethnic differences in clinical monitoring were seen pre-pandemic, though not in diabetes measures, these differences were either not impacted or reduced during the pandemic. We also showed that there were ethnic differences in hospital admissions, for many outcomes the pandemic did not impact these differences but there were some exceptions, in particular for diabetic ketoacidosis admissions in those of Black ethnicity and heart failure admissions for those of Black and Asian ethnicities. <h4>Implications of all the available evidence</h4> We found that the pandemic reduced ethnic inequalities for some outcomes (in hospitalisations for diabetic ketoacidosis and heart failure). However, these were driven by greater absolute increases in admissions for black and asian groups (diabetic ketoacidosis) and white groups (heart failure), which warrant further investigation to understand the underlying causes.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/05/2023.01.04.23284174.full.pdf; doi:https://doi.org/10.1101/2023.01.04.23284174; html:https://europepmc.org/article/PPR/PPR592262; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR592262&type=FILE&fileName=EMS159410-pdf.pdf&mimeType=application/pdf
 PPR397279,https://doi.org/10.1101/2021.09.16.21263629,Access to personal protective equipment in healthcare workers during the COVID-19 pandemic in the United Kingdom: results from a nationwide cohort study (UK-REACH),"Martin CA, Pan D, Nazareth J, Aujayeb A, Bryant L, Carr S, Gray LJ, Gregary B, Gupta A, Guyatt AL, Gopal A, Hine T, John C, McManus IC, Melbourne C, Nellums LB, Reza R, Simpson S, Tobin MD, Woolf K, Zingwe S, Khunti K, Pareek M.",,No Journal Info,2021,2021-09-21,Y,,,,"<h4>Objectives</h4> To determine the prevalence and predictors of self-reported access to appropriate personal protective equipment (aPPE) for healthcare workers (HCWs) in the United Kingdom (UK) during the first UK national COVID-19 lockdown (March 2020) and at the time of questionnaire response (December 2020 – February 2021). <h4>Design</h4> Two cross sectional analyses using data from a questionnaire-based cohort study. <h4>Setting</h4> Nationwide questionnaire from 4 th December 2020 to 28 th February 2021. <h4>Participants</h4> A representative sample of HCWs or ancillary workers in a UK healthcare setting aged 16 or over, registered with one of seven main UK healthcare regulatory bodies. <h4>Main outcome measure</h4> Binary measure of self-reported aPPE (access all of the time vs access most of the time or less frequently) at two timepoints: the first national lockdown in the UK (primary analysis) and at the time of questionnaire response (secondary analysis). <h4>Results</h4> 10,508 HCWs were included in the primary analysis, and 12,252 in the secondary analysis. 3702 (35.2%) of HCWs reported aPPE at all times in the primary analysis; 6806 (83.9%) reported aPPE at all times in the secondary analysis. After adjustment (for age, sex, ethnicity, migration status, occupation, aerosol generating procedure exposure, work sector, work region, working hours, night shift frequency and trust in employing organisation), older HCWs (per decade increase in age: aOR 1.2, 95% CI 1.16-1.26, p<0.001) and those working in Intensive Care Units (1.61, 1.38 – 1.89, p<0.001) were more likely to report aPPE at all times. Those from Asian ethnic groups compared to White (0.77, 0.67-0.89, p<0.001), those in allied health professional (AHPs) and dental roles (vs those in medical roles; AHPs: 0.77, 0.68 – 0.87, p<0.001; dental: 0.63, 0.49-0.81, p<0.001), and those who saw a higher number of COVID-19 patients compared to those who saw none (≥21 patients 0.74, 0.61-0.90, p=0.003) were less likely to report aPPE at all times in the primary analysis. aPPE at all times was also not uniform across UK regions (reported access being better in South West and North East England than London). Those who trusted their employing organisation to deal with concerns about unsafe clinical practice, compared to those who did not, were twice as likely to report aPPE at all times (2.18, 1.97-2.40, p<0.001). With the exception of occupation, these factors were also significantly associated with aPPE at all times in the secondary analysis. <h4>Conclusions</h4> We found that only a third of HCWs in the UK reported aPPE at all times during the period of the first lockdown and that aPPE had improved later in the pandemic. We also identified key sociodemographic and occupational determinants of aPPE during the first UK lockdown, the majority of which have persisted since lockdown was eased. These findings have important public health implications for HCWs, particularly as cases of infection and long-COVID continue to rise in the UK. <h4>Trial registration</h4> ISRCTN 11811602 <h4>What is already known on this topic</h4> Access to personal protective equipment (PPE) is crucial to protect healthcare workers (HCWs) from infection. Limited data exist concerning the prevalence of, and factors relating to, PPE access for HCWs in the United Kingdom (UK) during the COVID-19 pandemic. <h4>What this study adds</h4> Only a third of HCWs reported having access to appropriate PPE all of the time during the first UK national lockdown. Older HCWs, those working in Intensive Care Units and those who trusted their employing organisation to deal with concerns about unsafe clinical practice, were more likely to report access to adequate PPE. Those from Asian ethnic groups (compared to White ethnic groups) and those who saw a high number of COVID-19 were less likely to report access to adequate PPE. Our findings have important implications for the mental and physical health of HCWs working during the pandemic in the UK.",,pdf:https://discovery.ucl.ac.uk/10152293/1/Martin2022-PPE.pdf; doi:https://doi.org/10.1101/2021.09.16.21263629; html:https://europepmc.org/article/PPR/PPR397279; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR397279&type=FILE&fileName=EMS135495-pdf.pdf&mimeType=application/pdf
@@ -209,8 +209,8 @@ PPR215745,https://doi.org/10.1101/2020.09.15.20194795,"A short report: Acute, no
 PPR199535,https://doi.org/10.1101/2020.08.11.20172643,The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories,"Liu Y, Morgenstern C, Kelly J, Lowe R, Jit M, CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-08-12,Y,,,,"<h4>Introduction</h4> Non-pharmaceutical interventions (NPIs) are used to reduce transmission of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel restrictions, economic measures, and health system actions on SARS-CoV-2 transmission in 130 countries and territories. <h4>Methods</h4> We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission with data from January - June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number ( R t ) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes in R t , levels of NPI intensity, time-varying changes in NPI effect and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs. <h4>Results</h4> There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reduced R t . Another three NPIs (workplace closure, income support and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g., restrictions on 1000+ people gathering were not effective, restrictions on <10 people gathering was). Evidence supporting the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel controls, testing, contact tracing) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs. <h4>Conclusion</h4> Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission is complicated by temporal clustering, time-dependent variation in effects and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications taking into account these effects, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many although not all the actions policy-makers are taking to respond to the COVID-19 pandemic.",,pdf:https://europepmc.org/articles/pmc7861967?pdf=render; doi:https://doi.org/10.1101/2020.08.11.20172643; html:https://europepmc.org/article/PPR/PPR199535; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR199535&type=FILE&fileName=EMS92611-pdf.pdf&mimeType=application/pdf
 PPR593389,https://doi.org/10.1101/2023.01.05.23284214,"The impact of the COVID-19 pandemic on Antipsychotic Prescribing in individuals with autism, dementia, learning disability, serious mental illness or living in a care home: A federated analysis of 59 million patients’ primary care records in situ using OpenSAFELY","The OpenSAFELY Collaborative:, Macdonald O, Green A, Walker A, Croker R, Curtis H, Brown A, Butler-Cole B, Andrews C, Morton C, Evans D, Inglesby P, Dillingham I, Massey J, Fisher L, Bacon S, Davy S, Ward T, Hulme W, Morley J, Mehrkar A, Bates C, Cockburn J, Parry J, Hester F, Harper S, O’Hanlon S, Eavis A, Jarvis R, Avramov D, Wood I, Parkes N, Goldacre B, MacKenna B.",,No Journal Info,2023,2023-01-07,Y,,,,"<h4>Background</h4> The COVID-19 pandemic significantly affected health and social care services. We aimed to explore whether this impacted the prescribing rates of antipsychotics within at-risk populations. <h4>Methods</h4> With the approval of NHS England, we completed a retrospective cohort study, using the OpenSAFELY platform to explore primary care data of 59 million patients. We identified patients in five at-risk groups: autism, dementia, learning disability, serious mental illness and care home residents. We then calculated the monthly prevalence of antipsychotic prescribing in the population, as well as the incidence of new prescriptions in each month over the study period (Jan 2019-Dec 2021). <h4>Results</h4> The average monthly rate of antipsychotic prescribing increased in dementia from 82.75 patients prescribed an antipsychotic per 1000 patients (95% CI 82.30-83.19) in Q1 2019 to 90.1 (95% CI 89.68-90.60) in Q4 2021 and from 154.61 (95% CI 153.79-155.43) in Q1 2019 to 166.95 (95% CI 166.23-167.67) in Q4 2021 in care homes. There were notable spikes in the rate of new prescriptions issued to patients with dementia and in care homes. In learning disability and autism groups, the average monthly rate of prescribing per 1000 decreased from 122.97 (95% CI 122.29-123.66) in Q1 2019 to 119.29 (95% CI 118.68-119.91) in Q4 2021, and from 54.91 (95% CI 54.52-55.29) in Q1 2019 to 51.04 (95% CI 50.74-51.35) in Q4 2021 respectively. <h4>Conclusions</h4> During each of the lockdowns in 2020, we observed a significant spike in antipsychotic prescribing in the dementia and care home groups. We have shown that these peaks are likely due to prescribing of antipsychotics for palliative care purposes and may have been linked to pre-emptive prescribing, when on-site medical visits would have been restricted. Over the study period, we observed gradual increases in antipsychotic use in patients with dementia and in care homes and a decrease in their use in patients with learning disability or autism.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/07/2023.01.05.23284214.full.pdf; doi:https://doi.org/10.1101/2023.01.05.23284214; html:https://europepmc.org/article/PPR/PPR593389; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR593389&type=FILE&fileName=EMS159469-pdf.pdf&mimeType=application/pdf
 PPR438312,https://doi.org/10.1101/2021.12.28.21268461,Rapid turnaround multiplex sequencing of SARS-CoV-2: comparing tiling amplicon protocol performance,"Constantinides B, Webster H, Gentry J, Bastable J, Dunn L, Oakley S, Swann J, Sanderson N, Fowler PW, Ma G, Rodger G, Barrett L, Jeffery K, Peto TE, Stoesser N, Street T, Crook DW.",,No Journal Info,2022,2022-01-01,Y,,,,"Genome sequencing is pivotal to SARS-CoV-2 surveillance, elucidating the emergence and global dissemination of acquired genetic mutations. Amplicon sequencing has proven very effective for sequencing SARS-CoV-2, but prevalent mutations disrupting primer binding sites have necessitated the revision of sequencing protocols in order to maintain performance for emerging virus lineages. We compared the performance of Oxford Nanopore Technologies (ONT) Midnight and ARTIC tiling amplicon protocols using 196 Delta lineage SARS-CoV-2 clinical specimens, and 71 mostly Omicron lineage samples with S gene target failure (SGTF), reflecting circulating lineages in the United Kingdom during December 2021. 96-plexed nanopore sequencing was used. For Delta lineage samples, ARTIC v4 recovered the greatest proportion of ≥90% complete genomes (81.1%; 159/193), followed by Midnight (71.5%; 138/193) and ARTIC v3 (34.1%; 14/41). Midnight protocol however yielded higher average genome recovery (mean 98.8%) than ARTIC v4 (98.1%) and ARTIC v3 (75.4%), resulting in less ambiguous final consensus assemblies overall. Explaining these observations were ARTIC v4’s superior genome recovery in low viral titre/high cycle threshold (Ct) samples and inferior performance in high titre/low Ct samples, where Midnight excelled. We evaluated Omicron sequencing performance using a revised Midnight primer mix alongside prototype ARTIC v4.1 primers, head-to-head with the existing commercially available Midnight and ARTIC v4 protocols. The revised protocols both improved considerably the recovery of Omicron genomes and exhibited similar overall performance to one another. Revised Midnight protocol recovered ≥90% complete genomes for 85.9% (61/71) of Omicron samples vs. 88.7% (63/71) for ARTIC v4.1. Approximate cost per sample for Midnight (£12) is lower than ARTIC (£16) while hands-on time is considerably lower for Midnight (∼7 hours) than ARTIC protocols (∼9.5 hours).",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/01/2021.12.28.21268461.full.pdf; doi:https://doi.org/10.1101/2021.12.28.21268461; html:https://europepmc.org/article/PPR/PPR438312; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR438312&type=FILE&fileName=EMS142102-pdf.pdf&mimeType=application/pdf
-PPR441045,https://doi.org/10.1101/2022.01.11.22269017,Healthcare workers’ views on mandatory SARS-CoV-2 vaccination in the United Kingdom: findings from the UK-REACH prospective longitudinal cohort study,"Woolf K, Gogoi M, Martin CA, Papineni P, Papineni P, Lagrata S, Nellums LB, McManus IC, Guyatt AL, Melbourne C, Bryant L, Gupta A, John C, Carr S, Tobin MD, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M.",,No Journal Info,2022,2022-01-11,Y,,,,"<h4>Background</h4> Several countries now have mandatory SARS-CoV-2/COVID-19 vaccination for healthcare workers (HCWs) or the general population. HCWs’ views on this are largely unknown. <h4>Methods</h4> We administered an online questionnaire to 17891 United Kingdom (UK) HCWs in Spring 2021 as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) nationwide prospective cohort study. We categorised responses to a free-text question “What should society do if people don’t get vaccinated against COVID-19?” using content analysis. We collapsed categories into a binary variable: favours mandatory vaccination or not and used logistic regression to calculate its demographic predictors, and occupational, health and attitudinal predictors adjusted for demographics. <h4>Findings</h4> Of 5633 questionnaire respondents, 3235 answered the freetext question; 18% (n=578) of those favoured mandatory vaccination but the most frequent suggestion was education (32%, n=1047). Older HCWs, HCWs vaccinated against influenza (OR 1.48; 95%CI 1.10 – 1.99, vs none) and with more positive vaccination attitudes generally (OR 1.10; 95%CI 1.06 – 1.14) were more likely to favour mandatory vaccination (OR 1.26; 95%CI 1.17 – 1.37, per decade increase), whereas female HCWs (OR= 0.80, 95%CI 0.65 – 0.99, vs male), Black HCWs (OR= 0.48, 95%CI 0.26 – 0.87, vs White), those hesitant about COVID-19 vaccination (OR= 0.56; 95%CI 0.43 – 0.71, vs not hesitant), in an Allied Health Profession (OR 0.67; 95%CI 0.51 – 0.88, vs Medical), or who trusted their organisation (OR 0.78; 95%CI 0.63 – 0.96) were less likely to. <h4>Interpretation</h4> Only one in six of the HCWs in this large, diverse, UK-wide sample favoured mandatory vaccination. Building trust, educating and supporting HCWs who are hesitant about vaccination may be more acceptable, effective and equitable. <h4>Funding</h4> MRC-UK Research and Innovation grant (MR/V027549/1) and the Department of Health and Social Care via the National Institute for Health Research.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/11/2022.01.11.22269017.full.pdf; doi:https://doi.org/10.1101/2022.01.11.22269017; html:https://europepmc.org/article/PPR/PPR441045; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR441045&type=FILE&fileName=EMS142331-pdf.pdf&mimeType=application/pdf
 PPR211707,https://doi.org/10.1101/2020.09.04.20187781,Hydroxychloroquine for prevention of COVID-19 mortality: a population-based cohort study,"Rentsch CT, DeVito NJ, MacKenna B, Morton CE, Bhaskaran K, Brown JP, Schultze A, J Hulme W, Croker R, Walker AJ, Williamson EJ, Bates C, Bacon S, Mehrkar A, Curtis HJ, Evans D, Wing K, Inglesby P, Mathur R, Drysdale H, Wong AY, McDonald HI, Cockburn J, Forbes H, Parry J, Hester F, Harper S, Smeeth L, Douglas IJ, Dixon WG, Evans SJ, Tomlinson L, Goldacre B.",,No Journal Info,2020,2020-09-09,Y,,,,"<h4>Background</h4> Hydroxychloroquine has been shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, but early clinical studies found no benefit treating patients with coronavirus disease 2019 (COVID-19). We set out to evaluate the effectiveness of hydroxychloroquine for prevention, as opposed to treatment, of COVID-19 mortality. <h4>Methods</h4> We pre-specified and conducted an observational, population-based cohort study using national primary care data and linked death registrations in the OpenSAFELY platform, representing 40% of the general population in England. We used Cox regression to estimate the association between ongoing routine hydroxychloroquine use prior to the COVID-19 outbreak in England and risk of COVID-19 mortality among people with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Model adjustment was informed by a directed acyclic graph. <h4>Results</h4> Of 194,637 patients with RA or SLE, 30,569 (15.7%) received ≥ 2 prescriptions of hydroxychloroquine in the six months prior to 1 March 2020. Between 1 March 2020 and 13 July 2020, there were 547 COVID-19 deaths, 70 among hydroxychloroquine users. Estimated standardised cumulative COVID-19 mortality was 0.23% (95% CI 0.18–0.29) among users and 0.22% (95% CI 0.20–0.25) among non-users; an absolute difference of 0.008% (95% CI –0.051-0.066). After accounting for age, sex, ethnicity, use of other immunuosuppressives, and geographic region, no association with COVID-19 mortality was observed (HR 1.03, 95% CI 0.80–1.33). We found no evidence of interactions with age or other immunosuppressives. Quantitative bias analyses indicated observed associations were robust to missing information regarding additional biologic treatments for rheumatological disease. We observed similar associations with the negative control outcome of non-COVID-19 mortality. <h4>Conclusion</h4> We found no evidence of a difference in COVID-19 mortality among patients who received hydroxychloroquine for treatment of rheumatological disease prior to the COVID-19 outbreak in England. <h4>Research in context</h4> <h4>Evidence before this study</h4> Published trials and observational studies to date have shown no evidence of benefit of hydroxychloroquine as a treatment for hospitalised patients who already have COVID-19. A separate question remains: whether routine ongoing use of hydroxychloroquine in people without COVID-19 protects against new infections or severe outcomes. We searched MEDLINE/PubMed for pharmacoepidemiological studies evaluating hydroxychloroquine for prevention of severe COVID-19 outcomes. The keywords “hydroxychloroquine AND (COVID OR coronavirus OR SARS-CoV-2) AND (prophyl* OR prevent*) AND (rate OR hazard OR odds OR risk)” were used and results were filtered to articles from the last year with abstracts available. 109 papers were identified for screening; none investigated pre-exposure prophylactic use of hydroxychloroquine for prevention of severe COVID-19 outcomes. Clinical trials of prophylactic use of hydroxychloroquine are ongoing; however, the largest trial does not expect to meet recruitment targets due to “…unjustified extrapolation and exaggerated safety concerns together with intense politicisation and negative publicity.” In the absence of reported clinical trials, evidence can be generated from real-world data to support the need for randomised clinical trials. <h4>Added value of this study</h4> In this cohort study representing 40% of the population of England, we investigated whether routine use of hydroxychloroquine prior to the COVID-19 outbreak prevented COVID-19 mortality. Using robust pharmacoepidemiological methods, we found no evidence to support a substantial benefit of hydroxychloroquine in preventing COVID-19 mortality. At the same time, we have shown no significant harm, and this generates the equipoise to justify continuing randomised trials. We have demonstrated in this study that it is feasible to address specific hypotheses about medicines in a rapid and transparent manner to inform interim clinical decision making and support the need for large-scale, randomised trial data. <h4>Implications of all the available evidence</h4> This is the first study to investigate the ongoing routine use of hydroxychloroquine and risk of COVID-19 mortality in a general population. While we found no evidence of any protective benefit, due to the observational nature of the study, residual confounding remains a possibility. Completion of trials for prevention of severe outcomes is warranted, but prior to the completion of these, we found no evidence to support the use of hydroxychloroquine for prevention of COVID-19 mortality.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659478/1/rentsch_hcq.pdf; doi:https://doi.org/10.1101/2020.09.04.20187781; html:https://europepmc.org/article/PPR/PPR211707; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR211707&type=FILE&fileName=EMS94873-pdf.pdf&mimeType=application/pdf
+PPR441045,https://doi.org/10.1101/2022.01.11.22269017,Healthcare workers’ views on mandatory SARS-CoV-2 vaccination in the United Kingdom: findings from the UK-REACH prospective longitudinal cohort study,"Woolf K, Gogoi M, Martin CA, Papineni P, Papineni P, Lagrata S, Nellums LB, McManus IC, Guyatt AL, Melbourne C, Bryant L, Gupta A, John C, Carr S, Tobin MD, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M.",,No Journal Info,2022,2022-01-11,Y,,,,"<h4>Background</h4> Several countries now have mandatory SARS-CoV-2/COVID-19 vaccination for healthcare workers (HCWs) or the general population. HCWs’ views on this are largely unknown. <h4>Methods</h4> We administered an online questionnaire to 17891 United Kingdom (UK) HCWs in Spring 2021 as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) nationwide prospective cohort study. We categorised responses to a free-text question “What should society do if people don’t get vaccinated against COVID-19?” using content analysis. We collapsed categories into a binary variable: favours mandatory vaccination or not and used logistic regression to calculate its demographic predictors, and occupational, health and attitudinal predictors adjusted for demographics. <h4>Findings</h4> Of 5633 questionnaire respondents, 3235 answered the freetext question; 18% (n=578) of those favoured mandatory vaccination but the most frequent suggestion was education (32%, n=1047). Older HCWs, HCWs vaccinated against influenza (OR 1.48; 95%CI 1.10 – 1.99, vs none) and with more positive vaccination attitudes generally (OR 1.10; 95%CI 1.06 – 1.14) were more likely to favour mandatory vaccination (OR 1.26; 95%CI 1.17 – 1.37, per decade increase), whereas female HCWs (OR= 0.80, 95%CI 0.65 – 0.99, vs male), Black HCWs (OR= 0.48, 95%CI 0.26 – 0.87, vs White), those hesitant about COVID-19 vaccination (OR= 0.56; 95%CI 0.43 – 0.71, vs not hesitant), in an Allied Health Profession (OR 0.67; 95%CI 0.51 – 0.88, vs Medical), or who trusted their organisation (OR 0.78; 95%CI 0.63 – 0.96) were less likely to. <h4>Interpretation</h4> Only one in six of the HCWs in this large, diverse, UK-wide sample favoured mandatory vaccination. Building trust, educating and supporting HCWs who are hesitant about vaccination may be more acceptable, effective and equitable. <h4>Funding</h4> MRC-UK Research and Innovation grant (MR/V027549/1) and the Department of Health and Social Care via the National Institute for Health Research.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/01/11/2022.01.11.22269017.full.pdf; doi:https://doi.org/10.1101/2022.01.11.22269017; html:https://europepmc.org/article/PPR/PPR441045; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR441045&type=FILE&fileName=EMS142331-pdf.pdf&mimeType=application/pdf
 PPR296449,https://doi.org/10.1101/2021.03.11.21253364,Analysis of severe outcomes associated with the SARS-CoV-2 Variant of Concern 202012/01 in England using ICNARC Case Mix Programme and QResearch databases,"Patone M, Thomas K, Hatch R, Tan PS, Coupland C, Liao W, Mouncey P, Harrison D, Rowan K, Horby P, Watkinson P, Hippisley-Cox J.",,No Journal Info,2021,2021-03-12,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> A new, more transmissible variant of SARS-CoV-2, variant of concern (VOC) 202012/01 or lineage B.1.1.7, has emerged in the UK. We estimate the risk of critical care admission, mortality in critical ill patients, and overall mortality associated with VOC B.1.1.7 compared with the original variant. We also compare clinical outcomes between these variants ‘ groups. <h4>Methods</h4> We linked a large primary care (QResearch), the national critical care (ICNARC CMP) and the COVID-19 testing (PHE) database and extracted two cohorts. The first was used to explore the association between VOC B.1.1.7 and critical care admission and 28-day mortality. The second to determine the risk of mortality in critically ill patients with VOC B.1.1.7 compared to those without. We used Royston-Parmar models adjusted for age, sex, region, other socio-demographics and comorbidities (asthma, COPD, type I and II, hypertension). We reported information on types and duration of organ supports for the two variants ‘ groups. <h4>Findings</h4> The first cohort included 198,420 patients. Of these, 80,494 had VOC B.1.1.7, 712 were critically ill and 630 died by 28 days. The second cohort included 3432 critically ill patients. Of these, 2019 had VOC B.1.1.7 and 822 died at the end of critical care. Using the first cohort, we estimated adjusted hazard ratios for critical care admission and mortality to be 1.99 (95% CI: 1.59, 2.49) and 1.59 (95% CI: 1.25-2.03) for VOC B.1.1.7 compared with the original variant group, respectively. The adjusted hazard ratio for mortality in critical care, estimated using the second cohort, was 0.93 (95% CI 0.76-1.15) for patients with VOC B.1.1.7, compared to those without. <h4>Interpretation</h4> VOC B.1.1.7 appears to be more severe. Patients with VOC B.1.1.7 are at increased risk of critical care admission and mortality compared with patients without. For patients receiving critical care, mortality appears independent of virus strain. <h4>RESEARCH IN CONTEXT</h4> <h4>Evidence before this study</h4> A new variant of the SARS-CoV-2 virus, variant of concern (VOC) 202012/01, or lineage B.1.1.7, was detected in England in September 2020. The characteristics and outcomes of patients infected with VOC B.1.1.7 are not yet known. VOC B.1.1.7 has been associated with increased transmissibility. Early analyses have suggested infection with VOC B.1.1.7 may be associated with a higher risk of mortality compared with infection with other virus variants, but these analyses had either limited ability to adjust for key confounding variables or did not consider critical care admission. The effects of VOC B.1.1.7 on severe COVID-19 outcomes remain unclear. <h4>Added value of this study</h4> This study found a 60% higher risk of 28-day mortality associated with infection with VOC B.1.1.7 in patients tested in the community in comparison with the original variant, when adjusted for key confounding variables. The risk of critical care admission for those with VOC B.1.1.7 is double the risk associated with the original variant. For patients receiving critical care, the infecting variant is not associated with the risk of mortality at the end of critical care. <h4>Implications of all the available evidence</h4> The higher mortality and rate of critical care admission associated with VOC B.1.1.7, combined with its known increased transmissibility, are likely to put health care systems under further stress. These effects may be mitigated by the ongoing vaccination programme.",,doi:https://doi.org/10.1101/2021.03.11.21253364; html:https://europepmc.org/article/PPR/PPR296449; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR296449&type=FILE&fileName=EMS119297-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2021/03/12/2021.03.11.21253364.full.pdf
 PPR550426,https://doi.org/10.1101/2022.09.23.22280285,"Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial","RECOVERY Collaborative Group, Horby PW, Peto L, Staplin N, Campbell M, Pessoa-Amorim G, Mafham M, Emberson JR, Stewart R, Prudon B, Uriel A, Green CA, Dhasmana DJ, Malein F, Majumdar J, Collini P, Shurmer J, Yates B, Baillie JK, Buch MH, Day JN, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray M.",,No Journal Info,2022,2022-09-25,Y,,,,"<h4>SUMMARY</h4> <h4>Background</h4> Dimethyl fumarate (DMF) is an anti-inflammatory drug that has been proposed as a treatment for patients hospitalised with COVID-19 <h4>Methods</h4> This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised for COVID-19. In this initial assessment of DMF, performed at 27 UK hospitals, eligible and consenting adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF 120mg twice daily for 2 days followed by 240mg twice daily for 8 days, or until discharge if sooner. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale, assessed using a proportional odds model. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ). <h4>Findings</h4> Between 2 March 2021 and 18 November 2021, 713 patients were enrolled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients were receiving corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.85-1.46; p=0.42). There was no significant effect of DMF on any secondary outcome. As expected, DMF caused flushing and gastrointestinal symptoms, each in around 6% of patients, but no new adverse effects were identified. <h4>Interpretation</h4> In adults hospitalised with COVID-19, DMF was not associated with an improvement in clinical outcomes. <h4>Funding</h4> UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/09/25/2022.09.23.22280285.full.pdf; doi:https://doi.org/10.1101/2022.09.23.22280285; html:https://europepmc.org/article/PPR/PPR550426; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR550426&type=FILE&fileName=EMS154960-pdf.pdf&mimeType=application/pdf
 PPR279532,https://doi.org/10.1101/2021.02.04.21251087,Staff-Pupil SARS-CoV-2 Infection Pathways in Schools: A Population Level  Linked Data Approach,"Thompson DA, Abbasizanjani H, Fry R, Marchant E, Griffiths L, Akbari A, Hollinghurst J, North L, Lyons J, Torabi F, Davies G, Gravenor MB, Lyons R.",,No Journal Info,2021,2021-02-08,Y,,,,"<h4>Background</h4>  Better understanding of the role that children and school staff play in  the transmission of SARS-CoV-2 is essential to guide policy development on  controlling infection whilst minimising disruption to children’s education  and wellbeing. <h4>Methods</h4>  Our national e-cohort (n=500,779) study used anonymised linked data for  pupils, staff and associated households linked via educational settings. We  estimated the risk of testing positive for SARS-CoV-2 infection for staff  and pupils over the period August - December 2020, dependent on measures of  recent exposure to known cases linked to their educational  settings. <h4>Results</h4>  The total number of cases in a school was not associated with a  subsequent increase in the risk of testing positive (Staff OR per case 0.92,  95%CI 0.85, 1.00; Pupils OR per case 0.98, 95%CI 0.93, 1.02). Amongst  pupils, the number of recent cases within the same year group was  significantly associated with subsequent increased risk of testing positive  (OR per case 1.12, 95%CI 1.08 – 1.15). These effects were adjusted for a  range of demographic covariates, and in particular any known cases within  the same household, which had the strongest association with testing  positive (Staff OR 39.86, 95%CI 35.01, 45.38, pupil OR 9.39, 95%CI 8.94 –  9.88). <h4>Conclusions</h4>  In a national school cohort, the odds of staff testing positive for  SARS-CoV-2 infection were not significantly increased in the 14-day period  after case detection in the school. However, pupils were found to be at  increased risk, following cases appearing within their own year group, where  most of their contacts occur. Strong mitigation measures over the whole of  the study period may have reduced wider spread within the school  environment. <h4>What is known</h4>  Evidence of the role schools play in the transmission of  SARS-CoV-2 is limited Higher positivity rates are observed in school staff  compared to pupils Lack of evidence on transmission pathways transmission  into and within schools <h4>What this study adds</h4>  First UK national level study of transmission between  pupils and staff in a school environment during the  SARS-CoV-2 pandemic. Schools opening September-December 2020 was not  associated with an increased subsequent risk of testing  positive in staff Pupils were found to be at increased risk of testing  positive, following cases appearing within their own year  group",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56212/Download/56212__19426__59892786543a4e1983aa786d770d0e47.pdf; doi:https://doi.org/10.1101/2021.02.04.21251087; html:https://europepmc.org/article/PPR/PPR279532; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR279532&type=FILE&fileName=EMS116161-pdf.pdf&mimeType=application/pdf
@@ -283,8 +283,8 @@ PPR191930,https://doi.org/10.1101/2020.07.24.20161281,Strategies to reduce the r
 PPR319210,https://doi.org/10.1101/2021.04.30.21256119,Association between oral anticoagulants and COVID-19 related outcomes: two cohort studies,"The OpenSAFELY Collaborative, Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ.",,No Journal Info,2021,2021-04-30,Y,,,,"<h4>Objectives</h4> We investigated the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes, comparing current OAC use versus non-use in Study 1; and warfarin versus direct oral anticoagulants (DOACs) in Study 2. <h4>Design</h4> Two cohort studies, on behalf of NHS England. <h4>Setting</h4> Primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. <h4>Participants</h4> Study 1: 70,464 people with atrial fibrillation (AF) and CHA□DS□-VASc score of 2. Study 2: 372,746 people with non-valvular AF. <h4>Main outcome measures</h4> Time to test for SARS-CoV-2, testing positive for SARS-CoV-2, COVID-19 related hospital admission, COVID-19 deaths or non-COVID-19 deaths in Cox regression. <h4>Results</h4> In Study 1, we included 52,416 current OAC users and 18,048 non-users. We observed no difference in risk of being tested for SARS-CoV-2 associated with current use (adjusted HR, 1.01, 95%CI, 0.96 to 1.05) versus non-use. We observed a lower risk of testing positive for SARS-CoV-2 (adjusted HR, 0.73, 95%CI, 0.60 to 0.90), and COVID-19 deaths (adjusted HR, 0.69, 95%CI, 0.49 to 0.97) associated with current use versus non-use. In Study 2, we included 92,339 warfarin users and 280,407 DOAC users. We observed a lower risk of COVID-19 deaths (adjusted HR, 0.79, 95%CI, 0.76 to 0.83) associated with warfarin versus DOACs. Similar associations were found for all other outcomes. <h4>Conclusions</h4> Among people with AF and a CHA□DS□-VASc score of 2, those receiving OACs had a lower risk of receiving a positive COVID-19 test and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or more cautious behaviours leading to reduced infection risk. There was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin versus DOACs in people with non-valvular AF regardless of CHA□DS□-VASc score. <h4>Key points</h4> <h4>What is already known on this topic</h4> Current studies suggest that prophylactic or therapeutic anticoagulant use, particularly low molecular weight heparin, lower the risk of pulmonary embolism and mortality during hospitalisation among patients with COVID-19. Reduced vitamin K status has been reported to be correlated with severity of COVID-19. This could mean that warfarin, as a vitamin K antagonist, is associated with more severe COVID-19 disease than non-vitamin K anticoagulants. <h4>What this study adds</h4> In 70,464 people with atrial fibrillation, at the threshold of being treated with an OAC based on risk of stroke, we observed a lower risk of testing positive for SARS-CoV-2 and COVID-19 related deaths associated with routinely prescribed OACs, relative to non-use. This might be explained by OACs preventing severe COVID-19 outcomes, or more cautious behaviours and environmental factors reducing the risk of SARS-CoV-2 infection in those taking OACs. In 372,746 people with non-valvular atrial fibrillation, there was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin compared with DOACs.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/04/30/2021.04.30.21256119.full.pdf; doi:https://doi.org/10.1101/2021.04.30.21256119; html:https://europepmc.org/article/PPR/PPR319210; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR319210&type=FILE&fileName=EMS123890-pdf.pdf&mimeType=application/pdf
 PPR404742,https://doi.org/10.1101/2021.10.07.21264681,Monitoring sociodemographic inequality in COVID-19 vaccination coverage in England: a national linked data study,"Dolby T, Finning K, Baker A, Dowd L, Khunti K, Razieh C, Yates T, Nafilyan V.",,No Journal Info,2021,2021-10-07,Y,,,,"<h4>Background</h4> The UK began an ambitious COVID-19 vaccination programme on 8 th December 2020. This study describes variation in vaccination coverage by sociodemographic characteristics between December 2020 and August 2021. <h4>Methods</h4> Using population-level administrative records linked to the 2011 Census, we estimated monthly first dose vaccination rates by age group and sociodemographic characteristics amongst adults aged 18 years or over in England. We also present a tool to display the results interactively. <h4>Findings</h4> Our study population included 35,223,466 adults. A lower percentage of males than females were vaccinated in the young and middle age groups (18-59 years) but not in the older age groups. Vaccination rates were highest among individuals of White British and Indian ethnic backgrounds and lowest among Black Africans (aged ≥80 years) and Black Caribbeans (18-79 years). Differences by ethnic group emerged as soon as vaccination roll-out commenced and widened over time. Vaccination rates were also lower among individuals who identified as Muslim, lived in more deprived areas, reported having a disability, did not speak English as their main language, lived in rented housing, belonged to a lower socio-economic group, and had fewer qualifications. <h4>Interpretation</h4> We found inequalities in COVID-19 vaccination rates by sex, ethnicity, religion, area deprivation, disability status, English language proficiency, socio-economic position, and educational attainment, but some of these differences varied by age group. Research is urgently needed to understand why these inequalities exist and how they can be addressed. <h4>Research in context</h4> <h4>Evidence before this study</h4> We searched PubMed for publications on sociodemographic inequalities in COVID-19 vaccination coverage. Several studies have reported differences in coverage by characteristics such as ethnicity and religion, however these have focused on older adults and the clinically vulnerable who were initially prioritized for vaccination. There is little evidence on sociodemographic inequalities in vaccination coverage among younger adults and evidence is also lacking on coverage by a wider range of characteristics such as sex, disability status, English language proficiency, socio-economic position, and educational attainment. <h4>Added value of this study</h4> This study provides the first evidence for sociodemographic inequalities in COVID-19 vaccination coverage among the entire adult population in England, using population-level administrative records linked to the 2011 Census. By disaggregating the data by age group, we were able to show that disparities in coverage by some sociodemographic characteristics differed by age group. For example, a lower proportion of males than females were vaccinated in the young and middle age groups (18-59 years) but not in the older age groups, and vaccination rates were lowest among Black Africans in those aged ≥80 years but lowest among Black Caribbeans for all other age groups. Vaccination rates were also lower among individuals who identified as Muslim, lived in more deprived areas, reported having a disability, did not speak English as their main language, lived in rented housing, belonged to a lower socio-economic group, and had fewer qualifications. <h4>Implications of all the available evidence</h4> Many of the groups with the lowest rates of COVID-19 vaccination are also the groups that have been disproportionately affected by the pandemic, including severe illness and mortality. Research is urgently needed to understand why these disparities exist and how they can be addressed, for example through public health or community engagement programmes. Since the relationships between sociodemographic characteristics and vaccination coverage may differ by age group, it is important for future research to disaggregate by age group when examining these inequalities.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/07/2021.10.07.21264681.full.pdf; doi:https://doi.org/10.1101/2021.10.07.21264681; html:https://europepmc.org/article/PPR/PPR404742; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR404742&type=FILE&fileName=EMS136793-pdf.pdf&mimeType=application/pdf
 PPR252028,https://doi.org/10.1101/2020.12.08.20246231,Artificial intelligence-enabled analysis of UK and US public attitudes on Facebook and Twitter towards COVID-19 vaccinations,"Hussain A, Tahir A, Hussain Z, Sheikh Z, Gogate M, Dashtipour K, Ali A, Sheikh A.",,No Journal Info,2020,2020-12-11,Y,,,,"<h4>Background</h4> Global efforts towards the development and deployment of a vaccine for SARS-CoV-2 are rapidly advancing. We developed and applied an artificial-intelligence (AI)-based approach to analyse social-media public sentiment in the UK and the US towards COVID-19 vaccinations, to understand public attitude and identify topics of concern. <h4>Methods</h4> Over 300,000 social-media posts related to COVID-19 vaccinations were extracted, including 23,571 Facebook-posts from the UK and 144,864 from the US, along with 40,268 tweets from the UK and 98,385 from the US respectively, from 1 st March - 22 nd November 2020. We used natural language processing and deep learning based techniques to predict average sentiments, sentiment trends and topics of discussion. These were analysed longitudinally and geo-spatially, and a manual reading of randomly selected posts around points of interest helped identify underlying themes and validated insights from the analysis. <h4>Results</h4> We found overall averaged positive, negative and neutral sentiment in the UK to be 58%, 22% and 17%, compared to 56%, 24% and 18% in the US, respectively. Public optimism over vaccine development, effectiveness and trials as well as concerns over safety, economic viability and corporation control were identified. We compared our findings to national surveys in both countries and found them to correlate broadly. <h4>Conclusions</h4> AI-enabled social-media analysis should be considered for adoption by institutions and governments, alongside surveys and other conventional methods of assessing public attitude. This could enable real-time assessment, at scale, of public confidence and trust in COVID-19 vaccinations, help address concerns of vaccine-sceptics and develop more effective policies and communication strategies to maximise uptake.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/12/11/2020.12.08.20246231.full.pdf; doi:https://doi.org/10.1101/2020.12.08.20246231; html:https://europepmc.org/article/PPR/PPR252028; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR252028&type=FILE&fileName=EMS108377-pdf.pdf&mimeType=application/pdf
-PPR387421,https://doi.org/10.1101/2021.08.18.21262222,"Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: whole population cohort study in 46 million adults in England","CVD-COVID-UK consortium, Whiteley WN, Ip S, Cooper JA, Bolton T, Keene S, Walker V, Denholm R, Akbari A, Omigie E, Hollings S, Di Angelantonio E, Denaxas S, Wood A, Sterne JAC, Sudlow C, Writing committee.",,No Journal Info,2021,2021-08-23,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> Thromboses in unusual locations after the COVID-19 vaccine ChAdOx1-S have been reported. Better understanding of population-level thrombotic risks after COVID-19 vaccination is needed. <h4>Methods</h4> We analysed linked electronic health records from adults living in England, from 8 th December 2020 to 18 th March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous and thrombocytopenic outcomes 1-28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years, and adjusted for age, sex, comorbidities, and social and demographic factors. <h4>Results</h4> Of 46,162,942 adults, 21,193,814 (46%) had their first vaccination during follow-up. Adjusted HRs 1-28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 respectively, were 0.97 (95% CI: 0.90-1.05) and 0.58 (0.53–0.63) for venous thromboses, and 0.90 (0.86-0.95) and 0.76 (0.73-0.79) for arterial thromboses. Corresponding HRs for BNT162b2 were 0.81 (0.74–0.88) and 0.57 (0.53–0.62) for venous thromboses, and 0.94 (0.90-0.99) and 0.72 (0.70-0.75) for arterial thromboses. HRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and thrombocytopenia in adults aged <70 years were higher 1-28 days after ChAdOx1-S (adjusted HRs 2.27, 95% CI:1.33– 3.88 and 1.71, 1.35–2.16 respectively), but not after BNT162b2 (0.59, 0.24–1.45 and 1.00, 0.75–1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1-28 days after ChAdOx1-S were 0.9–3 per million, varying by age and sex. <h4>Conclusions</h4> Increases in ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic, events were generally lower after either vaccine.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa57688/Download/57688__23941__69a222d696ec4cd991ed01d7cb47ee8e.pdf; doi:https://doi.org/10.1101/2021.08.18.21262222; html:https://europepmc.org/article/PPR/PPR387421; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR387421&type=FILE&fileName=EMS134400-pdf.pdf&mimeType=application/pdf
 PPR208611,https://doi.org/10.1101/2020.09.02.20185173,"Characteristics and outcomes of 627 044 COVID-19 patients with and without obesity in the United States, Spain, and the United Kingdom","Recalde M, Roel E, Pistillo A, Sena AG, Prats-Uribe A, Ahmed W, Alghoul H, Alshammari TM, Alser O, Areia C, Burn E, Casajust P, Dawoud D, DuVall SL, Falconer T, Fernández-Bertolín S, Golozar A, Gong M, Lai LYH, Lane JC, Lynch KE, Matheny ME, Mehta PP, Morales DR, Natarjan K, Nyberg F, Posada JD, Reich CG, Schilling LM, Shah K, Shah NH, Subbian V, Zhang L, Zhu H, Ryan P, Prieto-Alhambra D, Kostka K, Duarte-Salles T.",,No Journal Info,2020,2020-09-03,Y,,,,"<h4>Background</h4> COVID-19 may differentially impact people with obesity. We aimed to describe and compare the demographics, comorbidities, and outcomes of obese patients with COVID-19 to those of non-obese patients with COVID-19, or obese patients with seasonal influenza. <h4>Methods</h4> We conducted a cohort study based on outpatient/inpatient care, and claims data from January to June 2020 from the US, Spain, and the UK. We used six databases standardized to the OMOP common data model. We defined two cohorts of patients diagnosed and/or hospitalized with COVID-19. We created corresponding cohorts for patients with influenza in 2017-2018. We followed patients from index date to 30 days or death. We report the frequency of socio-demographics, prior comorbidities, and 30-days outcomes (hospitalization, events, and death) by obesity status. <h4>Findings</h4> We included 627 044 COVID-19 (US: 502 650, Spain: 122 058, UK: 2336) and 4 549 568 influenza (US: 4 431 801, Spain: 115 224, UK: 2543) patients. The prevalence of obesity was higher among hospitalized COVID-19 (range: 38% to 54%) than diagnosed COVID-19 (30% to 47%), or diagnosed (15% to 47%) or hospitalized (27% to 48%) influenza patients. Obese hospitalized COVID-19 patients were more often female and younger than non-obese COVID-19 patients or obese influenza patients. Obese COVID-19 patients were more likely to have prior comorbidities, present with cardiovascular and respiratory events during hospitalization, require intensive services, or die compared to non-obese COVID-19 patients. Obese COVID-19 patients were more likely to require intensive services or die compared to obese influenza patients, despite presenting with fewer comorbidities. <h4>Interpretation</h4> We show that obesity is more common amongst COVID-19 than influenza patients, and that obese patients present with more severe forms of COVID-19 with higher hospitalization, intensive services, and fatality than non-obese patients. These data are instrumental for guiding preventive strategies of COVID-19 infection and complications. <h4>Funding</h4> The European Health Data & Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, and IQVIA. The University of Oxford received funding related to this work from the Bill & Melinda Gates Foundation (Investment ID INV-016201 and INV-019257). APU has received funding from the Medical Research Council (MRC) [MR/K501256/1, MR/N013468/1] and Fundación Alfonso Martín Escudero (FAME) (APU). VINCI [VA HSR RES 13-457] (SLD, MEM, KEL). JCEL has received funding from the Medical Research Council (MR/K501256/1) and Versus Arthritis (21605). No funders had a direct role in this study. The views and opinions expressed are those of the authors and do not necessarily reflect those of the Clinician Scientist Award programme, NIHR, Department of Veterans Affairs or the United States Government, NHS, or the Department of Health, England. <h4>Research in context</h4> <h4>Evidence before this study</h4> Previous evidence suggests that obese individuals are a high risk population for COVID-19 infection and complications. We searched PubMed for articles published from December 2019 until June 2020, using terms referring to SARS-CoV-2 or COVID-19 combined with terms for obesity. Few studies reported obesity and most of them were limited by small sample sizes and restricted to hospitalized patients. Further, they used different definitions for obesity (i.e. some reported together overweight and obesity, others only reported obesity with BMI>40kg/m 2 ). To date, no study has provided detailed information on the characteristics of obese COVID-19 patients, such as the prevalence of comorbidities or COVID-19 related outcomes. In addition, despite the fact that COVID-19 has been often compared to seasonal influenza, there are no studies assessing whether obese patients with COVID-19 differ from obese patients with seasonal influenza. <h4>Added value of this study</h4> We report the largest cohort of obese patients with COVID-19 and provide information on more than 29 000 aggregate characteristics publicly available. Our findings were consistent across the participating databases and countries. We found that the prevalence of obesity is higher among COVID-19 compared to seasonal influenza patients. Obese patients with COVID-19 are more commonly female and have worse outcomes than non-obese patients. Further, they have worse outcomes than obese patients with influenza, despite presenting with fewer comorbidities. <h4>Implications of all the available evidence</h4> Our results show that individuals with obesity present more comorbidities and worse outcomes for COVID-19 than non-obese patients. These findings may be useful in guiding clinical practice and future preventative strategies for obese individuals, as well as provide useful data to support subsequent association studies focussed on obesity and COVID-19.",,doi:https://doi.org/10.1101/2020.09.02.20185173; html:https://europepmc.org/article/PPR/PPR208611; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR208611&type=FILE&fileName=EMS94639-pdf.pdf&mimeType=application/pdf; pdf:https://www.medrxiv.org/content/medrxiv/early/2020/09/03/2020.09.02.20185173.full.pdf
+PPR387421,https://doi.org/10.1101/2021.08.18.21262222,"Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: whole population cohort study in 46 million adults in England","CVD-COVID-UK consortium, Whiteley WN, Ip S, Cooper JA, Bolton T, Keene S, Walker V, Denholm R, Akbari A, Omigie E, Hollings S, Di Angelantonio E, Denaxas S, Wood A, Sterne JAC, Sudlow C, Writing committee.",,No Journal Info,2021,2021-08-23,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> Thromboses in unusual locations after the COVID-19 vaccine ChAdOx1-S have been reported. Better understanding of population-level thrombotic risks after COVID-19 vaccination is needed. <h4>Methods</h4> We analysed linked electronic health records from adults living in England, from 8 th December 2020 to 18 th March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous and thrombocytopenic outcomes 1-28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years, and adjusted for age, sex, comorbidities, and social and demographic factors. <h4>Results</h4> Of 46,162,942 adults, 21,193,814 (46%) had their first vaccination during follow-up. Adjusted HRs 1-28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 respectively, were 0.97 (95% CI: 0.90-1.05) and 0.58 (0.53–0.63) for venous thromboses, and 0.90 (0.86-0.95) and 0.76 (0.73-0.79) for arterial thromboses. Corresponding HRs for BNT162b2 were 0.81 (0.74–0.88) and 0.57 (0.53–0.62) for venous thromboses, and 0.94 (0.90-0.99) and 0.72 (0.70-0.75) for arterial thromboses. HRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and thrombocytopenia in adults aged <70 years were higher 1-28 days after ChAdOx1-S (adjusted HRs 2.27, 95% CI:1.33– 3.88 and 1.71, 1.35–2.16 respectively), but not after BNT162b2 (0.59, 0.24–1.45 and 1.00, 0.75–1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1-28 days after ChAdOx1-S were 0.9–3 per million, varying by age and sex. <h4>Conclusions</h4> Increases in ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic, events were generally lower after either vaccine.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa57688/Download/57688__23941__69a222d696ec4cd991ed01d7cb47ee8e.pdf; doi:https://doi.org/10.1101/2021.08.18.21262222; html:https://europepmc.org/article/PPR/PPR387421; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR387421&type=FILE&fileName=EMS134400-pdf.pdf&mimeType=application/pdf
 PPR247301,https://doi.org/10.1101/2020.11.27.20238147,"Ethnicity, Household Composition and COVID-19 Mortality: A National Linked Data Study","Nafilyan V, Islam N, Ayoubkhani D, Gilles C, Katikireddi SV, Mathur R, Summerfield A, Tingay K, Tingay K, Asaria M, John A, Goldblatt P, Banerjee A, Khunti K.",,No Journal Info,2020,2020-12-02,Y,,,,"<h4>Background</h4> Ethnic minorities have experienced disproportionate COVID-19 mortality rates. We estimated associations between household composition and COVID-19 mortality in older adults (≥ 65 years) using a newly linked census-based dataset, and investigated whether living in a multi-generational household explained some of the elevated COVID-19 mortality amongst ethnic minority groups. <h4>Methods</h4> Using retrospective data from the 2011 Census linked to Hospital Episode Statistics (2017-2019) and death registration data (up to 27 th July 2020), we followed adults aged 65 years or over living in private households in England from 2 March 2020 until 27 July 2020 (n=10,078,568). We estimated hazard ratios (HRs) for COVID-19 death for people living in a multi-generational household compared with people living with another older adult, adjusting for geographical factors, socio-economic characteristics and pre-pandemic health. We conducted a causal mediation analysis to estimate the proportion of ethnic inequalities explained by living in a multi-generational household. <h4>Results</h4> Living in a multi-generational household was associated with an increased risk of COVID-19 death. After adjusting for confounding factors, the HRs for living in a multi-generational household with dependent children were 1.13 [95% confidence interval 1.01-1.27] and 1.17 [1.01-1.35] for older males and females. The HRs for living in a multi-generational household without dependent children were 1.03 [0.97 - 1.09] for older males and 1.22 [1.12 - 1.32] for older females. Living in a multi-generational household explained between 10% and 15% of the elevated risk of COVID-19 death among older females from South Asian background, but very little for South Asian males or people in other ethnic minority groups. <h4>Conclusion</h4> Older adults living with younger people are at increased risk of COVID-19 mortality, and this is a notable contributing factor to the excess risk experienced by older South Asian females compared to White females. Relevant public health interventions should be directed at communities where such multi-generational households are highly prevalent. <h4>Funding</h4> This research was funded by the Office for National Statistics.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0141076821999973; doi:https://doi.org/10.1101/2020.11.27.20238147; html:https://europepmc.org/article/PPR/PPR247301; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR247301&type=FILE&fileName=EMS107607-pdf.pdf&mimeType=application/pdf
 PPR556407,https://doi.org/10.1101/2022.10.07.22280819,A Multi-Granular Stacked Regression for Forecasting Long-Term Demand in Emergency Departments,"James C, Wood R, Denholm R.",,No Journal Info,2022,2022-10-10,Y,,,,"<h4>Background</h4> In the United Kingdom, Emergency Departments (EDs) are under significant pressure due to an ever-increasing number of attendances. Understanding how the capacity of other urgent care services and the health of a population may influence ED attendances is imperative for commissioners and policy makers to develop long-term strategies for reducing this pressure and improving quality and safety. <h4>Methods</h4> We developed a novel Multi-Granular Stacked Regression (MGSR) model using publicly available data to predict future mean monthly ED attendances within Clinical Commissioning Group regions in England. The MGSR combines measures of population health and health service capacity in other related settings. We assessed model performance using the R-squared statistic, measuring variance explained, and the Mean Absolute Percentage Error (MAPE), measuring forecasting accuracy. We used the MGSR to forecast ED demand over a 4-year period under hypothetical scenarios where service capacity is increased, or population health is improved. <h4>Results</h4> Measures of service capacity explain 41 ± 4% of the variance in monthly ED attendances and measures of population health explain 61 ± 25%. The MGSR leads to an overall improvement in performance, with an R-squared of 0.75 ± 0.03 and MAPE of 4% when forecasting mean monthly ED attendances per CCG. Using the MGSR to forecast long-term demand under different scenarios, we found improving population health would reduce peak ED attendances per CCG by approximately 600 per month after 2 years. <h4>Conclusions</h4> Combining models of population health and wider urgent care service capacity for predicting monthly ED attendances leads to an improved performance compared to each model individually. Policies designed to improve population health will reduce ED attendances and enhance quality and safety in the long-term.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/10/10/2022.10.07.22280819.full.pdf; doi:https://doi.org/10.1101/2022.10.07.22280819; html:https://europepmc.org/article/PPR/PPR556407; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR556407&type=FILE&fileName=EMS155538-pdf.pdf&mimeType=application/pdf
 PPR249199,https://doi.org/10.1101/2020.12.02.20242933,Pre-existing cardiovascular disease rather than cardiovascular risk factors drives mortality in COVID-19,"O’Gallagher K, Shek A, Bean DM, Bendayan R, Teo JTH, Dobson RJB, Shah AM, Zakeri R.",,No Journal Info,2020,2020-12-04,Y,,,,"<h4>Background</h4> The association between cardiovascular (CV) risk factors, such as hypertension and diabetes, established CV disease (CVD), and susceptibility to CV complications or mortality in COVID-19 remains unclear. <h4>Methods</h4> We conducted a cohort study of consecutive adults hospitalised for severe COVID-19 between 1 st March and 30 th June 2020. Pre-existing CVD, CV risk factors and associations with mortality and CV complications were ascertained. <h4>Findings</h4> Among 1,721 patients (median age 71 years, 57% male), 349 (20.3%) had pre-existing CVD (CVD), 888 (51.6%) had CV risk factors without CVD (RF-CVD), 484 (28.1%) had neither. Patients with CVD were older with a higher burden of non-CV comorbidities. During follow-up, 438 (25.5%) patients died: 37% with CVD, 25.7% with RF-CVD and 16.5% with neither. CVD was independently associated with in-hospital mortality among patients <70 years of age (adjusted HR 2.43 [95%CI 1.16-5.07]), but not in those ≥70 years (aHR 1.14 [95%CI 0.77-1.69]). RF-CVD were not independently associated with mortality in either age group (<70y aHR 1.21 [95%CI 0.72-2.01], ≥70y aHR 1.07 [95%CI 0.76-1.52]). Most CV complications occurred in patients with CVD (66%) versus RF-CVD (17%) or neither (11%; p<0.001). 213 [12.4%] patients developed venous thromboembolism (VTE). CVD was not an independent predictor of VTE. <h4>Interpretation</h4> In patients hospitalised with COVID-19, pre-existing established CVD appears to be a more important contributor to mortality than CV risk factors in the absence of CVD. CVD-related hazard may be mediated, in part, by new CV complications. Optimal care and vigilance for destabilised CVD are essential in this patient group.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-021-02137-9; doi:https://doi.org/10.1101/2020.12.02.20242933; html:https://europepmc.org/article/PPR/PPR249199; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR249199&type=FILE&fileName=EMS107885-pdf.pdf&mimeType=application/pdf
@@ -297,8 +297,8 @@ PPR341253,https://doi.org/10.1101/2021.05.18.21257267,"Colchicine in patients ad
 PPR245783,https://doi.org/10.1101/2020.11.24.20236802,"Characteristics, outcomes, and mortality amongst 133,589 patients with prevalent autoimmune diseases diagnosed with, and 48,418 hospitalised for COVID-19: a multinational distributed network cohort analysis","Tan EH, Sena AG, Prats-Uribe A, You SC, Ahmed W, Kostka K, Reich C, Duvall SL, Lynch KE, Matheny ME, Duarte-Salles T, Bertolin SF, Hripcsak G, Natarajan K, Falconer T, Spotnitz M, Ostropolets A, Blacketer C, Alshammari TM, Alghoul H, Alser O, Lane JC, Dawoud DM, Shah K, Yang Y, Zhang L, Areia C, Golozar A, Relcade M, Casajust P, Jonnagaddala J, Subbian V, Vizcaya D, Lai LY, Nyberg F, Morales DR, Posada JD, Shah NH, Gong M, Vivekanantham A, Abend A, Minty EP, Suchard M, Rijnbeek P, Ryan PB, Prieto-Alhambra D.",,No Journal Info,2020,2020-11-27,Y,,,,"<h4>Objective</h4> Patients with autoimmune diseases were advised to shield to avoid COVID-19, but information on their prognosis is lacking. We characterised 30-day outcomes and mortality after hospitalisation with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. <h4>Design</h4> Multinational network cohort study <h4>Setting</h4> Electronic health records data from Columbia University Irving Medical Center (CUIMC) (NYC, United States [US]), Optum [US], Department of Veterans Affairs (VA) (US), Information System for Research in Primary Care-Hospitalisation Linked Data (SIDIAP-H) (Spain), and claims data from IQVIA Open Claims (US) and Health Insurance and Review Assessment (HIRA) (South Korea). <h4>Participants</h4> All patients with prevalent autoimmune diseases, diagnosed and/or hospitalised between January and June 2020 with COVID-19, and similar patients hospitalised with influenza in 2017-2018 were included. <h4>Main outcome measures</h4> 30-day complications during hospitalisation and death <h4>Results</h4> We studied 133,589 patients diagnosed and 48,418 hospitalised with COVID-19 with prevalent autoimmune diseases. The majority of participants were female (60.5% to 65.9%) and aged ≥50 years. The most prevalent autoimmune conditions were psoriasis (3.5 to 32.5%), rheumatoid arthritis (3.9 to 18.9%), and vasculitis (3.3 to 17.6%). Amongst hospitalised patients, Type 1 diabetes was the most common autoimmune condition (4.8% to 7.5%) in US databases, rheumatoid arthritis in HIRA (18.9%), and psoriasis in SIDIAP-H (26.4%). Compared to 70,660 hospitalised with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2% to 4.3% versus 6.3% to 24.6%). <h4>Conclusions</h4> Patients with autoimmune diseases had high rates of respiratory complications and 30-day mortality following a hospitalization with COVID-19. Compared to influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality. Future studies should investigate predictors of poor outcomes in COVID-19 patients with autoimmune diseases. <h4>What is already known about this topic</h4> Patients with autoimmune conditions may be at increased risk of COVID-19 infection andcomplications. There is a paucity of evidence characterising the outcomes of hospitalised COVID-19 patients with prevalent autoimmune conditions. <h4>What this study adds</h4> Most people with autoimmune diseases who required hospitalisation for COVID-19 were women, aged 50 years or older, and had substantial previous comorbidities. Patients who were hospitalised with COVID-19 and had prevalent autoimmune diseases had higher prevalence of hypertension, chronic kidney disease, heart disease, and Type 2 diabetes as compared to those with prevalent autoimmune diseases who were diagnosed with COVID-19. A variable proportion of 6% to 25% across data sources died within one month of hospitalisation with COVID-19 and prevalent autoimmune diseases. For people with autoimmune diseases, COVID-19 hospitalisation was associated with worse outcomes and 30-day mortality compared to admission with influenza in the 2017-2018 season.",,pdf:https://academic.oup.com/rheumatology/article-pdf/60/SI/SI37/40544680/keab250.pdf; doi:https://doi.org/10.1101/2020.11.24.20236802; html:https://europepmc.org/article/PPR/PPR245783; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR245783&type=FILE&fileName=EMS107298-pdf.pdf&mimeType=application/pdf
 PPR362014,https://doi.org/10.2139/ssrn.3864079,Indirect Effects of the COVID-19 Pandemic on Childhood Infection in England: A Population Based Observational Study,"Kadambari S, Goldacre R, Morris E, Goldacre M, Pollard A.",,No Journal Info,2021,2021-06-21,N,,,,"Background: Children are largely unaffected following Sars-CoV-2 infection with low rates of significant disease and the inflammatory syndrome MIS-C. However, the lives of children have been substantially disrupted by the pandemic through physical distancing measures and the impact on health systems and economies. In this study, the impact of the COVID-19 pandemic on hospital admissions for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England was assessed along with associated mortality outcomes.<br><br>Methods: In this population-based observational study, we examined hospital admission data from every National Health Service hospital from Mar 1 2017 to Feb 28 2021. We report monthly and annual numbers of individuals hospitalised with 19 common childhood respiratory, severe invasive, and vaccine preventable infections. We compare the frequency of admissions for these conditions before and after the onset of the pandemic in England and calculate percentage changes since Mar 1 2020 for each infection overall and by demographic characteristics including age, region, deprivation, and comorbidity, and quantify mortality outcomes.<br><br>Findings: In the 12 months from Mar 1 2020, there were significant reductions compared with the preceding 36 months in the numbers of children admitted for every infection studied except pyelonephritis. These reductions were seen in all geographic regions, Index of Multiple Deprivation categories, ethnic groups and in those with underlying comorbidities. Among the respiratory infections, the greatest percentage reductions were for influenza where the number of individuals admitted decreased by 94% (95% CI 88, 97) from 5,061 (annual mean from Mar 1 2017 - Feb 29 2020) to 290 in the 12 months after Mar 1 2020, and for bronchiolitis where the number of individuals admitted decreased by over 80% (95% CI 78, 83) from 41,777 (annual mean 2017–2020) to 7,883 in 2020-21. Among the severe invasive infections, percentage decreases ranged from 20% (95% CI 13, 26) for osteomyelitis to 54% (95% CI 51, 56) for meningitis. Among the vaccine preventable infections, the greatest reduction was for measles, where the number of individuals admitted in the 12 months after Mar 1 2020 (n=12) was 92% lower (95% CI 84, 96) than the average number admitted in the previous three years (n=143). Admissions for <i>Neisseria meningitidis</i> decreased by 70% (95% CI 55, 80), and admissions for <i>Streptococcus pneumoniae</i>, <i>Haemophilus influenzae</i> and mumps more than halved. Alongside the decreases in admissions, there were also decreases in the absolute numbers of 60-day fatalities after admission for sepsis, meningitis, bronchiolitis, pneumonia, viral wheeze and upper respiratory tract infection (RTI). For pneumonia, although the absolute number of 60-day fatalities decreased (from a 3-year average of 159 to 115 after Mar 1 2020), the proportion of individuals admitted who died within 60 days increased (age-sex adjusted odds ratio 1.73, 95% CI 1.42, 2.11).<br><br>Interpretation: During the COVID-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions (NPIs)) and societal strategies (school closures, lockdowns and restricted travel) were used to reduce transmission of SARS CoV2 which have also significantly reduced transmission of common and severe childhood infections. NPIs could be used in the future to better protect healthcare systems and the most vulnerable children in society.<br><br>Funding Information: Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.<br><br>Declaration of Interests: None to declare. <br><br>Ethics Approval Statement: Ethical approval to study the record-linked datasets was obtained from the Central and South Bristol Multi-Centre Research Ethics Committee (04/Q2006/176). All patient records were pseudonymized by the data providers through encryption of personal identifiers.",,pdf:https://discovery.ucl.ac.uk/10158356/1/Indirect%20effects%20of%20the%20covid-19%20pandemic%20on%20childhood%20infection%20in%20England%20population%20based%20observational%20study.pdf; doi:https://doi.org/10.2139/ssrn.3864079; html:https://europepmc.org/article/PPR/PPR362014; doi:https://doi.org/10.2139/ssrn.3864079
 PPR157865,https://doi.org/10.1101/2020.04.27.20081810,Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics,"Messner CB, Demichev V, Wendisch D, Michalick L, White M, Freiwald A, Textoris-Taube K, Vernardis SI, Egger A, Kreidl M, Ludwig D, Kilian C, Agostini F, Zelezniak A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, von Kalle C, Campbell A, Hayward C, Porteous DJ, Marioni RE, Langenberg C, Lilley KS, Kuebler WM, Mülleder M, Drosten C, Witzenrath M, Kurth F, Sander LE, Ralser M.",,No Journal Info,2020,2020-05-03,Y,,,,"<h4>Summary</h4> The COVID-19 pandemic is an unprecedented global challenge. Highly variable in its presentation, spread and clinical outcome, novel point-of-care diagnostic classifiers are urgently required. Here, we describe a set of COVID-19 clinical classifiers discovered using a newly designed low-cost high-throughput mass spectrometry-based platform. Introducing a new sample preparation pipeline coupled with short-gradient high-flow liquid chromatography and mass spectrometry, our methodology facilitates clinical implementation and increases sample throughput and quantification precision. Providing a rapid assessment of serum or plasma samples at scale, we report 27 biomarkers that distinguish mild and severe forms of COVID-19, of which some may have potential as therapeutic targets. These proteins highlight the role of complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling upstream and downstream of Interleukin 6. Application of novel methodologies hence transforms proteomics from a research tool into a rapid-response, clinically actionable technology adaptable to infectious outbreaks. <h4>Highlights</h4> - A completely redesigned clinical proteomics platform increases throughput and precision while reducing costs. - 27 biomarkers are differentially expressed between WHO severity grades for COVID-19. - The study highlights potential therapeutic targets that include complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling both upstream and downstream of interleukin 6.",This study successfully uses mass spectrometry to distinguish mild and severe forms of COVID ,doi:https://doi.org/10.1016/j.cels.2020.05.012; doi:https://doi.org/10.1101/2020.04.27.20081810; html:https://europepmc.org/article/PPR/PPR157865; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR157865&type=FILE&fileName=EMS91998-pdf.pdf&mimeType=application/pdf
-PPR447330,https://doi.org/10.1101/2022.01.19.22268871,Cohort Profile: The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH),"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M.",,No Journal Info,2022,2022-01-27,Y,,,,"Key Features of the UK-REACH Cohort (Profile in a nutshell) The UK-REACH Cohort was established to understand why ethnic minority healthcare workers (HCWs) are at risk of poorer outcomes from COVID-19 when compared to their white ethnic counterparts in the United Kingdom (UK). Through study design, it contains a uniquely high percentage of participants from ethnic minority backgrounds about whom a wide range of qualitative and quantitative data has been collected. A total of 17891 HCWs aged 16-89 years (mean age: 44) have been recruited from across the UK via all major healthcare regulators, individual National Health Service (NHS) hospital trusts and UK HCW membership bodies who advertised the study to their registrants/staff to encourage participation in the study. Data available include linked healthcare records for 25 years from the date of consent and consent to obtain genomic sequencing data collected via saliva. Online questionnaires include information on demographics, COVID-19 exposures at work and home, redeployment in the workforce due to COVID-19, mental health measures, workforce attrition, and opinions on COVID-19 vaccines, with baseline (n=15 119), 6 (n=5632) and 12-month follow-up data captured. Request data access and collaborations by following documentation found at https://www.uk-reach.org/main/data_sharing .",,pdf:https://discovery.ucl.ac.uk/id/eprint/10154879/1/dyac171.pdf; doi:https://doi.org/10.1101/2022.01.19.22268871; html:https://europepmc.org/article/PPR/PPR447330; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR447330&type=FILE&fileName=EMS142772-pdf.pdf&mimeType=application/pdf
 PPR302424,https://doi.org/10.1101/2021.03.19.21253940,"COVID-19 Infection Risk amongst 14,104 Vaccinated Care Home Residents: A national observational longitudinal cohort study in Wales, United Kingdom, December 2020 to March 2021","Hollinghurst J, North L, Perry M, Akbari A, Gravenor MB, Lyons RA, Fry R.",,No Journal Info,2021,2021-03-24,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> Vaccinations for COVID-19 have been prioritised for older people living in care homes. However, vaccination trials included limited numbers of older people. <h4>Aim</h4> We aimed to study infection rates of SARS-CoV-2 for older care home residents following vaccination and identify factors associated with increased risk of infection. <h4>Study Design and Setting</h4> We conducted an observational data-linkage study including 14,104 vaccinated older care home residents in Wales (UK) using anonymised electronic health records and administrative data. <h4>Methods</h4> We used Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of testing positive for SARS-CoV-2 infection following vaccination, after landmark times of either 7 or 21-days post-vaccination. We adjusted hazard ratios for age, sex, frailty, prior SARS-CoV-2 infections and vaccination type. <h4>Results</h4> We observed a small proportion of care home residents with positive PCR tests following vaccination 1.05% (N=148), with 90% of infections occurring within 28-days. For the 7-day landmark analysis we found a reduced risk of SARS-CoV-2 infection for vaccinated individuals who had a previous infection; HR (95% confidence interval) 0.54 (0.30,0.95), and an increased HR for those receiving the Pfizer-BioNTECH vaccine compared to the Oxford-AstraZeneca; 3.83 (2.45,5.98). For the 21-day landmark analysis we observed high HRs for individuals with low and intermediate frailty compared to those without; 4.59 (1.23,17.12) and 4.85 (1.68,14.04) respectively. <h4>Conclusions</h4> Increased risk of infection after 21-days was associated with frailty. We found most infections occurred within 28-days of vaccination, suggesting extra precautions to reduce transmission risk should be taken in this time frame.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56588/Download/56588__19705__510f42860c3f499794d1ec266d43131d.pdf; doi:https://doi.org/10.1101/2021.03.19.21253940; html:https://europepmc.org/article/PPR/PPR302424; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR302424&type=FILE&fileName=EMS120789-pdf.pdf&mimeType=application/pdf
+PPR447330,https://doi.org/10.1101/2022.01.19.22268871,Cohort Profile: The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH),"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M.",,No Journal Info,2022,2022-01-27,Y,,,,"Key Features of the UK-REACH Cohort (Profile in a nutshell) The UK-REACH Cohort was established to understand why ethnic minority healthcare workers (HCWs) are at risk of poorer outcomes from COVID-19 when compared to their white ethnic counterparts in the United Kingdom (UK). Through study design, it contains a uniquely high percentage of participants from ethnic minority backgrounds about whom a wide range of qualitative and quantitative data has been collected. A total of 17891 HCWs aged 16-89 years (mean age: 44) have been recruited from across the UK via all major healthcare regulators, individual National Health Service (NHS) hospital trusts and UK HCW membership bodies who advertised the study to their registrants/staff to encourage participation in the study. Data available include linked healthcare records for 25 years from the date of consent and consent to obtain genomic sequencing data collected via saliva. Online questionnaires include information on demographics, COVID-19 exposures at work and home, redeployment in the workforce due to COVID-19, mental health measures, workforce attrition, and opinions on COVID-19 vaccines, with baseline (n=15 119), 6 (n=5632) and 12-month follow-up data captured. Request data access and collaborations by following documentation found at https://www.uk-reach.org/main/data_sharing .",,pdf:https://discovery.ucl.ac.uk/id/eprint/10154879/1/dyac171.pdf; doi:https://doi.org/10.1101/2022.01.19.22268871; html:https://europepmc.org/article/PPR/PPR447330; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR447330&type=FILE&fileName=EMS142772-pdf.pdf&mimeType=application/pdf
 PPR494479,https://doi.org/10.1101/2022.04.22.22274176,Association between household composition and severe COVID-19 outcomes in older people by ethnicity: an observational cohort study using the OpenSAFELY platform,"Wing K, Grint DJ, Mathur R, Gibbs HP, Hickman G, Nightingale E, Schultze A, Forbes H, Nafilyan V, Bhaskaran K, Williamson E, House T, Pellis L, Herrett E, Gautam N, Curtis HJ, Rentsch CT, Wong AY, MacKenna B, Mehrkar A, Bacon S, Douglas IJ, Evans SJ, Tomlinson L, Goldacre B, Eggo RM.",,No Journal Info,2022,2022-04-22,Y,,,,"Ethnic differences in the risk of severe COVID-19 may be linked to household composition. We quantified the association between household composition and risk of severe COVID-19 by ethnicity for older individuals. With the approval of NHS England, we analysed ethnic differences in the association between household composition and severe COVID-19 in people aged 67 or over in England. We defined households by number of generations living together, and used multivariable Cox regression stratified by location and wave of the pandemic and accounted for age, sex, comorbidities, smoking, obesity, housing density and deprivation. We included 2 692 223 people over 67 years in wave 1 (01/02/2020-31/08/2020) and 2 731 427 in wave 2 (01/09/2020-31/01/2021). Multigenerational living was associated with increased risk of severe COVID-19 for White and South Asian older people in both waves (e.g. wave 2, 67+ living with 3 other generations vs 67+ year olds only: White HR 1·61 95% CI 1·38-1·87, South Asian HR 1·76 95% CI 1·48-2·10), with a trend for increased risks of severe COVID-19 with increasing generations in wave 2. Multigenerational living was associated with severe COVID-19 in older adults. Older South Asian people are over-represented within multigenerational households in England, especially in the most deprived settings. The number of generations in a household, number of occupants, ethnicity and deprivation status are important considerations in the continued roll-out of COVID-19 vaccination and targeting of interventions for future pandemics. <h4>Funding</h4> This research was funded in part, by the Wellcome Trust. For the purpose of open access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4667116/7/Wing_etal_2022_Association-between-household-composition-and.pdf; doi:https://doi.org/10.1101/2022.04.22.22274176; html:https://europepmc.org/article/PPR/PPR494479; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR494479&type=FILE&fileName=EMS149524-pdf.pdf&mimeType=application/pdf
 PPR360911,https://doi.org/10.2139/ssrn.3854605,"Changes in Neonatal Admissions, Care Processes and Outcomes in England and Wales During the COVID-19 Pandemic","Greenbury SF, Longford NT, Ougham K, Angelini ED, Battersby C, Uthaya S, Modi N.",,No Journal Info,2021,2021-05-27,N,,,,"Background: The COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes, and outcomes.<br><br>Methods: We obtained information from the National Neonatal Research Database on all admissions to National Health Service neonatal units in England and Wales from 2012-2020. We evaluated admissions by gestational age, ethnicity, and Index of Multiple Deprivation, and key care processes and outcomes. We calculated the differences in numbers and rates between April-June 2020 (spring), the first three months of national lockdown and December 2019-February 2020 (winter), prior to introduction of mitigation measures (COVID period), and compared them with the corresponding differences in the seven previous years. We considered the COVID period highly unusual if the difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion.<br><br>Findings: Marked fluctuations occurred in all measures over the eight years with several highly unusual changes during the COVID period. Total admissions fell, having risen over all previous years (COVID difference: -1492; previous seven-year difference range: +100, +1617; p<0∙001); full-term Black admissions rose (+66; -64, +35; p<0∙001) whereas Asian (-137; -14, +101; p<0∙001) and White (-319; -235, +643: p<0∙001) admissions fell. Transfers to higher and lower designation neonatal units increased (+129; -4, +88; p<0∙001) and decreased (-47; -25, +12; p<0∙001), respectively. Total preterm admissions decreased (-350; -26, +479; p<0∙001). The fall in extremely preterm admissions was most marked in the two lowest socio-economic quintiles.<br><br>Interpretation: Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on Black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.<br><br>Funding Information: Medical Research Council; Health Data Research UK.<br><br>Declaration of Interests: NM reports grants outside the submitted work from the Medical Research Council, National Institute of Health Research, March of Dimes, British Heart Foundation, HCA International, Health Data Research UK, Shire Pharmaceuticals, Chiesi Pharmaceuticals, Prolacta Life Sciences, and Westminster Children’s Research Fund; NM is a member of the Nestle Scientific Advisory Board and accepts no personal remuneration for this role. NM reports travel and accommodation reimbursements from Chiesi, Nestle and Shire. All other authors report no declarations of interest.<br><br>Ethics Approval Statement: The study was undertaken under approval from the Health Research Authority and Health and Care Research Wales, and with the agreement of all NHS neonatal units in England and Wales.",,doi:https://doi.org/10.2139/ssrn.3854605; html:https://europepmc.org/article/PPR/PPR360911; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR360911&type=FILE&fileName=EMS128455-pdf.pdf&mimeType=application/pdf; doi:https://doi.org/10.2139/ssrn.3854605
 PPR201296,https://doi.org/10.1101/2020.08.12.20171405,OpenSAFELY: Do adults prescribed non-steroidal anti-inflammatory drugs have an increased risk of death from COVID-19?,"The OpenSAFELY Collaborative, Wong AY, MacKenna B, Morton CE, Schultze A, Walker AJ, Bhaskaran K, Brown JP, Brown JP, Rentsch CT, Williamson E, Drysdale H, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson L, Mathur R, Wing K, Forbes H, Parry J, Hester F, Harper S, Evans SJ, Smeeth L, Douglas IJ, Goldacre B.",,No Journal Info,2020,2020-08-14,Y,,,,"<h4>Importance</h4> There has been speculation that non-steroidal anti-inflammatory drugs (NSAIDs) may negatively affect coronavirus disease 2019 (COVID-19) outcomes, yet clinical evidence is limited. <h4>Objective</h4> To assess the association between NSAID use and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. <h4>Design</h4> Two cohort studies (1 st March-14 th June 2020). <h4>Setting</h4> Working on behalf of NHS England, we used routine clinical data from >17 million patients in England linked to death data from the Office for National Statistics. <h4>Participants</h4> Study 1: General population (people with an NSAID prescription in the last three years). Study 2: people with rheumatoid arthritis/osteoarthritis. <h4>Exposures</h4> Current NSAID prescription within the 4 months before 1 st March 2020. <h4>Main Outcome and Measure</h4> We used Cox regression to estimate hazard ratios (HRs) for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, adjusting for age, sex, comorbidities and other medications. <h4>Results</h4> In Study 1, we included 535,519 current NSAID users and 1,924,095 non-users in the general population. The crude HR for current use was 1.25 (95% CI, 1.07–1.46), versus non-use. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR, 0.95, 95% CI, 0.80–1.13) in the fully adjusted model. In Study 2, we included 1,711,052 people with rheumatoid arthritis/osteoarthritis, of whom 175,631 (10%) were current NSAID users. The crude HR for current use was 0.43 (95% CI, 0.36–0.52), versus non-use. In the fully adjusted model, we observed a lower risk of COVID-19 related death (HR, 0.78, 95% CI, 0.65–0.94) associated with current use of NSAID versus non-use. <h4>Conclusion and Relevance</h4> We found no evidence of a harmful effect of NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about therapeutic use of NSAIDs.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/08/14/2020.08.12.20171405.full.pdf; doi:https://doi.org/10.1101/2020.08.12.20171405; html:https://europepmc.org/article/PPR/PPR201296; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR201296&type=FILE&fileName=EMS95618-pdf.pdf&mimeType=application/pdf
@@ -363,13 +363,13 @@ PPR291776,https://doi.org/10.1101/2021.03.02.21252444,An overview of the Nationa
 PPR624483,https://doi.org/10.1101/2023.03.02.23286669,Use of a digital application to enhance communication and triage between care homes and National Health Service community services in the United Kingdom: a qualitative evaluation,"Russell S, Stocker R, Cockshott Z, Mason S, Knight J, Hanratty B, Preston N.",,No Journal Info,2023,2023-03-02,N,,,,"Recent years have seen a rise in digital interventions to improve coordination between care homes and NHS services, supporting remote sharing of data on the health of care home residents. Such interventions were key components in the response to the COVID-19 pandemic. This paper presents findings from the qualitative component of an evaluation of an implementation of the HealthCall Digital Care Homes application, across sites in northern England. The implementation commenced prior to the pandemic and continued throughout. Semi-structured, qualitative interviews were held with stakeholders. Interviews were conducted remotely (October 2020 -June 2021). Data were analysed via a reflexive thematic analysis then mapped against Normalization Process Theory (NPT) constructs (coherence, collective action, cognitive participation, and reflexive monitoring) providing a framework to assess implementation success. Thirty-five participants were recruited: 16 care home staff, six NHS community nurses, five relatives of care home residents, four HealthCall team members, three care home residents, and one local authority commissioner. Despite facing challenges such as apprehension towards digital technology among care home staff, the application was viewed positively across stakeholder groups. The HealthCall team maintained formal and informal feedback loop with stakeholders. This resulted in revisions to the intervention and implementation. Appropriate training and problem solving from the HealthCall team and buy-in from care home and NHS staff were key to achieving success across NPT constructs. While this implementation appears broadly successful, establishing rapport and maintaining ongoing support requires significant time, financial backing, and the right individuals in place across stakeholder groups to drive implementation and intervention evolution. The digital literacy of care home staff requires encouragement to enhance their readiness for digital interventions. The COVID-19 pandemic has pushed this agenda forward. Problems with stability across the workforce within care homes need to be addressed to avoid skill loss and support embeddedness of digital interventions. <h4>What is known about this topic?</h4> Improving healthcare delivery in UK care homes is a health policy priority. Digital interventions designed to enhance the referral process between care homes and NHS services and improve the healthcare delivery in care homes have become increasingly common in the UK. The HealthCall Digital Care Homes application is one such intervention. These interventions and their implementations require evaluation to ensure that they operate as intended, function coherently and are considered appropriate and legitimate to the care home setting. <h4>What this paper adds?</h4> The HealthCall Digital Care Homes app is a feasible, appropriate and legitimate intervention for referral, triage and health care support for non-urgent health care needs of care home residents. The ongoing involvement of end users in further developing the intervention, and the level of monitoring and support provided by the implementation team appears to be key to the implementation’s success. The digital preparedness of UK care homes is limited. Ensuring that care homes are digitally enabled, with a digitally literate workforce, should be a policy and research priority.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/03/02/2023.03.02.23286669.full.pdf; doi:https://doi.org/10.1101/2023.03.02.23286669; html:https://europepmc.org/article/PPR/PPR624483; doi:https://doi.org/10.1101/2023.03.02.23286669
 PPR116550,https://doi.org/10.1101/2020.03.05.20031773,Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship,"Russell TW, Hellewell J, Jarvis CI, Van Zandvoort K, Abbott S, Ratnayake R, Flasche S, Eggo RM, Edmunds WJ, Kucharski AJ, CMMID COVID-19 working group.",,No Journal Info,2020,2020-03-08,Y,,,,"Adjusting for delay from confirmation-to-death, we estimated case and infection fatality ratios (CFR, IFR) for COVID-19 on the Diamond Princess ship as 2.3% (0.75%–5.3%) and 1.2% (0.38–2.7%). Comparing deaths onboard with expected deaths based on naive CFR estimates using China data, we estimate IFR and CFR in China to be 0.5% (95% CI: 0.2–1.2%) and 1.1% (95% CI: 0.3–2.4%) respectively. <h4>Aim</h4> To estimate the infection and case fatality ratio of COVID-19, using data from passengers of the Diamond Princess cruise ship while correcting for delays between confirmation-and-death, and age-structure of the population.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.1101/2020.03.05.20031773; html:https://europepmc.org/article/PPR/PPR116550; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR116550&type=FILE&fileName=EMS89041-pdf.pdf&mimeType=application/pdf
 PPR204755,https://doi.org/10.1101/2020.08.21.20177808,Quarantine and testing strategies in contact tracing for SARS-CoV-2,"Quilty BJ, Clifford S, Flasche S, Kucharski AJ, Edmunds WJ, CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-08-24,Y,,,,"<h4>Summary</h4> Previous work has indicated that contact tracing and isolation of index case and quarantine of potential secondary cases can, in concert with physical distancing measures, be an effective strategy for reducing transmission of SARS-CoV-2 (1). Currently, contacts traced manually through the NHS Test and Trace scheme in the UK are asked to self-isolate for 14 days from the day they were exposed to the index case, which represents the upper bound for the incubation period (2). However, following previous work on screening strategies for air travellers (3,4) it may be possible that this quarantine period could be reduced if combined with PCR testing. Adapting the simulation model for contact tracing, we find that quarantine periods of at least 10 days combined with a PCR test on day 9 may largely emulate the results from a 14-day quarantine period in terms of the averted transmission potential from secondary cases (72% (95%UI: 3%, 100%) vs 75% (4%, 100%), respectively). These results assume the delays from testing index cases’ and tracing their contacts are minimised (no longer than 4.5 days on average). If secondary cases are traced and quarantined 1 day earlier on average, shorter quarantine periods of 8 days with a test on day 7 (76% (7%, 100%)) approach parity with the 14 day quarantine period with a 1 day longer delay to the index cases’ test. However, the risk of false-negative PCR tests early in a traced case’s infectious period likely prevents the use of testing to reduce quarantine periods further than this, and testing immediately upon tracing, with release if negative, will avert just 17% of transmission potential on average. In conclusion, the use of PCR testing is an effective strategy for reducing quarantine periods for secondary cases, while still reducing transmission of SARS-CoV-2, especially if delays in the test and trace system can be reduced, and may improve quarantine compliance rates.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/10/23/2020.08.21.20177808.full.pdf; doi:https://doi.org/10.1101/2020.08.21.20177808; html:https://europepmc.org/article/PPR/PPR204755; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR204755&type=FILE&fileName=EMS95490-pdf.pdf&mimeType=application/pdf
-PPR406625,https://doi.org/10.1101/2021.10.10.21264821,Modelling the effect of COVID-19 mass vaccination on acute admissions in a major English healthcare system,"Booton R, Powell A, Turner K, Wood R.",,No Journal Info,2021,2021-10-13,Y,,,,"<h4>Background</h4> Managing high levels of severe COVID-19 in the acute setting can impact upon the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible effect on future bed pressures remained subject to considerable uncertainty. This paper provides an account of how, in one healthcare system, operational decision-making and bed planning was supported through modelling the effect of a range of vaccination scenarios on future COVID-19 admissions. <h4>Methods</h4> An epidemiological model of the Susceptible-Exposed-Infectious-Recovered (SEIR) type was fitted to local data for the one-million resident healthcare system located in South West England. Model parameters and vaccination scenarios were calibrated through a system-wide multi-disciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists, and academics. From 4 March 2021 (the time of the study), scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021. <h4>Results</h4> Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert a third wave in autumn 2021 but would produce a median peak bed requirement approximately 6% (IQR: 1% to 24%) of that experienced during the second wave (January 2021). A two-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11% to 146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns) then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19% respectively, an amount which would seriously pressure hospital capacity. <h4>Conclusion</h4> Modelling provided support to senior managers in setting the number of acute and intensive care beds to make available for COVID-19 patients, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/13/2021.10.10.21264821.full.pdf; doi:https://doi.org/10.1101/2021.10.10.21264821; html:https://europepmc.org/article/PPR/PPR406625; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR406625&type=FILE&fileName=EMS136883-pdf.pdf&mimeType=application/pdf
 PPR361477,https://doi.org/10.1101/2021.06.24.21259277,Risk factors for long COVID: analyses of 10 longitudinal studies and electronic health records in the UK,"Thompson EJ, Williams DM, Walker AJ, Mitchell RE, Niedzwiedz CL, Yang TC, Huggins CF, Kwong ASF, Silverwood RJ, Gessa GD, Bowyer RC, Northstone K, Hou B, Green MJ, Dodgeon B, Doores KJ, Duncan EL, Williams FMK, Steptoe A, Porteous DJ, McEachan RRC, Tomlinson L, Goldacre B, Patalay P, Ploubidis GB, Katikireddi SV, Tilling K, Rentsch CT, Timpson NJ, Chaturvedi N, Steves CJ, OpenSAFELY Collaborative.",,No Journal Info,2021,2021-06-25,Y,,,,"<h4>Background</h4> The impact of long COVID is considerable, but risk factors are poorly characterised. We analysed symptom duration and risk factor from 10 longitudinal study (LS) samples and electronic healthcare records (EHR). <h4>Methods</h4> Samples: 6907 adults self-reporting COVID-19 infection from 48,901 participants in the UK LS, and 3,327 adults with COVID-19, were assigned a long COVID code from 1,199,812 individuals in primary care EHR. Outcomes for LS included symptom duration lasting 4+ weeks (long COVID) and 12+ weeks. Association with of age, sex, ethnicity, socioeconomic factors, smoking, general and mental health, overweight/obesity, diabetes, hypertension, hypercholesterolaemia, and asthma was assessed. <h4>Results</h4> In LS, symptoms impacted normal functioning for 12+ weeks in 1.2% (mean age 20 years) to 4.8% (mean age 63 y) of COVID-19 cases. Between 7.8% (mean age 28 y) and 17% (mean age 58 y) reported any symptoms for 12+ weeks, and greater proportions for 4+ weeks. Age was associated with a linear increased risk in long COVID between 20 and 70 years. Being female (LS: OR=1.49; 95%CI:1.24-1.79; EHR: OR=1.51 [1.41-1.61]), having poor pre-pandemic mental health (LS: OR=1.46 [1.17-1.83]; EHR: OR=1.57 [1.47-1.68]) and poor general health (LS: OR=1.62 [1.25-2.09]; EHR: OR=1.26; [1.18-1.35]) were associated with higher risk of long COVID. Individuals with asthma (LS: OR=1.32 [1.07-1.62]; EHR: OR=1.56 [1.46-1.67]), and overweight or obesity (LS: OR=1.25 [1.01-1.55]; EHR: OR=1.31 [1.21-1.42]) also had higher risk. Non-white ethnic minority groups had lower risk (LS: OR=0.32 [0.22-0.47]), a finding consistent in EHR. . Few participants had been hospitalised (0.8-5.2%). <h4>Conclusion</h4> Long COVID is associated with sociodemographic and pre-existing health factors. Further investigations into causality should inform strategies to address long COVID in the population.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/10/2021.06.24.21259277.full.pdf; doi:https://doi.org/10.1101/2021.06.24.21259277; html:https://europepmc.org/article/PPR/PPR361477; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR361477&type=FILE&fileName=EMS128902-pdf.pdf&mimeType=application/pdf
+PPR406625,https://doi.org/10.1101/2021.10.10.21264821,Modelling the effect of COVID-19 mass vaccination on acute admissions in a major English healthcare system,"Booton R, Powell A, Turner K, Wood R.",,No Journal Info,2021,2021-10-13,Y,,,,"<h4>Background</h4> Managing high levels of severe COVID-19 in the acute setting can impact upon the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible effect on future bed pressures remained subject to considerable uncertainty. This paper provides an account of how, in one healthcare system, operational decision-making and bed planning was supported through modelling the effect of a range of vaccination scenarios on future COVID-19 admissions. <h4>Methods</h4> An epidemiological model of the Susceptible-Exposed-Infectious-Recovered (SEIR) type was fitted to local data for the one-million resident healthcare system located in South West England. Model parameters and vaccination scenarios were calibrated through a system-wide multi-disciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists, and academics. From 4 March 2021 (the time of the study), scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021. <h4>Results</h4> Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert a third wave in autumn 2021 but would produce a median peak bed requirement approximately 6% (IQR: 1% to 24%) of that experienced during the second wave (January 2021). A two-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11% to 146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns) then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19% respectively, an amount which would seriously pressure hospital capacity. <h4>Conclusion</h4> Modelling provided support to senior managers in setting the number of acute and intensive care beds to make available for COVID-19 patients, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/13/2021.10.10.21264821.full.pdf; doi:https://doi.org/10.1101/2021.10.10.21264821; html:https://europepmc.org/article/PPR/PPR406625; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR406625&type=FILE&fileName=EMS136883-pdf.pdf&mimeType=application/pdf
 PPR362420,https://doi.org/10.1101/2021.06.24.21259374,A proteomic survival predictor for COVID-19 patients in intensive care,"Demichev V, Tober-Lau P, Nazarenko T, Aulakh SK, Whitwell H, Lemke O, Röhl A, Freiwald A, Mittermaier M, Szyrwiel L, Ludwig D, Correia-Melo C, Lippert LJ, Helbig ET, Stubbemann P, Olk N, Thibeault C, Grüning N, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, de Jarcy LB, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Spies C, Edel A, Müller NB, Enghard P, Zelezniak A, Bellmann-Weiler R, Weiss G, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Müller-Redetzky H, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, Kurth F, Ralser M, PA-COVID-19 Study group.",,No Journal Info,2021,2021-06-26,N,,,,"Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing the host physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index and APACHE II score were poor predictors of survival. Plasma proteomics instead identified 14 proteins that showed concentration trajectories different between survivors and non-survivors. A proteomic predictor trained on single samples obtained at the first time point at maximum treatment level (i.e. WHO grade 7) and weeks before the outcome, achieved accurate classification of survivors in an exploratory (AUROC 0.81) as well as in the independent validation cohort (AUROC of 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that predictors derived from plasma protein levels have the potential to substantially outperform current prognostic markers in intensive care. <h4>Trial registration</h4> German Clinical Trials Register DRKS00021688",,pdf:https://discovery.ucl.ac.uk/10142558/1/Nazarenko_journal.pdig.0000007.pdf; doi:https://doi.org/10.1101/2021.06.24.21259374; html:https://europepmc.org/article/PPR/PPR362420; doi:https://doi.org/10.1101/2021.06.24.21259374
 PPR269227,https://doi.org/10.1101/2021.01.15.21249756,Factors associated with deaths due to COVID-19 versus other causes: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform,"Bhaskaran K, Bacon S, Evans S, Bates C, Rentsch C, MacKenna B, Tomlinson L, Walker A, Schultze A, Morton C, Grint D, Mehrkar A, Eggo R, Inglesby P, Douglas I, McDonald H, Cockburn J, Williamson E, Evans D, Curtis H, Hulme W, Parry J, Hester F, Harper S, Spiegelhalter D, Smeeth L, Goldacre B.",,No Journal Info,2021,2021-01-20,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> Mortality from COVID-19 shows a strong relationship with age and pre-existing medical conditions, as does mortality from other causes. However it is unclear how specific factors are differentially associated with COVID-19 mortality as compared to mortality from other causes. <h4>Methods</h4> Working on behalf of NHS England, we carried out a cohort study within the OpenSAFELY platform. Primary care data from England were linked to national death registrations. We included all adults (aged ≥18 years) in the database on 1 st February 2020 and with >1 year of continuous prior registration, the cut-off date for deaths was 9 th November 2020. Associations between individual-level characteristics and COVID-19 and non-COVID deaths were estimated by fitting age- and sex-adjusted logistic models for these two outcomes. <h4>Results</h4> 17,456,515 individuals were included. 17,063 died from COVID-19 and 134,316 from other causes. Most factors associated with COVID-19 death were similarly associated with non-COVID death, but the magnitudes of association differed. Older age was more strongly associated with COVID-19 death than non-COVID death (e.g. ORs 40.7 [95% CI 37.7-43.8] and 29.6 [28.9-30.3] respectively for ≥80 vs 50-59 years), as was male sex, deprivation, obesity, and some comorbidities. Smoking, history of cancer and chronic liver disease had stronger associations with non-COVID than COVID-19 death. All non-white ethnic groups had higher odds than white of COVID-19 death (OR for Black: 2.20 [1.96-2.47], South Asian: 2.33 [2.16-2.52]), but lower odds than white of non-COVID death (Black: 0.88 [0.83-0.94], South Asian: 0.78 [0.75-0.81]). <h4>Interpretation</h4> Similar associations of most individual-level factors with COVID-19 and non-COVID death suggest that COVID-19 largely multiplies existing risks faced by patients, with some notable exceptions. Identifying the unique factors contributing to the excess COVID-19 mortality risk among non-white groups is a priority to inform efforts to reduce deaths from COVID-19. <h4>Funding</h4> Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2021.100109; doi:https://doi.org/10.1101/2021.01.15.21249756; html:https://europepmc.org/article/PPR/PPR269227; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR269227&type=FILE&fileName=EMS112324-pdf.pdf&mimeType=application/pdf
 PPR339051,https://doi.org/10.1101/2021.05.06.21256755,Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY,"The OpenSAFELY Collaborative, Walker AJ, MacKenna B, Inglesby P, Rentsch CT, Curtis HJ, Morton CE, Morley J, Mehrkar A, Bacon S, Hickman G, Bates C, Croker R, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Williamson EJ, Hulme WJ, McDonald HI, Tomlinson L, Mathur R, Eggo RM, Wing K, Wong AY, Forbes H, Tazare J, Parry J, Hester F, Harper S, O’Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Douglas IJ, Evans SJ, Smeeth L, Goldacre B.",,No Journal Info,2021,2021-05-13,Y,,,,"<h4>Background</h4> Long COVID is a term to describe new or persistent symptoms at least four weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were released in November 2020 in the UK, but it is not known how these codes have been used in practice. <h4>Methods</h4> Working on behalf of NHS England, we used OpenSAFELY data encompassing 96% of the English population. We measured the proportion of people with a recorded code for long COVID, overall and by demographic factors, electronic health record software system, and week. We also measured variation in recording amongst practices. <h4>Results</h4> Long COVID was recorded for 23,273 people. Coding was unevenly distributed amongst practices, with 26.7% of practices having not used the codes at all. Regional variation was high, ranging between 20.3 per 100,000 people for East of England (95% confidence interval 19.3-21.4) and 55.6 in London (95% CI 54.1-57.1). The rate was higher amongst women (52.1, 95% CI 51.3-52.9) compared to men (28.1, 95% CI 27.5-28.7), and higher amongst practices using EMIS software (53.7, 95% CI 52.9-54.4) compared to TPP software (20.9, 95% CI 20.3-21.4). <h4>Conclusions</h4> Long COVID coding in primary care is low compared with early reports of long COVID prevalence. This may reflect under-coding, sub-optimal communication of clinical terms, under-diagnosis, a true low prevalence of long COVID diagnosed by clinicians, or a combination of factors. We recommend increased awareness of diagnostic codes, to facilitate research and planning of services; and surveys of clinicians’ experiences, to complement ongoing patient surveys.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/05/13/2021.05.06.21256755.1.full.pdf; doi:https://doi.org/10.1101/2021.05.06.21256755; html:https://europepmc.org/article/PPR/PPR339051; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR339051&type=FILE&fileName=EMS124533-pdf.pdf&mimeType=application/pdf
-PPR644063,https://doi.org/10.1101/2023.04.06.23288168,Identification of a specific inflammatory protein biosignature in coronary and peripheral blood associated with increased risk of future cardiovascular events,"Proudfoot D, Gigante B, West NE, Hoole SP, Strawbridge RJ, Tremoli E, Baldassarre D, Williams S.",,No Journal Info,2023,2023-04-12,Y,,,,"<h4>Background and rationale</h4> As an adjunct to coronary intervention, the Liquid Biopsy System (LBS, PlaqueTec, UK) enables accurate intracoronary blood sampling as previously documented. Here we investigate variation between local coronary and remote (peripheral) levels of certain proteins and how this might relate to cardiovascular risk assessment. <h4>Methods and Results</h4> Coronary artery blood samples were collected from 12 patients with obstructive coronary plaques before percutaneous coronary intervention (PCI), using the LBS. Peripheral blood samples were also collected, before and after PCI. Protein levels in coronary and peripheral plasma samples were analysed by proximity extension assay (PEA, Olink) and results were compared with blood samples from healthy controls and reference cohorts. Before PCI, 10/12 patients showed elevations in hepatocyte growth factor (HGF), pappalysin-1 (PAPPA) and spondin-1 (SPON1), in some cases >10-fold greater in coronary compared with peripheral samples. Following PCI, involving iatrogenic plaque rupture prior to stenting, peripheral levels of these proteins were elevated to a similar degree as coronary levels. In the other 2 patients, peripheral elevations for HGF, PAPPA and SPON1 (all >90 th centile) were observed prior to PCI. This protein biosignature was absent in healthy controls but was detected in a minority of individuals in reference cohorts and associated with the occurrence of major adverse cardiovascular events (MACE) and mortality. <h4>Conclusions</h4> From investigation of coronary and peripheral blood samples, we identified a molecular signature, which when present in peripheral blood appears to portend worse outcomes. Measurement of these proteins could therefore aid identification of individuals at high risk of cardiovascular events. (see Graphical Abstract in Supplementary Figures) <h4>Graphical Abstract</h4> <h4>Translational Perspective</h4> Through sampling of local coronary blood, we discovered a novel protein biosignature consisting of a combination of elevated levels of HGF, PAPPA and SPON1. When this biosignature was assessed in peripheral samples from reference cardiovascular and Covid cohorts they associated with the occurrence of MACE and mortality. The biosignature protein levels correlated with markers of mast cell and neutrophil activity but not with CRP, possibly indicating a specific inflammatory status. Early detection of this protein signal has potential clinical utility to identify specific patients at increased risk of poor outcomes.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/04/12/2023.04.06.23288168.full.pdf; doi:https://doi.org/10.1101/2023.04.06.23288168; html:https://europepmc.org/article/PPR/PPR644063; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR644063&type=FILE&fileName=EMS174291-pdf.pdf&mimeType=application/pdf
 PPR410412,https://doi.org/10.1101/2021.10.18.21264686,Regional excess mortality during the 2020 COVID-19 pandemic: a study of five European countries,"Konstantinoudis G, Cameletti M, Gómez-Rubio V, León Gómez I, Pirani M, Baio G, Larrauri A, Riou J, Egger M, Vineis P, Blangiardo M.",,No Journal Info,2021,2021-10-23,Y,,,,"The impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015-2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15-20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/23/2021.10.18.21264686.full.pdf; doi:https://doi.org/10.1101/2021.10.18.21264686; html:https://europepmc.org/article/PPR/PPR410412; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR410412&type=FILE&fileName=EMS137364-pdf.pdf&mimeType=application/pdf
+PPR644063,https://doi.org/10.1101/2023.04.06.23288168,Identification of a specific inflammatory protein biosignature in coronary and peripheral blood associated with increased risk of future cardiovascular events,"Proudfoot D, Gigante B, West NE, Hoole SP, Strawbridge RJ, Tremoli E, Baldassarre D, Williams S.",,No Journal Info,2023,2023-04-12,Y,,,,"<h4>Background and rationale</h4> As an adjunct to coronary intervention, the Liquid Biopsy System (LBS, PlaqueTec, UK) enables accurate intracoronary blood sampling as previously documented. Here we investigate variation between local coronary and remote (peripheral) levels of certain proteins and how this might relate to cardiovascular risk assessment. <h4>Methods and Results</h4> Coronary artery blood samples were collected from 12 patients with obstructive coronary plaques before percutaneous coronary intervention (PCI), using the LBS. Peripheral blood samples were also collected, before and after PCI. Protein levels in coronary and peripheral plasma samples were analysed by proximity extension assay (PEA, Olink) and results were compared with blood samples from healthy controls and reference cohorts. Before PCI, 10/12 patients showed elevations in hepatocyte growth factor (HGF), pappalysin-1 (PAPPA) and spondin-1 (SPON1), in some cases >10-fold greater in coronary compared with peripheral samples. Following PCI, involving iatrogenic plaque rupture prior to stenting, peripheral levels of these proteins were elevated to a similar degree as coronary levels. In the other 2 patients, peripheral elevations for HGF, PAPPA and SPON1 (all >90 th centile) were observed prior to PCI. This protein biosignature was absent in healthy controls but was detected in a minority of individuals in reference cohorts and associated with the occurrence of major adverse cardiovascular events (MACE) and mortality. <h4>Conclusions</h4> From investigation of coronary and peripheral blood samples, we identified a molecular signature, which when present in peripheral blood appears to portend worse outcomes. Measurement of these proteins could therefore aid identification of individuals at high risk of cardiovascular events. (see Graphical Abstract in Supplementary Figures) <h4>Graphical Abstract</h4> <h4>Translational Perspective</h4> Through sampling of local coronary blood, we discovered a novel protein biosignature consisting of a combination of elevated levels of HGF, PAPPA and SPON1. When this biosignature was assessed in peripheral samples from reference cardiovascular and Covid cohorts they associated with the occurrence of MACE and mortality. The biosignature protein levels correlated with markers of mast cell and neutrophil activity but not with CRP, possibly indicating a specific inflammatory status. Early detection of this protein signal has potential clinical utility to identify specific patients at increased risk of poor outcomes.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/04/12/2023.04.06.23288168.full.pdf; doi:https://doi.org/10.1101/2023.04.06.23288168; html:https://europepmc.org/article/PPR/PPR644063; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR644063&type=FILE&fileName=EMS174291-pdf.pdf&mimeType=application/pdf
 PPR178438,https://doi.org/10.1101/2020.06.18.20134742,Racial and ethnic determinants of Covid-19 risk,"Lo C, Nguyen LH, Drew DA, Graham MS, Warner ET, Joshi AD, Astley CM, Guo C, Ma W, Mehta RS, Kwon S, Song M, Davies R, Capdevila J, Lee KA, Lochlainn MN, Varsavsky T, Sudre CH, Wolf J, Cozier YC, Rosenberg L, Wilkens LR, Haiman CA, Le Marchand L, Palmer JR, Spector TD, Ourselin S, Steves CJ, Chan AT.",,No Journal Info,2020,2020-06-20,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> Racial and ethnic minorities have disproportionately high hospitalization rates and mortality related to the novel coronavirus disease 2019 (Covid-19). There are comparatively scant data on race and ethnicity as determinants of infection risk. <h4>Methods</h4> We used a smartphone application (beginning March 24, 2020 in the United Kingdom [U.K.] and March 29, 2020 in the United States [U.S.]) to recruit 2,414,601 participants who reported their race/ethnicity through May 25, 2020 and employed logistic regression to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for a positive Covid-19 test among racial and ethnic groups. <h4>Results</h4> We documented 8,858 self-reported cases of Covid-19 among 2,259,841 non-Hispanic white; 79 among 9,615 Hispanic; 186 among 18,176 Black; 598 among 63,316 Asian; and 347 among 63,653 other racial minority participants. Compared with non-Hispanic white participants, the risk for a positive Covid-19 test was increased across racial minorities (aORs ranging from 1.24 to 3.51). After adjustment for socioeconomic indices and Covid-19 exposure risk factors, the associations (aOR [95% CI]) were attenuated but remained significant for Hispanic (1.58 [1.24-2.02]) and Black participants (2.56 [1.93-3.39]) in the U.S. and South Asian (1.52 [1.38-1.67]) and Middle Eastern participants (1.56 [1.25-1.95]) in the U.K. A higher risk of Covid-19 and seeking or receiving treatment was also observed for several racial/ethnic minority subgroups. <h4>Conclusions</h4> Our results demonstrate an increase in Covid-19 risk among racial and ethnic minorities not completely explained by other risk factors for Covid-19, comorbidities, and sociodemographic characteristics. Further research investigating these disparities are needed to inform public health measures.",,pdf:http://www.thelancet.com/article/S2589537021003096/pdf; doi:https://doi.org/10.1101/2020.06.18.20134742; html:https://europepmc.org/article/PPR/PPR178438; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR178438&type=FILE&fileName=EMS88297-pdf.pdf&mimeType=application/pdf
 PPR237625,https://doi.org/10.1101/2020.11.09.20228015,A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome,"Demichev V, Tober-Lau P, Nazarenko T, Thibeault C, Whitwell H, Lemke O, Röhl A, Freiwald A, Szyrwiel L, Ludwig D, Correia-Melo C, Helbig ET, Stubbemann P, Grüning N, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Mittermaier M, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, de Jarcy LB, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Enghard P, Zelezniak A, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Müller-Redetzky H, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, Ralser M, Kurth F, PA-COVID-19 Study group.",,No Journal Info,2020,2020-11-12,Y,,,,"COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. There is an urgent need for predictive markers that can guide clinical decision-making, inform about the effect of experimental therapies, and point to novel therapeutic targets. Here, we characterize the time-dependent progression of COVID-19 through different stages of the disease, by measuring 86 accredited diagnostic parameters and plasma proteomes at 687 sampling points, in a cohort of 139 patients during hospitalization. We report that the time-resolved patient molecular phenotypes reflect an initial spike in the systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution and immunomodulation. Further, we show that the early host response is predictive for the disease trajectory and gives rise to proteomic and diagnostic marker signatures that classify the need for supplemental oxygen therapy and mechanical ventilation, and that predict the time to recovery of mildly ill patients. In severely ill patients, the molecular phenotype of the early host response predicts survival, in two independent cohorts and weeks before outcome. We also identify age-specific molecular response to COVID-19, which involves increased inflammation and lipoprotein dysregulation in older patients. Our study provides a deep and time resolved molecular characterization of COVID-19 disease progression, and reports biomarkers for risk-adapted treatment strategies and molecular disease monitoring. Our study demonstrates accurate prognosis of COVID-19 outcome from proteomic signatures recorded weeks earlier.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/11/12/2020.11.09.20228015.full.pdf; doi:https://doi.org/10.1101/2020.11.09.20228015; html:https://europepmc.org/article/PPR/PPR237625; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR237625&type=FILE&fileName=EMS104194-pdf.pdf&mimeType=application/pdf
 PPR290304,https://doi.org/10.1101/2021.02.27.21252593,Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study,"Dobbs TD, Gibson JAG, Fowler AJ, Abbott TE, Shahid T, Torabi F, Griffiths R, Lyons RA, Pearse RM, Whitaker IS.",,No Journal Info,2021,2021-03-01,Y,,,,"<h4>Objectives</h4> To report the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic. <h4>Design and setting</h4> Analysis of electronic health record data from the National Health Service (NHS) in England and Wales. <h4>Methods</h4> We used hospital episode statistics for all adult patients undergoing surgery between 1 st January 2020 and 31 st December 2020. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from the years 2016-2019 with the actual number of procedures in 2020. We estimated the cumulative number of cancelled procedures by 31 st December 2021 according patterns of activity in 2020. <h4>Results</h4> The total number of surgical procedures carried out in England and Wales in 2020 was 3,102,674 compared to the predicted number of 4,671,338. This represents a 33.6% reduction in the national volume of surgical activity. There were 763,730 emergency surgical procedures (13.4% reduction), compared to 2,338,944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1,568,664. We estimate that this will increase to 2,358,420 by 31 st December 2021. <h4>Conclusions</h4> The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in over 1,568,664 cancelled operations. This deficit will continue to grow in 2021. <h4>Summary boxes</h4> <h4>What is already known on this topic</h4> The COVID-19 pandemic necessitated a rapid change in the provision of care, including the suspension of a large proportion of surgical activity Surgical activity has yet to return to normal and has been further impacted by subsequent waves of the pandemic This will lead to a large backlog of cases <h4>What this study adds</h4> 3,102,674 surgical procedures were performed in England and Wales during 2020, a 33.6% reduction on the expected yearly surgical activity Over 1.5 million procedures were not performed, with this deficit likely to continue to grow to 2.3 million by the end of 2021 This deficit is the equivalent of more than 6 months of pre-pandemic surgical activity, requiring a monumental financial and logistic challenge to manage",,pdf:https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/71298/2/Abbott%20Surgical%20activity%20in%20England%202021%20Published.pdf; doi:https://doi.org/10.1101/2021.02.27.21252593; html:https://europepmc.org/article/PPR/PPR290304; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR290304&type=FILE&fileName=EMS117861-pdf.pdf&mimeType=application/pdf
@@ -404,8 +404,8 @@ PPR172592,https://doi.org/10.1101/2020.06.05.20121962,TRACKing Excess Deaths (TR
 PPR594314,https://doi.org/10.1101/2023.01.06.23284202,Long Covid symptoms and diagnosis in primary care: a cohort study using structured and unstructured data in The Health Improvement Network primary care database,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,No Journal Info,2023,2023-01-09,Y,,,,"<h4>BACKGROUND</h4> Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes. Our objectives were to compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis. <h4>METHODS</h4> We used primary care electronic health record data from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and ‘Long Covid’ diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis. <h4>FINDINGS</h4> We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.99, 95% confidence interval (CI) 3.59, 4.44), shortness of breath (aHR 3.14, 95% CI 2.88, 3.42), palpitations (aHR 2.75, 95% CI 2.28, 3.32), and phlegm (aHR 2.88, 95% CI 2.30, 3.61). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression. <h4>CONCLUSION</h4> Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/09/2023.01.06.23284202.full.pdf; doi:https://doi.org/10.1101/2023.01.06.23284202; html:https://europepmc.org/article/PPR/PPR594314; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR594314&type=FILE&fileName=EMS159579-pdf.pdf&mimeType=application/pdf
 PPR630660,https://doi.org/10.1101/2023.03.10.23286918,Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats,"Steinfeldt J, Wild B, Buergel T, Pietzner M, Upmeier zu Belzen J, Vauvelle A, Hegselmann S, Denaxas S, Hemingway H, Langenberg C, Landmesser U, Deanfield J, Eils R.",,No Journal Info,2023,2023-03-15,Y,,,,"The COVID-19 pandemic exposed, with few exceptions, a global deficiency in delivering systematic, data-driven guidance to protect citizens and coordinate vaccination programs. At the same time, medical histories are routinely recorded in most healthcare systems and are instantly available for risk assessment. Here, we demonstrate the utility of medical history in determining the risk for 1,883 diseases across clinical specialties and facilitating the rapid response to emerging health threats at the example of COVID-19. We developed a neural network to learn disease-specific risk states from routinely collected health records of 502,460 UK Biobank participants, demonstrating risk stratification for nearly all conditions, and validated this model on 229,830 individuals from the All of US cohort. When integrated into Cox Proportional Hazard Models, we observed significant discriminative improvements over basic demographic predictors for 1,774 (94.3%). After transferring the unmodified risk models to the All of US cohort, the discriminate improvements were replicated for 1,347 (89.8%) of 1,500 investigated endpoints, demonstrating model generalizability across healthcare systems and historically underrepresented groups. We then show that these risk states can be used to identify individuals vulnerable to severe COVID-19 and mortality. Our study demonstrates the currently underused potential of medical history to rapidly respond to emerging health threats by systematically estimating risk for thousands of diseases at once at minimal cost.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/03/16/2023.03.10.23286918.full.pdf; doi:https://doi.org/10.1101/2023.03.10.23286918; html:https://europepmc.org/article/PPR/PPR630660
 PPR308156,https://doi.org/10.1101/2021.04.02.21254818,Covid-19 does not look like what you are looking for: Clustering symptoms by nation and multi-morbidities reveal substantial differences to the classical symptom triad,"Kadirvelu B, Burcea G, Quint JK, Costelloe CE, Faisal AA.",,No Journal Info,2021,2021-04-07,Y,,,,"<h4>ABSTRACT</h4> COVID-19 is by convention characterised by a triad of symptoms: cough, fever and loss of taste/smell. The aim of this study was to examine clustering of COVID-19 symptoms based on underlying chronic disease and geographical location. Using a large global symptom survey of 78,299 responders in 190 different countries, we examined symptom profiles in relation to geolocation (grouped by country) and underlying chronic disease (single, co- or multi-morbidities) associated with a positive COVID-19 test result using statistical and machine learning methods to group populations by underlying disease, countries, and symptoms. Taking the responses of 7980 responders with a COVID-19 positive test in the top 5 contributing countries, we find that the most frequently reported symptoms differ across the globe: For example, fatigue 4108(51.5%), headache 3640(45.6%) and loss of smell and taste 3563(44.6%) are the most reported symptoms globally. However, symptom patterns differ by continent; India reported a significantly lower proportion of headache (22.8% vs 45.6%, p<0.05) and itchy eyes (7.0% vs. 15.3%, p<0.05) than other countries, as does Pakistan (33.6% vs 45.6%, p<0.05 and 8.6% vs 15.3%, p<0.05). Mexico and Brazil report significantly less of these symptoms. As with geographic location, we find people differed in their reported symptoms, if they suffered from specific underlying diseases. For example, COVID-19 positive responders with asthma or other lung disease were more likely to report shortness of breath as a symptom, compared with COVID-19 positive responders who had no underlying disease (25.3% vs. 13.7%, p<0.05, and 24.2 vs.13.7%, p<0.05). Responders with no underlying chronic diseases were more likely to report loss of smell and tastes as a symptom (46%), compared with the responders with type 1 diabetes (21.3%), Type 2 diabetes (33.5%) lung disease (29.3%), or hypertension (37.8%). Global symptom ranking differs markedly from the well-known and commonly described symptoms for COVID-19, which are based on a few localised studies. None of the five countries studied in depth recorded cough or temperature as the most common symptoms. The most common symptoms reported were fatigue and loss of smell and taste. Amongst responders from Brazil cough was the second most frequently reported symptom, after fatigue. Moreover, we find that across countries and based on underlying chronic diseases, there are significant differences in symptom profiles at presentation, that cannot be fully explained by the different chronic disease profiles of these countries, and may be caused by differences in climate, environment and ethnicities. These factors uncovered by our global comorbidity survey of COVID-19 positive tested people may contribute to the apparent large asymptotic COVID-19 spread and put patients with underlying disease systematically more at risk. <h4>Executive Summary</h4> <h4>Evidence before this work</h4> An early meta-analysis of epidemiological variation in COVID-19 inside and outside China studied patient characteristics including, gender, age, fatality rate, and symptoms of fever, cough, shortness of breath and diarrhoea in COVID-19 patients. They found that important symptom differences existed in patients in China compared to other countries and recommended that clinical symptoms of COVID-19 should not be generalized to fever, shortness of breath and cough only, but other symptoms such as diarrhoea are also shown to be prevalent in patients with COVID-19. <h4>Added value of this work</h4> W e find that across countries and based on underlying chronic diseases, there are significant differences in symptom profiles at presentation, that cannot be fully explained by the different chronic disease profiles of these countries, and may be caused by differences in climate, environment and ethnicities. <h4>Implications of the evidence</h4> These factors, uncovered by our global comorbidity survey of COVID-19 positive tested people may contribute to the apparent large asymptotic COVID-19 spread and put patients with underlying disease systematically more at risk.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/04/07/2021.04.02.21254818.full.pdf; doi:https://doi.org/10.1101/2021.04.02.21254818; html:https://europepmc.org/article/PPR/PPR308156; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR308156&type=FILE&fileName=EMS121846-pdf.pdf&mimeType=application/pdf
-PPR263081,https://doi.org/10.1101/2021.01.06.21249352,OpenSAFELY NHS Service Restoration Observatory 1: describing trends and variation in primary care clinical activity for 23.3 million patients in England during the first wave of COVID-19,"The OpenSAFELY Collaborative, Curtis HJ, MacKenna B, MacKenna B, Croker R, Inglesby P, Walker AJ, Morley J, Mehrkar A, Morton CE, Bacon S, Hickman G, Bates C, Morley J, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson E, Hulme W, McDonald HI, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wing K, Wong AY, Forbes H, Parry J, Hester F, Harper S, Evans SJ, Douglas IJ, Smeeth L, Goldacre B.",,No Journal Info,2021,2021-01-08,Y,,,,"<h4>Background</h4> The COVID-19 pandemic has disrupted healthcare activity globally. The NHS in England stopped most non-urgent work by March 2020, but later recommended that services should be restored to near-normal levels before winter where possible. The authors are developing the OpenSAFELY NHS Service Restoration Observatory , using data to describe changes in service activity during COVID-19, and reviewing signals for action with commissioners, researchers and clinicians. Here we report phase one: generating, managing, and describing the data. <h4>Objective</h4> To describe the volume and variation of coded clinical activity in English primary care across 23.8 million patients’ records, taking respiratory disease and laboratory procedures as key examples. <h4>Methods</h4> Working on behalf of NHS England we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care EHR data on 23.8 million patients; and conducted a population cohort-based study to describe activity using CTV3 coding hierarchy and keyword searches from January 2019-September 2020. <h4>Results</h4> Much activity recorded in general practice declined to some extent during the pandemic, but largely recovered by September 2020, with some exceptions. There was a large drop in coded activity for commonly used laboratory tests, with broad recovery to pre-pandemic levels by September. One exception was blood coagulation tests such as International Normalised Ratio (INR), with a smaller reduction (median tests per 1000 patients in 2020: February 8.0; April 6.2; September 7.0). The overall pattern of recording for respiratory symptoms was less affected, following an expected seasonal pattern and classified as “no change” from the previous year. Respiratory tract infections exhibited a sustained drop compared with pre-pandemic levels, not returning to pre-pandemic levels by September 2020. Various COVID-19 codes increased through the period. We observed a small decline associated with high level codes for long-term respiratory conditions such as chronic obstructive pulmonary disease (COPD) and asthma. Asthma annual reviews experienced a small drop but since recovered, while COPD annual reviews remain below baseline. <h4>Conclusions</h4> We successfully delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. The COVD-19 pandemic led to a substantial change in healthcare activity. Most laboratory tests showed substantial reduction, largely recovering to near-normal levels by September 2020, with some important tests less affected. Records of respiratory infections decreased with the exception of codes related to COVID-19, whilst activity of other respiratory disease codes was mixed. We are expanding the NHS Service Restoration Observatory in collaboration with clinicians, commissioners and researchers and welcome feedback.",,pdf:https://bjgp.org/content/bjgp/72/714/e63.full.pdf; doi:https://doi.org/10.1101/2021.01.06.21249352; html:https://europepmc.org/article/PPR/PPR263081; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR263081&type=FILE&fileName=EMS110198-pdf.pdf&mimeType=application/pdf
 PPR187554,https://doi.org/10.1101/2020.07.14.20152629,COVID-19 infection and attributable mortality in UK care homes: Cohort study using active surveillance and electronic records (March-June 2020),"Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hemingway H, Hayward A, Shallcross L.",,No Journal Info,2020,2020-07-15,Y,,,,"<h4>Background</h4> Epidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic. <h4>Methods</h4> Cohort study of 179 UK care homes with 9,339 residents and 11,604 staff.We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality, and estimate attributable mortality. <h4>Results</h4> 2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff respectively. 121/179 (67.6%) care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection. 217/607 residents with confirmed infection died (case-fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was two-fold higher in care homes with outbreaks versus those without (adjusted HR 2.2 [1.8; 2.6]). <h4>Conclusions</h4> <h4>Findingss: </h4>uggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.",,doi:https://doi.org/10.1101/2020.07.14.20152629; html:https://europepmc.org/article/PPR/PPR187554; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR187554&type=FILE&fileName=EMS87167-pdf.pdf&mimeType=application/pdf; pdf:https://discovery.ucl.ac.uk/10122604/10/Dutey-Magni_afab060.pdf
+PPR263081,https://doi.org/10.1101/2021.01.06.21249352,OpenSAFELY NHS Service Restoration Observatory 1: describing trends and variation in primary care clinical activity for 23.3 million patients in England during the first wave of COVID-19,"The OpenSAFELY Collaborative, Curtis HJ, MacKenna B, MacKenna B, Croker R, Inglesby P, Walker AJ, Morley J, Mehrkar A, Morton CE, Bacon S, Hickman G, Bates C, Morley J, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson E, Hulme W, McDonald HI, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wing K, Wong AY, Forbes H, Parry J, Hester F, Harper S, Evans SJ, Douglas IJ, Smeeth L, Goldacre B.",,No Journal Info,2021,2021-01-08,Y,,,,"<h4>Background</h4> The COVID-19 pandemic has disrupted healthcare activity globally. The NHS in England stopped most non-urgent work by March 2020, but later recommended that services should be restored to near-normal levels before winter where possible. The authors are developing the OpenSAFELY NHS Service Restoration Observatory , using data to describe changes in service activity during COVID-19, and reviewing signals for action with commissioners, researchers and clinicians. Here we report phase one: generating, managing, and describing the data. <h4>Objective</h4> To describe the volume and variation of coded clinical activity in English primary care across 23.8 million patients’ records, taking respiratory disease and laboratory procedures as key examples. <h4>Methods</h4> Working on behalf of NHS England we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care EHR data on 23.8 million patients; and conducted a population cohort-based study to describe activity using CTV3 coding hierarchy and keyword searches from January 2019-September 2020. <h4>Results</h4> Much activity recorded in general practice declined to some extent during the pandemic, but largely recovered by September 2020, with some exceptions. There was a large drop in coded activity for commonly used laboratory tests, with broad recovery to pre-pandemic levels by September. One exception was blood coagulation tests such as International Normalised Ratio (INR), with a smaller reduction (median tests per 1000 patients in 2020: February 8.0; April 6.2; September 7.0). The overall pattern of recording for respiratory symptoms was less affected, following an expected seasonal pattern and classified as “no change” from the previous year. Respiratory tract infections exhibited a sustained drop compared with pre-pandemic levels, not returning to pre-pandemic levels by September 2020. Various COVID-19 codes increased through the period. We observed a small decline associated with high level codes for long-term respiratory conditions such as chronic obstructive pulmonary disease (COPD) and asthma. Asthma annual reviews experienced a small drop but since recovered, while COPD annual reviews remain below baseline. <h4>Conclusions</h4> We successfully delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. The COVD-19 pandemic led to a substantial change in healthcare activity. Most laboratory tests showed substantial reduction, largely recovering to near-normal levels by September 2020, with some important tests less affected. Records of respiratory infections decreased with the exception of codes related to COVID-19, whilst activity of other respiratory disease codes was mixed. We are expanding the NHS Service Restoration Observatory in collaboration with clinicians, commissioners and researchers and welcome feedback.",,pdf:https://bjgp.org/content/bjgp/72/714/e63.full.pdf; doi:https://doi.org/10.1101/2021.01.06.21249352; html:https://europepmc.org/article/PPR/PPR263081; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR263081&type=FILE&fileName=EMS110198-pdf.pdf&mimeType=application/pdf
 PPR384592,https://doi.org/10.1101/2021.08.17.21260846,"COVID-19 Infection, Admission and Death Amongst People with Rare Autoimmune Rheumatic Disease in England. Results from the RECORDER Project","Rutter M, Lanyon PC, Grainge MJ, Hubbard R, Peach E, Bythell M, Stilwell P, Aston J, Stevens S, Pearce FA.",,No Journal Info,2021,2021-08-18,Y,,,,"<h4>Objectives</h4> To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared to the general population. <h4>Methods</h4> We used Hospital Episode Statistics to identify all people alive 01 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. <h4>Results</h4> We identified a cohort of 168,680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardised infection rate was 1.54 (95% CI 1.50-1.59) times higher than in the general population. 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardised mortality rate for COVID-19-related death was 2.41 (2.30 – 2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. <h4>Conclusions</h4> During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared to the general population. These increases were seen despite shielding policies. <h4>Key Messages</h4> People with RAIRD were at increased risk of COVID-19 infection during the first wave. Compared to the general population, they had over twice the risk of COVID-19-related death. These increased risks were seen despite shielding policies in place in England.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/09/04/2021.08.17.21260846.full.pdf; doi:https://doi.org/10.1101/2021.08.17.21260846; html:https://europepmc.org/article/PPR/PPR384592; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR384592&type=FILE&fileName=EMS133258-pdf.pdf&mimeType=application/pdf
 PPR232332,https://doi.org/10.1101/2020.10.29.20222174,COVID-19 collateral: Indirect acute effects of the pandemic on physical and mental health in the UK,"Mansfield KE, Mathur R, Tazare J, Henderson AD, Mulick A, Carreira H, Matthews AA, Bidulka P, Gayle A, Forbes H, Cook S, Wong AY, Strongman H, Wing K, Warren-Gash C, Cadogan SL, Smeeth L, Hayes JF, Quint JK, McKee M, M Langan S.",,No Journal Info,2020,2020-10-30,Y,,,,"<h4>ABSTRACT</h4> <h4>Background</h4> Concerns have been raised that the response to the UK COVID-19 pandemic may have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We asked what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic? <h4>Methods</h4> Using electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (2017-2020), we calculated weekly primary care contacts for selected acute physical and mental health conditions (including: anxiety, depression, acute alcohol-related events, asthma and chronic obstructive pulmonary disease [COPD] exacerbations, cardiovascular and diabetic emergencies). We used interrupted time series (ITS) analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (‘lockdown’) compared to the period prior to their introduction in March 2020. <h4>Findings</h4> The overall population included 9,863,903 individuals on 1 st January 2017. Primary care contacts for all conditions dropped dramatically after introduction of population-wide restrictions. By July 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. The largest reductions were for contacts for: diabetic emergencies (OR: 0.35, 95% CI: 0.25-0.50), depression (OR: 0.53, 95% CI: 0.52-0.53), and self-harm (OR: 0.56, 95% CI: 0.54-0.58). <h4>Interpretation</h4> There were substantial reductions in primary care contacts for acute physical and mental conditions with restrictions, with limited recovery by July 2020. It is likely that much of the deficit in care represents unmet need, with implications for subsequent morbidity and premature mortality. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people experiencing the conditions and healthcare provision. Maintaining access must be a key priority in future public health planning (including further restrictions). <h4>Funding</h4> Wellcome Trust Senior Fellowship (SML), Health Data Research UK. <h4>RESULTS IN CONTEXT</h4> <h4>Evidence before this study</h4> A small study in 47 GP practices in a largely deprived, urban area of the UK (Salford) reported that primary care consultations for four broad diagnostic groups (circulatory disease, common mental health problems, type 2 diabetes mellitus and malignant cancer) declined by 16-50% between March and May 2020, compared to what was expected based on data from January 2010 to March 2020. We searched Medline for other relevant evidence of the indirect effect of the COVID-19 pandemic on physical and mental health from inception to September 25 th 2020, for articles published in English, with titles including the search terms (“covid*” or “coronavirus” or “sars-cov-2”), and title or abstracts including the search terms (“indirect impact” or “missed diagnos*” or “missing diagnos*” or “delayed diagnos*” or ((“present*” or “consult*” or “engag*” or “access*”) AND (“reduction” or “decrease” or “decline”)). We found no further studies investigating the change in primary care contacts for specific physical- and mental-health conditions indirectly resulting from the COVID-19 pandemic or its control measures. There has been a reduction in hospital admissions and presentations to accident and emergency departments in the UK, particularly for myocardial infarctions and cerebrovascular accidents. However, there is no published evidence specifically investigating the changes in primary care contacts for severe acute physical and mental health conditions. <h4>Added value of this study</h4> To our knowledge this is the first study to explore changes in healthcare contacts for acute physical and mental health conditions in a large population representative of the UK. We used electronic primary care health records of nearly 10 million individuals across the UK to investigate the indirect impact of COVID-19 on primary care contacts for mental health, acute alcohol-related events, asthma/chronic obstructive pulmonary disease (COPD) exacerbations, and cardiovascular and diabetic emergencies up to July 2020. For all conditions studied, we found primary care contacts dropped dramatically following the introduction of population-wide restriction measures in March 2020. By July 2020, with the exception of unstable angina and acute alcohol-related events, primary care contacts for all conditions studied had not recovered to pre-lockdown levels. In the general population, estimates of the absolute reduction in the number of primary care contacts up to July 2020, compared to what we would expect from previous years varied from fewer than 10 contacts per million for some cardiovascular outcomes, to 12,800 per million for depression and 6,600 for anxiety. In people with COPD, we estimated there were 43,900 per million fewer contacts for COPD exacerbations up to July 2020 than what we would expect from previous years. <h4>Implicatins of all the available evidence</h4> While our results may represent some genuine reduction in disease frequency (e.g. the restriction measures may have improved diabetic glycaemic control due to more regular daily routines at home), it is more likely the reduced primary care conatcts we saw represent a substantial burden of unmet need (particularly for mental health conditions) that may be reflected in subsequent increased mortality and morbidity. Health service providers should take steps to prepare for increased demand in the coming months and years due to the short and longterm ramifications of reduced access to care for severe acute physical and mental health conditions. Maintaining access to primary care is key to future public health planning in relation to the pandemic.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/10/30/2020.10.29.20222174.full.pdf; doi:https://doi.org/10.1101/2020.10.29.20222174; html:https://europepmc.org/article/PPR/PPR232332; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR232332&type=FILE&fileName=EMS102733-pdf.pdf&mimeType=application/pdf
 PPR414478,https://doi.org/10.1101/2021.11.01.21265660,"Association between mobility, non-pharmaceutical interventions, and COVID-19 transmission in Ghana: a modelling study using mobile phone data","Gibbs H, Liu Y, Abbott S, Baffoe-Nyarko I, Laryea DO, Akyereko E, Kuma-Aboagye P, Asante I, Mitjà O, Ampofo W, Asiedu-Bekoe F, Marks M, Eggo RM, LSHTM CMMID COVID-19 working group.",,No Journal Info,2021,2021-11-02,Y,,,,"<h4>Background</h4> Governments around the world have implemented non-pharmaceutical interventions to limit the transmission of COVID-19. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of how NPI measures are reflected in indicators of human mobility. Further, there is a lack of understanding about how findings from high-income settings correspond to low and middle-income contexts. <h4>Methods</h4> In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of R t , a real-time measure of the intensity of COVID-19 transmission. We construct a multilevel generalised linear mixed model, combining local disease surveillance data from subnational districts of Ghana with the timing of NPIs and indicators of human mobility from Google and Vodafone Ghana. <h4>Findings</h4> We observe a relationship between reductions in human mobility and decreases in R t during the early stages of the COVID-19 epidemic in Ghana. We find that the strength of this relationship varies through time, decreasing after the most stringent period of interventions in the early epidemic. <h4>Interpretation</h4> Our findings demonstrate how the association of NPI and mobility indicators with COVID-19 transmission may vary through time. Further, we demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity and monitor the impact of NPI policies. <h4>Research in Context</h4> <h4>Evidence before this study</h4> We searched PubMed and preprint archives for articles published in English that contained information about the COVID-19 pandemic published up to Nov 1, 2021, using the search terms “coronavirus”, “CoV”, “COVID-19”, “mobility”, “movement”, and “flow”. The data thus far suggests that NPI measures including physical distancing, reduction of travel, and use of personal protective equipment have been demonstrated to reduce COVID-19 transmission. Much of the existing research focuses on comparisons of NPI stringency with COVID-19 transmission among different high-income countries, or on high-income countries, leaving critical questions about the applicability of these findings to low- and middle-income settings. <h4>Added value of this study</h4> We used a detailed COVID-19 surveillance dataset from Ghana, and unique high resolution spatial data on human mobility from Vodafone Ghana as well as Google smartphone GPS location data. We show how human mobility and NPI stringency were associated with changes in the effective reproduction number (R t ). We further demonstrate how this association was strongest in the early COVID-19 outbreak in Ghana, decreasing after the relaxation of national restrictions. <h4>Implications of all the available evidence</h4> The change in association between human mobility, NPI stringency, and R t may reflect a “decoupling” of NPI stringency and human mobility from disease transmission in Ghana as the COVID-19 epidemic progressed. This finding provides public health decision makers with important insights for the understanding of the utility of mobility data for predicting the spread of COVID-19.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575146; doi:https://doi.org/10.1101/2021.11.01.21265660; html:https://europepmc.org/article/PPR/PPR414478; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR414478&type=FILE&fileName=EMS137953-pdf.pdf&mimeType=application/pdf
@@ -435,8 +435,8 @@ PPR230607,https://doi.org/10.1101/2020.10.26.20219576,Impact of the COVID-19 pan
 PPR208637,https://doi.org/10.1101/2020.09.02.20186502,Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection,"Jombart T, Ghozzi S, Schumacher D, Leclerc QJ, Jit M, Flasche S, Greaves F, Ward T, Eggo RM, Nightingale E, Meakin S, Brady OJ, Medley GF, Höhle M, Edmunds WJ, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group.",,No Journal Info,2020,2020-09-03,Y,,,,"As several countries gradually release social distancing measures, rapid detection of new localised COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (Automatic Selection of Models and Outlier Detection for Epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterise the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggest ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. We illustrate our method using publicly available data of NHS Pathways reporting potential COVID-19 cases in England at a fine spatial scale, for which we provide a template automated analysis pipeline. ASMODEE is implemented in the free R package trendbreaker .",,doi:https://doi.org/10.1098/rstb.2020.0266; doi:https://doi.org/10.1101/2020.09.02.20186502; html:https://europepmc.org/article/PPR/PPR208637; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR208637&type=FILE&fileName=EMS94645-pdf.pdf&mimeType=application/pdf
 PPR568016,https://doi.org/10.1101/2022.11.06.22281986,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,No Journal Info,2022,2022-11-07,Y,,,,"<h4>Background</h4> Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic. <h4>Methods</h4> Routinely collected data for public hospitals in the Western Cape, South Africa from the 27 th August 2020 to 11 th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort. <h4>Results</h4> We analysed 305,564, derivation 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment. <h4>Conclusion</h4> The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings. <h4>What is already known on this subject</h4> Uneven vaccination in low- and middle-income countries (LMICs) coupled with less resilient health care provision mean that emergency health care systems in LMICs may still be at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-stratification scores may help rapidly triage need for hospitalisation. However, those proposed for use in the ED for patients with suspected COVID-19 have been developed and validated in high-income settings. <h4>What this study adds</h4> The LMIC-PRIEST score has been robustly developed using a large routine dataset from the Western Cape, South Africa and is directly applicable to existing triage practices in LMICs. External validation across both income settings and COVID-19 variants showed good discrimination and high sensitivity (at lower thresholds) to a composite outcome indicating need for inpatient admission from the ED <h4>How this study might affect research, practice or policy</h4> Use of the LMIC-PRIEST score at thresholds of three or less would allow identification of very low-risk patients (negative predictive value ≥0.99) across all settings assessed During periods of increased demand, this could allow the rapid identification and discharge of patients from the ED using information collected at initial assessment.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9665341; doi:https://doi.org/10.1101/2022.11.06.22281986; html:https://europepmc.org/article/PPR/PPR568016; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR568016&type=FILE&fileName=EMS156830-pdf.pdf&mimeType=application/pdf
 PPR509645,https://doi.org/10.1101/2022.06.23.22276802,OpenSAFELY: Representativeness of Electronic Health Record platform OpenSAFELY-TPP data compared to the population of England,"Andrews CD, Schultze A, Curtis HJ, Hulme WJ, Hulme WJ, Tazare J, Evans SJ, Mehrkhar A, Bacon S, Hickman G, Bates C, Parry J, Hester F, Harper S, Cockburn J, Evans D, Ward T, Davey S, Inglesby P, Goldacre B, MacKenna B, Tomlinson L, Walker AJ.",,No Journal Info,2022,2022-06-23,Y,,,,"<h4>Background</h4> Since its inception in March 2020, data from the OpenSAFELY-TPP electronic health record platform has been used for more than 50 studies relating to the global COVID-19 emergency. OpenSAFELY-TPP data is derived from practices in England using SystmOne software, and has been used for the majority of these studies. We set out to investigate the representativeness of OpenSAFELY-TPP data by comparing it to national population estimates. <h4>Methods</h4> With the approval of NHS England, we describe the age, sex, Index of Multiple Deprivation and ethnicity of the OpenSAFELY-TPP population compared to national estimates from the Office for National Statistics. The five leading causes of death occurring between the 1st January 2020 and the 31st December 2020 were also compared to deaths registered in England during the same period. <h4>Results</h4> Despite regional variations, TPP is largely representative of the general population of England in terms of IMD (all within 1.1 percentage points), age, sex (within 0.1 percentage points), ethnicity and causes of death. The proportion of the five leading causes of death is broadly similar to those reported by ONS (all within 1 percentage point). <h4>Conclusions</h4> Data made available via OpenSAFELY-TPP is broadly representative of the English population. <h4>Summary</h4> Users of OpenSAFELY must consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research. Although the coverage of TPP practices varies regionally across England, TPP registered patients are generally representative of the English population as a whole in terms of key demographic characteristics. <h4>Key messages</h4> There is regional variability across England in terms of key population characteristics Users of OpenSAFELY should carefully consider the issues of representativeness, generalisability and external validity associated with using TPP data for health research. TPP registered patients are a representative sub-sample of the English population as a whole in terms of age, sex, IMD and ethnicity. The proportions of the five leading causes of death in TPP in 2020 are broadly similar to those reported by ONS.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4667127/1/Andrews_etal_2022_OpenSAFELY-representativeness-of-electronic-health.pdf; doi:https://doi.org/10.1101/2022.06.23.22276802; html:https://europepmc.org/article/PPR/PPR509645; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR509645&type=FILE&fileName=EMS146338-pdf.pdf&mimeType=application/pdf
-PPR245483,https://doi.org/10.1101/2020.11.25.20229088,"Use of dialysis, tracheostomy, and extracorporeal membrane oxygenation among 842,928 patients hospitalized with COVID-19 in the United States","Burn E, Sena AG, Prats-Uribe A, Spotnitz M, DuVall S, Lynch KE, Matheny ME, Nyberg F, Ahmed W, Alser O, Alghoul H, Alshammari T, Zhang L, Casajust P, Areia C, Shah K, Reich C, Blacketer C, Andryc A, Fortin S, Natarajan K, Gong M, Golozar A, Morales D, Rijnbeek P, Subbian V, Roel E, Recalde M, Lane JC, Vizcaya D, Posada JD, Shah NH, Jonnagaddala J, Lai LYH, Avilés-Jurado FX, Hripcsak G, Suchard MA, Ranzani OT, Ryan P, Prieto-Alhambra D, Kostka K, Duarte-Salles T.",,No Journal Info,2020,2020-11-27,Y,,,,"<h4>Objective</h4> To estimate the proportion of patients hospitalized with COVID-19 who undergo dialysis, tracheostomy, and extracorporeal membrane oxygenation (ECMO). <h4>Design</h4> A network cohort study. <h4>Setting</h4> Seven databases from the United States containing routinely-collected patient data: HealthVerity, Premier, IQVIA Hospital CDM, IQVIA Open Claims, Optum EHR, Optum SES, and VA-OMOP. <h4>Patients</h4> Patients hospitalized with a clinical diagnosis or a positive test result for COVID-19. <h4>Interventions</h4> Dialysis, tracheostomy, and ECMO. <h4>Measurements and Main Results</h4> 842,928 patients hospitalized with COVID-19 were included (22,887 from HealthVerity, 77,853 from IQVIA Hospital CDM, 533,997 from IQVIA Open Claims, 36,717 from Optum EHR, 4,336 from OPTUM SES, 156,187 from Premier, and 10,951 from VA-OMOP). Across the six databases, 35,192 (4.17% [95% CI: 4.13% to 4.22%]) patients received dialysis, 6,950 (0.82% [0.81% to 0.84%]) had a tracheostomy, and 1,568 (0.19% [95% CI: 0.18% to 0.20%]) patients underwent ECMO over the 30 days following hospitalization. Use of ECMO was more common among patients who were younger, male, and with fewer comorbidities. Tracheostomy was broadly used for a similar proportion of patients regardless of age, sex, or comorbidity. While dialysis was generally used for a similar proportion among younger and older patients, it was more frequent among male patients and among those with chronic kidney disease. <h4>Conclusion</h4> Use of dialysis among those hospitalized with COVID-19 is high at around 4%. Although less than one percent of patients undergo tracheostomy and ECMO, the absolute numbers of patients who have undergone these interventions is substantial.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709172; doi:https://doi.org/10.1101/2020.11.25.20229088; html:https://europepmc.org/article/PPR/PPR245483; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR245483&type=FILE&fileName=EMS107292-pdf.pdf&mimeType=application/pdf
 PPR138670,https://doi.org/10.1101/2020.03.31.20049023,Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK,"Jarvis CI, Van Zandvoort K, Gimma A, Prem K, Klepac P, Rubin GJ, Edmunds WJ, CMMID COVID-19 working group.",,No Journal Info,2020,2020-04-03,Y,,,,"<h4>Background</h4> To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number ( R 0 , the average number of secondary cases generated per case). <h4>Methods</h4> We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire documents the age and location of contacts and as well as a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday 24th March, one day after a “ lockdown” was implemented across the UK. We compared measured contact patterns during the “ lockdown” to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. <h4>Findings</h4> We found a 73% reduction in the average daily number of contacts observed per participant (from 10.2 to 2.9). This would be sufficient to reduce R 0 from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37 - 0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22 - 0.53) for physical contacts only. <h4>Interpretation</h4> The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance. <h4>Research in context</h4> <h4>Evidence before this study</h4> Many governments have adopted physical distancing measures to mitigate the impact of the COVID-19 pandemic. However, it is unclear to what extent these measures reduce the number of contacts and therefore transmission. We searched PubMed and medRxiv on March 28, 2020, with the terms “ (coronavirus OR COVID-19 OR influenza) AND ((school OR work) AND (closure OR holiday)) AND (contact OR mixing)” and identified 59 and 17 results, respectively. Only one study conducted in China during the COVID-19 pandemic reported a reduction in daily contacts outside the home during the period of “ lockdown”. We found no other published articles that empirically quantify the impact of these measures on age- and location-specific mixing patterns. <h4>Added value of this study</h4> By surveying adults’ behaviour in the UK during a period of stringent physical distancing (“ lockdown”) and comparing the results to previously collected data, we found a large reduction in daily contacts particularly outside the home, resulting in a marked reduction in the estimated reproduction number from 2.6 to 0.62 (95% bootstrapped confidence interval [CI] 0.37 - 0.89). This method allows for rapid assessment of changes in the reproduction number that is unaffected by reporting delays. <h4>Implications of all the available evidence</h4> Changes in human contact behaviour drive respiratory infection rates. Understanding these changes at different stages of the COVID-19 pandemic allows us to rapidly quantify the impact of physical distancing measures on the transmission of pathogens.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01597-8; doi:https://doi.org/10.1101/2020.03.31.20049023; html:https://europepmc.org/article/PPR/PPR138670; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR138670&type=FILE&fileName=EMS89599-pdf.pdf&mimeType=application/pdf
+PPR245483,https://doi.org/10.1101/2020.11.25.20229088,"Use of dialysis, tracheostomy, and extracorporeal membrane oxygenation among 842,928 patients hospitalized with COVID-19 in the United States","Burn E, Sena AG, Prats-Uribe A, Spotnitz M, DuVall S, Lynch KE, Matheny ME, Nyberg F, Ahmed W, Alser O, Alghoul H, Alshammari T, Zhang L, Casajust P, Areia C, Shah K, Reich C, Blacketer C, Andryc A, Fortin S, Natarajan K, Gong M, Golozar A, Morales D, Rijnbeek P, Subbian V, Roel E, Recalde M, Lane JC, Vizcaya D, Posada JD, Shah NH, Jonnagaddala J, Lai LYH, Avilés-Jurado FX, Hripcsak G, Suchard MA, Ranzani OT, Ryan P, Prieto-Alhambra D, Kostka K, Duarte-Salles T.",,No Journal Info,2020,2020-11-27,Y,,,,"<h4>Objective</h4> To estimate the proportion of patients hospitalized with COVID-19 who undergo dialysis, tracheostomy, and extracorporeal membrane oxygenation (ECMO). <h4>Design</h4> A network cohort study. <h4>Setting</h4> Seven databases from the United States containing routinely-collected patient data: HealthVerity, Premier, IQVIA Hospital CDM, IQVIA Open Claims, Optum EHR, Optum SES, and VA-OMOP. <h4>Patients</h4> Patients hospitalized with a clinical diagnosis or a positive test result for COVID-19. <h4>Interventions</h4> Dialysis, tracheostomy, and ECMO. <h4>Measurements and Main Results</h4> 842,928 patients hospitalized with COVID-19 were included (22,887 from HealthVerity, 77,853 from IQVIA Hospital CDM, 533,997 from IQVIA Open Claims, 36,717 from Optum EHR, 4,336 from OPTUM SES, 156,187 from Premier, and 10,951 from VA-OMOP). Across the six databases, 35,192 (4.17% [95% CI: 4.13% to 4.22%]) patients received dialysis, 6,950 (0.82% [0.81% to 0.84%]) had a tracheostomy, and 1,568 (0.19% [95% CI: 0.18% to 0.20%]) patients underwent ECMO over the 30 days following hospitalization. Use of ECMO was more common among patients who were younger, male, and with fewer comorbidities. Tracheostomy was broadly used for a similar proportion of patients regardless of age, sex, or comorbidity. While dialysis was generally used for a similar proportion among younger and older patients, it was more frequent among male patients and among those with chronic kidney disease. <h4>Conclusion</h4> Use of dialysis among those hospitalized with COVID-19 is high at around 4%. Although less than one percent of patients undergo tracheostomy and ECMO, the absolute numbers of patients who have undergone these interventions is substantial.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709172; doi:https://doi.org/10.1101/2020.11.25.20229088; html:https://europepmc.org/article/PPR/PPR245483; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR245483&type=FILE&fileName=EMS107292-pdf.pdf&mimeType=application/pdf
 PPR241564,https://doi.org/10.2139/ssrn.3719882,COVID-19 Collateral: Indirect Acute Effects of the Pandemic on Physical and Mental Health in the UK,"Mansfield KE, Mathur R, Tazare J, Henderson A, Mulick A, Carreira H, Matthews AA, Bidulka P, Gayle A, Forbes H, Strongman H, Cook S, Wong AY, Strongman H, Wing K, Warren-Gash C, Cadogan S, Smeeth L, Hayes JF, Quint J, McKee M, Langan S.",,No Journal Info,2020,2020-11-03,N,,,,"Background:  Concerns have been raised that the response to the UK COVID-19 pandemic may have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We asked what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic?<br><br>Methods:  Using electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (2017-2020), we calculated weekly primary care contacts for selected acute physical and mental health conditions (including: anxiety, depression, acute alcohol-related events, asthma and chronic obstructive pulmonary disease [COPD] exacerbations, cardiovascular and diabetic emergencies). We used interrupted time series (ITS) analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (‘lockdown’) compared to the period prior to their introduction in March 2020.<br><br>Findings:  The overall population included 9,863,903 individuals on 1st  January 2017. Primary care contacts for all conditions dropped dramatically after introduction of population-wide restrictions. By July 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. The largest reductions were for contacts for: diabetic emergencies (OR: 0.35, 95% CI: 0.25-0.50), depression (OR: 0.53, 95% CI: 0.52-0.53), and self-harm (OR: 0.56, 95% CI: 0.54-0.58).<br><br>Interpretation:  There were substantial reductions in primary care contacts for acute physical and mental conditions with restrictions, with limited recovery by July 2020. It is likely that much of the deficit in care represents unmet need, with implications for subsequent morbidity and premature mortality. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people experiencing the conditions and healthcare provision. Maintaining access must be a key priority in future public health planning (including further restrictions).<br><br>Funding:  Wellcome Trust Senior Fellowship (SML), Health Data Research UK.<br><br>Declaration of Interests: All authors have completed the ICMJE uniform disclosure form (www.icmje.org/coi_disclosure.pdf). MM is a member of Independent SAGE, Dr. Warren-Gash reports grants from Wellcome Trust, during the conduct of the study, Liam Smeeth, is a non-executive director of the MHRA. All other authors have nothing to declare. <br><br>Ethics Approval Statement:  The study was approved by the London School of Hygiene and Tropical Medicine Research Ethics Committee (Reference: 22143 /RR/18495) and by the CPRD Independent Scientific Advisory Committee (ISAC Protocol Number: 20_089R2).",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659229/1/2020.10.29.20222174v1.full.pdf; doi:https://doi.org/10.2139/ssrn.3719882; html:https://europepmc.org/article/PPR/PPR241564; doi:https://doi.org/10.2139/ssrn.3719882
 PPR179130,https://doi.org/10.1101/2020.06.22.20137182,Obesity during the COVID-19 pandemic: cause of high risk or an effect of lockdown? A population-based electronic health record analysis in 1 958 184 individuals.,"Katsoulis M, Pasea L, Lai A, Dobson RJ, Denaxas S, Hemingway H, Banerjee A.",,No Journal Info,2020,2020-06-23,Y,,,,"<h4>Background: </h4> Obesity is a modifiable risk factor for coronavirus(COVID-19)-related mortality. We estimated excess mortality in obesity, both 'direct', through infection, and 'indirect', through changes in healthcare, and also due to potential increasing obesity during lockdown. <h4>Methods:</h4> In population-based electronic health records for 1 958 638 individuals in England, we estimated 1-year mortality risk('direct' and 'indirect' effects) for obese individuals, incorporating: (i)pre-COVID-19 risk by age, sex and comorbidities, (ii)population infection rate, and (iii)relative impact on mortality(relative risk, RR: 1.2, 1.5, 2.0 and 3.0). Using causal inference models, we estimated impact of change in body-mass index(BMI) and physical activity during 3-month lockdown on 1-year incidence for high-risk conditions(cardiovascular diseases, CVD; diabetes; chronic obstructive pulmonary disease, COPD and chronic kidney disease, CKD), accounting for confounders. <h4>Findings:</h4> For severely obese individuals (3.5% at baseline), at 10% population infection rate, we estimated direct impact of 240 and 479 excess deaths in England at RR 1.5 and 2.0 respectively, and indirect effect of 383 to 767 excess deaths, assuming 40% and 80% will be affected at RR=1.2. Due to BMI change during the lockdown, we estimated that 97 755 (5.4%: normal weight to overweight, 5.0%: overweight to obese and 1.3%: obese to severely obese) to 434 104 individuals (15%: normal weight to overweight, 15%: overweight to obese and 6%: obese to severely obese) individuals would be at higher risk for COVID-19 over one year. Interpretation: Prevention of obesity and physical activity are at least as important as physical isolation of severely obese individuals during the pandemic.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/06/23/2020.06.22.20137182.full.pdf; doi:https://doi.org/10.1101/2020.06.22.20137182; html:https://europepmc.org/article/PPR/PPR179130; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR179130&type=FILE&fileName=EMS88420-pdf.pdf&mimeType=application/pdf
 PPR179144,https://doi.org/10.1101/2020.06.21.20136853,Modelling the impact of lockdown easing measures on cumulative COVID-19 cases and deaths in England,"Ziauddeen H, Subramaniam N, Gurdasani D.",,No Journal Info,2020,2020-06-23,Y,,,,"<h4>Background</h4> As countries begin to ease the lockdown measures instituted to control the COVID-19 pandemic, there is a risk of a resurgence of the pandemic, and early reports of this are already emerging from some countries. Unlike many other countries, the UK started easing lockdown in England when levels of community transmission were still high, and this could have a major impact on case numbers and deaths. However thus far, the likely impacts of easing restrictions at this point in the pandemic have not been quantified. Using a Bayesian model, we assessed the potential impacts of successive lockdown easing measures in England, focussing on scenarios where the reproductive number ( R ) remains ≤1 in line with the UK government’s stated aim. <h4>Methods</h4> We developed a Bayesian model to infer incident cases and R in England, from incident death data from the Office of National Statistics. We then used this to forecast excess cases and deaths in multiple plausible scenarios in which R increases at one or more time points, compared to a baseline scenario where R remains unchanged by the easing of lockdown. <h4>Findings</h4> The model inferred an R of 0.752 on the 13 th May when England first started easing lockdown. In the most conservative scenario where R increases to 0.80 as lockdown was eased further on 1 st June and then remained constant, the model predicts an excess 257 (95% 108-492) deaths and 26,447 (95% CI 11,105-50,549) cumulative cases over 90 days. In the scenario with maximal increases in R (but staying ≤1) with successive easing of lockdown, the model predicts 3,174 (95% 1,334-6,060) excess cumulative deaths and 421,310 (95% 177,012-804,811) excess cases. <h4>Results</h4> When levels of transmission are high, even small changes in R with easing of lockdown can have significant impacts on expected cases and deaths, even if R remains ≤1. This will have a major impact on population health, tracing systems and health care services in England.. Following an elimination strategy rather than one of maintenance of R below 1 would substantially mitigate the impact of the COVID-19 epidemic within England. This study provides urgently needed information for developing public health policy for the next stages of the pandemic.",,pdf:https://europepmc.org/articles/pmc8438582?pdf=render; doi:https://doi.org/10.1101/2020.06.21.20136853; html:https://europepmc.org/article/PPR/PPR179144; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR179144&type=FILE&fileName=EMS88438-pdf.pdf&mimeType=application/pdf
diff --git a/data/covid/papers.csv b/data/covid/papers.csv
index 84f5dadc..4cb55e3b 100644
--- a/data/covid/papers.csv
+++ b/data/covid/papers.csv
@@ -47,8 +47,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 35140406,https://doi.org/10.1038/s41591-022-01701-w,Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil.,"Cerqueira-Silva T, Katikireddi SV, de Araujo Oliveira V, Flores-Ortiz R, Júnior JB, Paixão ES, Robertson C, Penna GO, Werneck GL, Barreto ML, Pearce N, Sheikh A, Barral-Netto M, Boaventura VS.",,Nature medicine,2022,2022-02-09,Y,,,,"There is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14-30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3-55.7) against confirmed infection and 82.1% (95% CI: 81.4-82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1-36.2) against infection and 72.5% (95% CI: 70.9-74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0-94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1-98.1) 14-30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly.",,pdf:https://www.nature.com/articles/s41591-022-01701-w.pdf; doi:https://doi.org/10.1038/s41591-022-01701-w; html:https://europepmc.org/articles/PMC9018414; pdf:https://europepmc.org/articles/PMC9018414?pdf=render
 36253471,https://doi.org/10.1038/s41467-022-33937-y,A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection.,"Calvert C, Carruthers J, Denny C, Donaghy J, Hillman S, Hopcroft LEM, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Moore E, Pan J, Taylor B, Almaghrabi F, Auyeung B, Bhaskaran K, Gibbons CL, Katikireddi SV, McCowan C, Murray J, O'Leary M, Ritchie LD, Shah SA, Simpson CR, Robertson C, Sheikh A, Stock SJ, Wood R.",,Nature communications,2022,2022-10-17,Y,,,,"Data on the safety of COVID-19 vaccines in early pregnancy are limited. We conducted a national, population-based, matched cohort study assessing associations between COVID-19 vaccination and miscarriage prior to 20 weeks gestation and, separately, ectopic pregnancy. We identified women in Scotland vaccinated between 6 weeks preconception and 19 weeks 6 days gestation (for miscarriage; n = 18,780) or 2 weeks 6 days gestation (for ectopic; n = 10,570). Matched, unvaccinated women from the pre-pandemic and, separately, pandemic periods were used as controls. Here we show no association between vaccination and miscarriage (adjusted Odds Ratio [aOR], pre-pandemic controls = 1.02, 95% Confidence Interval [CI] = 0.96-1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92-1.38). We undertook additional analyses examining confirmed SARS-CoV-2 infection as the exposure and similarly found no association with miscarriage or ectopic pregnancy. Our findings support current recommendations that vaccination remains the safest way for pregnant women to protect themselves and their babies from COVID-19.",,doi:https://doi.org/10.1038/s41467-022-33937-y; html:https://europepmc.org/articles/PMC9574832; pdf:https://europepmc.org/articles/PMC9574832?pdf=render; pdf:https://www.nature.com/articles/s41467-022-33937-y.pdf
 35387486,https://doi.org/10.1161/circulationaha.121.057888,Genetic Landscape of the ACE2 Coronavirus Receptor.,"Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klarić L, Pirastu N, Ning Z, Zheng C, Wang Y, Huang T, He Y, Guo H, Ying K, Gustafsson S, Prins B, Ramisch A, Dermitzakis ET, Png G, Eriksson N, Haessler J, Hu X, Zanetti D, Boutin T, Hwang SJ, Wheeler E, Pietzner M, Raffield LM, Kalnapenkis A, Peters JE, Viñuela A, Gilly A, Elmståhl S, Dedoussis G, Petrie JR, Polašek O, Folkersen L, Chen Y, Yao C, Võsa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium†, IMI-DIRECT Consortium†, Esko T, Enroth S, Johansson Å, Gyllensten U, Langenberg C, Levy D, Hayward C, Assimes TL, Kooperberg C, Manichaikul AW, Siegbahn A, Wallentin L, Lind L, Zeggini E, Schwenk JM, Butterworth AS, Michaëlsson K, Pawitan Y, Joshi PK, Baillie JK, Mälarstig A, Reiner AP, Wilson JF, Shen X.",,Circulation,2022,2022-04-07,Y,Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2,,,"<h4>Background</h4>SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.<h4>Methods</h4>We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.<h4>Results</h4>We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; <i>P</i>=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; <i>P</i>=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; <i>P</i>=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.<h4>Conclusions</h4>Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render
-PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform,"Zheng B, Tazare J, Nab L, Green A, Curtis H, Mahalingasivam V, Herrett E, Costello R, Eggo R, Speed V, Bacon S, Bates C, Parry J, Cockburn J, Hester F, Harper S, Schaffer A, Hulme W, Mehrkar A, Evans S, MacKenna B, Goldacre B, Douglas I, Tomlinson L.",,The Lancet regional health. Europe,2023,2023-10-08,Y,Comparative Effectiveness; Real-world Data; Covid-19; Sotrovimab; Paxlovid,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624988/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624988/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?pdf=render
 35429382,https://doi.org/10.1093/infdis/jiac146,Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Antibody Levels Following Second Dose of ChAdOx1 nCov-19 or BNT162b2 Vaccine in Residents of Long-term Care Facilities in England (VIVALDI).,"Stirrup O, Krutikov M, Tut G, Palmer T, Bone D, Bruton R, Fuller C, Azmi B, Lancaster T, Sylla P, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Giddings R, Nacer-Laidi H, Baynton V, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,The Journal of infectious diseases,2022,2022-11-01,Y,Antibodies; Vaccination; Waning; Long-term Care Facilities; Covid-19,,,"General population studies have shown strong humoral response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations, but published data are scarce. We measured SARS-CoV-2 anti-spike antibody levels in long-term care facility residents and staff following a second vaccination dose with Oxford-AstraZeneca or Pfizer-BioNTech. Vaccination elicited robust antibody responses in older residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047242; doi:https://doi.org/10.1093/infdis/jiac146; html:https://europepmc.org/articles/PMC9047242; pdf:https://europepmc.org/articles/PMC9047242?pdf=render
+PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform,"Zheng B, Tazare J, Nab L, Green A, Curtis H, Mahalingasivam V, Herrett E, Costello R, Eggo R, Speed V, Bacon S, Bates C, Parry J, Cockburn J, Hester F, Harper S, Schaffer A, Hulme W, Mehrkar A, Evans S, MacKenna B, Goldacre B, Douglas I, Tomlinson L.",,The Lancet regional health. Europe,2023,2023-10-08,Y,Comparative Effectiveness; Real-world Data; Covid-19; Sotrovimab; Paxlovid,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624988/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624988/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?pdf=render
 34514500,https://doi.org/10.1093/infdis/jiab459,The Impact of Cocirculating Pathogens on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Coronavirus Disease 2019 Surveillance: How Concurrent Epidemics May Introduce Bias and Decrease the Observed SARS-CoV-2 Percentage Positivity.,"Kovacevic A, Eggo RM, Baguelin M, Domenech de Cellès M, Opatowski L.",,The Journal of infectious diseases,2022,2022-01-01,Y,Mathematical Modeling; Multiplex Testing; Sars-cov-2; Covid-19 Surveillance; Cocirculating Respiratory Viruses,,,"<h4>Background</h4>Circulation of seasonal non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory viruses with syndromic overlap during the coronavirus disease 2019 (COVID-19) pandemic may alter the quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures.<h4>Methods</h4>Using a multipathogen susceptible-exposed-infectious-recovered (SEIR) transmission model formalizing cocirculation of SARS-CoV-2 and another respiratory virus, we assessed how an outbreak of secondary virus may affect 2 COVID-19 surveillance indicators: testing demand and positivity. Using simulation, we assessed to what extent the use of multiplex polymerase chain reaction tests on a subsample of symptomatic individuals can help correct the observed SARS-CoV-2 percentage positivity and improve surveillance quality.<h4>Results</h4>We find that a non-SARS-CoV-2 epidemic strongly increases SARS-CoV-2 daily testing demand and artificially reduces the observed SARS-CoV-2 percentage positivity for the duration of the outbreak. We estimate that performing 1 multiplex test for every 1000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percentage positivity.<h4>Conclusions</h4>This study showed that cocirculating respiratory viruses can distort SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex polymerase chain reaction tests, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.",,pdf:https://academic.oup.com/jid/article-pdf/225/2/199/42224165/jiab459.pdf; doi:https://doi.org/10.1093/infdis/jiab459; html:https://europepmc.org/articles/PMC8763960; pdf:https://europepmc.org/articles/PMC8763960?pdf=render
 34430796,https://doi.org/10.1016/j.mayocpiqo.2021.08.011,Association Between Accelerometer-Assessed Physical Activity and Severity of COVID-19 in UK Biobank.,"Rowlands AV, Dempsey PC, Gillies C, Kloecker DE, Razieh C, Chudasama Y, Islam N, Zaccardi F, Lawson C, Norris T, Davies MJ, Khunti K, Yates T.",,"Mayo Clinic proceedings. Innovations, quality & outcomes",2021,2021-08-20,Y,"Mvpa, Moderate To Vigorous Physical Activity; Covid-19, Coronavirus Disease 2019; Sars-cov-2, Severe Acute Respiratory Syndrome Coronavirus 2",,,"<h4>Objective</h4>To quantify the association between accelerometer-assessed physical activity and coronavirus disease 2019 (COVID-19) outcomes.<h4>Methods</h4>Data from 82,253 UK Biobank participants with accelerometer data (measured 2013-2015), complete covariate data, and linked COVID-19 data from March 16, 2020, to March 16, 2021, were included. Two outcomes were investigated: severe COVID-19 (positive test result from in-hospital setting or COVID-19 as primary cause of death) and nonsevere COVID-19 (positive test result from community setting). Logistic regressions were used to assess associations with moderate to vigorous physical activity (MVPA), total activity, and intensity gradient. A higher intensity gradient indicates a higher proportion of vigorous activity.<h4>Results</h4>Average MVPA was 48.1 (32.7) min/d. Physical activity was associated with lower odds of severe COVID-19 (adjusted odds ratio per standard deviation increase: MVPA, 0.75 [95% CI, 0.67 to 0.85]; total, 0.83 [0.74 to 0.92]; intensity, 0.77 [0.70 to 0.86]), with stronger associations in women (MVPA, 0.63 [0.52 to 0.77]; total, 0.76 [0.64 to 0.90]; intensity, 0.63 [0.53 to 0.74]) than in men (MVPA, 0.84 [0.73 to 0.97]; total, 0.88 [0.77 to 1.01]; intensity, 0.88 [0.77 to 1.00]). In contrast, when mutually adjusted, total activity was associated with higher odds of a nonsevere infection (1.10 [1.04 to 1.16]), whereas the intensity gradient was associated with lower odds (0.91 [0.86 to 0.97]).<h4>Conclusion</h4>Odds of severe COVID-19 were approximately 25% lower per standard deviation (∼30 min/d) MVPA. A greater proportion of vigorous activity was associated with lower odds of severe and nonsevere infections. The association between total activity and higher odds of a nonsevere infection may be through greater community engagement and thus more exposure to the virus. Results support calls for public health messaging highlighting the potential of MVPA for reducing the odds of severe COVID-19.",,pdf:https://figshare.com/articles/journal_contribution/Association_between_accelerometer-assessed_physical_activity_and_severity_of_COVID-19_in_UK_Biobank_/16998997/1/files/31446568.pdf; doi:https://doi.org/10.1016/j.mayocpiqo.2021.08.011; html:https://europepmc.org/articles/PMC8376658; pdf:https://europepmc.org/articles/PMC8376658?pdf=render
 35038629,https://doi.org/10.1016/j.puhe.2021.12.010,Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.,"Bradley DT, Murphy S, McWilliams P, Arnold S, Lavery S, Murphy J, de Lusignan S, Hobbs R, Tsang RSM, Akbari A, Torabi F, Beggs J, Chuter A, Shi T, Vasileiou E, Robertson C, Sheikh A, Reid H, O'Reilly D.",,Public health,2022,2021-12-18,Y,Vaccination; outbreak; Care Homes; Covid-19; Sars-cov-2,,,"<h4>Objectives</h4>At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI).<h4>Study design</h4>We undertook an ecological study using routinely available national data.<h4>Methods</h4>We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure.<h4>Results</h4>Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity.<h4>Conclusions</h4>These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683272; doi:https://doi.org/10.1016/j.puhe.2021.12.010; html:https://europepmc.org/articles/PMC8683272; pdf:https://europepmc.org/articles/PMC8683272?pdf=render
@@ -113,9 +113,9 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 35104837,https://doi.org/10.1038/s41586-022-04474-x,Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity.,"Meng B, Abdullahi A, Ferreira IATM, Goonawardane N, Saito A, Kimura I, Yamasoba D, Gerber PP, Fatihi S, Rathore S, Zepeda SK, Papa G, Kemp SA, Ikeda T, Toyoda M, Tan TS, Kuramochi J, Mitsunaga S, Ueno T, Shirakawa K, Takaori-Kondo A, Brevini T, Mallery DL, Charles OJ, CITIID-NIHR BioResource COVID-19 Collaboration, Genotype to Phenotype Japan (G2P-Japan) Consortium, Ecuador-COVID19 Consortium, Bowen JE, Joshi A, Walls AC, Jackson L, Martin D, Smith KGC, Bradley J, Briggs JAG, Choi J, Madissoon E, Meyer KB, Mlcochova P, Ceron-Gutierrez L, Doffinger R, Teichmann SA, Fisher AJ, Pizzuto MS, de Marco A, Corti D, Hosmillo M, Lee JH, James LC, Thukral L, Veesler D, Sigal A, Sampaziotis F, Goodfellow IG, Matheson NJ, Sato K, Gupta RK.",,Nature,2022,2022-02-01,Y,,,,"The SARS-CoV-2 Omicron BA.1 variant emerged in 2021<sup>1</sup> and has multiple mutations in its spike protein<sup>2</sup>. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron's evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways<sup>3</sup> demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.",,pdf:https://www.nature.com/articles/s41586-022-04474-x.pdf; doi:https://doi.org/10.1038/s41586-022-04474-x; html:https://europepmc.org/articles/PMC8942856; pdf:https://europepmc.org/articles/PMC8942856?pdf=render
 35973468,https://doi.org/10.1016/j.jviromet.2022.114607,Evaluation of the impact of pre-analytical conditions on sample stability for the detection of SARS-CoV-2 RNA.,"Mosscrop L, Watber P, Elliot P, Cooke G, Barclay W, Freemont PS, Rosadas C, Taylor GP.",,Journal of virological methods,2022,2022-08-13,Y,RNA; Diagnosis; Rt-qpcr; Sample Stability; Sars-cov-2,,,"Demand for accurate SARS-CoV-2 diagnostics is high. Most samples in the UK are collected in the community and rely on the postal service for delivery to the laboratories. The current recommendation remains that swabs should be collected in Viral Transport Media (VTM) and transported with a cold chain to the laboratory for RNA extraction and RT-qPCR. This is not always possible. We aimed to test the stability of SARS-CoV-2 RNA subjected to different pre-analytical conditions. Swabs were dipped into PBS containing cultured SARS-CoV-2 and placed in either a dry tube or a tube containing either normal saline or VTM. The tubes were then stored at different temperatures (20-50 °C) for variable periods (8 h to 5 days). Samples were tested by RT-qPCR targeting SARS-CoV-2 E gene. VTM outperformed swabs in saline and dry swabs in all conditions. Samples in VTM were stable, independent of a cold chain, for 5 days, with a maximum increase in cycle threshold (Ct) of 1.34 when held at 40 °C. Using normal saline as the transport media resulted in a loss of sensitivity (increased Ct) over time and with increasing temperature (up to 7.8 cycles compared to VTM). SARS-CoV-2 was not detected in 3/9 samples in normal saline when tested after 120 h incubation. Transportation of samples in VTM provides a high level of confidence in the results despite the potential for considerable, uncontrolled variation in temperature and longer transportation periods. False negative results may be seen after 96 h in saline and viral loads will appear lower.",,doi:https://doi.org/10.1016/j.jviromet.2022.114607; doi:https://doi.org/10.1016/j.jviromet.2022.114607; html:https://europepmc.org/articles/PMC9374597; pdf:https://europepmc.org/articles/PMC9374597?pdf=render
 37528841,https://doi.org/10.1016/j.eclinm.2023.102064,Repeated antibiotic exposure and risk of hospitalisation and death following COVID-19 infection (OpenSAFELY): a matched case-control study.,"Yang YT, Wong D, Ashcroft DM, Massey J, MacKenna B, Fisher L, Mehrkar A, Bacon SC, OpenSAFELY collaborative, Hand K, Zhong X, Fahmi A, Goldacre B, van Staa T, Palin V.",,EClinicalMedicine,2023,2023-07-05,Y,Antibiotics; Primary Care; Severe Outcome; Covid-19,,,"<h4>Background</h4>Identifying potential risk factors related to severe COVID-19 outcomes is important. Repeated intermittent antibiotic use is known be associated with adverse outcomes. This study aims to examine whether prior frequent antibiotic exposure is associated with severe COVID-19 outcomes.<h4>Methods</h4>With the approval of NHS England, we used the OpenSAFELY platform, which integrated primary and secondary care, COVID-19 test, and death registration data. This matched case-control study included 0.67 million patients (aged 18-110 years) from an eligible 2.47 million patients with incident COVID-19 by matching with replacement. Inclusion criteria included registration within one general practice for at least 3 years and infection with incident COVID-19. Cases were identified according to different severity of COVID-19 outcomes. Cases and eligible controls were 1:6 matched on age, sex, region of GP practice, and index year and month of COVID-19 infection. Five quintile groups, based on the number of previous 3-year antibiotic prescriptions, were created to indicate the frequency of prior antibiotic exposure. Conditional logistic regression used to compare the differences between case and control groups, adjusting for ethnicity, body mass index, comorbidities, vaccination history, deprivation, and care home status. Sensitivity analyses were done to explore potential confounding and the effects of missing data.<h4>Findings</h4>Based on our inclusion criteria, between February 1, 2020 and December 31, 2021, 98,420 patients were admitted to hospitals and 22,660 died. 55 unique antibiotics were prescribed. A dose-response relationship between number of antibiotic prescriptions and risk of severe COVID-19 outcome was observed. Patients in the highest quintile with history of prior antibiotic exposure had 1.80 times greater odds of hospitalisation compared to patients without antibiotic exposure (adjusted odds ratio [OR] 1.80, 95% Confidence Interval [CI] 1.75-1.84). Similarly, the adjusted OR for hospitalised patients with death outcomes was 1.34 (95% CI 1.28-1.41). Larger number of prior antibiotic type was also associated with more severe COVID-19 related hospital admission. The adjusted OR of quintile 5 exposure (the most frequent) with more than 3 antibiotic types was around 2 times larger than quintile 1 (only 1 type; OR 1.80, 95% CI 1.75-1.84 vs. OR 1.03, 95% CI 1.01-1.05).<h4>Interpretation</h4>Our observational study has provided evidence that antibiotic exposure frequency and diversity may be associated with COVID-19 severity, potentially suggesting adverse effects of repeated intermittent antibiotic use. Future work could work to elucidate causal links and potential mechanisms. Antibiotic stewardship should put more emphasis on long-term antibiotic exposure and its adverse outcome to increase the awareness of appropriate antibiotics use.<h4>Funding</h4>Health Data Research UK and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102064; html:https://europepmc.org/articles/PMC10388579; pdf:https://europepmc.org/articles/PMC10388579?pdf=render
-36841835,https://doi.org/10.1038/s41541-023-00614-0,Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.,"Holt H, Jolliffe DA, Talaei M, Faustini S, Vivaldi G, Greenig M, Richter AG, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Davies GA, Shaheen SO, Martineau AR.",,NPJ vaccines,2023,2023-02-25,Y,,,,"Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.",,pdf:https://www.nature.com/articles/s41541-023-00614-0.pdf; doi:https://doi.org/10.1038/s41541-023-00614-0; html:https://europepmc.org/articles/PMC9959934; pdf:https://europepmc.org/articles/PMC9959934?pdf=render
 35608440,https://doi.org/10.1126/science.abq4411,Twin peaks: The Omicron SARS-CoV-2 BA.1 and BA.2 epidemics in England.,"Elliott P, Eales O, Steyn N, Tang D, Bodinier B, Wang H, Elliott J, Whitaker M, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Donnelly CA, Chadeau-Hyam M.",,"Science (New York, N.Y.)",2022,2022-06-24,Y,,,,"Rapid transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has led to record-breaking incidence rates around the world. The Real-time Assessment of Community Transmission-1 (REACT-1) study has tracked SARS-CoV-2 infection in England using reverse transcription polymerase chain reaction (RT-PCR) results from self-administered throat and nose swabs from randomly selected participants aged 5 years and older approximately monthly from May 2020 to March 2022. Weighted prevalence in March 2022 was the highest recorded in REACT-1 at 6.37% (<i>N</i> = 109,181), with the Omicron BA.2 variant largely replacing the BA.1 variant. Prevalence was increasing overall, with the greatest increase in those aged 65 to 74 years and 75 years and older. This was associated with increased hospitalizations and deaths, but at much lower levels than in previous waves against a backdrop of high levels of vaccination.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161371; doi:https://doi.org/10.1126/science.abq4411; html:https://europepmc.org/articles/PMC9161371; pdf:https://europepmc.org/articles/PMC9161371?pdf=render
 35915784,https://doi.org/10.1016/j.lanepe.2022.100462,Omicron SARS-CoV-2 epidemic in England during February 2022: A series of cross-sectional community surveys.,"Chadeau-Hyam M, Tang D, Eales O, Bodinier B, Wang H, Jonnerby J, Whitaker M, Elliott J, Haw D, Walters CE, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,The Lancet regional health. Europe,2022,2022-07-28,Y,"Rt-pcr, Reverse Transcription Polymerase Chain Reaction; Ct, Cycle Threshold; Nhs, National Health Service; Covid-19; Sars-cov-2; Omicron Variant; Ba.2 Sublineage; Random Community Surveys; Ukhsa, Uk Health Security Agency; B-spline, Basis Spline; Ltla, Lower-tier Local Authority; P-spline, Penalised Spline; Rim, Random Iterative Method",,,"<h4>Background</h4>The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.<h4>Methods</h4>In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).<h4>Findings</h4>We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76-3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91-0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0-0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: <i>N</i>=1047, 64.8% (62.4-67.2) were BA.1; <i>N</i>=568, 35.2% (32.8-37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34-0.41). The highest proportion of BA.2 among positives was found in London.<h4>Interpretation</h4>In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.<h4>Funding</h4>Department of Health and Social Care, England.",,doi:https://doi.org/10.1016/j.lanepe.2022.100462; doi:https://doi.org/10.1016/j.lanepe.2022.100462; html:https://europepmc.org/articles/PMC9330654; pdf:https://europepmc.org/articles/PMC9330654?pdf=render
+36841835,https://doi.org/10.1038/s41541-023-00614-0,Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.,"Holt H, Jolliffe DA, Talaei M, Faustini S, Vivaldi G, Greenig M, Richter AG, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Davies GA, Shaheen SO, Martineau AR.",,NPJ vaccines,2023,2023-02-25,Y,,,,"Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.",,pdf:https://www.nature.com/articles/s41541-023-00614-0.pdf; doi:https://doi.org/10.1038/s41541-023-00614-0; html:https://europepmc.org/articles/PMC9959934; pdf:https://europepmc.org/articles/PMC9959934?pdf=render
 35970827,https://doi.org/10.1038/s41467-022-32264-6,"Second-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland.","Simpson CR, Kerr S, Katikireddi SV, McCowan C, Ritchie LD, Pan J, Stock SJ, Rudan I, Tsang RSM, de Lusignan S, Hobbs FDR, Akbari A, Lyons RA, Robertson C, Sheikh A.",,Nature communications,2022,2022-08-15,Y,,,,"We investigated thrombocytopenic, thromboembolic and hemorrhagic events following a second dose of ChAdOx1 and BNT162b2 using a self-controlled case series analysis. We used a national prospective cohort with 2.0 million(m) adults vaccinated with two doses of ChAdOx or 1.6 m with BNT162b2. The incidence rate ratio (IRR) for idiopathic thrombocytopenic purpura (ITP) 14-20 days post-ChAdOx1 second dose was 2.14, 95% confidence interval (CI) 0.90-5.08. The incidence of ITP post-second dose ChAdOx1 was 0.59 (0.37-0.89) per 100,000 doses. No evidence of an increased risk of CVST was found for the 0-27 day risk period (IRR 0.83, 95% CI 0.16 to 4.26). However, few (≤5) events arose within this risk period. It is perhaps noteworthy that these events all clustered in the 7-13 day period (IRR 4.06, 95% CI 0.94 to 17.51). No other associations were found for second dose ChAdOx1, or any association for second dose BNT162b2 vaccination. Second dose ChAdOx1 vaccination was associated with increased borderline risks of ITP and CVST events. However, these events were rare thus providing reassurance about the safety of these vaccines. Further analyses including more cases are required to determine more precisely the risk profile for ITP and CVST after a second dose of ChAdOx1 vaccine.",,pdf:https://www.nature.com/articles/s41467-022-32264-6.pdf; doi:https://doi.org/10.1038/s41467-022-32264-6; html:https://europepmc.org/articles/PMC9377297; pdf:https://europepmc.org/articles/PMC9377297?pdf=render
 36609574,https://doi.org/10.1038/s41467-022-35771-8,A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection.,"Calvert C, Carruthers J, Denny C, Donaghy J, Hopcroft LEM, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Moore E, Taylor B, Loane M, Dolk H, Morris J, Auyeung B, Bhaskaran K, Gibbons CL, Katikireddi SV, O'Leary M, McAllister D, Shi T, Simpson CR, Robertson C, Sheikh A, Stock SJ, Wood R.",,Nature communications,2023,2023-01-06,Y,,,,"Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.",,pdf:https://www.nature.com/articles/s41467-022-35771-8.pdf; doi:https://doi.org/10.1038/s41467-022-35771-8; html:https://europepmc.org/articles/PMC9821346; pdf:https://europepmc.org/articles/PMC9821346?pdf=render
 36745545,https://doi.org/10.1099/mgen.0.000887,The use of representative community samples to assess SARS-CoV-2 lineage competition: Alpha outcompetes Beta and wild-type in England from January to March 2021.,"Eales O, Page AJ, Tang SN, Walters CE, Wang H, Haw D, Trotter AJ, Le Viet T, Foster-Nyarko E, Prosolek S, Atchison C, Ashby D, Cooke G, Barclay W, Donnelly CA, O'Grady J, Volz E, The Covid-Genomics Uk Cog-Uk Consortium, Darzi A, Ward H, Elliott P, Riley S.",,Microbial genomics,2023,2023-02-01,Y,,,,"Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy and will be a high priority for public health for the foreseeable future. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained using a variety of methods all of which are known to contain biases. As a case study, using an approach which is largely free of biases, we here describe lineage dynamics and phylogenetic relationships of the Alpha and Beta variant in England during the first 3 months of 2021 using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the Alpha variant (first identified in Kent) becoming predominant, driven by a reproduction number 0.3 higher than for the prior wild-type. During January, positive samples were more likely to be Alpha in those aged 18 to 54 years old. Although individuals infected with the Alpha variant were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild-type, they were more likely to be antibody-positive 6 weeks after infection. Further, viral load was higher in those infected with the Alpha variant as measured by cycle threshold (Ct) values. The presence of infections with non-imported Beta variant (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing. These results highlight how sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance during periods of lineage diversity.",,doi:https://doi.org/10.1099/mgen.0.000887; html:https://europepmc.org/articles/PMC9997751; pdf:https://europepmc.org/articles/PMC9997751?pdf=render
@@ -146,9 +146,9 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 34301672,https://doi.org/10.1136/bmjopen-2021-053402,Sociodemographic inequality in COVID-19 vaccination coverage among elderly adults in England: a national linked data study.,"Nafilyan V, Dolby T, Razieh C, Gaughan CH, Morgan J, Ayoubkhani D, Walker S, Khunti K, Glickman M, Yates T.",,BMJ open,2021,2021-07-23,Y,Infection control; epidemiology; Covid-19,,,"<h4>Objective</h4>To examine inequalities in COVID-19 vaccination rates among elderly adults in England.<h4>Design</h4>Cohort study.<h4>Setting</h4>People living in private households and communal establishments in England.<h4>Participants</h4>6 655 672 adults aged ≥70 years (mean 78.8 years, 55.2% women) who were alive on 15 March 2021.<h4>Main outcome measures</h4>Having received the first dose of a vaccine against COVID-19 by 15 March 2021. We calculated vaccination rates and estimated unadjusted and adjusted ORs using logistic regression models.<h4>Results</h4>By 15 March 2021, 93.2% of people living in England aged 70 years and over had received at least one dose of a COVID-19 vaccine. While vaccination rates differed across all factors considered apart from sex, the greatest disparities were seen between ethnic and religious groups. The lowest rates were in people of black African and black Caribbean ethnic backgrounds, where only 67.2% and 73.8% had received a vaccine, with adjusted odds of not being vaccinated at 5.01 (95% CI 4.86 to 5.16) and 4.85 (4.75 to 4.96) times greater than the white British group. The proportion of individuals self-identifying as Muslim and Buddhist who had received a vaccine was 79.1% and 84.1%, respectively. Older age, greater area deprivation, less advantaged socioeconomic position (proxied by living in a rented home), being disabled and living either alone or in a multigenerational household were also associated with higher odds of not having received the vaccine.<h4>Conclusion</h4>Research is now urgently needed to understand why disparities exist in these groups and how they can best be addressed through public health policy and community engagement.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e053402.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053402; html:https://europepmc.org/articles/PMC8313303; pdf:https://europepmc.org/articles/PMC8313303?pdf=render
 34132940,https://doi.org/10.1007/s10654-021-00765-1,Ethnic differences in COVID-19 mortality during the first two waves of the Coronavirus Pandemic: a nationwide cohort study of 29 million adults in England.,"Nafilyan V, Islam N, Mathur R, Ayoubkhani D, Banerjee A, Glickman M, Humberstone B, Diamond I, Khunti K.",,European journal of epidemiology,2021,2021-06-16,Y,Mortality; Ethnicity; Covid-19,,,"Ethnic minorities have experienced disproportionate COVID-19 mortality rates in the UK and many other countries. We compared the differences in the risk of COVID-19 related death between ethnic groups in the first and second waves the of COVID-19 pandemic in England. We also investigated whether the factors explaining differences in COVID-19 death between ethnic groups changed between the two waves. Using data from the Office for National Statistics Public Health Data Asset, a linked dataset combining the 2011 Census with primary care and hospital records and death registrations, we conducted an observational cohort study to examine differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24th January 2020 until 31st August 2020) and the first part of the second wave (from 1st September to 28th December 2020). We estimated age-standardised mortality rates (ASMR) in the two waves stratified by ethnic groups and sex. We also estimated hazard ratios (HRs) for ethnic-minority groups compared with the White British population, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions. The study population included over 28.9 million individuals aged 30-100 years living in private households. In the first wave, all ethnic minority groups had a higher risk of COVID-19 related death compared to the White British population. In the second wave, the risk of COVID-19 death remained elevated for people from Pakistani (ASMR: 339.9 [95% CI: 303.7-376.2] and 166.8 [141.7-191.9] deaths per 100,000 population in men and women) and Bangladeshi (318.7 [247.4-390.1] and 127.1 [91.1-171.3] in men and women) background but not for people from Black ethnic groups. Adjustment for geographical factors explained a large proportion of the differences in COVID-19 mortality in the first wave but not in the second wave. Despite an attenuation of the elevated risk of COVID-19 mortality after adjusting for sociodemographic characteristics and health status, the risk was substantially higher in people from Bangladeshi and Pakistani background in both the first and the second waves. Between the first and second waves of the pandemic, the reduction in the difference in COVID-19 mortality between people from Black ethnic background and people from the White British group shows that ethnic inequalities in COVID-19 mortality can be addressed. The continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy changes.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00765-1.pdf; doi:https://doi.org/10.1007/s10654-021-00765-1; html:https://europepmc.org/articles/PMC8206182; pdf:https://europepmc.org/articles/PMC8206182?pdf=render
 36098502,https://doi.org/10.7554/elife.78427,"Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.","Stirrup O, Blackstone J, Mapp F, MacNeil A, Panca M, Holmes A, Machin N, Shin GY, Mahungu T, Saeed K, Saluja T, Taha Y, Mahida N, Pope C, Chawla A, Cutino-Moguel MT, Tamuri A, Williams R, Darby A, Robertson DL, Flaviani F, Nastouli E, Robson S, Smith D, Loose M, Laing K, Monahan I, Kele B, Haldenby S, George R, Bashton M, Witney AA, Byott M, Coll F, Chapman M, Peacock SJ, COG-UK HOCI Investigators, COVID-19 Genomics UK (COG-UK) consortium, Hughes J, Nebbia G, Partridge DG, Parker M, Price JR, Peters C, Roy S, Snell LB, de Silva TI, Thomson E, Flowers P, Copas A, Breuer J.",,eLife,2022,2022-09-13,Y,Human; Microbiology; Infectious disease; Molecular epidemiology; Infection control; epidemiology; Global Health; Hospital-acquired Infection; Infection Prevention; Viral Genomics; Healthcare-associated Infection; Covid-19,,,"<h4>Background</h4>Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings.<h4>Methods</h4>We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated.<h4>Results</h4>A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p<i>=</i>0.14) or rapid (0.85, 0.48-1.50; p<i>=</i>0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources.<h4>Conclusions</h4>While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.<h4>Funding</h4>COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute.<h4>Clinical trial number</h4>NCT04405934.",,doi:https://doi.org/10.7554/elife.78427; doi:https://doi.org/10.7554/eLife.78427; html:https://europepmc.org/articles/PMC9596156; pdf:https://europepmc.org/articles/PMC9596156?pdf=render
-36609412,https://doi.org/10.1136/archdischild-2022-324713,"Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study.","Goulding A, McQuaid F, Lindsay L, Agrawal U, Auyeung B, Calvert C, Carruthers J, Denny C, Donaghy J, Hillman S, Hopcroft L, Hopkins L, McCowan C, McLaughlin T, Moore E, Ritchie L, Simpson CR, Taylor B, Fenton L, Pollock L, Gale C, Kurinczuk JJ, Robertson C, Sheikh A, Stock S, Wood R.",,Archives of disease in childhood. Fetal and neonatal edition,2023,2023-01-06,Y,epidemiology; Neonatology; Covid-19,,,"<h4>Objectives</h4>To examine neonates in Scotland aged 0-27 days with SARS-CoV-2 infection confirmed by viral testing; the risk of confirmed neonatal infection by maternal and infant characteristics; and hospital admissions associated with confirmed neonatal infections.<h4>Design</h4>Population-based cohort study.<h4>Setting and population</h4>All live births in Scotland, 1 March 2020-31 January 2022.<h4>Results</h4>There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100 000 live births (141/92 009, 0.15%). Among infants born to women with confirmed infection around the time of birth, the confirmed neonatal infection rate was 1812 per 100 000 live births (15/828, 1.8%). Two-thirds (92/141, 65.2%) of neonates with confirmed infection had an associated admission to neonatal or (more commonly) paediatric care. Six of these babies (6/92, 6.5%) were admitted to neonatal and/or paediatric intensive care; however, none of these six had COVID-19 recorded as their main diagnosis. There were no neonatal deaths among babies with confirmed infection.<h4>Implications and relevance</h4>Confirmed neonatal SARS-CoV-2 infection was uncommon over the first 23 months of the pandemic in Scotland. Secular trends in the neonatal confirmed infection rate broadly followed those seen in the general population, although at a lower level. Maternal confirmed infection at birth was associated with an increased risk of neonatal confirmed infection. Two-thirds of neonates with confirmed infection had an associated admission to hospital, with resulting implications for the baby, family and services, although their outcomes were generally good. Ascertainment of confirmed infection depends on the extent of testing, and this is likely to have varied over time and between groups: the extent of unconfirmed infection is inevitably unknown.",,pdf:https://fn.bmj.com/content/fetalneonatal/early/2023/01/05/archdischild-2022-324713.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-324713; html:https://europepmc.org/articles/PMC10313998; pdf:https://europepmc.org/articles/PMC10313998?pdf=render
 35790970,https://doi.org/10.1186/s12913-022-08202-z,Access to personal protective equipment in healthcare workers during the COVID-19 pandemic in the United Kingdom: results from a nationwide cohort study (UK-REACH).,"Martin CA, Pan D, Nazareth J, Aujayeb A, Bryant L, Carr S, Gray LJ, Gregary B, Gupta A, Guyatt AL, Gopal A, Hine T, John C, McManus IC, Melbourne C, Nellums LB, Reza R, Simpson S, Tobin MD, Woolf K, Zingwe S, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,BMC health services research,2022,2022-07-05,Y,Personal Protective Equipment; Ethnicity; Healthcare Worker; Ppe; Covid-19,,,"<h4>Background</h4>Healthcare workers (HCWs) are at high risk of SARS-CoV-2 infection. Effective use of personal protective equipment (PPE) reduces this risk. We sought to determine the prevalence and predictors of self-reported access to appropriate PPE (aPPE) for HCWs in the UK during the COVID-19 pandemic.<h4>Methods</h4>We conducted cross sectional analyses using data from a nationwide questionnaire-based cohort study administered between December 2020-February 2021. The outcome was a binary measure of self-reported aPPE (access all of the time vs access most of the time or less frequently) at two timepoints: the first national lockdown in the UK in March 2020 (primary analysis) and at the time of questionnaire response (secondary analysis).<h4>Results</h4>Ten thousand five hundred eight HCWs were included in the primary analysis, and 12,252 in the secondary analysis. 35.2% of HCWs reported aPPE at all times in the primary analysis; 83.9% reported aPPE at all times in the secondary analysis. In the primary analysis, after adjustment (for age, sex, ethnicity, migration status, occupation, aerosol generating procedure exposure, work sector and region, working hours, night shift frequency and trust in employing organisation), older HCWs and those working in Intensive Care Units were more likely to report aPPE at all times. Asian HCWs (aOR:0.77, 95%CI 0.67-0.89 [vs White]), those in allied health professional and dental roles (vs those in medical roles), and those who saw a higher number of COVID-19 patients compared to those who saw none (≥ 21 patients/week 0.74, 0.61-0.90) were less likely to report aPPE at all times. Those who trusted their employing organisation to deal with concerns about unsafe clinical practice, compared to those who did not, were twice as likely to report aPPE at all times. Significant predictors were largely unchanged in the secondary analysis.<h4>Conclusions</h4>Only a third of HCWs in the UK reported aPPE at all times during the first lockdown and that aPPE had improved later in the pandemic. We also identified key determinants of aPPE during the first UK lockdown, which have mostly persisted since lockdown was eased. These findings have important implications for the safe delivery of healthcare during the pandemic.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-022-08202-z; doi:https://doi.org/10.1186/s12913-022-08202-z; html:https://europepmc.org/articles/PMC9255515; pdf:https://europepmc.org/articles/PMC9255515?pdf=render
 35879616,https://doi.org/10.1038/s41591-022-01909-w,Symptoms and risk factors for long COVID in non-hospitalized adults.,"Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S.",,Nature medicine,2022,2022-07-25,Y,,,,"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.",,doi:https://doi.org/10.1038/s41591-022-01909-w; html:https://europepmc.org/articles/PMC9388369; pdf:https://europepmc.org/articles/PMC9388369?pdf=render; pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf
+36609412,https://doi.org/10.1136/archdischild-2022-324713,"Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study.","Goulding A, McQuaid F, Lindsay L, Agrawal U, Auyeung B, Calvert C, Carruthers J, Denny C, Donaghy J, Hillman S, Hopcroft L, Hopkins L, McCowan C, McLaughlin T, Moore E, Ritchie L, Simpson CR, Taylor B, Fenton L, Pollock L, Gale C, Kurinczuk JJ, Robertson C, Sheikh A, Stock S, Wood R.",,Archives of disease in childhood. Fetal and neonatal edition,2023,2023-01-06,Y,epidemiology; Neonatology; Covid-19,,,"<h4>Objectives</h4>To examine neonates in Scotland aged 0-27 days with SARS-CoV-2 infection confirmed by viral testing; the risk of confirmed neonatal infection by maternal and infant characteristics; and hospital admissions associated with confirmed neonatal infections.<h4>Design</h4>Population-based cohort study.<h4>Setting and population</h4>All live births in Scotland, 1 March 2020-31 January 2022.<h4>Results</h4>There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100 000 live births (141/92 009, 0.15%). Among infants born to women with confirmed infection around the time of birth, the confirmed neonatal infection rate was 1812 per 100 000 live births (15/828, 1.8%). Two-thirds (92/141, 65.2%) of neonates with confirmed infection had an associated admission to neonatal or (more commonly) paediatric care. Six of these babies (6/92, 6.5%) were admitted to neonatal and/or paediatric intensive care; however, none of these six had COVID-19 recorded as their main diagnosis. There were no neonatal deaths among babies with confirmed infection.<h4>Implications and relevance</h4>Confirmed neonatal SARS-CoV-2 infection was uncommon over the first 23 months of the pandemic in Scotland. Secular trends in the neonatal confirmed infection rate broadly followed those seen in the general population, although at a lower level. Maternal confirmed infection at birth was associated with an increased risk of neonatal confirmed infection. Two-thirds of neonates with confirmed infection had an associated admission to hospital, with resulting implications for the baby, family and services, although their outcomes were generally good. Ascertainment of confirmed infection depends on the extent of testing, and this is likely to have varied over time and between groups: the extent of unconfirmed infection is inevitably unknown.",,pdf:https://fn.bmj.com/content/fetalneonatal/early/2023/01/05/archdischild-2022-324713.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-324713; html:https://europepmc.org/articles/PMC10313998; pdf:https://europepmc.org/articles/PMC10313998?pdf=render
 34304048,https://doi.org/10.1016/j.ebiom.2021.103485,Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.,"Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, Allara E, Angelantonio ED, Butterworth AS, Wood AM, Thompson JR, Petersen SE, Harvey NC, Danesh JN, Samani NJ, Nelson CP.",,EBioMedicine,2021,2021-07-23,Y,,,,"Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.",,doi:https://doi.org/10.1016/j.ebiom.2021.103485; doi:https://doi.org/10.1016/j.ebiom.2021.103485; html:https://europepmc.org/articles/PMC8299112; pdf:https://europepmc.org/articles/PMC8299112?pdf=render
 35793922,https://doi.org/10.1136/bmjopen-2021-059385,Deriving and validating a risk prediction model for long COVID-19: protocol for an observational cohort study using linked Scottish data.,"Daines L, Mulholland RH, Vasileiou E, Hammersley V, Weatherill D, Katikireddi SV, Kerr S, Moore E, Pesenti E, Quint JK, Shah SA, Shi T, Simpson CR, Robertson C, Sheikh A.",,BMJ open,2022,2022-07-06,Y,Public Health; Protocols & Guidelines; Covid-19,,,"<h4>Introduction</h4>COVID-19 is commonly experienced as an acute illness, yet some people continue to have symptoms that persist for weeks, or months (commonly referred to as 'long-COVID'). It remains unclear which patients are at highest risk of developing long-COVID. In this protocol, we describe plans to develop a prediction model to identify individuals at risk of developing long-COVID.<h4>Methods and analysis</h4>We will use the national Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, a population-level linked dataset of routine electronic healthcare data from 5.4 million individuals in Scotland. We will identify potential indicators for long-COVID by identifying patterns in primary care data linked to information from out-of-hours general practitioner encounters, accident and emergency visits, hospital admissions, outpatient visits, medication prescribing/dispensing and mortality. We will investigate the potential indicators of long-COVID by performing a matched analysis between those with a positive reverse transcriptase PCR (RT-PCR) test for SARS-CoV-2 infection and two control groups: (1) individuals with at least one negative RT-PCR test and never tested positive; (2) the general population (everyone who did not test positive) of Scotland. Cluster analysis will then be used to determine the final definition of the outcome measure for long-COVID. We will then derive, internally and externally validate a prediction model to identify the epidemiological risk factors associated with long-COVID.<h4>Ethics and dissemination</h4>The EAVE II study has obtained approvals from the Research Ethics Committee (reference: 12/SS/0201), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279). Study findings will be published in peer-reviewed journals and presented at conferences. Understanding the predictors for long-COVID and identifying the patient groups at greatest risk of persisting symptoms will inform future treatments and preventative strategies for long-COVID.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/7/e059385.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059385; html:https://europepmc.org/articles/PMC9260199; pdf:https://europepmc.org/articles/PMC9260199?pdf=render
 35104687,https://doi.org/10.1016/j.retram.2022.103333,A common TMPRSS2 variant has a protective effect against severe COVID-19.,"David A, Parkinson N, Peacock TP, Pairo-Castineira E, Khanna T, Cobat A, Tenesa A, Sancho-Shimizu V, GenOMICC Consortium, ISARIC4C Investigators, Casanova JL, Abel L, Barclay WS, Baillie JK, Sternberg MJ.",,Current research in translational medicine,2022,2022-01-10,Y,Tmprss2; Covid-19; Sars-cov-2; Targeting The Host To Prevent Covid19 Severity,,,"<h4>Background</h4>The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus' spike protein, facilitating entry into target cells. We hypothesized that naturally-occurring TMPRSS2 human genetic variants affecting the structure and function of the TMPRSS2 protein may modulate the severity of SARS-CoV-2 infection.<h4>Methods</h4>We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760 C>T, p.V160M), which has a minor allele frequency ranging from 0.14 in Ashkenazi Jewish to 0.38 in East Asians. We analysed the association between the rs12329760 and COVID-19 severity in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units recruited as part of the GenOMICC (Genetics Of Mortality In Critical Care) study. Logistic regression analyses were adjusted for sex, age and deprivation index. For in vitro studies, HEK293 cells were co-transfected with ACE2 and either TMPRSS2 wild type or mutant (TMPRSS2<sub>V160M</sub>). A SARS-CoV-2 pseudovirus entry assay was used to investigate the ability of TMPRSS2<sub>V160M</sub> to promote viral entry.<h4>Results</h4>We show that the T allele of rs12329760 is associated with a reduced likelihood of developing severe COVID-19 (OR 0.87, 95%CI:0.79-0.97, p = 0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p = 1.3 × 10<sup>-3</sup>). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, affects the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells.<h4>Conclusion</h4>TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID-19. Further studies are needed to assess the expression of TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID-19. Clinical trials are needed to confirm this.",,doi:https://doi.org/10.1016/j.retram.2022.103333; doi:https://doi.org/10.1016/j.retram.2022.103333; html:https://europepmc.org/articles/PMC8743599; pdf:https://europepmc.org/articles/PMC8743599?pdf=render
@@ -168,9 +168,9 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 37748493,https://doi.org/10.1016/s2213-2600(23)00262-x,"Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.",C-MORE/PHOSP-COVID Collaborative Group.,,The Lancet. Respiratory medicine,2023,2023-09-22,Y,,,,"<h4>Introduction</h4>The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.<h4>Methods</h4>In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.<h4>Findings</h4>Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5-5·8]; p<sub>adjusted</sub>=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32-4·82]; p<sub>adjusted</sub>=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23-11·88]; p<sub>adjusted</sub>=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.<h4>Interpretation</h4>After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.<h4>Funding</h4>UK Research and Innovation and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?pdf=render
 33243817,https://doi.org/10.1136/bmjopen-2020-042813,COVID-19 in Pregnancy in Scotland (COPS): protocol for an observational study using linked Scottish national data.,"Stock SJ, McAllister D, Vasileiou E, Simpson CR, Stagg HR, Agrawal U, McCowan C, Hopkins L, Donaghy J, Ritchie L, Robertson C, Sheikh A, Wood R.",,BMJ open,2020,2020-11-26,Y,Obstetrics; epidemiology; Neonatology; Perinatology; Covid-19,,,"<h4>Introduction</h4>The effects of SARS-CoV-2 in pregnancy are not fully delineated. We will describe the incidence of COVID-19 in pregnancy at population level in Scotland, in a prospective cohort study using linked data. We will determine associations between COVID-19 and adverse pregnancy, neonatal and maternal outcomes and the proportion of confirmed cases of SARS-CoV-2 infection in neonates associated with maternal COVID-19.<h4>Methods and analysis</h4>Prospective cohort study using national linked data sets. We will include all women in Scotland, UK, who were pregnant on or became pregnant after, 1 March 2020 (the date of the first confirmed case of SARS-CoV-2 infection in Scotland) and all births in Scotland from 1 March 2020 onwards. Individual-level data will be extracted from data sets containing details of all livebirths, stillbirth, terminations of pregnancy and miscarriages and ectopic pregnancies treated in hospital or attending general practice. Records will be linked within the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, which includes primary care records, virology and serology results and details of COVID-19 Community Hubs and Assessment Centre contacts and deaths. We will perform analyses using definitions for confirmed, probable and possible COVID-19 and report serology results (where available). Outcomes will include congenital anomaly, miscarriage, stillbirth, termination of pregnancy, preterm birth, neonatal infection, severe maternal disease and maternal deaths. We will perform descriptive analyses and appropriate modelling, adjusting for demographic and pregnancy characteristics and the presence of comorbidities. The cohort will provide a platform for future studies of the effectiveness and safety of therapeutic interventions and immunisations for COVID-19 and their effects on childhood and developmental outcomes.<h4>Ethics and dissemination</h4>COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e042813.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042813; html:https://europepmc.org/articles/PMC7691999; pdf:https://europepmc.org/articles/PMC7691999?pdf=render
 35192598,https://doi.org/10.1371/journal.pmed.1003927,"First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis: A pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales.","Kerr S, Joy M, Torabi F, Bedston S, Akbari A, Agrawal U, Beggs J, Bradley D, Chuter A, Docherty AB, Ford D, Hobbs R, Katikireddi SV, Lowthian E, de Lusignan S, Lyons R, Marple J, McCowan C, McGagh D, McMenamin J, Moore E, Murray JK, Owen RK, Pan J, Ritchie L, Shah SA, Shi T, Stock S, Tsang RSM, Vasileiou E, Woolhouse M, Simpson CR, Robertson C, Sheikh A.",,PLoS medicine,2022,2022-02-22,Y,,,,"<h4>Background</h4>Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales.<h4>Methods and findings</h4>We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates.<h4>Conclusions</h4>In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003927&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003927; html:https://europepmc.org/articles/PMC8863261; pdf:https://europepmc.org/articles/PMC8863261?pdf=render
-36680646,https://doi.org/10.1007/s10654-022-00962-6,Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.,"Bowyer RCE, Huggins C, Toms R, Shaw RJ, Hou B, Thompson EJ, Kwong ASF, Williams DM, Kibble M, Ploubidis GB, Timpson NJ, Sterne JAC, Chaturvedi N, Steves CJ, Tilling K, Silverwood RJ, CONVALESCENCE Study.",,European journal of epidemiology,2023,2023-01-21,Y,Clustering; Longitudinal Studies; Symptom Patterns; Covid-19; Long Covid,,,"Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00962-6.pdf; doi:https://doi.org/10.1007/s10654-022-00962-6; html:https://europepmc.org/articles/PMC9860244; pdf:https://europepmc.org/articles/PMC9860244?pdf=render
 32873607,https://doi.org/10.1136/bmjresp-2020-000644,Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area.,"Sapey E, Gallier S, Mainey C, Nightingale P, McNulty D, Crothers H, Evison F, Reeves K, Pagano D, Denniston AK, Nirantharakumar K, Diggle P, Ball S, All clinicians and students at University Hospitals Birmingham NHS Foundation Trust.",,BMJ open respiratory research,2020,2020-09-01,Y,Viral infection; respiratory infection; Clinical Epidemiology,,,"<h4>Background</h4>Studies suggest that certain black and Asian minority ethnic groups experience poorer outcomes from COVID-19, but these studies have not provided insight into potential reasons for this. We hypothesised that outcomes would be poorer for those of South Asian ethnicity hospitalised from a confirmed SARS-CoV-2 infection, once confounding factors, health-seeking behaviours and community demographics were considered, and that this might reflect a more aggressive disease course in these patients.<h4>Methods</h4>Patients with confirmed SARS-CoV-2 infection requiring admission to University Hospitals Birmingham NHS Foundation Trust (UHB) in Birmingham, UK between 10 March 2020 and 17 April 2020 were included. Standardised admission ratio (SAR) and standardised mortality ratio (SMR) were calculated using observed COVID-19 admissions/deaths and 2011 census data. Adjusted HR for mortality was estimated using Cox proportional hazard model adjusting and propensity score matching.<h4>Results</h4>All patients admitted to UHB with COVID-19 during the study period were included (2217 in total). 58% were male, 69.5% were white and the majority (80.2%) had comorbidities. 18.5% were of South Asian ethnicity, and these patients were more likely to be younger and have no comorbidities, but twice the prevalence of diabetes than white patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted and they were more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death, both by Cox regression (HR 1.4, 95% CI 1.2 to 1.8), after adjusting for age, sex, deprivation and comorbidities, and by propensity score matching, matching for the same factors but categorising ethnicity into South Asian or not (HR 1.3, 95% CI 1.0 to 1.6).<h4>Conclusions</h4>Those of South Asian ethnicity appear at risk of worse COVID-19 outcomes. Further studies need to establish the underlying mechanistic pathways.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000644.full.pdf; doi:https://doi.org/10.1136/bmjresp-2020-000644; html:https://europepmc.org/articles/PMC7467523; pdf:https://europepmc.org/articles/PMC7467523?pdf=render
 34018481,https://doi.org/10.2807/1560-7917.es.2021.26.20.2100428,The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant.,"Hodgson D, Flasche S, Jit M, Kucharski AJ, CMMID COVID-19 Working Group, Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-05-01,Y,Vaccination; Herd immunity; Seroprevalence; Sars-cov-2,,,"We assess the feasibility of reaching the herd immunity threshold against SARS-CoV-2 through vaccination, considering vaccine effectiveness (VE), transmissibility of the virus and the level of pre-existing immunity in populations, as well as their age structure. If highly transmissible variants of concern become dominant in areas with low levels of naturally-acquired immunity and/or in populations with large proportions of < 15 year-olds, control of infection without non-pharmaceutical interventions may only be possible with a VE ≥ 80%, and coverage extended to children.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/20/eurosurv-26-20-1.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.20.2100428&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428; html:https://europepmc.org/articles/PMC8138959; pdf:https://europepmc.org/articles/PMC8138959?pdf=render
+36680646,https://doi.org/10.1007/s10654-022-00962-6,Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.,"Bowyer RCE, Huggins C, Toms R, Shaw RJ, Hou B, Thompson EJ, Kwong ASF, Williams DM, Kibble M, Ploubidis GB, Timpson NJ, Sterne JAC, Chaturvedi N, Steves CJ, Tilling K, Silverwood RJ, CONVALESCENCE Study.",,European journal of epidemiology,2023,2023-01-21,Y,Clustering; Longitudinal Studies; Symptom Patterns; Covid-19; Long Covid,,,"Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00962-6.pdf; doi:https://doi.org/10.1007/s10654-022-00962-6; html:https://europepmc.org/articles/PMC9860244; pdf:https://europepmc.org/articles/PMC9860244?pdf=render
 34446426,https://doi.org/10.1136/bmj.n1931,Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study.,"Hippisley-Cox J, Patone M, Mei XW, Saatci D, Dixon S, Khunti K, Zaccardi F, Watkinson P, Shankar-Hari M, Doidge J, Harrison DA, Griffin SJ, Sheikh A, Coupland CAC.",,BMJ (Clinical research ed.),2021,2021-08-26,Y,,,,"<h4>Objective</h4>To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults.<h4>Design</h4>Self-controlled case series study using national data on covid-19 vaccination and hospital admissions.<h4>Setting</h4>Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom's health service (NHS).<h4>Participants</h4>29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study.<h4>Main outcome measures</h4>The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events.<h4>Results</h4>The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test.<h4>Conclusion</h4>Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.",,pdf:https://www.bmj.com/content/bmj/374/bmj.n1931.full.pdf; doi:https://doi.org/10.1136/bmj.n1931; html:https://europepmc.org/articles/PMC8388189; pdf:https://europepmc.org/articles/PMC8388189?pdf=render
 34942103,https://doi.org/10.1016/s0140-6736(21)02754-9,"Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil.","Katikireddi SV, Cerqueira-Silva T, Vasileiou E, Robertson C, Amele S, Pan J, Taylor B, Boaventura V, Werneck GL, Flores-Ortiz R, Agrawal U, Docherty AB, McCowan C, McMenamin J, Moore E, Ritchie LD, Rudan I, Shah SA, Shi T, Simpson CR, Barreto ML, Oliveira VA, Barral-Netto M, Sheikh A.",,"Lancet (London, England)",2022,2021-12-20,Y,,,,"<h4>Background</h4>Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants-especially delta (B.1.617.2)-is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon).<h4>Methods</h4>In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2-3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs.<h4>Findings</h4>1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54-2·62) at 10-11 weeks, 3·01 (2·26-3·99) at 14-15 weeks, and 5·43 (4·00-7·38) at 18-19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01-2·61) at 10-11 weeks, 3·10 (2·63-3·64) at 14-15 weeks, and 4·71 (3·83-5·78) at 18-19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7-87·0) at 2-3 weeks, to 75·9% (72·9-78·6) at 14-15 weeks, and 63·7% (59·6-67·4) at 18-19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4-87·3) at 2-3 weeks, to 59·7% (54·6-64·2) at 14-15 weeks, and 42·2% (32·4-50·6) at 18-19 weeks.<h4>Interpretation</h4>We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19.<h4>Funding</h4>UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.<h4>Translation</h4>For the Portuguese translation of the abstract see Supplementary Materials section.",,pdf:http://www.thelancet.com/article/S0140673621027549/pdf; doi:https://doi.org/10.1016/S0140-6736(21)02754-9; html:https://europepmc.org/articles/PMC8687670
 33728401,https://doi.org/10.1038/s42254-020-0178-4,Modelling COVID-19.,"Vespignani A, Tian H, Dye C, Lloyd-Smith JO, Eggo RM, Shrestha M, Scarpino SV, Gutierrez B, Kraemer MUG, Wu J, Leung K, Leung GM.",,Nature reviews. Physics,2020,2020-05-06,Y,Applied Mathematics; Complex Networks,,,"As the COVID-19 pandemic continues, mathematical epidemiologists share their views on what models reveal about how the disease has spread, the current state of play and what work still needs to be done.",Vespignani et al. used mathematical models to model the epidemic of covid-19 and to predict future scenarios for possible interventions and inform policy and practice.,pdf:https://www.nature.com/articles/s42254-020-0178-4.pdf; doi:https://doi.org/10.1038/s42254-020-0178-4; html:https://europepmc.org/articles/PMC7201389; pdf:https://europepmc.org/articles/PMC7201389?pdf=render
@@ -257,8 +257,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 36436752,https://doi.org/10.1016/j.ijid.2022.11.024,"Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa.","Davies MA, Morden E, Rousseau P, Arendse J, Bam JL, Boloko L, Cloete K, Cohen C, Chetty N, Dane P, Heekes A, Hsiao NY, Hunter M, Hussey H, Jacobs T, Jassat W, Kariem S, Kassanjee R, Laenen I, Roux SL, Lessells R, Mahomed H, Maughan D, Meintjes G, Mendelson M, Mnguni A, Moodley M, Murie K, Naude J, Ntusi NAB, Paleker M, Parker A, Pienaar D, Preiser W, Prozesky H, Raubenheimer P, Rossouw L, Schrueder N, Smith B, Smith M, Solomon W, Symons G, Taljaard J, Wasserman S, Wilkinson RJ, Wolmarans M, Wolter N, Boulle A.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2023,2022-11-24,Y,"Covid-19; Omicron; Ba.4; Ba.5; Death, Severe Hospitalization",,,"<h4>Objectives</h4>We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.<h4>Methods</h4>We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection.<h4>Results</h4>Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective.<h4>Conclusion</h4>Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective.",,doi:https://doi.org/10.1016/j.ijid.2022.11.024; doi:https://doi.org/10.1016/j.ijid.2022.11.024; html:https://europepmc.org/articles/PMC9686046; pdf:https://europepmc.org/articles/PMC9686046?pdf=render
 34870142,https://doi.org/10.1016/j.infpip.2021.100192,"Effectiveness of infection prevention and control interventions, excluding personal protective equipment, to prevent nosocomial transmission of SARS-CoV-2: a systematic review and call for action.","Jafari Y, Yin M, Lim C, Pople D, Evans S, Stimson J, Pham TM, LSHTM CMMID COVID-19 working group, Read JM, Robotham JV, Cooper BS, Knight GM.",,Infection prevention in practice,2022,2021-11-29,Y,,,,"Many infection prevention and control (IPC) interventions have been adopted by hospitals to limit nosocomial transmission of SARS-CoV-2. The aim of this systematic review is to identify evidence on the effectiveness of these interventions. We conducted a literature search of five databases (OVID MEDLINE, Embase, CENTRAL, COVID-19 Portfolio (pre-print), Web of Science). SWIFT ActiveScreener software was used to screen English titles and abstracts published between 1st January 2020 and 6th April 2021. Intervention studies, defined by Cochrane Effective Practice and Organisation of Care, that evaluated IPC interventions with an outcome of SARS-CoV-2 infection in either patients or healthcare workers were included. Personal protective equipment (PPE) was excluded as this intervention had been previously reviewed. Risks of bias were assessed using the Cochrane tool for randomised trials (RoB2) and non-randomized studies of interventions (ROBINS-I). From 23,156 screened articles, we identified seven articles that met the inclusion criteria, all of which evaluated interventions to prevent infections in healthcare workers and the majority of which were focused on effectiveness of prophylaxes. Due to heterogeneity in interventions, we did not conduct a meta-analysis. All agents used for prophylaxes have little to no evidence of effectiveness against SARS-CoV-2 infections. We did not find any studies evaluating the effectiveness of interventions including but not limited to screening, isolation and improved ventilation. There is limited evidence from interventional studies, excluding PPE, evaluating IPC measures for SARS-CoV-2. This review calls for urgent action to implement such studies to inform policies to protect our most vulnerable populations and healthcare workers.",,doi:https://doi.org/10.1016/j.infpip.2021.100192; doi:https://doi.org/10.1016/j.infpip.2021.100192; html:https://europepmc.org/articles/PMC8628369; pdf:https://europepmc.org/articles/PMC8628369?pdf=render
 35715350,https://doi.org/10.1016/j.vaccine.2022.06.010,Safety of COVID-19 vaccination and acute neurological events: A self-controlled case series in England using the OpenSAFELY platform.,"Walker JL, Schultze A, Tazare J, Tamborska A, Singh B, Donegan K, Stowe J, Morton CE, Hulme WJ, Curtis HJ, Williamson EJ, Mehrkar A, Eggo RM, Rentsch CT, Mathur R, Bacon S, Walker AJ, Davy S, Evans D, Inglesby P, Hickman G, MacKenna B, Tomlinson L, Ca Green A, Fisher L, Cockburn J, Parry J, Hester F, Harper S, Bates C, Evans SJ, Solomon T, Andrews NJ, Douglas IJ, Goldacre B, Smeeth L, McDonald HI.",,Vaccine,2022,2022-06-07,Y,Transverse Myelitis; Guillain-barré Syndrome; Vaccine Safety; Self-controlled Case Series; Bell’s Palsy; Covid-19 Vaccines,,,"<h4>Introduction</h4>We investigated the potential association of COVID-19 vaccination with three acute neurological events: Guillain-Barré syndrome (GBS), transverse myelitis and Bell's palsy.<h4>Methods</h4>With the approval of NHS England we analysed primary care data from >17 million patients in England linked to emergency care, hospital admission and mortality records in the OpenSAFELY platform. Separately for each vaccine brand, we used a self-controlled case series design to estimate the incidence rate ratio for each outcome in the period following vaccination (4-42 days for GBS, 4-28 days for transverse myelitis and Bell's palsy) compared to a within-person baseline, using conditional Poisson regression.<h4>Results</h4>Among 7,783,441 ChAdOx1 vaccinees, there was an increased rate of GBS (N = 517; incidence rate ratio 2·85; 95% CI2·33-3·47) and Bell's palsy (N = 5,350; 1·39; 1·27-1·53) following a first dose of ChAdOx1 vaccine, corresponding to 11.0 additional cases of GBS and 17.9 cases of Bell's palsy per 1 million vaccinees if causal. For GBS this applied to the first, but not the second, dose. There was no clear evidence of an association of ChAdOx1 vaccination with transverse myelitis (N = 199; 1·51; 0·96-2·37). Among 5,729,152 BNT162b2 vaccinees, there was no evidence of any association with GBS (N = 283; 1·09; 0·75-1·57), transverse myelitis (N = 109; 1·62; 0·86-3·03) or Bell's palsy (N = 3,609; 0·89; 0·76-1·03). Among 255,446 mRNA-1273 vaccine recipients there was no evidence of an association with Bell's palsy (N = 78; 0·88, 0·32-2·42).<h4>Conclusions</h4>COVID-19 vaccines save lives, but it is important to understand rare adverse events. We observed a short-term increased rate of Guillain-Barré syndrome and Bell's palsy after first dose of ChAdOx1 vaccine. The absolute risk, assuming a causal effect attributable to vaccination, was low.",,doi:https://doi.org/10.1016/j.vaccine.2022.06.010; doi:https://doi.org/10.1016/j.vaccine.2022.06.010; html:https://europepmc.org/articles/PMC9170533; pdf:https://europepmc.org/articles/PMC9170533?pdf=render
-36720568,https://doi.org/10.1136/bmjopen-2022-066164,Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study.,"OpenSAFELY Collaborative, Parker EP, Tazare J, Hulme WJ, Bates C, Carr EJ, Cockburn J, Curtis HJ, Fisher L, Green AC, Harper S, Hester F, Horne EM, Loud F, Lyon S, Mahalingasivam V, Mehrkar A, Nab L, Parry J, Santhakumaran S, Steenkamp R, Sterne JA, Walker AJ, Williamson EJ, Willicombe M, Zheng B, Goldacre B, Nitsch D, Tomlinson LA.",,BMJ open,2023,2023-01-31,Y,Public Health; Kidney & Urinary Tract Disorders; Covid-19,,,"<h4>Objective</h4>To characterise factors associated with COVID-19 vaccine uptake among people with kidney disease in England.<h4>Design</h4>Retrospective cohort study using the OpenSAFELY-TPP platform, performed with the approval of NHS England.<h4>Setting</h4>Individual-level routine clinical data from 24 million people across GPs in England using TPP software. Primary care data were linked directly with COVID-19 vaccine records up to 31 August 2022 and with renal replacement therapy (RRT) status via the UK Renal Registry (UKRR).<h4>Participants</h4>A cohort of adults with stage 3-5 chronic kidney disease (CKD) or receiving RRT at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate (eGFR) or inclusion in the UKRR.<h4>Main outcome measures</h4>Dose-specific vaccine coverage over time was determined from 1 December 2020 to 31 August 2022. Individual-level factors associated with receipt of a 3-dose or 4-dose vaccine series were explored via Cox proportional hazards models.<h4>Results</h4>992 205 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 31 August 2022 was 97.5%, 97.0% and 93.9% for doses 1, 2 and 3, respectively, and 81.9% for dose 4 among individuals with one or more indications for eligibility. Delayed 3-dose vaccine uptake was associated with younger age, minority ethnicity, social deprivation and severe mental illness-associations that were consistent across CKD severity subgroups, dialysis patients and kidney transplant recipients. Similar associations were observed for 4-dose uptake.<h4>Conclusion</h4>Although high primary vaccine and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across clinical and demographic groups and 4-dose coverage is suboptimal. Targeted interventions are needed to identify barriers to vaccine uptake among under-vaccinated subgroups identified in the present study.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/1/e066164.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066164; html:https://europepmc.org/articles/PMC9890277; pdf:https://europepmc.org/articles/PMC9890277?pdf=render
 32614817,https://doi.org/10.1371/journal.pcbi.1008031,Estimation of country-level basic reproductive ratios for novel Coronavirus (SARS-CoV-2/COVID-19) using synthetic contact matrices.,"Hilton J, Keeling MJ.",,PLoS computational biology,2020,2020-07-02,Y,,,,"The 2019-2020 pandemic of atypical pneumonia (COVID-19) caused by the virus SARS-CoV-2 has spread globally and has the potential to infect large numbers of people in every country. Estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of human contacts through which the disease can spread, which is itself dependent on population age structure and household composition. Here we introduce a transmission model combining age-stratified contact frequencies with age-dependent susceptibility, probability of clinical symptoms, and transmission from asymptomatic (or mild) cases, which we use to estimate the country-specific basic reproductive ratio of COVID-19 for 152 countries. Using early outbreak data from China and a synthetic contact matrix, we estimate an age-stratified transmission structure which can then be extrapolated to 151 other countries for which synthetic contact matrices also exist. This defines a set of country-specific transmission structures from which we can calculate the basic reproductive ratio for each country. Our predicted R0 is critically sensitive to the intensity of transmission from asymptomatic cases; with low asymptomatic transmission the highest values are predicted across Eastern Europe and Japan and the lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly. If asymptomatic cases have comparable transmission to detected cases, the pattern is reversed. Our results demonstrate the importance of age-specific heterogeneities going beyond contact structure to the spread of COVID-19. These heterogeneities give COVID-19 the capacity to spread particularly quickly in countries with older populations, and that intensive control measures are likely to be necessary to impede its progress in these countries.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008031&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1008031; html:https://europepmc.org/articles/PMC7363110; pdf:https://europepmc.org/articles/PMC7363110?pdf=render
+36720568,https://doi.org/10.1136/bmjopen-2022-066164,Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study.,"OpenSAFELY Collaborative, Parker EP, Tazare J, Hulme WJ, Bates C, Carr EJ, Cockburn J, Curtis HJ, Fisher L, Green AC, Harper S, Hester F, Horne EM, Loud F, Lyon S, Mahalingasivam V, Mehrkar A, Nab L, Parry J, Santhakumaran S, Steenkamp R, Sterne JA, Walker AJ, Williamson EJ, Willicombe M, Zheng B, Goldacre B, Nitsch D, Tomlinson LA.",,BMJ open,2023,2023-01-31,Y,Public Health; Kidney & Urinary Tract Disorders; Covid-19,,,"<h4>Objective</h4>To characterise factors associated with COVID-19 vaccine uptake among people with kidney disease in England.<h4>Design</h4>Retrospective cohort study using the OpenSAFELY-TPP platform, performed with the approval of NHS England.<h4>Setting</h4>Individual-level routine clinical data from 24 million people across GPs in England using TPP software. Primary care data were linked directly with COVID-19 vaccine records up to 31 August 2022 and with renal replacement therapy (RRT) status via the UK Renal Registry (UKRR).<h4>Participants</h4>A cohort of adults with stage 3-5 chronic kidney disease (CKD) or receiving RRT at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate (eGFR) or inclusion in the UKRR.<h4>Main outcome measures</h4>Dose-specific vaccine coverage over time was determined from 1 December 2020 to 31 August 2022. Individual-level factors associated with receipt of a 3-dose or 4-dose vaccine series were explored via Cox proportional hazards models.<h4>Results</h4>992 205 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 31 August 2022 was 97.5%, 97.0% and 93.9% for doses 1, 2 and 3, respectively, and 81.9% for dose 4 among individuals with one or more indications for eligibility. Delayed 3-dose vaccine uptake was associated with younger age, minority ethnicity, social deprivation and severe mental illness-associations that were consistent across CKD severity subgroups, dialysis patients and kidney transplant recipients. Similar associations were observed for 4-dose uptake.<h4>Conclusion</h4>Although high primary vaccine and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across clinical and demographic groups and 4-dose coverage is suboptimal. Targeted interventions are needed to identify barriers to vaccine uptake among under-vaccinated subgroups identified in the present study.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/1/e066164.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066164; html:https://europepmc.org/articles/PMC9890277; pdf:https://europepmc.org/articles/PMC9890277?pdf=render
 37182748,https://doi.org/10.1016/j.jinf.2023.05.010,The impact of COVID-19 on antibiotic prescribing in primary care in England: Evaluation and risk prediction of appropriateness of type and repeat prescribing.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Journal of infection,2023,2023-05-12,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"<h4>Background</h4>This study aimed to predict risks of potentially inappropriate antibiotic type and repeat prescribing and assess changes during COVID-19.<h4>Methods</h4>With the approval of NHS England, we used OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system and selected patients prescribed antibiotics from 2019 to 2021. Multinomial logistic regression models predicted patient's probability of receiving inappropriate antibiotic type or repeat antibiotic course for each common infection.<h4>Results</h4>The population included 9.1 million patients with 29.2 million antibiotic prescriptions. 29.1% of prescriptions were identified as repeat prescribing. Those with same day incident infection coded in the EHR had considerably lower rates of repeat prescribing (18.0%) and 8.6% had potentially inappropriate type. No major changes in the rates of repeat antibiotic prescribing during COVID-19 were found. In the 10 risk prediction models, good levels of calibration and moderate levels of discrimination were found.<h4>Conclusions</h4>Our study found no evidence of changes in level of inappropriate or repeat antibiotic prescribing after the start of COVID-19. Repeat antibiotic prescribing was frequent and varied according to regional and patient characteristics. There is a need for treatment guidelines to be developed around antibiotic failure and clinicians provided with individualised patient information.",,doi:https://doi.org/10.1016/j.jinf.2023.05.010; doi:https://doi.org/10.1016/j.jinf.2023.05.010; html:https://europepmc.org/articles/PMC10176893; pdf:https://europepmc.org/articles/PMC10176893?pdf=render
 35226680,https://doi.org/10.1371/journal.pone.0264023,"COVID-19 mitigation measures in primary schools and association with infection and school staff wellbeing: An observational survey linked with routine data in Wales, UK.","Marchant E, Griffiths L, Crick T, Fry R, Hollinghurst J, James M, Cowley L, Abbasizanjani H, Torabi F, Thompson DA, Kennedy J, Akbari A, Gravenor MB, Lyons RA, Brophy S.",,PloS one,2022,2022-02-28,Y,,,,"<h4>Introduction</h4>School-based COVID-19 mitigation strategies have greatly impacted the primary school day (children aged 3-11) including: wearing face coverings, two metre distancing, no mixing of children, and no breakfast clubs or extra-curricular activities. This study examines these mitigation measures and association with COVID-19 infection, respiratory infection, and school staff wellbeing between October to December 2020 in Wales, UK.<h4>Methods</h4>A school staff survey captured self-reported COVID-19 mitigation measures in the school, participant anxiety and depression, and open-text responses regarding experiences of teaching and implementing measures. These survey responses were linked to national-scale COVID-19 test results data to examine association of measures in the school and the likelihood of a positive (staff or pupil) COVID-19 case in the school (clustered by school, adjusted for school size and free school meals using logistic regression). Linkage was conducted through the SAIL (Secure Anonymised Information Linkage) Databank.<h4>Results</h4>Responses were obtained from 353 participants from 59 primary schools within 15 of 22 local authorities. Having more direct non-household contacts was associated with a higher likelihood of COVID-19 positive case in the school (1-5 contacts compared to none, OR 2.89 (1.01, 8.31)) and a trend to more self-reported cold symptoms. Staff face covering was not associated with a lower odds of school COVID-19 cases (mask vs. no covering OR 2.82 (1.11, 7.14)) and was associated with higher self-reported cold symptoms. School staff reported the impacts of wearing face coverings on teaching, including having to stand closer to pupils and raise their voices to be heard. 67.1% were not able to implement two metre social distancing from pupils. We did not find evidence that maintaining a two metre distance was associated with lower rates of COVID-19 in the school.<h4>Conclusions</h4>Implementing, adhering to and evaluating COVID-19 mitigation guidelines is challenging in primary school settings. Our findings suggest that reducing non-household direct contacts lowers infection rates. There was no evidence that face coverings, two metre social distancing or stopping children mixing was associated with lower odds of COVID-19 or cold infection rates in the school. Primary school staff found teaching challenging during COVID-19 restrictions, especially for younger learners and those with additional learning needs.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264023&type=printable; doi:https://doi.org/10.1371/journal.pone.0264023; html:https://europepmc.org/articles/PMC8884508; pdf:https://europepmc.org/articles/PMC8884508?pdf=render
 34183342,https://doi.org/10.1136/bmjopen-2020-046392,"United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): a retrospective cohort study using linked routinely collected data, study protocol.","Teece L, Gray LJ, Melbourne C, Orton C, Ford DV, Martin CA, McAllister D, Khunti K, Tobin M, John C, Abrams KR, Pareek M, UK-REACH Study Collaborative Group.",,BMJ open,2021,2021-06-28,Y,epidemiology; Public Health; Adult Intensive & Critical Care; Covid-19,,,"<h4>Introduction</h4>COVID-19 has spread rapidly worldwide, causing significant morbidity and mortality. People from ethnic minorities, particularly those working in healthcare settings, have been disproportionately affected. Current evidence of the association between ethnicity and COVID-19 outcomes in people working in healthcare settings is insufficient to inform plans to address health inequalities.<h4>Methods and analysis</h4>This study combines anonymised human resource databases with professional registration and National Health Service data sets to assess associations between ethnicity and COVID-19 diagnosis, hospitalisation and death in healthcare workers in the UK. Adverse COVID-19 outcomes will be assessed between 1 February 2020 (date following first confirmed COVID-19 case in UK) and study end date (31 January 2021), allowing 1-year of follow-up. Planned analyses include multivariable Poisson, logistic and flexible parametric time-to-event regression within each country, adjusting for core predictors, followed by meta-analysis of country-specific results to produce combined effect estimates for the UK. Mediation analysis methods will be explored to examine the direct, indirect and mediated interactive effects between ethnicity, occupational group and COVID-19 outcomes.<h4>Ethics and dissemination</h4>Ethical approval for the UK-REACH programme has been obtained via the expedited HRA COVID-19 processes (REC ref: 20/HRA/4718, IRAS ID: 288316). Research information will be anonymised via the Secure Anonymised Information Linkage Databank before release to researchers. Study results will be submitted for publication in an open access peer-reviewed journal and made available on our dedicated website (https://uk-reach.org/).<h4>Trial registration number</h4>ISRCTN11811602.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?pdf=render
@@ -286,13 +286,13 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 35365070,https://doi.org/10.1186/s12879-022-07268-8,Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study.,"Rosello A, Barnard RC, Smith DRM, Evans S, Grimm F, Davies NG, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Modelling Working Group, Deeny SR, Knight GM, Edmunds WJ.",,BMC infectious diseases,2022,2022-04-01,Y,PCR; Testing; mathematical model; Long-term Care Facility; Care Home; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2,,,"<h4>Background</h4>COVID-19 outbreaks still occur in English care homes despite the interventions in place.<h4>Methods</h4>We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (PCR), enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics.<h4>Results</h4>The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing.<h4>Conclusions</h4>Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks.",,pdf:https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-022-07268-8; doi:https://doi.org/10.1186/s12879-022-07268-8; html:https://europepmc.org/articles/PMC8972713; pdf:https://europepmc.org/articles/PMC8972713?pdf=render
 35611160,https://doi.org/10.1016/j.eclinm.2022.101462,Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Agrawal U, Moore E, Simpson CR, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,EClinicalMedicine,2022,2022-05-20,Y,Pandemic; Healthcare Inequalities; Covid-19; Sars-cov-2; Interrupted Time Series Analysis; Healthcare Disruption,,,"<h4>Background</h4>Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.<h4>Methods</h4>We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted.<h4>Findings</h4>Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively.<h4>Interpretation</h4>Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely.<h4>Funding</h4>This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.",,pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101462; html:https://europepmc.org/articles/PMC9121886; pdf:https://europepmc.org/articles/PMC9121886?pdf=render
 36374585,https://doi.org/10.1177/01410768221131897,Using national electronic health records for pandemic preparedness: validation of a parsimonious model for predicting excess deaths among those with COVID-19-a data-driven retrospective cohort study.,"Mizani MA, Dashtban A, Pasea L, Lai AG, Thygesen J, Tomlinson C, Handy A, Mamza JB, Morris T, Khalid S, Zaccardi F, Macleod MJ, Torabi F, Canoy D, Akbari A, Berry C, Bolton T, Nolan J, Khunti K, Denaxas S, Hemingway H, Sudlow C, Banerjee A, CVD-COVID-UK Consortium.",,Journal of the Royal Society of Medicine,2023,2022-11-14,N,Infectious diseases; Clinical; epidemiology; Public Health; Health Informatics,,,"<h4>Objectives</h4>To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths.<h4>Design</h4>An EHR-based, retrospective cohort study.<h4>Setting</h4>Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE).<h4>Participants</h4>In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.<h4>Main outcome measures</h4>One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.<h4>Results</h4>From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31-4.38) and IR was 6.27% (95% CI, 6.26-6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79.<h4>Conclusions</h4>We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; doi:https://doi.org/10.1177/01410768221131897; html:https://europepmc.org/articles/PMC9909113; pdf:https://europepmc.org/articles/PMC9909113?pdf=render; doi:https://doi.org/10.1177/01410768221131897
-35585575,https://doi.org/10.1186/s12889-022-13219-4,The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.,"McCarthy CV, O'Mara O, van Leeuwen E, CMMID COVID-19 Working Group, Jit M, Sandmann F.",,BMC public health,2022,2022-05-18,Y,Vaccination; mathematical model; Public Health; Prisons; Covid-19,,,"<h4>Background</h4>High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community.<h4>Methods</h4>We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals who are incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths.<h4>Results</h4>Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50 years old averted one death for every 104 vaccination courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points.<h4>Conclusions</h4>The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render
 34732073,https://doi.org/10.1161/strokeaha.121.034787,"Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study.","Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribbers T, Nieuwkamp DJ, van Houwelingen RC, Dias A, van Uden IWM, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJH, de Graaf MT, Brouwers PJAM, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM, CAPACITY-COVID Collaborative Consortium*.",,Stroke,2021,2021-11-04,Y,Intensive care units; Pulmonary embolism; incidence; Hospital Mortality; Patient Discharge; Covid-19,,,"<h4>Background and purpose</h4>The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.<h4>Methods</h4>We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.<h4>Results</h4>We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; <i>P</i>=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke.<h4>Conclusions</h4>In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.",,pdf:https://europepmc.org/articles/pmc8607920?pdf=render; doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render
+35585575,https://doi.org/10.1186/s12889-022-13219-4,The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.,"McCarthy CV, O'Mara O, van Leeuwen E, CMMID COVID-19 Working Group, Jit M, Sandmann F.",,BMC public health,2022,2022-05-18,Y,Vaccination; mathematical model; Public Health; Prisons; Covid-19,,,"<h4>Background</h4>High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community.<h4>Methods</h4>We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals who are incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths.<h4>Results</h4>Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50 years old averted one death for every 104 vaccination courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points.<h4>Conclusions</h4>The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render
 33541353,https://doi.org/10.1186/s12916-020-01872-8,The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories.,"Liu Y, Morgenstern C, Kelly J, Lowe R, CMMID COVID-19 Working Group, Jit M.",,BMC medicine,2021,2021-02-05,Y,Quantitative; Pandemic; Health Impact Assessment; Public Health Intervention; Longitudinal Analysis; Policy Evaluation; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2,,,"<h4>Background</h4>Non-pharmaceutical interventions (NPIs) are used to reduce transmission of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel restrictions, economic measures, and health system actions on SARS-CoV-2 transmission in 130 countries and territories.<h4>Methods</h4>We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission using data from January to June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number (R<sub>t</sub>) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes in R<sub>t</sub>, levels of NPI intensity, time-varying changes in NPI effect, and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs.<h4>Results</h4>There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reduced R<sub>t</sub>. Another three NPIs (workplace closure, income support, and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g. restrictions on 1000+ people gathering were not effective, restrictions on < 10 people gathering were). Evidence about the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel controls, testing, contact tracing) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs. Effect sizes varied depending on whether or not we included data after peak NPI intensity.<h4>Conclusion</h4>Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission is complicated by temporal clustering, time-dependent variation in effects, and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many, although not all, actions policy-makers are taking to respond to the COVID-19 pandemic.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01872-8; doi:https://doi.org/10.1186/s12916-020-01872-8; html:https://europepmc.org/articles/PMC7861967; pdf:https://europepmc.org/articles/PMC7861967?pdf=render
 35308309,https://doi.org/10.1016/j.eclinm.2022.101346,"Healthcare workers' views on mandatory SARS-CoV-2 vaccination in the UK: A cross-sectional, mixed-methods analysis from the UK-REACH study.","Woolf K, Gogoi M, Martin CA, Papineni P, Lagrata S, Nellums LB, McManus IC, Guyatt AL, Melbourne C, Bryant L, Gupta A, John C, Carr S, Tobin MD, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,EClinicalMedicine,2022,2022-03-15,Y,,,,"<h4>Background</h4>Several countries now have mandatory SARS-CoV-2 vaccination for healthcare workers (HCWs) or the general population. HCWs' views on this are largely unknown. Using data from the nationwide UK-REACH study we aimed to understand UK HCW's views on improving SARS-CoV-2 vaccination coverage, including mandatory vaccination.<h4>Methods</h4>Between 21st April and 26th June 2021, we administered an online questionnaire via email to 17 891 UK HCWs recruited as part of a longitudinal cohort from across the UK who had previously responded to a baseline questionnaire (primarily recruited through email) as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) nationwide prospective cohort study. We categorised responses to a free-text question ""What should society do if people do not get vaccinated against COVID-19?"" using qualitative content analysis. We collapsed categories into a binary variable: favours mandatory vaccination or not, using logistic regression to calculate its demographic predictors, and its occupational, health, and attitudinal predictors adjusted for demographics.<h4>Findings</h4>Of 5633 questionnaire respondents, 3235 answered the free text question. Median age of free text responders was 47 years (IQR 36-56) and 2705 (74.3%) were female. 18% (<i>n</i> = 578) favoured mandatory vaccination (201 [6%] participants for HCWs and others working with vulnerable populations; 377 [12%] for the general population), but the most frequent suggestion was education (32%, <i>n</i> = 1047). Older HCWs (OR 1.84; 95% CI 1.44-2.34 [≥55 years vs 16 years to <40 years]), HCWs vaccinated against influenza (OR 1.49; 95% CI 1.11-2.01 [2 vaccines vs none]), and with more positive vaccination attitudes generally (OR 1.10; 95% CI 1.06-1.15) were more likely to favour mandatory vaccination, whereas female HCWs (OR= 0.79, 95% CI 0.63-0.96, vs male HCWs) and Black HCWs (OR=0.46, 95% CI 0.25-0.85, vs white HCWs) were less likely to.<h4>Interpretation</h4>Only one in six of the HCWs in this large, diverse, UK-wide sample favoured mandatory vaccination. Building trust, educating, and supporting HCWs who are hesitant about vaccination may be more acceptable, effective, and equitable.<h4>Funding</h4>MRC-UK Research and Innovation grant (MR/V027549/1) and the Department of Health and Social Care (DHSC) via the National Institute for Health Research (NIHR). Core funding was also provided by NIHR Biomedical Research Centres.",,pdf:http://www.thelancet.com/article/S2589537022000761/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101346; html:https://europepmc.org/articles/PMC8923694; pdf:https://europepmc.org/articles/PMC8923694?pdf=render
 32220655,https://doi.org/10.1016/s2468-2667(20)30073-6,"The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study.","Prem K, Liu Y, Russell TW, Kucharski AJ, Eggo RM, Davies N, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Jit M, Klepac P.",,The Lancet. Public health,2020,2020-03-25,Y,,,,"<h4>Background</h4>In December, 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures in response to the outbreak, including extended school and workplace closures. We aimed to estimate the effects of physical distancing measures on the progression of the COVID-19 epidemic, hoping to provide some insights for the rest of the world.<h4>Methods</h4>To examine how changes in population mixing have affected outbreak progression in Wuhan, we used synthetic location-specific contact patterns in Wuhan and adapted these in the presence of school closures, extended workplace closures, and a reduction in mixing in the general community. Using these matrices and the latest estimates of the epidemiological parameters of the Wuhan outbreak, we simulated the ongoing trajectory of an outbreak in Wuhan using an age-structured susceptible-exposed-infected-removed (SEIR) model for several physical distancing measures. We fitted the latest estimates of epidemic parameters from a transmission model to data on local and internationally exported cases from Wuhan in an age-structured epidemic framework and investigated the age distribution of cases. We also simulated lifting of the control measures by allowing people to return to work in a phased-in way and looked at the effects of returning to work at different stages of the underlying outbreak (at the beginning of March or April).<h4>Findings</h4>Our projections show that physical distancing measures were most effective if the staggered return to work was at the beginning of April; this reduced the median number of infections by more than 92% (IQR 66-97) and 24% (13-90) in mid-2020 and end-2020, respectively. There are benefits to sustaining these measures until April in terms of delaying and reducing the height of the peak, median epidemic size at end-2020, and affording health-care systems more time to expand and respond. However, the modelled effects of physical distancing measures vary by the duration of infectiousness and the role school children have in the epidemic.<h4>Interpretation</h4>Restrictions on activities in Wuhan, if maintained until April, would probably help to delay the epidemic peak. Our projections suggest that premature and sudden lifting of interventions could lead to an earlier secondary peak, which could be flattened by relaxing the interventions gradually. However, there are limitations to our analysis, including large uncertainties around estimates of R<sub>0</sub> and the duration of infectiousness.<h4>Funding</h4>Bill & Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.",,pdf:https://repository.publisso.de/resource/frl:6420088/data; doi:https://doi.org/10.1016/S2468-2667(20)30073-6; html:https://europepmc.org/articles/PMC7158905
-37088955,https://doi.org/10.1177/02692163231167212,"Deaths at home, area-based deprivation and the effect of the Covid-19 pandemic: An analysis of mortality data across four nations.","Leniz J, Davies JM, Bone AE, Hocaoglu M, Verne J, Barclay S, Murtagh FEM, Fraser LK, Higginson IJ, Sleeman KE.",,Palliative medicine,2023,2023-04-23,Y,Mortality; Palliative care; Terminal Care; Inequalities; Place Of Death; Deprivation; Pandemics; Socio-economic Position; Covid-19,,,"<h4>Background</h4>The number and proportion of home deaths in the UK increased during the Covid-19 pandemic. It is not known whether these changes were experienced disproportionately by people from different socioeconomic groups.<h4>Aim</h4>To examine the association between home death and socioeconomic position during the Covid-19 pandemic, and how this changed between 2019 and 2020.<h4>Design</h4>Retrospective cohort study using population-based individual-level mortality data.<h4>Setting/participants</h4>All registered deaths in England, Wales, Scotland and Northern Ireland. The proportion of home deaths between 28th March and 31st December 2020 was compared with the same period in 2019. We used Poisson regression models to evaluate the association between decedent's area-based level of deprivation and risk of home death, as well as the interaction between deprivation and year of death, for each nation separately.<h4>Results</h4>Between the 28th March and 31st December 2020, 409,718 deaths were recorded in England, 46,372 in Scotland, 26,410 in Wales and 13,404 in Northern Ireland. All four nations showed an increase in the adjusted proportion of home deaths between 2019 and 2020, ranging from 21 to 28%. This increase was lowest for people living in the most deprived areas in all nations, with evidence of a deprivation gradient in England.<h4>Conclusions</h4>The Covid-19 pandemic exacerbated a previously described socioeconomic inequality in place of death in the UK. Further research to understand the reasons for this change and if this inequality has been sustained is needed.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125882; doi:https://doi.org/10.1177/02692163231167212; html:https://europepmc.org/articles/PMC10125882; pdf:https://europepmc.org/articles/PMC10125882?pdf=render
 33875444,https://doi.org/10.1136/bmjopen-2020-045077,COVID-19 in patients with hepatobiliary and pancreatic diseases: a single-centre cross-sectional study in East London.,"Dayem Ullah AZM, Sivapalan L, Kocher HM, Chelala C.",,BMJ open,2021,2021-04-19,Y,Pancreatic Disease; Hepatobiliary Disease; Covid-19,,,"<h4>Objective</h4>To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.<h4>Participants</h4>EL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.<h4>Main outcome measure</h4>COVID-19 incidence and mortality.<h4>Results</h4>Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).<h4>Conclusions</h4>In this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/4/e045077.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-045077; html:https://europepmc.org/articles/PMC8057071; pdf:https://europepmc.org/articles/PMC8057071?pdf=render
+37088955,https://doi.org/10.1177/02692163231167212,"Deaths at home, area-based deprivation and the effect of the Covid-19 pandemic: An analysis of mortality data across four nations.","Leniz J, Davies JM, Bone AE, Hocaoglu M, Verne J, Barclay S, Murtagh FEM, Fraser LK, Higginson IJ, Sleeman KE.",,Palliative medicine,2023,2023-04-23,Y,Mortality; Palliative care; Terminal Care; Inequalities; Place Of Death; Deprivation; Pandemics; Socio-economic Position; Covid-19,,,"<h4>Background</h4>The number and proportion of home deaths in the UK increased during the Covid-19 pandemic. It is not known whether these changes were experienced disproportionately by people from different socioeconomic groups.<h4>Aim</h4>To examine the association between home death and socioeconomic position during the Covid-19 pandemic, and how this changed between 2019 and 2020.<h4>Design</h4>Retrospective cohort study using population-based individual-level mortality data.<h4>Setting/participants</h4>All registered deaths in England, Wales, Scotland and Northern Ireland. The proportion of home deaths between 28th March and 31st December 2020 was compared with the same period in 2019. We used Poisson regression models to evaluate the association between decedent's area-based level of deprivation and risk of home death, as well as the interaction between deprivation and year of death, for each nation separately.<h4>Results</h4>Between the 28th March and 31st December 2020, 409,718 deaths were recorded in England, 46,372 in Scotland, 26,410 in Wales and 13,404 in Northern Ireland. All four nations showed an increase in the adjusted proportion of home deaths between 2019 and 2020, ranging from 21 to 28%. This increase was lowest for people living in the most deprived areas in all nations, with evidence of a deprivation gradient in England.<h4>Conclusions</h4>The Covid-19 pandemic exacerbated a previously described socioeconomic inequality in place of death in the UK. Further research to understand the reasons for this change and if this inequality has been sustained is needed.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125882; doi:https://doi.org/10.1177/02692163231167212; html:https://europepmc.org/articles/PMC10125882; pdf:https://europepmc.org/articles/PMC10125882?pdf=render
 33031764,https://doi.org/10.1016/s0140-6736(20)32013-4,"Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2020,2020-10-05,Y,,,,"<h4>Background</h4>Lopinavir-ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir-ritonavir improves outcomes in patients admitted to hospital with COVID-19.<h4>Methods</h4>In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir-ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.<h4>Findings</h4>Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir-ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir-ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91-1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91-1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99-1·20; p=0·092).<h4>Interpretation</h4>In patients admitted to hospital with COVID-19, lopinavir-ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir-ritonavir for treatment of patients admitted to hospital with COVID-19.<h4>Funding</h4>Medical Research Council and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S0140673620320134/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32013-4; html:https://europepmc.org/articles/PMC7535623
 34340970,https://doi.org/10.3399/bjgp.2021.0301,Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records <i>in situ</i> using OpenSAFELY.,"Walker AJ, MacKenna B, Inglesby P, Tomlinson L, Rentsch CT, Curtis HJ, Morton CE, Morley J, Mehrkar A, Bacon S, Hickman G, Bates C, Croker R, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Williamson EJ, Hulme WJ, McDonald HI, Mathur R, Eggo RM, Wing K, Wong AY, Forbes H, Tazare J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Douglas IJ, Evans SJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-10-28,Y,Primary Health Care; General Practice; Electronic Health Records; Covid-19; Long Covid,,,"<h4>Background</h4>Long COVID describes new or persistent symptoms at least 4 weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were recently created.<h4>Aim</h4>To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time.<h4>Design and setting</h4>Population-based cohort study in English primary care.<h4>Method</h4>Working on behalf of NHS England, OpenSAFELY data were used encompassing 96% of the English population between 1 February 2020 and 25 May 2021. The proportion of people with a recorded code for long COVID was measured overall and by demographic factors, electronic health record software system (EMIS or TPP), and week.<h4>Results</h4>Long COVID was recorded for 23 273 people. Coding was unevenly distributed among practices, with 26.7% of practices having never used the codes. Regional variation ranged between 20.3 per 100 000 people for East of England (95% confidence interval [CI] = 19.3 to 21.4) and 55.6 per 100 000 people in London (95% CI = 54.1 to 57.1). Coding was higher among females (52.1, 95% CI = 51.3 to 52.9) than males (28.1, 95% CI = 27.5 to 28.7), and higher among practices using EMIS (53.7, 95% CI = 52.9 to 54.4) than those using TPP (20.9, 95% CI = 20.3 to 21.4).<h4>Conclusion</h4>Current recording of long COVID in primary care is very low, and variable between practices. This may reflect patients not presenting; clinicians and patients holding different diagnostic thresholds; or challenges with the design and communication of diagnostic codes. Increased awareness of diagnostic codes is recommended to facilitate research and planning of services, and also surveys with qualitative work to better evaluate clinicians' understanding of the diagnosis.",,pdf:https://bjgp.org/content/bjgp/71/712/e806.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0301; html:https://europepmc.org/articles/PMC8340730; pdf:https://europepmc.org/articles/PMC8340730?pdf=render
 33342219,https://doi.org/10.1161/circoutcomes.120.007085,Estimating the Effect of Reduced Attendance at Emergency Departments for Suspected Cardiac Conditions on Cardiac Mortality During the COVID-19 Pandemic.,"Katsoulis M, Gomes M, Lai AG, Henry A, Denaxas S, Lagiou P, Nafilyan V, Humberstone B, Banerjee A, Hemingway H, Lumbers RT.",,Circulation. Cardiovascular quality and outcomes,2021,2020-12-20,Y,"Cardiovascular diseases; Coronavirus; Pandemic; Heart Disease; Death, Sudden, Cardiac",,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCOUTCOMES.120.007085; doi:https://doi.org/10.1161/CIRCOUTCOMES.120.007085; html:https://europepmc.org/articles/PMC7819531; pdf:https://europepmc.org/articles/PMC7819531?pdf=render
@@ -332,8 +332,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 32119825,https://doi.org/10.1016/s2214-109x(20)30074-7,Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts.,"Hellewell J, Abbott S, Gimma A, Bosse NI, Jarvis CI, Russell TW, Munday JD, Kucharski AJ, Edmunds WJ, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Funk S, Eggo RM.",,The Lancet. Global health,2020,2020-02-28,Y,,Improving Public Health,COVID-19,"<h4>Background</h4>Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19.<h4>Methods</h4>We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R<sub>0</sub>), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort.<h4>Findings</h4>Simulated outbreaks starting with five initial cases, an R<sub>0</sub> of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R<sub>0</sub> was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R<sub>0</sub> of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R<sub>0</sub> of 2·5 more than 70% of contacts had to be traced, and for an R<sub>0</sub> of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R<sub>0</sub> was 1·5. For R<sub>0</sub> values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset.<h4>Interpretation</h4>In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts.<h4>Funding</h4>Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2214109X20300747/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30074-7; html:https://europepmc.org/articles/PMC7097845; pdf:https://europepmc.org/articles/PMC7097845?pdf=render
 35567479,https://doi.org/10.1093/rheumatology/keac283,Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulnerability is associated with increased mortality.,"Cooksey R, Underwood J, Brophy S, Atkinson M, Kennedy J, Choy E.",,"Rheumatology (Oxford, England)",2022,2022-06-01,Y,RA; As; PSA; Electronic Health Records; Covid-19; Inflammatory Arthritis,,,"<h4>Objectives</h4>Investigate whether individuals with inflammatory arthritis (IA), their treatments and shielding status affect the risk of adverse outcomes from COVID-19 for the entire population of Wales, UK.<h4>Methods</h4>Retrospective, population-based cohort study using linked, anonymized electronic health data from SAIL Databank, including primary/secondary care, rheumatology, Office for National Statistics Mortality and COVID-19 laboratory data. Individuals aged 18 years and over testing positive for COVID-19 between March 2020 and May 2021 with READ Codes present for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis formed the study cases.<h4>Results</h4>A total of 1966 people with IA and 166 602 without tested positive for COVID-19. The incidence rate was 3.5% (1966/56 914) in IA, vs 6% in the general population (166 602/2 760 442), (difference: 2.5%, 95% CI: 2.4%, 2.7%, P ≤0.001). In an adjusted Cox proportional hazard model, IA was not associated with higher mortality (HR: 0.56, 95% CI: 0.18, 1.64, P=0.286). Significant risk factors included shielding (HR: 1.52, 95% CI: 1.40, 1.64, P ≤0.001), hospitalization for previous infections (HR: 1.20, 95% CI: 1.12, 1.28, P ≤0.001), hospitalizations one year pre-pandemic (HR: 1.34, 95% CI: 1.25, 1.44, P ≤0.001) and glucocorticoid use (HR: 1.17, 95% CI: 1.09, 1.25, P ≤0.001).<h4>Conclusions</h4>Individuals with IA had a lower incidence of COVID-19, probably due to shielding. IA was not associated with increased mortality following COVID-19 infection; being vulnerable (shielded), comorbidities and other factors were associated with increased risk. These key risk factors can identify individuals with IA at greater risk from COVID-19 and advised to shield during high community prevalence.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62372/Download/62372__26337__5539f4f995224d80a2156218d11a03cb.pdf; doi:https://doi.org/10.1093/rheumatology/keac283; html:https://europepmc.org/articles/PMC9248059; pdf:https://europepmc.org/articles/PMC9248059?pdf=render
 34308406,https://doi.org/10.1016/j.lanepe.2021.100180,Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: Results from the UK-REACH prospective nationwide cohort study.,"Woolf K, McManus IC, Martin CA, Nellums LB, Guyatt AL, Melbourne C, Bryant L, Gogoi M, Wobi F, Al-Oraibi A, Hassan O, Gupta A, John C, Tobin MD, Carr S, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,The Lancet regional health. Europe,2021,2021-07-19,Y,,,,"<h4>Background</h4>In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs.<h4>Methods</h4>Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis.<h4>Findings</h4>11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks.<h4>Interpretation</h4>Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Emphasis should be placed on the safety and benefit of SARS-CoV-2 vaccination in pregnancy and in those with previous COVID-19. Public health communications should be inclusive, non-stigmatising and utilise trusted networks.<h4>Funding</h4>UKRI-MRC and NIHR.",,doi:https://doi.org/10.1016/j.lanepe.2021.100180; doi:https://doi.org/10.1016/j.lanepe.2021.100180; html:https://europepmc.org/articles/PMC8287519; pdf:https://europepmc.org/articles/PMC8287519?pdf=render
-34972825,https://doi.org/10.1038/s41564-021-01029-0,Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.,"Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.",,Nature microbiology,2022,2021-12-31,Y,,,,"Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, R<sub>t</sub>, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and R<sub>t</sub>. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of R<sub>t</sub> are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and R<sub>t</sub> that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.",,pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render
 33879890,https://doi.org/10.1038/s41591-021-01329-2,Single-cell multi-omics analysis of the immune response in COVID-19.,"Stephenson E, Reynolds G, Botting RA, Calero-Nieto FJ, Morgan MD, Tuong ZK, Bach K, Sungnak W, Worlock KB, Yoshida M, Kumasaka N, Kania K, Engelbert J, Olabi B, Spegarova JS, Wilson NK, Mende N, Jardine L, Gardner LCS, Goh I, Horsfall D, McGrath J, Webb S, Mather MW, Lindeboom RGH, Dann E, Huang N, Polanski K, Prigmore E, Gothe F, Scott J, Payne RP, Baker KF, Hanrath AT, Schim van der Loeff ICD, Barr AS, Sanchez-Gonzalez A, Bergamaschi L, Mescia F, Barnes JL, Kilich E, de Wilton A, Saigal A, Saleh A, Janes SM, Smith CM, Gopee N, Wilson C, Coupland P, Coxhead JM, Kiselev VY, van Dongen S, Bacardit J, King HW, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID-19 BioResource Collaboration, Rostron AJ, Simpson AJ, Hambleton S, Laurenti E, Lyons PA, Meyer KB, Nikolić MZ, Duncan CJA, Smith KGC, Teichmann SA, Clatworthy MR, Marioni JC, Göttgens B, Haniffa M.",,Nature medicine,2021,2021-04-20,Y,,,,"Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16<sup>+</sup>C1QA/B/C<sup>+</sup>) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34<sup>+</sup> hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8<sup>+</sup> T cells and an increased ratio of CD8<sup>+</sup> effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.",,pdf:https://www.nature.com/articles/s41591-021-01329-2.pdf; doi:https://doi.org/10.1038/s41591-021-01329-2; html:https://europepmc.org/articles/PMC8121667; pdf:https://europepmc.org/articles/PMC8121667?pdf=render
+34972825,https://doi.org/10.1038/s41564-021-01029-0,Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.,"Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.",,Nature microbiology,2022,2021-12-31,Y,,,,"Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, R<sub>t</sub>, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and R<sub>t</sub>. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of R<sub>t</sub> are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and R<sub>t</sub> that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.",,pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render
 37253531,https://doi.org/10.1136/bmjgh-2022-009997,Effectiveness of a multicomponent intervention to face the COVID-19 pandemic in Rio de Janeiro's favelas: difference-in-differences analysis.,"Batista-da-Silva AA, Moraes CB, Bozza HR, Bastos LDSL, Ranzani OT, Hamacher S, Bozza FA, Comitê Gestor Conexão Saúde.",,BMJ global health,2023,2023-05-01,Y,"Control strategies; Public Health; Intervention Study; Infections, Diseases, Disorders, Injuries; Covid-19",,,"<h4>Introduction</h4>Few community-based interventions addressing the transmission control and clinical management of COVID-19 cases have been reported, especially in poor urban communities from low-income and middle-income countries. Here, we analyse the impact of a multicomponent intervention that combines community engagement, mobile surveillance, massive testing and telehealth on COVID-19 cases detection and mortality rates in a large vulnerable community (<i>Complexo da Maré</i>) in Rio de Janeiro, Brazil.<h4>Methods</h4>We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in <i>Maré,</i> before (March-August 2020) and after the intervention (September 2020 to April 2021), compared with equivalent local vulnerable communities. We applied a negative binomial regression model to estimate the intervention effect in weekly cases and mortality rates in <i>Maré</i>.<h4>Results</h4>Before the intervention, <i>Maré</i> presented lower rates of reported COVID-19 cases compared with the control group (1373 vs 1579 cases/100 000 population), comparable mortality rates (309 vs 287 deaths/100 000 population) and higher case fatality rates (13.7% vs 12.2%). After the intervention, <i>Maré</i> displayed a 154% (95% CI 138.6% to 170.4%) relative increase in reported case rates. Relative changes in reported death rates were -60% (95% CI -69.0% to -47.9%) in Maré and -28% (95% CI -42.0% to -9.8%) in the control group. The case fatality rate was reduced by 77% (95% CI -93.1% to -21.1%) in <i>Maré</i> and 52% (95% CI -81.8% to -29.4%) in the control group. The DID showed a reduction of 46% (95% CI 17% to 65%) of weekly reported deaths and an increased 23% (95% CI 5% to 44%) of reported cases in <i>Maré</i> after intervention onset.<h4>Conclusion</h4>An integrated intervention combining communication, surveillance and telehealth, with a strong community engagement component, could reduce COVID-19 mortality and increase case detection in a large vulnerable community in Rio de Janeiro. These findings show that investment in community-based interventions may reduce mortality and improve pandemic control in poor communities from low-income and middle-income countries.",,doi:https://doi.org/10.1136/bmjgh-2022-009997; doi:https://doi.org/10.1136/bmjgh-2022-009997; html:https://europepmc.org/articles/PMC10230340; pdf:https://europepmc.org/articles/PMC10230340?pdf=render
 36820079,https://doi.org/10.1183/23120541.00274-2022,Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19.,"Daines L, Zheng B, Elneima O, Harrison E, Lone NI, Hurst JR, Brown JS, Sapey E, Chalmers JD, Quint JK, Pfeffer P, Siddiqui S, Walker S, Poinasamy K, McAuley H, Sereno M, Shikotra A, Singapuri A, Docherty AB, Marks M, Toshner M, Howard LS, Horsley A, Jenkins G, Porter JC, Ho LP, Raman B, Wain LV, Brightling CE, Evans RA, Heaney LG, De Soyza A, Sheikh A.",,ERJ open research,2023,2023-01-01,Y,,,,"<h4>Background</h4>Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation.<h4>Methods</h4>PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness.<h4>Results</h4>We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21).<h4>Conclusions</h4>Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/01/26/23120541.00274-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00274-2022; html:https://europepmc.org/articles/PMC9790090; pdf:https://europepmc.org/articles/PMC9790090?pdf=render
 37067557,https://doi.org/10.1007/s00134-023-07039-2,Variants of concern and clinical outcomes in critically ill COVID-19 patients.,DP-EFFECT-BRAZIL investigators.,,Intensive care medicine,2023,2023-04-17,Y,,,,,,pdf:https://link.springer.com/content/pdf/10.1007/s00134-023-07039-2.pdf; doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render
@@ -343,8 +343,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 35151397,https://doi.org/10.1016/s0140-6736(22)00163-5,"Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-02-01,Y,,,,"<h4>Background</h4>Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19.<h4>Methods</h4>RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).<h4>Findings</h4>Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69-0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86-1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab.<h4>Interpretation</h4>In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline.<h4>Funding</h4>UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/95149/5/1-s2.0-S0140673622001635-main.pdf; doi:https://doi.org/10.1016/S0140-6736(22)00163-5; html:https://europepmc.org/articles/PMC8830904
 32951042,https://doi.org/10.1093/ageing/afaa207,"The impact of COVID-19 on adjusted mortality risk in care homes for older adults in Wales, UK: a retrospective population-based cohort study for mortality in 2016-2020. ","Hollinghurst J, Lyons J, Fry R, Akbari A, Gravenor M, Watkins A, Verity F, Lyons RA.",,Age and ageing,2021,2021-01-01,Y,,,,"mortality in care homes has had a prominent focus during the COVID-19 outbreak. Care homes are particularly vulnerable to the spread of infectious diseases, which may lead to increased mortality risk. Multiple and interconnected challenges face the care home sector in the prevention and management of outbreaks of COVID-19, including adequate supply of personal protective equipment, staff shortages and insufficient or lack of timely COVID-19 testing. to analyse the mortality of older care home residents in Wales during COVID-19 lockdown and compare this across the population of Wales and the previous 4 years. we used anonymised electronic health records and administrative data from the secure anonymised information linkage databank to create a cross-sectional cohort study. We anonymously linked data for Welsh residents to mortality data up to the 14th June 2020. we calculated survival curves and adjusted Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of mortality. We adjusted HRs for age, gender, social economic status and prior health conditions. survival curves show an increased proportion of deaths between 23rd March and 14th June 2020 in care homes for older people, with an adjusted HR of 1.72 (1.55, 1.90) compared with 2016. Compared with the general population in 2016-2019, adjusted care home mortality HRs for older adults rose from 2.15 (2.11, 2.20) in 2016-2019 to 2.94 (2.81, 3.08) in 2020. the survival curves and increased HRs show a significantly increased risk of death in the 2020 study periods.",,pdf:https://academic.oup.com/ageing/article-pdf/50/1/25/42362959/afaa207.pdf; doi:https://doi.org/10.1093/ageing/afaa207; html:https://europepmc.org/articles/PMC7546151; pdf:https://europepmc.org/articles/PMC7546151?pdf=render
 33087383,https://doi.org/10.1136/bmjopen-2020-043010,Understanding and responding to COVID-19 in Wales: protocol for a privacy-protecting data platform for enhanced epidemiology and evaluation of interventions. ,"Lyons J, Akbari A, Torabi F, Davies GI, North L, Griffiths R, Bailey R, Hollinghurst J, Fry R, Turner SL, Thompson D, Rafferty J, Mizen A, Orton C, Thompson S, Au-Yeung L, Cross L, Gravenor MB, Brophy S, Lucini B, John A, Szakmany T, Davies J, Davies C, Thomas DR, Williams C, Emmerson C, Cottrell S, Connor TR, Taylor C, Pugh RJ, Diggle P, John G, Scourfield S, Hunt J, Cunningham AM, Helliwell K, Lyons R.",,BMJ open,2020,2020-10-21,Y,,,,"The emergence of the novel respiratory SARS-CoV-2 and subsequent COVID-19 pandemic have required rapid assimilation of population-level data to understand and control the spread of infection in the general and vulnerable populations. Rapid analyses are needed to inform policy development and target interventions to at-risk groups to prevent serious health outcomes. We aim to provide an accessible research platform to determine demographic, socioeconomic and clinical risk factors for infection, morbidity and mortality of COVID-19, to measure the impact of COVID-19 on healthcare utilisation and long-term health, and to enable the evaluation of natural experiments of policy interventions. Two privacy-protecting population-level cohorts have been created and derived from multisourced demographic and healthcare data. The C20 cohort consists of 3.2 million people in Wales on the 1 January 2020 with follow-up until 31 May 2020. The complete cohort dataset will be updated monthly with some individual datasets available daily. The C16 cohort consists of 3 million people in Wales on the 1 January 2016 with follow-up to 31 December 2019. C16 is designed as a counterfactual cohort to provide contextual comparative population data on disease, health service utilisation and mortality. Study outcomes will: (a) characterise the epidemiology of COVID-19, (b) assess socioeconomic and demographic influences on infection and outcomes, (c) measure the impact of COVID-19 on short -term and longer-term population outcomes and (d) undertake studies on the transmission and spatial spread of infection. The Secure Anonymised Information Linkage-independent Information Governance Review Panel has approved this study. The study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/10/e043010.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043010; html:https://europepmc.org/articles/PMC7580065; pdf:https://europepmc.org/articles/PMC7580065?pdf=render
-36987388,https://doi.org/10.1177/08862605231163885,Characterizing the Differences in Descriptions of Violence on Reddit During the COVID-19 Pandemic.,"Li L, Neubauer L, Stewart R, Roberts A.",,Journal of interpersonal violence,2023,2023-03-28,Y,Increase rate; Data Classification; Reddit; Violence Types,,,"Concerns have been raised over the experiences of violence such as domestic violence (DV) and intimate partner violence (IPV) during the COVID-19 pandemic. Social media such as Reddit represent an alternative outlet for reporting experiences of violence where healthcare access has been limited. This study analyzed seven violence-related subreddits to investigate the trends of different violence patterns from January 2018 to February 2022 to enhance the health-service providers' existing service or provide some new perspective for existing violence research. Specifically, we collected violence-related texts from Reddit using keyword searching and identified six major types with supervised machine learning classifiers: DV, IPV, physical violence, sexual violence, emotional violence, and nonspecific violence or others. The increase rate (IR) of each violence type was calculated and temporally compared in five phases of the pandemic. The phases include one pre-pandemic phase (<i>Phase 0</i>, the date before February 26, 2020) and four pandemic phases (<i>Phases 1-4</i>) with separation dates of June 17, 2020, September 7, 2020, and June 4, 2021. We found that the number of IPV-related posts increased most in the earliest phase; however, that for COVID-citing IPV was highest in the mid-pandemic phase. IRs for DV, IPV, and emotional violence also showed increases across all pandemic phases, with IRs of 26.9%, 58.8%, and 28.8%, respectively, from the pre-pandemic to the first pandemic phase. In the other three pandemic phases, all the IRs for these three types of violence were positive, though lower than the IRs in the first pandemic phase. The findings highlight the importance of identifying and providing help to those who suffer from such violent experiences and support the role of social media site monitoring as a means of informative surveillance for help-providing authorities and violence research groups.",,doi:https://doi.org/10.1177/08862605231163885; doi:https://doi.org/10.1177/08862605231163885; html:https://europepmc.org/articles/PMC10064198; pdf:https://europepmc.org/articles/PMC10064198?pdf=render
 36276403,https://doi.org/10.3389/fpubh.2022.875198,The mental health experiences of ethnic minorities in the UK during the Coronavirus pandemic: A qualitative exploration.,"Van Bortel T, Lombardo C, Guo L, Solomon S, Martin S, Hughes K, Weeks L, Crepaz-Keay D, McDaid S, Chantler O, Thorpe L, Morton A, Davidson G, John A, Kousoulis AA.",,Frontiers in public health,2022,2022-10-06,Y,Mental health; United Kingdom; Inequalities; Ethnic Minorities; Covid-19; Coronavirus Pandemic; Bame Ethnicity,,,"<h4>Background</h4>Worldwide, the Coronavirus pandemic has had a major impact on people's health, lives, and livelihoods. However, this impact has not been felt equally across various population groups. People from ethnic minority backgrounds in the UK have been more adversely affected by the pandemic, especially in terms of their physical health. Their mental health, on the other hand, has received less attention. This study aimed to explore the mental health experiences of UK adults from ethnic minorities during the Coronavirus pandemic. This work forms part of our wider long-term UK population study ""Mental Health in the Pandemic.""<h4>Methods</h4>We conducted an exploratory qualitative study with people from ethnic minority communities across the UK. A series of in-depth interviews were conducted with 15 women, 14 men and 1 non-binary person from ethnic minority backgrounds, aged between 18 and 65 years old (mean age = 40). We utilized purposefully selected maximum variation sampling in order to capture as wide a variety of views, perceptions and experiences as possible. Inclusion criteria: adults (18+) from ethnic minorities across the UK; able to provide full consent to participate; able to participate in a video- or phone-call interview. All interviews took place <i>via</i> MS Teams or Zoom. The gathered data were transcribed verbatim and underwent thematic analysis following Braun and Clarke carried out using NVivo 12 software.<h4>Results</h4>The qualitative data analysis yielded seven overarching themes: (1) pandemic-specific mental health and wellbeing experiences; (2) issues relating to the media; (3) coping mechanisms; (4) worries around and attitudes toward vaccination; (5) suggestions for support in moving forward; (6) best and worst experiences during pandemic and lockdowns; (7) biggest areas of change in personal life. Generally, participants' mental health experiences varied with some not being affected by the pandemic in a way related to their ethnicity, some sharing positive experiences and coping strategies (exercising more, spending more time with family, community cohesion), and some expressing negative experiences (eating or drinking more, feeling more isolated, or even racism and abuse, especially toward Asian communities). Concerns were raised around trust issues in relation to the media, the inadequate representation of ethnic minorities, and the spread of fake news especially on social media. Attitudes toward vaccinations varied too, with some people more willing to have the vaccine than others.<h4>Conclusion</h4>This study's findings highlight the diversity in the pandemic mental health experiences of ethnic minorities in the UK and has implications for policy, practice and further research. To enable moving forward beyond the pandemic, our study surfaced the need for culturally appropriate mental health support, financial support (as a key mental health determinant), accurate media representation, and clear communication messaging from the Governments of the UK.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.875198/pdf; doi:https://doi.org/10.3389/fpubh.2022.875198; html:https://europepmc.org/articles/PMC9582845; pdf:https://europepmc.org/articles/PMC9582845?pdf=render
+36987388,https://doi.org/10.1177/08862605231163885,Characterizing the Differences in Descriptions of Violence on Reddit During the COVID-19 Pandemic.,"Li L, Neubauer L, Stewart R, Roberts A.",,Journal of interpersonal violence,2023,2023-03-28,Y,Increase rate; Data Classification; Reddit; Violence Types,,,"Concerns have been raised over the experiences of violence such as domestic violence (DV) and intimate partner violence (IPV) during the COVID-19 pandemic. Social media such as Reddit represent an alternative outlet for reporting experiences of violence where healthcare access has been limited. This study analyzed seven violence-related subreddits to investigate the trends of different violence patterns from January 2018 to February 2022 to enhance the health-service providers' existing service or provide some new perspective for existing violence research. Specifically, we collected violence-related texts from Reddit using keyword searching and identified six major types with supervised machine learning classifiers: DV, IPV, physical violence, sexual violence, emotional violence, and nonspecific violence or others. The increase rate (IR) of each violence type was calculated and temporally compared in five phases of the pandemic. The phases include one pre-pandemic phase (<i>Phase 0</i>, the date before February 26, 2020) and four pandemic phases (<i>Phases 1-4</i>) with separation dates of June 17, 2020, September 7, 2020, and June 4, 2021. We found that the number of IPV-related posts increased most in the earliest phase; however, that for COVID-citing IPV was highest in the mid-pandemic phase. IRs for DV, IPV, and emotional violence also showed increases across all pandemic phases, with IRs of 26.9%, 58.8%, and 28.8%, respectively, from the pre-pandemic to the first pandemic phase. In the other three pandemic phases, all the IRs for these three types of violence were positive, though lower than the IRs in the first pandemic phase. The findings highlight the importance of identifying and providing help to those who suffer from such violent experiences and support the role of social media site monitoring as a means of informative surveillance for help-providing authorities and violence research groups.",,doi:https://doi.org/10.1177/08862605231163885; doi:https://doi.org/10.1177/08862605231163885; html:https://europepmc.org/articles/PMC10064198; pdf:https://europepmc.org/articles/PMC10064198?pdf=render
 33328453,https://doi.org/10.1038/s41467-020-19996-z,Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2020,2020-12-16,Y,,,,"Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).",,pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render
 35434685,https://doi.org/10.1016/j.lanepe.2022.100381,Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.,"Liu Y, Pearson CAB, Sandmann FG, Barnard RC, Kim JH, CMMID COVID-19 Working Group, Flasche S, Jit M, Abbas K.",,The Lancet regional health. Europe,2022,2022-04-11,Y,"Quantitative Methods; Mathematical Modelling; Public Health Intervention; Vaccine Policy; Ve, Vaccine Efficacy; Covid-19; Sars-cov-2; Voc, Variant Of Concern; Aefi, Adverse Events Following Immunisation; Mic, Middle Income Country",,,"<h4>Background</h4>In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.<h4>Methods</h4>We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.<h4>Findings</h4>In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.<h4>Interpretation</h4>We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.<h4>Funding</h4>World Health Organization.",,doi:https://doi.org/10.1016/j.lanepe.2022.100381; doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render
 36476601,https://doi.org/10.1186/s12911-022-02055-6,Neural-signature methods for structured EHR prediction.,"Vauvelle A, Creed P, Denaxas S.",,BMC medical informatics and decision making,2022,2022-12-07,Y,Machine Learning; Electronic Healthcare Records; Signature Methods,,,"Models that can effectively represent structured Electronic Healthcare Records (EHR) are central to an increasing range of applications in healthcare. Due to the sequential nature of health data, Recurrent Neural Networks have emerged as the dominant component within state-of-the-art architectures. The signature transform represents an alternative modelling paradigm for sequential data. This transform provides a non-learnt approach to creating a fixed vector representation of temporal features and has shown strong performances across an increasing number of domains, including medical data. However, the signature method has not yet been applied to structured EHR data. To this end, we follow recent work that enables the signature to be used as a differentiable layer within a neural architecture enabling application in high dimensional domains where calculation would have previously been intractable. Using a heart failure prediction task as an exemplar, we provide an empirical evaluation of different variations of the signature method and compare against state-of-the-art baselines. This first application of neural-signature methods in real-world healthcare data shows a competitive performance when compared to strong baselines and thus warrants further investigation within the health domain.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02055-6; doi:https://doi.org/10.1186/s12911-022-02055-6; html:https://europepmc.org/articles/PMC9730578; pdf:https://europepmc.org/articles/PMC9730578?pdf=render
@@ -368,8 +368,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 37080124,https://doi.org/10.1016/j.seizure.2023.04.006,COVID-19 vaccination uptake in people with epilepsy in wales.,"Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",,Seizure,2023,2023-04-06,Y,"Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",,,"<h4>Purpose</h4>People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.<h4>Methods</h4>We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.<h4>Results</h4>There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.<h4>Conclusions</h4>COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",,doi:https://doi.org/10.1016/j.seizure.2023.04.006; doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render
 33901420,https://doi.org/10.1016/s0140-6736(21)00677-2,Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study.,"Vasileiou E, Simpson CR, Shi T, Kerr S, Agrawal U, Akbari A, Bedston S, Beggs J, Bradley D, Chuter A, de Lusignan S, Docherty AB, Ford D, Hobbs FR, Joy M, Katikireddi SV, Marple J, McCowan C, McGagh D, McMenamin J, Moore E, Murray JL, Pan J, Ritchie L, Shah SA, Stock S, Torabi F, Tsang RS, Wood R, Woolhouse M, Robertson C, Sheikh A.",,"Lancet (London, England)",2021,2021-04-23,Y,,,,"<h4>Background</h4>The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19.<h4>Methods</h4>We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19-EAVE II-database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1-adjusted rate ratio) following the first dose of vaccine.<h4>Findings</h4>Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85-94) for reduced COVID-19 hospital admission at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75-94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72-89 at 28-34 days post-vaccination).<h4>Interpretation</h4>Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding.<h4>Funding</h4>UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK.",,pdf:http://www.thelancet.com/article/S0140673621006772/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00677-2; html:https://europepmc.org/articles/PMC8064669
 37717030,https://doi.org/10.1186/s13756-023-01280-6,The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.,"Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",,Antimicrobial resistance and infection control,2023,2023-09-16,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"<h4>Background</h4>There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.<h4>Methods</h4>With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.<h4>Results</h4>Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.<h4>Conclusions</h4>Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",,doi:https://doi.org/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render
-35087703,https://doi.org/10.5334/aogh.3465,Household Air Pollution and Respiratory Symptoms a Month Before and During the Stringent COVID-19 Lockdown Levels 5 and 4 in South Africa.,"Wright CY, Kapwata T, Abdelatif N, Batini C, Wernecke B, Kunene Z, Millar DA, Mathee A, Street R, Panchal R, Hansell A, Cordell R, Hey JV.",,Annals of global health,2022,2022-01-10,Y,,,,"<h4>Background</h4>Household air pollution (HAP) is associated with adverse human health impacts. During COVID-19 Lockdown Levels 5 and 4 (the most stringent levels), South Africans remained at home, potentially increasing their exposure to HAP.<h4>Objectives</h4>To investigate changes in fuel use behaviours/patterns of use affecting HAP exposure and associated HAP-related respiratory health outcomes during COVID-19 Lockdown Levels 5 and 4.<h4>Methods</h4>This was a cross-sectional online and telephonic survey of participants from an existing database. Logistic regression and McNemar's test were used to analyse household-level data.<h4>Results</h4>Among 2 505 participants, while electricity was the main energy source for cooking and heating the month before and during Lockdown Levels 5 and 4, some households used less electricity during Lockdown Levels 5 and 4 or switched to ""dirty fuels."" One third of participants reported presence of environmental tobacco smoke in the home, a source of HAP associated with respiratory illnesses. Prevalence of HAP-related respiratory health outcomes were <10% (except dry cough). Majority of households reported cooking more, cleaning more and spending more time indoors during Lockdown Levels 5 and 4 - potentially exposed to HAP.<h4>Conclusion</h4>Should South Africa return to Lockdown Levels 5 or 4, awareness raising about the risks associated with HAP as well as messaging information for prevention of exposure to HAP, including environmental tobacco smoke, and associated adverse health impacts will be necessary.",,pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?pdf=render
 34461893,https://doi.org/10.1186/s12916-021-02096-0,The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study.,"Wilde H, Mellan T, Hawryluk I, Dennis JM, Denaxas S, Pagel C, Duncan A, Bhatt S, Flaxman S, Mateen BA, Vollmer SJ.",,BMC medicine,2021,2021-08-30,Y,Critical Care; Hospital Mortality; Quality Of Healthcare; Public Health Surveillance; Coronavirus Infection,,,"<h4>Background</h4>The literature paints a complex picture of the association between mortality risk and ICU strain. In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain.<h4>Methods</h4>A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease).<h4>Results</h4>One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (< 45% relative to the baseline) [OR 0.83 (95% PCI 0.75 to 0.94)].<h4>Conclusion</h4>Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Further research is required to establish if this is a causal relationship or whether it reflects strain on other operational factors such as staff. If causal, the result highlights the importance of strategies to keep ICU occupancy low to mitigate the impact of this type of resource saturation.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02096-0; doi:https://doi.org/10.1186/s12916-021-02096-0; html:https://europepmc.org/articles/PMC8404408; pdf:https://europepmc.org/articles/PMC8404408?pdf=render
+35087703,https://doi.org/10.5334/aogh.3465,Household Air Pollution and Respiratory Symptoms a Month Before and During the Stringent COVID-19 Lockdown Levels 5 and 4 in South Africa.,"Wright CY, Kapwata T, Abdelatif N, Batini C, Wernecke B, Kunene Z, Millar DA, Mathee A, Street R, Panchal R, Hansell A, Cordell R, Hey JV.",,Annals of global health,2022,2022-01-10,Y,,,,"<h4>Background</h4>Household air pollution (HAP) is associated with adverse human health impacts. During COVID-19 Lockdown Levels 5 and 4 (the most stringent levels), South Africans remained at home, potentially increasing their exposure to HAP.<h4>Objectives</h4>To investigate changes in fuel use behaviours/patterns of use affecting HAP exposure and associated HAP-related respiratory health outcomes during COVID-19 Lockdown Levels 5 and 4.<h4>Methods</h4>This was a cross-sectional online and telephonic survey of participants from an existing database. Logistic regression and McNemar's test were used to analyse household-level data.<h4>Results</h4>Among 2 505 participants, while electricity was the main energy source for cooking and heating the month before and during Lockdown Levels 5 and 4, some households used less electricity during Lockdown Levels 5 and 4 or switched to ""dirty fuels."" One third of participants reported presence of environmental tobacco smoke in the home, a source of HAP associated with respiratory illnesses. Prevalence of HAP-related respiratory health outcomes were <10% (except dry cough). Majority of households reported cooking more, cleaning more and spending more time indoors during Lockdown Levels 5 and 4 - potentially exposed to HAP.<h4>Conclusion</h4>Should South Africa return to Lockdown Levels 5 or 4, awareness raising about the risks associated with HAP as well as messaging information for prevention of exposure to HAP, including environmental tobacco smoke, and associated adverse health impacts will be necessary.",,pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?pdf=render
 34458849,https://doi.org/10.1093/oxfimm/iqab014,Protease inhibitor plasma concentrations associate with COVID-19 infection.,"Medjeral-Thomas NR, Troldborg A, Hansen AG, Pihl R, Clarke CL, Peters JE, Thomas DC, Willicombe M, Palarasah Y, Botto M, Pickering MC, Thiel S.",,Oxford open immunology,2021,2021-07-07,Y,Coronavirus; Protease inhibitors; innate immunity; Covid-19,,,"Protease inhibitors influence a range of innate immunity and inflammatory pathways. We quantified plasma concentrations of key anti-inflammatory protease inhibitors in chronic haemodialysis patients with coronavirus disease 2019 (COVID-19). The samples were collected early in the disease course to determine whether plasma protease inhibitor levels associated with the presence and severity of COVID-19. We used antibody-based immunoassays to measure plasma concentrations of C1 esterase inhibitor, alpha2-macroglobulin, antithrombin and inter-alpha-inhibitor heavy chain 4 (ITIH4) in 100 serial samples from 27 haemodialysis patients with COVID-19. ITIH4 was tested in two assays, one measuring intact ITIH4 and another also detecting any fragmented ITIH4 (total ITIH4). Control cohorts were 32 haemodialysis patients without COVID-19 and 32 healthy controls. We compared protease inhibitor concentration based on current and future COVID-19 severity and with C-reactive protein. Results were adjusted for repeated measures and multiple comparisons. Analysis of all available samples demonstrated lower plasma C1 esterase inhibitor and α2M and higher total ITIH4 in COVID-19 compared with dialysis controls. These differences were also seen in the first sample collected after COVID-19 diagnosis, a median of 4 days from diagnostic swab. Plasma ITIH4 levels were higher in severe than the non-severe COVID-19. Serum C-reactive protein correlated positively with plasma levels of antithrombin, intact ITIH4 and total ITIH4. In conclusion, plasma protease inhibitor concentrations are altered in COVID-19.",,pdf:https://academic.oup.com/ooim/article-pdf/2/1/iqab014/48744499/iqab014.pdf; doi:https://doi.org/10.1093/oxfimm/iqab014; html:https://europepmc.org/articles/PMC8371939; pdf:https://europepmc.org/articles/PMC8371939?pdf=render
 33316211,https://doi.org/10.1016/s2352-3018(20)30305-2,HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform.,"Bhaskaran K, Rentsch CT, MacKenna B, Schultze A, Mehrkar A, Bates CJ, Eggo RM, Morton CE, Bacon SCJ, Inglesby P, Douglas IJ, Walker AJ, McDonald HI, Cockburn J, Williamson EJ, Evans D, Forbes HJ, Curtis HJ, Hulme WJ, Parry J, Hester F, Harper S, Evans SJW, Smeeth L, Goldacre B.",,The lancet. HIV,2021,2020-12-11,Y,,,,"<h4>Background</h4>Whether HIV infection is associated with risk of death due to COVID-19 is unclear. We aimed to investigate this association in a large-scale population-based study in England.<h4>Methods</h4>We did a retrospective cohort study. Working on behalf of NHS England, we used the OpenSAFELY platform to analyse routinely collected electronic primary care data linked to national death registrations. We included all adults (aged ≥18 years) alive and in follow-up on Feb 1, 2020, and with at least 1 year of continuous registration with a general practitioner before this date. People with a primary care record for HIV infection were compared with people without HIV. The outcome was COVID-19 death, defined as the presence of International Classification of Diseases 10 codes U07.1 or U07.2 anywhere on the death certificate. Cox regression models were used to estimate the association between HIV infection and COVID-19 death; they were initially adjusted for age and sex, then we added adjustment for index of multiple deprivation and ethnicity, and then for a broad range of comorbidities. Interaction terms were added to assess effect modification by age, sex, ethnicity, comorbidities, and calendar time.<h4>Results</h4>17 282 905 adults were included, of whom 27 480 (0·16%) had HIV recorded. People living with HIV were more likely to be male, of Black ethnicity, and from a more deprived geographical area than the general population. 14 882 COVID-19 deaths occurred during the study period, with 25 among people with HIV. People living with HIV had higher risk of COVID-19 death than those without HIV after adjusting for age and sex: hazard ratio (HR) 2·90 (95% CI 1·96-4·30; p<0·0001). The association was attenuated, but risk remained high, after adjustment for deprivation, ethnicity, smoking and obesity: adjusted HR 2·59 (95% CI 1·74-3·84; p<0·0001). There was some evidence that the association was larger among people of Black ethnicity: HR 4·31 (95% CI 2·42-7·65) versus 1·84 (1·03-3·26) in non-Black individuals (p-interaction=0·044).<h4>Interpretation</h4>People with HIV in the UK seem to be at increased risk of COVID-19 mortality. Targeted policies should be considered to address this raised risk as the pandemic response evolves.<h4>Funding</h4>Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2352301820303052/pdf; doi:https://doi.org/10.1016/S2352-3018(20)30305-2; html:https://europepmc.org/articles/PMC7773630; pdf:https://europepmc.org/articles/PMC7773630?pdf=render
 33758017,https://doi.org/10.1126/science.abf9648,The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia.,"Pavelka M, Van-Zandvoort K, Abbott S, Sherratt K, Majdan M, CMMID COVID-19 working group, Inštitút Zdravotných Analýz, Jarčuška P, Krajčí M, Flasche S, Funk S.",,"Science (New York, N.Y.)",2021,2021-03-23,Y,,,,"Slovakia conducted multiple rounds of population-wide rapid antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% confidence interval: 57 to 58%) within 1 week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic growth of 4.4% (1.1 to 6.9%) per day preceding the mass testing campaign, the estimated decrease in prevalence compared with a scenario of unmitigated growth was 70% (67 to 73%). Modeling indicated that this decrease could not be explained solely by infection control measures but required the addition of the isolation and quarantine of household members of those testing positive.",,pdf:https://www.science.org/cms/asset/e974db95-138d-4a9f-aa91-2f8f6c705f36/pap.pdf; doi:https://doi.org/10.1126/science.abf9648; html:https://europepmc.org/articles/PMC8139426; pdf:https://europepmc.org/articles/PMC8139426?pdf=render
@@ -378,8 +378,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 33667930,https://doi.org/10.1016/j.ijmedinf.2021.104400,Real-time spatial health surveillance: Mapping the UK COVID-19 epidemic.,"Fry R, Hollinghurst J, Stagg HR, Thompson DA, Fronterre C, Orton C, Lyons RA, Ford DV, Sheikh A, Diggle PJ.",,International journal of medical informatics,2021,2021-01-28,Y,,,,"Introduction The COVID-19 pandemic has highlighted the need for robust data linkage systems and methods for identifying outbreaks of disease in near real-time. Objectives The primary objective of this study was to develop a real-time geospatial surveillance system to monitor the spread of COVID-19 across the UK. Methods Using self-reported app data and the Secure Anonymised Information Linkage (SAIL) Databank, we demonstrate the use of sophisticated spatial modelling for near-real-time prediction of COVID-19 prevalence at small-area resolution to inform strategic government policy areas. Results We demonstrate that using a combination of crowd-sourced app data and sophisticated geo-statistical techniques it is possible to predict hot spots of COVID-19 at fine geographic scales, nationally. We are also able to produce estimates of their precision, which is an important pre-requisite to an effective control strategy to guard against over-reaction to potentially spurious features of 'best guess' predictions. Conclusion In the UK, important emerging risk-factors such as social deprivation or ethnicity vary over small distances, hence risk needs to be modelled at fine spatial resolution to avoid aggregation bias. We demonstrate that existing geospatial statistical methods originally developed for global health applications are well-suited to this task and can be used in an anonymised databank environment, thus preserving the privacy of the individuals who contribute their data.",,doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; html:https://europepmc.org/articles/PMC7843148
 35476839,https://doi.org/10.1371/journal.pone.0266967,"Healthcare contacts with self-harm during COVID-19: An e-cohort whole-population-based study using individual-level linked routine electronic health records in Wales, UK, 2016-March 2021.","DelPozo-Banos M, Lee SC, Friedmann Y, Akbari A, Torabi F, Lloyd K, Lyons RA, John A.",,PloS one,2022,2022-04-27,Y,,,,"<h4>Introduction</h4>Reduced rates of help seeking by those who self-harmed during the COVID-19 pandemic have been reported.<h4>Objectives</h4>To understand changes in healthcare service contacts for self-harm during the COVID-19 pandemic across primary, emergency and secondary care.<h4>Methods</h4>This retrospective cohort study used routine electronic healthcare data for Wales, United Kingdom, from 2016 to March 14, 2021. Population-based data from primary care, emergency departments and hospital admissions were linked at individual-level. All Welsh residents aged ≥10 years over the study period were included in the study. Primary, emergency and secondary care contacts with self-harm at any time between 2016 and March 14, 2021 were identified. Outcomes were counts, incidence, prevalence and proportion of self-harm contacts relative to all contacts in each and all settings, as well as the proportion of people contacting one or more settings with self-harm. Weekly trends were modelled using generalised estimated equations, with differences between 2020 (to March 2021) and comparison years 2016-2018 (to March 2017-2019) quantified using difference in differences, from which mean rate of odds ratios (μROR) across years was reported.<h4>Results</h4>The study included 3,552,210 individuals over the study period. Self-harm contacts reduced across services in March and December 2020 compared to previous years. Primary care contacts with self-harm reduced disproportionately compared to non-self-harm contacts (μROR = 0.7, p<0.05), while their proportion increased in emergency departments during April 2020 (μROR = 1.3, p<0.05 in 2/3 comparison years) and hospital admissions during April-May 2020 (μROR = 1.2, p<0.05 in 2/3 comparison years). Despite this, those who self-harmed in April 2020 were more likely to be seen in primary care than other settings compared to previous years (μROR = 1.2, p<0.05). A lower proportion of those with self-harm contacts in emergency departments were subsequently admitted to hospital in December 2020 compared to previous years (μROR = 0.5, p<0.05).<h4>Conclusions</h4>These findings suggest that those who self-harmed during the COVID-19 pandemic may have been less likely to seek help, and those who did so faced more stringent criteria for admission. Communications encouraging those who self-harm to seek help during pandemics may be beneficial. However, this needs to be supported by maintained provision of mental health services.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266967&type=printable; doi:https://doi.org/10.1371/journal.pone.0266967; html:https://europepmc.org/articles/PMC9045644; pdf:https://europepmc.org/articles/PMC9045644?pdf=render
 36526323,https://doi.org/10.1136/bmjopen-2022-068252,"Identification of risk factors associated with prolonged hospital stay following primary knee replacement surgery: a retrospective, longitudinal observational study.","Wilson R, Margelyte R, Redaniel MT, Eyles E, Jones T, Penfold C, Blom A, Elliott A, Harper A, Keen T, Pitt M, Judge A.",,BMJ open,2022,2022-12-16,Y,Knee; Rheumatology; Statistics & Research Methods; Orthopaedic & Trauma Surgery; Adult Orthopaedics,,,"<h4>Objectives</h4>To identify risk factors associated with prolonged length of hospital stay and staying in hospital longer than medically necessary following primary knee replacement surgery.<h4>Design</h4>Retrospective, longitudinal observational study.<h4>Setting</h4>Elective knee replacement surgeries between 2016 and 2019 were identified using routinely collected data from an NHS Trust in England.<h4>Participants</h4>There were 2295 knee replacement patients with complete data included in analysis. The mean age was 68 (SD 11) and 60% were female.<h4>Outcome measures</h4>We assessed a binary length of stay outcome (>7 days), a continuous length of stay outcome (≤30 days) and a binary measure of whether patients remained in hospital when they were medically fit for discharge.<h4>Results</h4>The mean length of stay was 5.0 days (SD 3.9), 15.4% of patients were in hospital for >7 days and 7.1% remained in hospital when they were medically fit for discharge. Longer length of stay was associated with older age (<i>b=</i>0.08, 95% CI 0.07 to 0.09), female sex (<i>b</i>=0.36, 95% CI 0.06 to 0.67), high deprivation (<i>b</i>=0.98, 95% CI 0.47 to 1.48) and more comorbidities (<i>b</i>=2.48, 95% CI 0.15 to 4.81). Remaining in hospital beyond being medically fit for discharge was associated with older age (OR=1.07, 95% CI 1.05 to 1.09), female sex (OR=1.71, 95% CI 1.19 to 2.47) and high deprivation (OR=2.27, 95% CI 1.27 to 4.06).<h4>Conclusions</h4>The regression models could be used to identify which patients are likely to occupy hospital beds for longer. This could be helpful in scheduling operations to aid hospital efficiency by planning these patients' operations for when the hospital is less busy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e068252.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068252; html:https://europepmc.org/articles/PMC9764602; pdf:https://europepmc.org/articles/PMC9764602?pdf=render
-37429634,https://doi.org/10.3399/bjgpo.2023.0057,UK research data resources based on primary care electronic health records: review and summary for potential users.,"Edwards L, Pickett J, Ashcroft DM, Dambha-Miller H, Majeed A, Mallen C, Petersen I, Qureshi N, van Staa T, Abel G, Carvalho C, Denholm R, Kontopantelis E, Macaulay A, Macleod J.",,BJGP open,2023,2023-09-19,N,Population; Primary Health Care; Electronic Health Records; Primary Care Databases; Population Level Linked Data,,,"<h4>Background</h4>The range and scope of electronic health record (EHR) data assets in the UK has recently increased, which has been mainly in response to the COVID-19 pandemic. Summarising and comparing the large primary care resources will help researchers to choose the data resources most suited to their needs.<h4>Aim</h4>To describe the current landscape of UK EHR databases and considerations of access and use of these resources relevant to researchers.<h4>Design & setting</h4>Narrative review of EHR databases in the UK.<h4>Method</h4>Information was collected from the Health Data Research Innovation Gateway, publicly available websites and other published data, and from key informants. The eligibility criteria were population-based open-access databases sampling EHRs across the whole population of one or more countries in the UK. Published database characteristics were extracted and summarised, and these were corroborated with resource providers. Results were synthesised narratively.<h4>Results</h4>Nine large national primary care EHR data resources were identified and summarised. These resources are enhanced by linkage to other administrative data to a varying extent. Resources are mainly intended to support observational research, although some can support experimental studies. There is considerable overlap of populations covered. While all resources are accessible to bona fide researchers, access mechanisms, costs, timescales, and other considerations vary across databases.<h4>Conclusion</h4>Researchers are currently able to access primary care EHR data from several sources. Choice of data resource is likely to be driven by project needs and access considerations. The landscape of data resources based on primary care EHRs in the UK continues to evolve.",,doi:https://doi.org/10.3399/bjgpo.2023.0057; doi:https://doi.org/10.3399/BJGPO.2023.0057
 34011491,https://doi.org/10.1136/bmj.n1137,Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries.,"Islam N, Shkolnikov VM, Acosta RJ, Klimkin I, Kawachi I, Irizarry RA, Alicandro G, Khunti K, Yates T, Jdanov DA, White M, Lewington S, Lacey B.",,BMJ (Clinical research ed.),2021,2021-05-19,Y,,,,"<h4>Objective</h4>To estimate the direct and indirect effects of the covid-19 pandemic on mortality in 2020 in 29 high income countries with reliable and complete age and sex disaggregated mortality data.<h4>Design</h4>Time series study of high income countries.<h4>Setting</h4>Austria, Belgium, Czech Republic, Denmark, England and Wales, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, the Netherlands, New Zealand, Northern Ireland, Norway, Poland, Portugal, Scotland, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, and United States.<h4>Participants</h4>Mortality data from the Short-term Mortality Fluctuations data series of the Human Mortality Database for 2016-20, harmonised and disaggregated by age and sex.<h4>Interventions</h4>Covid-19 pandemic and associated policy measures.<h4>Main outcome measures</h4>Weekly excess deaths (observed deaths versus expected deaths predicted by model) in 2020, by sex and age (0-14, 15-64, 65-74, 75-84, and ≥85 years), estimated using an over-dispersed Poisson regression model that accounts for temporal trends and seasonal variability in mortality.<h4>Results</h4>An estimated 979 000 (95% confidence interval 954 000 to 1 001 000) excess deaths occurred in 2020 in the 29 high income countries analysed. All countries had excess deaths in 2020, except New Zealand, Norway, and Denmark. The five countries with the highest absolute number of excess deaths were the US (458 000, 454 000 to 461 000), Italy (89 100, 87 500 to 90 700), England and Wales (85 400, 83 900 to 86 800), Spain (84 100, 82 800 to 85 300), and Poland (60 100, 58 800 to 61 300). New Zealand had lower overall mortality than expected (-2500, -2900 to -2100). In many countries, the estimated number of excess deaths substantially exceeded the number of reported deaths from covid-19. The highest excess death rates (per 100 000) in men were in Lithuania (285, 259 to 311), Poland (191, 184 to 197), Spain (179, 174 to 184), Hungary (174, 161 to 188), and Italy (168, 163 to 173); the highest rates in women were in Lithuania (210, 185 to 234), Spain (180, 175 to 185), Hungary (169, 156 to 182), Slovenia (158, 132 to 184), and Belgium (151, 141 to 162). Little evidence was found of subsequent compensatory reductions following excess mortality.<h4>Conclusion</h4>Approximately one million excess deaths occurred in 2020 in these 29 high income countries. Age standardised excess death rates were higher in men than women in almost all countries. Excess deaths substantially exceeded reported deaths from covid-19 in many countries, indicating that determining the full impact of the pandemic on mortality requires assessment of excess deaths. Many countries had lower deaths than expected in children <15 years. Sex inequality in mortality widened further in most countries in 2020.",,pdf:https://www.bmj.com/content/bmj/373/bmj.n1137.full.pdf; doi:https://doi.org/10.1136/bmj.n1137; html:https://europepmc.org/articles/PMC8132017; pdf:https://europepmc.org/articles/PMC8132017?pdf=render
+37429634,https://doi.org/10.3399/bjgpo.2023.0057,UK research data resources based on primary care electronic health records: review and summary for potential users.,"Edwards L, Pickett J, Ashcroft DM, Dambha-Miller H, Majeed A, Mallen C, Petersen I, Qureshi N, van Staa T, Abel G, Carvalho C, Denholm R, Kontopantelis E, Macaulay A, Macleod J.",,BJGP open,2023,2023-09-19,N,Population; Primary Health Care; Electronic Health Records; Primary Care Databases; Population Level Linked Data,,,"<h4>Background</h4>The range and scope of electronic health record (EHR) data assets in the UK has recently increased, which has been mainly in response to the COVID-19 pandemic. Summarising and comparing the large primary care resources will help researchers to choose the data resources most suited to their needs.<h4>Aim</h4>To describe the current landscape of UK EHR databases and considerations of access and use of these resources relevant to researchers.<h4>Design & setting</h4>Narrative review of EHR databases in the UK.<h4>Method</h4>Information was collected from the Health Data Research Innovation Gateway, publicly available websites and other published data, and from key informants. The eligibility criteria were population-based open-access databases sampling EHRs across the whole population of one or more countries in the UK. Published database characteristics were extracted and summarised, and these were corroborated with resource providers. Results were synthesised narratively.<h4>Results</h4>Nine large national primary care EHR data resources were identified and summarised. These resources are enhanced by linkage to other administrative data to a varying extent. Resources are mainly intended to support observational research, although some can support experimental studies. There is considerable overlap of populations covered. While all resources are accessible to bona fide researchers, access mechanisms, costs, timescales, and other considerations vary across databases.<h4>Conclusion</h4>Researchers are currently able to access primary care EHR data from several sources. Choice of data resource is likely to be driven by project needs and access considerations. The landscape of data resources based on primary care EHRs in the UK continues to evolve.",,doi:https://doi.org/10.3399/bjgpo.2023.0057; doi:https://doi.org/10.3399/BJGPO.2023.0057
 36716318,https://doi.org/10.1371/journal.pmed.1004174,Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A Mendelian randomisation study.,"Hamilton FW, Thomas M, Arnold D, Palmer T, Moran E, Mentzer AJ, Maskell N, Baillie K, Summers C, Hingorani A, MacGowan A, Khandaker GM, Mitchell R, Davey Smith G, Ghazal P, Timpson NJ.",,PLoS medicine,2023,2023-01-30,Y,,,,"<h4>Background</h4>Sepsis is characterised by dysregulated, life-threatening immune responses, which are thought to be driven by cytokines such as interleukin 6 (IL-6). Genetic variants in IL6R known to down-regulate IL-6 signalling are associated with improved Coronavirus Disease 2019 (COVID-19) outcomes, a finding later confirmed in randomised trials of IL-6 receptor antagonists (IL6RAs). We hypothesised that blockade of IL6R could also improve outcomes in sepsis.<h4>Methods and findings</h4>We performed a Mendelian randomisation (MR) analysis using single nucleotide polymorphisms (SNPs) in and near IL6R to evaluate the likely causal effects of IL6R blockade on sepsis (primary outcome), sepsis severity, other infections, and COVID-19 (secondary outcomes). We weighted SNPs by their effect on CRP and combined results across them in inverse variance weighted meta-analysis, proxying the effect of IL6RA. Our outcomes were measured in UK Biobank, FinnGen, the COVID-19 Host Genetics Initiative (HGI), and the GenOSept and GainS consortium. We performed several sensitivity analyses to test assumptions of our methods, including utilising variants around CRP and gp130 in a similar analysis. In the UK Biobank cohort (N = 486,484, including 11,643 with sepsis), IL6R blockade was associated with a decreased risk of our primary outcome, sepsis (odds ratio (OR) = 0.80; 95% confidence interval (CI) 0.66 to 0.96, per unit of natural log-transformed CRP decrease). The size of this effect increased with severity, with larger effects on 28-day sepsis mortality (OR = 0.74; 95% CI 0.47 to 1.15); critical care admission with sepsis (OR = 0.48, 95% CI 0.30 to 0.78) and critical care death with sepsis (OR = 0.37, 95% CI 0.14 to 0.98). Similar associations were seen with severe respiratory infection: OR for pneumonia in critical care 0.69 (95% CI 0.49 to 0.97) and for sepsis survival in critical care (OR = 0.22; 95% CI 0.04 to 1.31) in the GainS and GenOSept consortium, although this result had a large degree of imprecision. We also confirm the previously reported protective effect of IL6R blockade on severe COVID-19 (OR = 0.69, 95% CI 0.57 to 0.84) in the COVID-19 HGI, which was of similar magnitude to that seen in sepsis. Sensitivity analyses did not alter our primary results. These results are subject to the limitations and assumptions of MR, which in this case reflects interpretation of these SNP effects as causally acting through blockade of IL6R, and reflect lifetime exposure to IL6R blockade, rather than the effect of therapeutic IL6R blockade.<h4>Conclusions</h4>IL6R blockade is causally associated with reduced incidence of sepsis. Similar but imprecisely estimated results supported a causal effect also on sepsis related mortality and critical care admission with sepsis. These effects are comparable in size to the effect seen in severe COVID-19, where IL-6 receptor antagonists were shown to improve survival. These data suggest that a randomised trial of IL-6 receptor antagonists in sepsis should be considered.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004174&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004174; html:https://europepmc.org/articles/PMC9925069; pdf:https://europepmc.org/articles/PMC9925069?pdf=render
 33419870,https://doi.org/10.1136/bmjhci-2020-100254,Network graph representation of COVID-19 scientific publications to aid knowledge discovery. ,"Cernile G, Heritage T, Sebire NJ, Gordon B, Schwering T, Kazemlou S, Borecki Y.",,BMJ health & care informatics,2021,2021-01-01,Y,,,,"Numerous scientific journal articles related to COVID-19 have been rapidly published, making navigation and understanding of relationships difficult. A graph network was constructed from the publicly available COVID-19 Open Research Dataset (CORD-19) of COVID-19-related publications using an engine leveraging medical knowledge bases to identify discrete medical concepts and an open-source tool (Gephi) to visualise the network. The network shows connections between diseases, medications and procedures identified from the title and abstract of 195 958 COVID-19-related publications (CORD-19 Dataset). Connections between terms with few publications, those unconnected to the main network and those irrelevant were not displayed. Nodes were coloured by knowledge base and the size of the node related to the number of publications containing the term. The data set and visualisations were made publicly accessible via a webtool. Knowledge management approaches (text mining and graph networks) can effectively allow rapid navigation and exploration of entity inter-relationships to improve understanding of diseases such as COVID-19.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100254.full.pdf; doi:https://doi.org/10.1136/bmjhci-2020-100254; html:https://europepmc.org/articles/PMC7798427; pdf:https://europepmc.org/articles/PMC7798427?pdf=render
 32835195,https://doi.org/10.1016/s2589-7500(20)30134-5,The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK.,"Drake TM, Docherty AB, Weiser TG, Yule S, Sheikh A, Harrison EM.",,The Lancet. Digital health,2020,2020-06-12,Y,,,,,,doi:https://doi.org/10.1016/s2589-7500(20)30134-5; doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render
@@ -394,15 +394,15 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 36446465,https://doi.org/10.1136/bmjopen-2022-065142,"Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.","Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ.",,BMJ open,2022,2022-11-29,Y,epidemiology; Public Health; Protocols & Guidelines; Covid-19,,,"<h4>Introduction</h4>The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.<h4>Methods and analysis</h4>Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.<h4>Ethics and dissemination</h4>Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.<h4>Trial registration number</h4>NCT05240742.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render
 36982069,https://doi.org/10.3390/ijerph20065161,The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.,"Lavalle R, Condominas E, Haro JM, Giné-Vázquez I, Bailon R, Laporta E, Garcia E, Kontaxis S, Alacid GR, Lombardini F, Preti A, Peñarrubia-Maria MT, Coromina M, Arranz B, Vilella E, Rubio-Alacid E, Radar-Mdd Spain, Matcham F, Lamers F, Hotopf M, Penninx BWJH, Annas P, Narayan V, Simblett SK, Siddi S, The Radar-Cns Consortium.",,International journal of environmental research and public health,2023,2023-03-15,Y,Quarantine; Depression; Anxiety; Spain; Lockdown; Remote Measurement Technology; Sars-cov-2; Decentralized Study,,,"The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the ""new normality"", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.",,pdf:https://www.mdpi.com/1660-4601/20/6/5161/pdf?version=1678866764; doi:https://doi.org/10.3390/ijerph20065161; html:https://europepmc.org/articles/PMC10048808; pdf:https://europepmc.org/articles/PMC10048808?pdf=render
 35027740,https://doi.org/10.1038/s41588-021-00996-8,Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19.,"Huffman JE, Butler-Laporte G, Khan A, Pairo-Castineira E, Drivas TG, Peloso GM, Nakanishi T, COVID-19 Host Genetics Initiative, Ganna A, Verma A, Baillie JK, Kiryluk K, Richards JB, Zeberg H.",,Nature genetics,2022,2022-01-13,Y,,,,"The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.",,pdf:https://www.nature.com/articles/s41588-021-00996-8.pdf; doi:https://doi.org/10.1038/s41588-021-00996-8; html:https://europepmc.org/articles/PMC8837537; pdf:https://europepmc.org/articles/PMC8837537?pdf=render
-36992188,https://doi.org/10.3390/vaccines11030604,"Household Composition and Inequalities in COVID-19 Vaccination in Wales, UK.","Lench A, Perry M, Johnson RD, Fry R, Richardson G, Lyons RA, Akbari A, Edwards A, Collins B, Joseph-Williams N, Cooper A, Cottrell S.",,Vaccines,2023,2023-03-07,Y,Vaccines; Vaccination; Households; Inequalities; Immunisation; Household Composition; Inequities; Covid-19,,,"The uptake of COVID-19 vaccination in Wales is high at a population level but many inequalities exist. Household composition may be an important factor in COVID-19 vaccination uptake due to the practical, social, and psychological implications associated with different living arrangements. In this study, the role of household composition in the uptake of COVID-19 vaccination in Wales was examined with the aim of identifying areas for intervention to address inequalities. Records within the Wales Immunisation System (WIS) COVID-19 vaccination register were linked to the Welsh Demographic Service Dataset (WDSD; a population register for Wales) held within the Secure Anonymised Information Linkage (SAIL) databank. Eight household types were defined based on household size, the presence or absence of children, and the presence of single or multiple generations. Uptake of the second dose of any COVID-19 vaccine was analysed using logistic regression. Gender, age group, health board, rural/urban residential classification, ethnic group, and deprivation quintile were included as covariates for multivariable regression. Compared to two-adult households, all other household types were associated with lower uptake. The most significantly reduced uptake was observed for large, multigenerational, adult group households (aOR 0.45, 95%CI 0.43-0.46). Comparing multivariable regression with and without incorporation of household composition as a variable produced significant differences in odds of vaccination for health board, age group, and ethnic group categories. These results indicate that household composition is an important factor for the uptake of COVID-19 vaccination and consideration of differences in household composition is necessary to mitigate vaccination inequalities.",,pdf:https://www.mdpi.com/2076-393X/11/3/604/pdf?version=1678670919; doi:https://doi.org/10.3390/vaccines11030604; html:https://europepmc.org/articles/PMC10055803; pdf:https://europepmc.org/articles/PMC10055803?pdf=render
 33745917,https://doi.org/10.1016/j.jinf.2021.03.011,"The dynamics of procalcitonin in COVID-19 patients admitted to Intensive care unit - a multi-centre cohort study in the South West of England, UK.","Williams P, McWilliams C, Soomro K, Harding I, Gurney S, Thomas M, Albur M, Martin Williams O.",,The Journal of infection,2021,2021-03-18,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970419; doi:https://doi.org/10.1016/j.jinf.2021.03.011; html:https://europepmc.org/articles/PMC7970419; pdf:https://europepmc.org/articles/PMC7970419?pdf=render
+36992188,https://doi.org/10.3390/vaccines11030604,"Household Composition and Inequalities in COVID-19 Vaccination in Wales, UK.","Lench A, Perry M, Johnson RD, Fry R, Richardson G, Lyons RA, Akbari A, Edwards A, Collins B, Joseph-Williams N, Cooper A, Cottrell S.",,Vaccines,2023,2023-03-07,Y,Vaccines; Vaccination; Households; Inequalities; Immunisation; Household Composition; Inequities; Covid-19,,,"The uptake of COVID-19 vaccination in Wales is high at a population level but many inequalities exist. Household composition may be an important factor in COVID-19 vaccination uptake due to the practical, social, and psychological implications associated with different living arrangements. In this study, the role of household composition in the uptake of COVID-19 vaccination in Wales was examined with the aim of identifying areas for intervention to address inequalities. Records within the Wales Immunisation System (WIS) COVID-19 vaccination register were linked to the Welsh Demographic Service Dataset (WDSD; a population register for Wales) held within the Secure Anonymised Information Linkage (SAIL) databank. Eight household types were defined based on household size, the presence or absence of children, and the presence of single or multiple generations. Uptake of the second dose of any COVID-19 vaccine was analysed using logistic regression. Gender, age group, health board, rural/urban residential classification, ethnic group, and deprivation quintile were included as covariates for multivariable regression. Compared to two-adult households, all other household types were associated with lower uptake. The most significantly reduced uptake was observed for large, multigenerational, adult group households (aOR 0.45, 95%CI 0.43-0.46). Comparing multivariable regression with and without incorporation of household composition as a variable produced significant differences in odds of vaccination for health board, age group, and ethnic group categories. These results indicate that household composition is an important factor for the uptake of COVID-19 vaccination and consideration of differences in household composition is necessary to mitigate vaccination inequalities.",,pdf:https://www.mdpi.com/2076-393X/11/3/604/pdf?version=1678670919; doi:https://doi.org/10.3390/vaccines11030604; html:https://europepmc.org/articles/PMC10055803; pdf:https://europepmc.org/articles/PMC10055803?pdf=render
 32991065,https://doi.org/10.1111/dom.14203,Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study.,"Sainsbury C, Wang J, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, Chandan JS, Anand A, Cooper J, Okoth K, Subramanian A, Bangash MN, Taverner T, Hanif W, Ghosh S, Narendran P, Cheng KK, Marshall T, Gkoutos G, Toulis K, Thomas N, Tahrani A, Adderley NJ, Haroon S, Nirantharakumar K.",,"Diabetes, obesity & metabolism",2021,2020-10-19,Y,Type 2 diabetes; Dpp-4 Inhibitor; Pharmaco-epidemiology; Sglt2 Inhibitor; Antidiabetic Drug,,,"Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dom.14203; doi:https://doi.org/10.1111/dom.14203; html:https://europepmc.org/articles/PMC7537530; pdf:https://europepmc.org/articles/PMC7537530?pdf=render
 33995410,https://doi.org/10.3389/fimmu.2021.671052,Plasma Lectin Pathway Complement Proteins in Patients With COVID-19 and Renal Disease.,"Medjeral-Thomas NR, Troldborg A, Hansen AG, Gisby J, Clarke CL, Prendecki M, McAdoo SP, Sandhu E, Lightstone L, Thomas DC, Willicombe M, Botto M, Peters JE, Pickering MC, Thiel S.",,Frontiers in immunology,2021,2021-04-29,Y,Complement; Lectin; Coronavirus; Chronic Kidney Disease; Covid-19,,,"We do not understand why non-white ethnicity and chronic kidney disease increase susceptibility to COVID-19. The lectin pathway of complement activation is a key contributor to innate immunity and inflammation. Concentrations of plasma lectin pathway proteins influence pathway activity and vary with ethnicity. We measured circulating lectin proteins in a multi-ethnic cohort of chronic kidney disease patients with and without COVID19 infection to determine if lectin pathway activation was contributing to COVID19 severity. We measured 11 lectin proteins in serial samples from a cohort of 33 patients with chronic kidney impairment and COVID19. Controls were single plasma samples from 32 patients on dialysis and 32 healthy individuals. We demonstrated multiple associations between recognition molecules and associated proteases of the lectin pathway and COVID-19, including COVID-19 severity. Some of these associations were unique to patients of Asian and White ethnicity. Our novel findings demonstrate that COVID19 infection alters the concentration of plasma lectin proteins and some of these changes were linked to ethnicity. This suggests a role for the lectin pathway in the host response to COVID-19 and suggest that variability within this pathway may contribute to ethnicity-associated differences in susceptibility to severe COVID-19.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2021.671052/pdf; doi:https://doi.org/10.3389/fimmu.2021.671052; html:https://europepmc.org/articles/PMC8118695; pdf:https://europepmc.org/articles/PMC8118695?pdf=render
 32619549,https://doi.org/10.1016/j.cels.2020.05.012,Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection.,"Messner CB, Demichev V, Wendisch D, Michalick L, White M, Freiwald A, Textoris-Taube K, Vernardis SI, Egger AS, Kreidl M, Ludwig D, Kilian C, Agostini F, Zelezniak A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, von Kalle C, Campbell A, Hayward C, Porteous DJ, Marioni RE, Langenberg C, Lilley KS, Kuebler WM, Mülleder M, Drosten C, Suttorp N, Witzenrath M, Kurth F, Sander LE, Ralser M.",,Cell systems,2020,2020-06-02,Y,Mass spectrometry; High-throughput Proteomics; Swath-ms; Antiviral Immune Response; Clinical Classifiers; Covid-19 Infection,,,"The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up to 180 samples per day, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, this work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.",,doi:https://doi.org/10.1016/j.cels.2020.05.012; doi:https://doi.org/10.1016/j.cels.2020.05.012; html:https://europepmc.org/articles/PMC7264033
 37248229,https://doi.org/10.1038/s41467-023-38756-3,Evidence-driven spatiotemporal COVID-19 hospitalization prediction with Ising dynamics.,"Gao J, Heintz J, Mack C, Glass L, Cross A, Sun J.",,Nature communications,2023,2023-05-29,Y,,,,"In this work, we aim to accurately predict the number of hospitalizations during the COVID-19 pandemic by developing a spatiotemporal prediction model. We propose HOIST, an Ising dynamics-based deep learning model for spatiotemporal COVID-19 hospitalization prediction. By drawing the analogy between locations and lattice sites in statistical mechanics, we use the Ising dynamics to guide the model to extract and utilize spatial relationships across locations and model the complex influence of granular information from real-world clinical evidence. By leveraging rich linked databases, including insurance claims, census information, and hospital resource usage data across the U.S., we evaluate the HOIST model on the large-scale spatiotemporal COVID-19 hospitalization prediction task for 2299 counties in the U.S. In the 4-week hospitalization prediction task, HOIST achieves 368.7 mean absolute error, 0.6 [Formula: see text] and 0.89 concordance correlation coefficient score on average. Our detailed number needed to treat (NNT) and cost analysis suggest that future COVID-19 vaccination efforts may be most impactful in rural areas. This model may serve as a resource for future county and state-level vaccination efforts.",,doi:https://doi.org/10.1038/s41467-023-38756-3; doi:https://doi.org/10.1038/s41467-023-38756-3; html:https://europepmc.org/articles/PMC10226446; pdf:https://europepmc.org/articles/PMC10226446?pdf=render
 36240828,https://doi.org/10.1016/s2214-109x(22)00358-8,Prediction of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study.,"Ali ST, Lau YC, Shan S, Ryu S, Du Z, Wang L, Xu XK, Chen D, Xiong J, Tae J, Tsang TK, Wu P, Lau EHY, Cowling BJ.",,The Lancet. Global health,2022,2022-11-01,Y,,,,"<h4>Background</h4>The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics.<h4>Methods</h4>For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect.<h4>Findings</h4>We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes.<h4>Interpretation</h4>Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community.<h4>Funding</h4>Health and Medical Research Fund, Hong Kong.",,pdf:https://www.repository.cam.ac.uk/bitstreams/bb5465bd-c08f-4c3d-ab0e-87fee39fc92b/download; doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849
-33725121,https://doi.org/10.1093/rheumatology/keab250,COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.,"Tan EH, Sena AG, Prats-Uribe A, You SC, Ahmed WU, Kostka K, Reich C, Duvall SL, Lynch KE, Matheny ME, Duarte-Salles T, Bertolin SF, Hripcsak G, Natarajan K, Falconer T, Spotnitz M, Ostropolets A, Blacketer C, Alshammari TM, Alghoul H, Alser O, Lane JCE, Dawoud DM, Shah K, Yang Y, Zhang L, Areia C, Golozar A, Recalde M, Casajust P, Jonnagaddala J, Subbian V, Vizcaya D, Lai LYH, Nyberg F, Morales DR, Posada JD, Shah NH, Gong M, Vivekanantham A, Abend A, Minty EP, Suchard M, Rijnbeek P, Ryan PB, Prieto-Alhambra D.",,"Rheumatology (Oxford, England)",2021,2021-10-01,Y,Mortality; Hospitalization; Open Science; Autoimmune Condition; Observational Health Data Sciences And Informatics (Ohdsi); Observational Medical Outcomes Partnership (Omop); Covid-19,,,"<h4>Objective</h4>Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.<h4>Methods</h4>A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization.<h4>Results</h4>We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%).<h4>Conclusion</h4>Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.",,pdf:https://academic.oup.com/rheumatology/article-pdf/60/SI/SI37/40544680/keab250.pdf; doi:https://doi.org/10.1093/rheumatology/keab250; html:https://europepmc.org/articles/PMC7989171; pdf:https://europepmc.org/articles/PMC7989171?pdf=render
 33782427,https://doi.org/10.1038/s41598-021-86266-3,Analysis of temporal trends in potential COVID-19 cases reported through NHS Pathways England.,"Leclerc QJ, Nightingale ES, Abbott S, CMMID COVID-19 Working Group, Jombart T.",,Scientific reports,2021,2021-03-29,Y,,,,"The National Health Service (NHS) Pathways triage system collates data on enquiries to 111 and 999 services in England. Since the 18th of March 2020, these data have been made publically available for potential COVID-19 symptoms self-reported by members of the public. Trends in such reports over time are likely to reflect behaviour of the ongoing epidemic within the wider community, potentially capturing valuable information across a broader severity profile of cases than hospital admission data. We present a fully reproducible analysis of temporal trends in NHS Pathways reports until 14th May 2020, nationally and regionally, and demonstrate that rates of growth/decline and effective reproduction number estimated from these data may be useful in monitoring transmission. This is a particularly pressing issue as lockdown restrictions begin to be lifted and evidence of disease resurgence must be constantly reassessed. We further assess the correlation between NHS Pathways reports and a publicly available NHS dataset of COVID-19-associated deaths in England, finding that enquiries to 111/999 were strongly associated with daily deaths reported 16 days later. Our results highlight the potential of NHS Pathways as the basis of an early warning system. However, this dataset relies on self-reported symptoms, which are at risk of being severely biased. Further detailed work is therefore necessary to investigate potential behavioural issues which might otherwise explain our conclusions.",,pdf:https://www.nature.com/articles/s41598-021-86266-3.pdf; doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?pdf=render
+33725121,https://doi.org/10.1093/rheumatology/keab250,COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.,"Tan EH, Sena AG, Prats-Uribe A, You SC, Ahmed WU, Kostka K, Reich C, Duvall SL, Lynch KE, Matheny ME, Duarte-Salles T, Bertolin SF, Hripcsak G, Natarajan K, Falconer T, Spotnitz M, Ostropolets A, Blacketer C, Alshammari TM, Alghoul H, Alser O, Lane JCE, Dawoud DM, Shah K, Yang Y, Zhang L, Areia C, Golozar A, Recalde M, Casajust P, Jonnagaddala J, Subbian V, Vizcaya D, Lai LYH, Nyberg F, Morales DR, Posada JD, Shah NH, Gong M, Vivekanantham A, Abend A, Minty EP, Suchard M, Rijnbeek P, Ryan PB, Prieto-Alhambra D.",,"Rheumatology (Oxford, England)",2021,2021-10-01,Y,Mortality; Hospitalization; Open Science; Autoimmune Condition; Observational Health Data Sciences And Informatics (Ohdsi); Observational Medical Outcomes Partnership (Omop); Covid-19,,,"<h4>Objective</h4>Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.<h4>Methods</h4>A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization.<h4>Results</h4>We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%).<h4>Conclusion</h4>Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.",,pdf:https://academic.oup.com/rheumatology/article-pdf/60/SI/SI37/40544680/keab250.pdf; doi:https://doi.org/10.1093/rheumatology/keab250; html:https://europepmc.org/articles/PMC7989171; pdf:https://europepmc.org/articles/PMC7989171?pdf=render
 35671273,https://doi.org/10.1371/journal.pone.0268837,Optimising the balance of acute and intermediate care capacity for the complex discharge pathway: Computer modelling study during COVID-19 recovery in England.,"Onen-Dumlu Z, Harper AL, Forte PG, Powell AL, Pitt M, Vasilakis C, Wood RM.",,PloS one,2022,2022-06-07,Y,,,,"<h4>Objectives</h4>While there has been significant research on the pressures facing acute hospitals during the COVID-19 pandemic, there has been less interest in downstream community services which have also been challenged in meeting demand. This study aimed to estimate the theoretical cost-optimal capacity requirement for 'step down' intermediate care services within a major healthcare system in England, at a time when considerable uncertainty remained regarding vaccination uptake and the easing of societal restrictions.<h4>Methods</h4>Demand for intermediate care was projected using an epidemiological model (for COVID-19 demand) and regressing upon public mobility (for non-COVID-19 demand). These were inputted to a computer simulation model of patient flow from acute discharge readiness to bedded and home-based Discharge to Assess (D2A) intermediate care services. Cost-optimal capacity was defined as that which yielded the lowest total cost of intermediate care provision and corresponding acute discharge delays.<h4>Results</h4>Increased intermediate care capacity is likely to bring about lower system-level costs, with the additional D2A investment more than offset by substantial reductions in costly acute discharge delays (leading also to improved patient outcome and experience). Results suggest that completely eliminating acute 'bed blocking' is unlikely economical (requiring large amounts of downstream capacity), and that health systems should instead target an appropriate tolerance based upon the specific characteristics of the pathway.<h4>Conclusions</h4>Computer modelling can be a valuable asset for determining optimal capacity allocation along the complex care pathway. With results supporting a Business Case for increased downstream capacity, this study demonstrates how modelling can be applied in practice and provides a blueprint for use alongside the freely-available model code.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0268837&type=printable; doi:https://doi.org/10.1371/journal.pone.0268837; html:https://europepmc.org/articles/PMC9173611; pdf:https://europepmc.org/articles/PMC9173611?pdf=render
 32997638,https://doi.org/10.1109/jbhi.2020.3027987,A Novel Intelligent Computational Approach to Model Epidemiological Trends and Assess the Impact of Non-Pharmacological Interventions for COVID-19.,"Ren J, Yan Y, Zhao H, Ma P, Zabalza J, Hussain Z, Luo S, Dai Q, Zhao S, Sheikh A, Hussain A, Li H.",,IEEE journal of biomedical and health informatics,2020,2020-12-04,Y,,,,"The novel coronavirus disease 2019 (COVID-19) pandemic has led to a worldwide crisis in public health. It is crucial we understand the epidemiological trends and impact of non-pharmacological interventions (NPIs), such as lockdowns for effective management of the disease and control of its spread. We develop and validate a novel intelligent computational model to predict epidemiological trends of COVID-19, with the model parameters enabling an evaluation of the impact of NPIs. By representing the number of daily confirmed cases (NDCC) as a time-series, we assume that, with or without NPIs, the pattern of the pandemic satisfies a series of Gaussian distributions according to the central limit theorem. The underlying pandemic trend is first extracted using a singular spectral analysis (SSA) technique, which decomposes the NDCC time series into the sum of a small number of independent and interpretable components such as a slow varying trend, oscillatory components and structureless noise. We then use a mixture of Gaussian fitting (GF) to derive a novel predictive model for the SSA extracted NDCC incidence trend, with the overall model termed SSA-GF. Our proposed model is shown to accurately predict the NDCC trend, peak daily cases, the length of the pandemic period, the total confirmed cases and the associated dates of the turning points on the cumulated NDCC curve. Further, the three key model parameters, specifically, the amplitude (alpha), mean (mu), and standard deviation (sigma) are linked to the underlying pandemic patterns, and enable a directly interpretable evaluation of the impact of NPIs, such as strict lockdowns and travel restrictions. The predictive model is validated using available data from China and South Korea, and new predictions are made, partially requiring future validation, for the cases of Italy, Spain, the UK and the USA. Comparative results demonstrate that the introduction of consistent control measures across countries can lead to development of similar parametric models, reflected in particular by relative variations in their underlying sigma, alpha and mu values. The paper concludes with a number of open questions and outlines future research directions.",,pdf:https://ieeexplore.ieee.org/ielx7/6221020/9281055/09210178.pdf; doi:https://doi.org/10.1109/JBHI.2020.3027987; html:https://europepmc.org/articles/PMC8545177; pdf:https://europepmc.org/articles/PMC8545177?pdf=render
 32814572,https://doi.org/10.1186/s12916-020-01712-9,The effect of travel restrictions on the geographical spread of COVID-19 between large cities in China: a modelling study.,"Quilty BJ, Diamond C, Liu Y, Gibbs H, Russell TW, Jarvis CI, Prem K, Pearson CAB, Clifford S, Flasche S, CMMID COVID-19 working group, Klepac P, Eggo RM, Jit M.",,BMC medicine,2020,2020-08-19,Y,China; Wuhan; Mobility; Delay; Outbreaks; Modelling; Travel Restrictions; Covid-19; Sars-cov-2; Cordon Sanitaire,,,"<h4>Background</h4>To contain the spread of COVID-19, a cordon sanitaire was put in place in Wuhan prior to the Lunar New Year, on 23 January 2020. We assess the efficacy of the cordon sanitaire to delay the introduction and onset of local transmission of COVID-19 in other major cities in mainland China.<h4>Methods</h4>We estimated the number of infected travellers from Wuhan to other major cities in mainland China from November 2019 to February 2020 using previously estimated COVID-19 prevalence in Wuhan and publicly available mobility data. We focused on Beijing, Chongqing, Hangzhou, and Shenzhen as four representative major cities to identify the potential independent contribution of the cordon sanitaire and holiday travel. To do this, we simulated outbreaks generated by infected arrivals in these destination cities using stochastic branching processes. We also modelled the effect of the cordon sanitaire in combination with reduced transmissibility scenarios to simulate the effect of local non-pharmaceutical interventions.<h4>Results</h4>We find that in the four cities, given the potentially high prevalence of COVID-19 in Wuhan between December 2019 and early January 2020, local transmission may have been seeded as early as 1-8 January 2020. By the time the cordon sanitaire was imposed, infections were likely in the thousands. The cordon sanitaire alone did not substantially affect the epidemic progression in these cities, although it may have had some effect in smaller cities. Reduced transmissibility resulted in a notable decrease in the incidence of infection in the four studied cities.<h4>Conclusions</h4>Our results indicate that sustained transmission was likely occurring several weeks prior to the implementation of the cordon sanitaire in four major cities of mainland China and that the observed decrease in incidence was likely attributable to other non-pharmaceutical, transmission-reducing interventions.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01712-9; doi:https://doi.org/10.1186/s12916-020-01712-9; html:https://europepmc.org/articles/PMC7437104; pdf:https://europepmc.org/articles/PMC7437104?pdf=render
@@ -476,8 +476,8 @@ PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’
 33704068,https://doi.org/10.7554/elife.64827,Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death.,"Gisby J, Clarke CL, Medjeral-Thomas N, Malik TH, Papadaki A, Mortimer PM, Buang NB, Lewis S, Pereira M, Toulza F, Fagnano E, Mawhin MA, Dutton EE, Tapeng L, Richard AC, Kirk PD, Behmoaras J, Sandhu E, McAdoo SP, Prendecki MF, Pickering MC, Botto M, Willicombe M, Thomas DC, Peters JE.",,eLife,2021,2021-03-11,Y,Human; Cytokines; Proteomics; Inflammation; Medicine; Biomarkers; immunology; Longitudinal; End-stage Kidney Disease; Covid-19,,,"End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.",,doi:https://doi.org/10.7554/elife.64827; doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?pdf=render
 33024096,https://doi.org/10.1038/s41467-020-18783-0,Changing travel patterns in China during the early stages of the COVID-19 pandemic.,"Gibbs H, Liu Y, Pearson CAB, Jarvis CI, Grundy C, Quilty BJ, Diamond C, LSHTM CMMID COVID-19 working group, Eggo RM.",,Nature communications,2020,2020-10-06,Y,,,,"Understanding changes in human mobility in the early stages of the COVID-19 pandemic is crucial for assessing the impacts of travel restrictions designed to reduce disease spread. Here, relying on data from mainland China, we investigate the spatio-temporal characteristics of human mobility between 1st January and 1st March 2020, and discuss their public health implications. An outbound travel surge from Wuhan before travel restrictions were implemented was also observed across China due to the Lunar New Year, indicating that holiday travel may have played a larger role in mobility changes compared to impending travel restrictions. Holiday travel also shifted healthcare pressure related to COVID-19 towards locations with lower healthcare capacity. Network analyses showed no sign of major changes in the transportation network after Lunar New Year. Changes observed were temporary and did not lead to structural reorganisation of the transportation network during the study period.",,pdf:https://www.nature.com/articles/s41467-020-18783-0.pdf; doi:https://doi.org/10.1038/s41467-020-18783-0; html:https://europepmc.org/articles/PMC7538915; pdf:https://europepmc.org/articles/PMC7538915?pdf=render
 37198478,https://doi.org/10.1038/s41586-023-06034-3,GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.,"Pairo-Castineira E, Rawlik K, Bretherick AD, Qi T, Wu Y, Nassiri I, McConkey GA, Zechner M, Klaric L, Griffiths F, Oosthuyzen W, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Morrice K, Keating S, Maslove D, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Begg C, Walsh T, Tenesa A, Flores C, Riancho JA, Rojas-Martinez A, Lapunzina P, GenOMICC Investigators, SCOURGE Consortium, ISARICC Investigators, 23andMe COVID-19 Team, Yang J, Ponting CP, Wilson JF, Vitart V, Abedalthagafi M, Luchessi AD, Parra EJ, Cruz R, Carracedo A, Fawkes A, Murphy L, Rowan K, Pereira AC, Law A, Fairfax B, Hendry SC, Baillie JK.",,Nature,2023,2023-05-17,Y,,,,"Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown<sup>1</sup> to be highly efficient for discovery of genetic associations<sup>2</sup>. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group<sup>3</sup>. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).",,pdf:https://www.nature.com/articles/s41586-023-06034-3.pdf; doi:https://doi.org/10.1038/s41586-023-06034-3; html:https://europepmc.org/articles/PMC10208981; pdf:https://europepmc.org/articles/PMC10208981?pdf=render
-35505938,https://doi.org/10.1016/j.eclinm.2022.101417,Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort.,"Hampshire A, Chatfield DA, MPhil AM, Jolly A, Trender W, Hellyer PJ, Giovane MD, Newcombe VFJ, Outtrim JG, Warne B, Bhatti J, Pointon L, Elmer A, Sithole N, Bradley J, Kingston N, Sawcer SJ, Bullmore ET, Rowe JB, Menon DK, Cambridge NeuroCOVID Group, the NIHR COVID-19 BioResource, and Cambridge NIHR Clinical Research Facility.",,EClinicalMedicine,2022,2022-04-28,Y,Memory; Cognition; Attention; Planning; Cognitive Assessment; Reasoning; Covid-19,,,"<h4>Background</h4>Preliminary evidence has highlighted a possible association between severe COVID-19 and persistent cognitive deficits. Further research is required to confirm this association, determine whether cognitive deficits relate to clinical features from the acute phase or to mental health status at the point of assessment, and quantify rate of recovery.<h4>Methods</h4>46 individuals who received critical care for COVID-19 at Addenbrooke's hospital between 10th March 2020 and 31st July 2020 (16 mechanically ventilated) underwent detailed computerised cognitive assessment alongside scales measuring anxiety, depression and post-traumatic stress disorder under supervised conditions at a mean follow up of 6.0 (± 2.1) months following acute illness. Patient and matched control (<i>N</i> = 460) performances were transformed into standard deviation from expected scores, accounting for age and demographic factors using <i>N</i> = 66,008 normative datasets. Global accuracy and response time composites were calculated (G_SScore & G_RT). Linear modelling predicted composite score deficits from acute severity, mental-health status at assessment, and time from hospital admission. The pattern of deficits across tasks was qualitatively compared with normal age-related decline, and early-stage dementia.<h4>Findings</h4>COVID-19 survivors were less accurate (G_SScore=-0.53SDs) and slower (G_RT=+0.89SDs) in their responses than expected compared to their matched controls. Acute illness, but not chronic mental health, significantly predicted cognitive deviation from expected scores (G_SScore (<i>p</i>=​​0.0037) and G_RT (<i>p</i> = 0.0366)). The most prominent task associations with COVID-19 were for higher cognition and processing speed, which was qualitatively distinct from the profiles of normal ageing and dementia and similar in magnitude to the effects of ageing between 50 and 70 years of age. A trend towards reduced deficits with time from illness (r∼=0.15) did not reach statistical significance.<h4>Interpretation</h4>Cognitive deficits after severe COVID-19 relate most strongly to acute illness severity, persist long into the chronic phase, and recover slowly if at all, with a characteristic profile highlighting higher cognitive functions and processing speed.<h4>Funding</h4>This work was funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC), NIHR Cambridge Clinical Research Facility (BRC-1215-20014), the Addenbrooke's Charities Trust and NIHR COVID-19 BioResource RG9402. AH is funded by the UK Dementia Research Institute Care Research and Technology Centre and Imperial College London Biomedical Research Centre. ETB and DKM are supported by NIHR Senior Investigator awards. JBR is supported by the Wellcome Trust (220258) and Medical Research Council (SUAG/051 G101400). VFJN is funded by an Academy of Medical Sciences/ The Health Foundation Clinician Scientist Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S258953702200147X/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101417; html:https://europepmc.org/articles/PMC9048584; pdf:https://europepmc.org/articles/PMC9048584?pdf=render
 32907855,https://doi.org/10.1136/bmj.m3339,Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score.,"Knight SR, Ho A, Pius R, Buchan I, Carson G, Drake TM, Dunning J, Fairfield CJ, Gamble C, Green CA, Gupta R, Halpin S, Hardwick HE, Holden KA, Horby PW, Jackson C, Mclean KA, Merson L, Nguyen-Van-Tam JS, Norman L, Noursadeghi M, Olliaro PL, Pritchard MG, Russell CD, Shaw CA, Sheikh A, Solomon T, Sudlow C, Swann OV, Turtle LC, Openshaw PJ, Baillie JK, Semple MG, Docherty AB, Harrison EM, ISARIC4C investigators.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"<h4>Objective</h4>To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19).<h4>Design</h4>Prospective observational cohort study.<h4>Setting</h4>International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium-ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020<i>.</i> PARTICIPANTS: Adults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction.<h4>Main outcome measure</h4>In-hospital mortality.<h4>Results</h4>35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73).<h4>Conclusions</h4>An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations.<h4>Study registration</h4>ISRCTN66726260.",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3339.full.pdf; doi:https://doi.org/10.1136/bmj.m3339; html:https://europepmc.org/articles/PMC7116472; pdf:https://europepmc.org/articles/PMC7116472?pdf=render
+35505938,https://doi.org/10.1016/j.eclinm.2022.101417,Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort.,"Hampshire A, Chatfield DA, MPhil AM, Jolly A, Trender W, Hellyer PJ, Giovane MD, Newcombe VFJ, Outtrim JG, Warne B, Bhatti J, Pointon L, Elmer A, Sithole N, Bradley J, Kingston N, Sawcer SJ, Bullmore ET, Rowe JB, Menon DK, Cambridge NeuroCOVID Group, the NIHR COVID-19 BioResource, and Cambridge NIHR Clinical Research Facility.",,EClinicalMedicine,2022,2022-04-28,Y,Memory; Cognition; Attention; Planning; Cognitive Assessment; Reasoning; Covid-19,,,"<h4>Background</h4>Preliminary evidence has highlighted a possible association between severe COVID-19 and persistent cognitive deficits. Further research is required to confirm this association, determine whether cognitive deficits relate to clinical features from the acute phase or to mental health status at the point of assessment, and quantify rate of recovery.<h4>Methods</h4>46 individuals who received critical care for COVID-19 at Addenbrooke's hospital between 10th March 2020 and 31st July 2020 (16 mechanically ventilated) underwent detailed computerised cognitive assessment alongside scales measuring anxiety, depression and post-traumatic stress disorder under supervised conditions at a mean follow up of 6.0 (± 2.1) months following acute illness. Patient and matched control (<i>N</i> = 460) performances were transformed into standard deviation from expected scores, accounting for age and demographic factors using <i>N</i> = 66,008 normative datasets. Global accuracy and response time composites were calculated (G_SScore & G_RT). Linear modelling predicted composite score deficits from acute severity, mental-health status at assessment, and time from hospital admission. The pattern of deficits across tasks was qualitatively compared with normal age-related decline, and early-stage dementia.<h4>Findings</h4>COVID-19 survivors were less accurate (G_SScore=-0.53SDs) and slower (G_RT=+0.89SDs) in their responses than expected compared to their matched controls. Acute illness, but not chronic mental health, significantly predicted cognitive deviation from expected scores (G_SScore (<i>p</i>=​​0.0037) and G_RT (<i>p</i> = 0.0366)). The most prominent task associations with COVID-19 were for higher cognition and processing speed, which was qualitatively distinct from the profiles of normal ageing and dementia and similar in magnitude to the effects of ageing between 50 and 70 years of age. A trend towards reduced deficits with time from illness (r∼=0.15) did not reach statistical significance.<h4>Interpretation</h4>Cognitive deficits after severe COVID-19 relate most strongly to acute illness severity, persist long into the chronic phase, and recover slowly if at all, with a characteristic profile highlighting higher cognitive functions and processing speed.<h4>Funding</h4>This work was funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC), NIHR Cambridge Clinical Research Facility (BRC-1215-20014), the Addenbrooke's Charities Trust and NIHR COVID-19 BioResource RG9402. AH is funded by the UK Dementia Research Institute Care Research and Technology Centre and Imperial College London Biomedical Research Centre. ETB and DKM are supported by NIHR Senior Investigator awards. JBR is supported by the Wellcome Trust (220258) and Medical Research Council (SUAG/051 G101400). VFJN is funded by an Academy of Medical Sciences/ The Health Foundation Clinician Scientist Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S258953702200147X/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101417; html:https://europepmc.org/articles/PMC9048584; pdf:https://europepmc.org/articles/PMC9048584?pdf=render
 36648008,https://doi.org/10.1111/iwj.14088,"Evaluating the cost of managing patients with cellulitis in Wales, UK: A 20-year population-scale study.","Humphreys I, Akbari A, Griffiths R, Graham-Woollard D, Morgan K, Noble-Jones R, Gabe-Walters M, Thomas M.",,International wound journal,2023,2023-01-17,Y,Longitudinal data; Cellulitis; Lymphoedema; Economic Burden; Sail Databank,,,"This study aimed to estimate costs associated with managing patients with cellulitis from the UK National Health Service (NHS) perspective. The analysis was undertaken through the Secure Anonymised Information Linkage Databank, which brings together population-scale, individual-level anonymised linked data from a wide range of sources, including 80% of primary care general practices within Wales (population coverage ~3.2 million). The data covered a 20-year period from 1999 to 2019. All patients linked to the relevant codes were tracked through primary care settings, recording the number of general practice visits (number of days with an event recorded) and number of in-patient stays. Resources were valued in monetary terms (£ sterling), with costs determined from national published sources of unit costs. These resources were then extrapolated out to reflect UK NHS costs. This is the first attempt to estimate the financial burden of cellulitis using routine data sources on a national scale. The estimated direct annual costs to the Welsh NHS (£28 554 338) are considerable. In-Patient events and length of stay costs are the main cost drivers, with annual Welsh NHS estimates of £19 664 126 with primary care events costing £8 890 212. Initiatives to support patients and healthcare professionals in identifying early signs/risks of cellulitis, improve the accuracy of initial diagnosis, prevent cellulitis recurrence, and improve evidence-based treatment pathways would result in major financial savings, to both the Welsh and UK NHS. In light of these findings, Wales has developed the innovative National Lymphoedema cellulitis Improvement Programme to address these burdens; providing a proactive model of cellulitis care.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/iwj.14088; doi:https://doi.org/10.1111/iwj.14088; html:https://europepmc.org/articles/PMC10333041; pdf:https://europepmc.org/articles/PMC10333041?pdf=render
 36649943,https://doi.org/10.1136/bmjoq-2021-001704,Benefits of electronic charts in intensive care and during a world health pandemic: advantages of the technology age.,"Pankhurst T, Lucas L, Ryan S, Ragdale C, Gyves H, Denner L, Young I, Rathbone L, Shah A, McKee D, Coleman JJ, Evison F, Atia J, Rosser D, Garrick M, Baker R, Gallier S, Ball S.",,BMJ open quality,2023,2023-01-01,Y,Evaluation Methodology; Critical Care; Electronic Health Records,,,"<h4>Aims and objectives</h4>This study sets out to describe benefits from the implementation of electronic observation charting in intensive care units (ICU). This was an extension to the existing hospital wide digital health system. We evaluated error reduction, time-savings and the costs associated with conversion from paper to digital records. The world health emergency of COVID-19 placed extraordinary strain on ICU and staff opinion was evaluated to test how well the electronic system performed.<h4>Methods</h4>A clinically led project group working directly with programmers developed an electronic patient record for intensive care. Data error rates, time to add data and to make calculations were studied before and after the introduction of electronic charts. User feedback was sought pre and post go-live (during the COVID-19 pandemic) and financial implications were calculated by the hospital finance teams.<h4>Results</h4>Error rates equating to 219 000/year were avoided by conversion to electronic charts. Time saved was the equivalent of a nursing shift each day. Recurrent cost savings per year were estimated to be £257k. Staff were overwhelmingly positive about electronic charts in ICU, even during a health pandemic and despite redeployment into intensive care where they were using the electronic charts for the first time.<h4>Discussion</h4>Electronic ICU charts have been successfully introduced into our institution with benefits in terms of patient safety through error reduction and improved care through release of nursing time. Costs have been reduced. Staff feel supported by the digital system and report it to be helpful even during redeployment and in the unfamiliar environment of intensive care.",,pdf:https://bmjopenquality.bmj.com/content/bmjqir/12/1/e001704.full.pdf; doi:https://doi.org/10.1136/bmjoq-2021-001704; html:https://europepmc.org/articles/PMC9853220; pdf:https://europepmc.org/articles/PMC9853220?pdf=render
 34270458,https://doi.org/10.4269/ajtmh.21-0482,The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.,"Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",,The American journal of tropical medicine and hygiene,2021,2021-07-16,Y,,,,"The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",,pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render
@@ -495,16 +495,16 @@ PMC9644982,https://doi.org/,Assessing the impacts of COVID-19 on Care Homes in W
 33612430,https://doi.org/10.1016/s2589-7500(21)00017-0,Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study.,"Mansfield KE, Mathur R, Tazare J, Henderson AD, Mulick AR, Carreira H, Matthews AA, Bidulka P, Gayle A, Forbes H, Cook S, Wong AYS, Strongman H, Wing K, Warren-Gash C, Cadogan SL, Smeeth L, Hayes JF, Quint JK, McKee M, Langan SM.",,The Lancet. Digital health,2021,2021-02-18,Y,,,,"<h4>Background</h4>There are concerns that the response to the COVID-19 pandemic in the UK might have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic.<h4>Methods</h4>Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8-28).<h4>Findings</h4>The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25-0·50]), depression (0·53 [0·52-0·53]), and self-harm (0·56 [0·54-0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89-1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66-0·67], eating disorders 0·62 [0·59-0·66], obsessive-compulsive disorder [0·69 [0·64-0·74]], self-harm 0·56 [0·54-0·58], severe mental illness 0·80 [0·78-0·83], stroke 0·59 [0·56-0·62], transient ischaemic attack 0·63 [0·58-0·67], heart failure 0·62 [0·60-0·64], myocardial infarction 0·72 [0·68-0·77], unstable angina 0·72 [0·60-0·87], venous thromboembolism 0·94 [0·90-0·99], and asthma exacerbation 0·88 [0·86-0·90]). By July, 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels.<h4>Interpretation</h4>There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision.<h4>Funding</h4>Wellcome Trust Senior Fellowship, Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2589750021000170/pdf; doi:https://doi.org/10.1016/S2589-7500(21)00017-0; html:https://europepmc.org/articles/PMC7985613; pdf:https://europepmc.org/articles/PMC7985613?pdf=render
 34098341,https://doi.org/10.1016/j.ebiom.2021.103414,Accuracy of four lateral flow immunoassays for anti SARS-CoV-2 antibodies: a head-to-head comparative study.,"Jones HE, Mulchandani R, Taylor-Phillips S, Ades AE, Shute J, Perry KR, Chandra NL, Brooks T, Charlett A, Hickman M, Oliver I, Kaptoge S, Danesh J, Di Angelantonio E, Wyllie D, COMPARE study investigators, EDSAB-HOME investigators.",,EBioMedicine,2021,2021-06-04,Y,Seroepidemiology; Rapid Testing; Serosurveillance; Lateral Flow Devices; Covid-19,,,"<h4>Background</h4>SARS-CoV-2 antibody tests are used for population surveillance and might have a future role in individual risk assessment. Lateral flow immunoassays (LFIAs) can deliver results rapidly and at scale, but have widely varying accuracy.<h4>Methods</h4>In a laboratory setting, we performed head-to-head comparisons of four LFIAs: the Rapid Test Consortium's AbC-19<sup>TM</sup> Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test. We analysed blood samples from 2,847 key workers and 1,995 pre-pandemic blood donors with all four devices.<h4>Findings</h4>We observed a clear trade-off between sensitivity and specificity: the IgG band of the SureScreen device and the AbC-19<sup>TM</sup> device had higher specificities but OrientGene and Biomerica higher sensitivities. Based on analysis of pre-pandemic samples, SureScreen IgG band had the highest specificity (98.9%, 95% confidence interval 98.3 to 99.3%), which translated to the highest positive predictive value across any pre-test probability: for example, 95.1% (95% uncertainty interval 92.6, 96.8%) at 20% pre-test probability. All four devices showed higher sensitivity at higher antibody concentrations (""spectrum effects""), but the extent of this varied by device.<h4>Interpretation</h4>The estimates of sensitivity and specificity can be used to adjust for test error rates when using these devices to estimate the prevalence of antibody. If tests were used to determine whether an individual has SARS-CoV-2 antibodies, in an example scenario in which 20% of individuals have antibodies we estimate around 5% of positive results on the most specific device would be false positives.<h4>Funding</h4>Public Health England.",,pdf:https://research-information.bris.ac.uk/files/280339070/1_s2.0_S2352396421002073_main.pdf; doi:https://doi.org/10.1016/j.ebiom.2021.103414; html:https://europepmc.org/articles/PMC8176919; pdf:https://europepmc.org/articles/PMC8176919?pdf=render
 33444539,https://doi.org/10.1016/s2213-2600(20)30559-2,Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study.,"Gupta RK, Harrison EM, Ho A, Docherty AB, Knight SR, van Smeden M, Abubakar I, Lipman M, Quartagno M, Pius R, Buchan I, Carson G, Drake TM, Dunning J, Fairfield CJ, Gamble C, Green CA, Halpin S, Hardwick HE, Holden KA, Horby PW, Jackson C, Mclean KA, Merson L, Nguyen-Van-Tam JS, Norman L, Olliaro PL, Pritchard MG, Russell CD, Scott-Brown J, Shaw CA, Sheikh A, Solomon T, Sudlow C, Swann OV, Turtle L, Openshaw PJM, Baillie JK, Semple MG, Noursadeghi M, ISARIC4C Investigators.",,The Lancet. Respiratory medicine,2021,2021-01-11,Y,,,,"<h4>Background</h4>Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions.<h4>Methods</h4>We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London).<h4>Findings</h4>74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [-0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model.<h4>Interpretation</h4>The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19.<h4>Funding</h4>National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/85694/9/ISARIC%204C%20Deterioration%20model.pdf; doi:https://doi.org/10.1016/S2213-2600(20)30559-2; html:https://europepmc.org/articles/PMC7832571
-35861678,https://doi.org/10.2196/36989,Developing a Long COVID Phenotype for Postacute COVID-19 in a National Primary Care Sentinel Cohort: Observational Retrospective Database Analysis.,"Mayor N, Meza-Torres B, Okusi C, Delanerolle G, Chapman M, Wang W, Anand S, Feher M, Macartney J, Byford R, Joy M, Gatenby P, Curcin V, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-11,Y,Phenotype; Surveillance; epidemiology; Public Health; Hospitalization; Social Class; Disease Management; General Practitioners; Ethnicity; Electronic Health Record; Medical Record Systems; Systematized Nomenclature Of Medicine; Computerized; Bioportal; Biomedical Ontologies; Data Accuracy; Digital Tool; Covid-19; Sars-cov-2; Long Covid; Postacute Covid-19 Syndrome; Data Extracts,,,"<h4>Background</h4>Following COVID-19, up to 40% of people have ongoing health problems, referred to as postacute COVID-19 or long COVID (LC). LC varies from a single persisting symptom to a complex multisystem disease. Research has flagged that this condition is underrecorded in primary care records, and seeks to better define its clinical characteristics and management. Phenotypes provide a standard method for case definition and identification from routine data and are usually machine-processable. An LC phenotype can underpin research into this condition.<h4>Objective</h4>This study aims to develop a phenotype for LC to inform the epidemiology and future research into this condition. We compared clinical symptoms in people with LC before and after their index infection, recorded from March 1, 2020, to April 1, 2021. We also compared people recorded as having acute infection with those with LC who were hospitalized and those who were not.<h4>Methods</h4>We used data from the Primary Care Sentinel Cohort (PCSC) of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database. This network was recruited to be nationally representative of the English population. We developed an LC phenotype using our established 3-step ontological method: (1) ontological step (defining the reasoning process underpinning the phenotype, (2) coding step (exploring what clinical terms are available, and (3) logical extract model (testing performance). We created a version of this phenotype using Protégé in the ontology web language for BioPortal and using PhenoFlow. Next, we used the phenotype to compare people with LC (1) with regard to their symptoms in the year prior to acquiring COVID-19 and (2) with people with acute COVID-19. We also compared hospitalized people with LC with those not hospitalized. We compared sociodemographic details, comorbidities, and Office of National Statistics-defined LC symptoms between groups. We used descriptive statistics and logistic regression.<h4>Results</h4>The long-COVID phenotype differentiated people hospitalized with LC from people who were not and where no index infection was identified. The PCSC (N=7.4 million) includes 428,479 patients with acute COVID-19 diagnosis confirmed by a laboratory test and 10,772 patients with clinically diagnosed COVID-19. A total of 7471 (1.74%, 95% CI 1.70-1.78) people were coded as having LC, 1009 (13.5%, 95% CI 12.7-14.3) had a hospital admission related to acute COVID-19, and 6462 (86.5%, 95% CI 85.7-87.3) were not hospitalized, of whom 2728 (42.2%) had no COVID-19 index date recorded. In addition, 1009 (13.5%, 95% CI 12.73-14.28) people with LC were hospitalized compared to 17,993 (4.5%, 95% CI 4.48-4.61; P<.001) with uncomplicated COVID-19.<h4>Conclusions</h4>Our LC phenotype enables the identification of individuals with the condition in routine data sets, facilitating their comparison with unaffected people through retrospective research. This phenotype and study protocol to explore its face validity contributes to a better understanding of LC.",,pdf:https://publichealth.jmir.org/2022/8/e36989/PDF; doi:https://doi.org/10.2196/36989; html:https://europepmc.org/articles/PMC9374163
 34868617,https://doi.org/10.1177/20552076211048654,Towards nationally curated data archives for clinical radiology image analysis at scale: Learnings from national data collection in response to a pandemic.,"Cushnan D, Berka R, Bertolli O, Williams P, Schofield D, Joshi I, Favaro A, Halling-Brown M, Imreh G, Jefferson E, Sebire NJ, Reilly G, Rodrigues JCL, Robinson G, Copley S, Malik R, Bloomfield C, Gleeson F, Crotty M, Denton E, Dickson J, Leeming G, Hardwick HE, Baillie K, Openshaw PJ, Semple MG, Rubin C, Howlett A, Rockall AG, Bhayat A, Fascia D, Sudlow C, NCCID Collaborative, Jacob J.",,Digital health,2021,2021-01-01,Y,Artificial intelligence; Medicine; Imaging; general; Radiology; Respiratory; Machine Learning; Coronavirus Sars-Cov-2 Disease,,,"The prevalence of the coronavirus SARS-CoV-2 disease has resulted in the unprecedented collection of health data to support research. Historically, coordinating the collation of such datasets on a national scale has been challenging to execute for several reasons, including issues with data privacy, the lack of data reporting standards, interoperable technologies, and distribution methods. The coronavirus SARS-CoV-2 disease pandemic has highlighted the importance of collaboration between government bodies, healthcare institutions, academic researchers and commercial companies in overcoming these issues during times of urgency. The National COVID-19 Chest Imaging Database, led by NHSX, British Society of Thoracic Imaging, Royal Surrey NHS Foundation Trust and Faculty, is an example of such a national initiative. Here, we summarise the experiences and challenges of setting up the National COVID-19 Chest Imaging Database, and the implications for future ambitions of national data curation in medical imaging to advance the safe adoption of artificial intelligence in healthcare.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/20552076211048654; doi:https://doi.org/10.1177/20552076211048654; html:https://europepmc.org/articles/PMC8637703; pdf:https://europepmc.org/articles/PMC8637703?pdf=render
+35861678,https://doi.org/10.2196/36989,Developing a Long COVID Phenotype for Postacute COVID-19 in a National Primary Care Sentinel Cohort: Observational Retrospective Database Analysis.,"Mayor N, Meza-Torres B, Okusi C, Delanerolle G, Chapman M, Wang W, Anand S, Feher M, Macartney J, Byford R, Joy M, Gatenby P, Curcin V, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-11,Y,Phenotype; Surveillance; epidemiology; Public Health; Hospitalization; Social Class; Disease Management; General Practitioners; Ethnicity; Electronic Health Record; Medical Record Systems; Systematized Nomenclature Of Medicine; Computerized; Bioportal; Biomedical Ontologies; Data Accuracy; Digital Tool; Covid-19; Sars-cov-2; Long Covid; Postacute Covid-19 Syndrome; Data Extracts,,,"<h4>Background</h4>Following COVID-19, up to 40% of people have ongoing health problems, referred to as postacute COVID-19 or long COVID (LC). LC varies from a single persisting symptom to a complex multisystem disease. Research has flagged that this condition is underrecorded in primary care records, and seeks to better define its clinical characteristics and management. Phenotypes provide a standard method for case definition and identification from routine data and are usually machine-processable. An LC phenotype can underpin research into this condition.<h4>Objective</h4>This study aims to develop a phenotype for LC to inform the epidemiology and future research into this condition. We compared clinical symptoms in people with LC before and after their index infection, recorded from March 1, 2020, to April 1, 2021. We also compared people recorded as having acute infection with those with LC who were hospitalized and those who were not.<h4>Methods</h4>We used data from the Primary Care Sentinel Cohort (PCSC) of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database. This network was recruited to be nationally representative of the English population. We developed an LC phenotype using our established 3-step ontological method: (1) ontological step (defining the reasoning process underpinning the phenotype, (2) coding step (exploring what clinical terms are available, and (3) logical extract model (testing performance). We created a version of this phenotype using Protégé in the ontology web language for BioPortal and using PhenoFlow. Next, we used the phenotype to compare people with LC (1) with regard to their symptoms in the year prior to acquiring COVID-19 and (2) with people with acute COVID-19. We also compared hospitalized people with LC with those not hospitalized. We compared sociodemographic details, comorbidities, and Office of National Statistics-defined LC symptoms between groups. We used descriptive statistics and logistic regression.<h4>Results</h4>The long-COVID phenotype differentiated people hospitalized with LC from people who were not and where no index infection was identified. The PCSC (N=7.4 million) includes 428,479 patients with acute COVID-19 diagnosis confirmed by a laboratory test and 10,772 patients with clinically diagnosed COVID-19. A total of 7471 (1.74%, 95% CI 1.70-1.78) people were coded as having LC, 1009 (13.5%, 95% CI 12.7-14.3) had a hospital admission related to acute COVID-19, and 6462 (86.5%, 95% CI 85.7-87.3) were not hospitalized, of whom 2728 (42.2%) had no COVID-19 index date recorded. In addition, 1009 (13.5%, 95% CI 12.73-14.28) people with LC were hospitalized compared to 17,993 (4.5%, 95% CI 4.48-4.61; P<.001) with uncomplicated COVID-19.<h4>Conclusions</h4>Our LC phenotype enables the identification of individuals with the condition in routine data sets, facilitating their comparison with unaffected people through retrospective research. This phenotype and study protocol to explore its face validity contributes to a better understanding of LC.",,pdf:https://publichealth.jmir.org/2022/8/e36989/PDF; doi:https://doi.org/10.2196/36989; html:https://europepmc.org/articles/PMC9374163
 33472631,https://doi.org/10.1186/s12916-020-01893-3,Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.,"Carr E, Bendayan R, Bean D, Stammers M, Wang W, Zhang H, Searle T, Kraljevic Z, Shek A, Phan HTT, Muruet W, Gupta RK, Shinton AJ, Wyatt M, Shi T, Zhang X, Pickles A, Stahl D, Zakeri R, Noursadeghi M, O'Gallagher K, Rogers M, Folarin A, Karwath A, Wickstrøm KE, Köhn-Luque A, Slater L, Cardoso VR, Bourdeaux C, Holten AR, Ball S, McWilliams C, Roguski L, Borca F, Batchelor J, Amundsen EK, Wu X, Gkoutos GV, Sun J, Pinto A, Guthrie B, Breen C, Douiri A, Wu H, Curcin V, Teo JT, Shah AM, Dobson RJB.",,BMC medicine,2021,2021-01-21,Y,Prediction model; Blood parameters; Covid-19; News2 Score,,,"<h4>Background</h4>The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification.<h4>Methods</h4>Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models.<h4>Results</h4>A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites.<h4>Conclusions</h4>NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01893-3; doi:https://doi.org/10.1186/s12916-020-01893-3; html:https://europepmc.org/articles/PMC7817348; pdf:https://europepmc.org/articles/PMC7817348?pdf=render
 32613083,https://doi.org/10.12688/wellcomeopenres.15922.2,"Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data.","Aldridge RW, Lewer D, Katikireddi SV, Mathur R, Pathak N, Burns R, Fragaszy EB, Johnson AM, Devakumar D, Abubakar I, Hayward A.",,Wellcome open research,2020,2020-06-24,Y,Mortality; Minority Ethnic Groups; Covid-19; Sars-cov-2,,,"<b>Background</b>: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. <b>Methods</b>: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. <b>Results</b>: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. <b>Conclusion:</b> Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications.",,doi:https://doi.org/10.12688/wellcomeopenres.15922.2; html:https://europepmc.org/articles/PMC7317462; pdf:https://europepmc.org/articles/PMC7317462?pdf=render
 34286192,https://doi.org/10.7861/fhj.2021-0083,Making trials part of good clinical care: lessons from the RECOVERY trial.,"Pessoa-Amorim G, Campbell M, Fletcher L, Horby P, Landray M, Mafham M, Haynes R.",,Future healthcare journal,2021,2021-07-01,N,Recovery; RANDOMISED CONTROLLED TRIALS; evidence-based medicine; Quality-by-design; Covid-19,,,"When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.",,pdf:https://www.rcpjournals.org/content/futurehosp/8/2/e243.full.pdf; doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083
 PMC9645061,https://doi.org/,Using population-scale medication data to evaluate the impact of the COVID-19 pandemic on the usage of analgesics by cancer patients.,"Han J, Akbari A, Torabi F, Griffiths R, Lyons J, Rolles M, Arnold C, Huws D, Lawler M, Lyons R.",,International journal of population data science,,2022-11-25,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9645061; pdf:https://europepmc.org/articles/PMC9645061?pdf=render
-37284234,https://doi.org/10.1140/epjds/s13688-023-00391-9,"The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.","Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",,EPJ data science,2023,2023-06-05,Y,Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19,,,"Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming ""digital residents."" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",,doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render
 33414147,https://doi.org/10.1136/bmjopen-2020-041536,Estimating the COVID-19 epidemic trajectory and hospital capacity requirements in South West England: a mathematical modelling framework.,"Booton RD, MacGregor L, Vass L, Looker KJ, Hyams C, Bright PD, Harding I, Lazarus R, Hamilton F, Lawson D, Danon L, Pratt A, Wood R, Brooks-Pollock E, Turner KME.",,BMJ open,2021,2021-01-07,Y,Infection control; epidemiology; Public Health,,,"<h4>Objectives</h4>To develop a regional model of COVID-19 dynamics for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West England (SW) as an example case.<h4>Design</h4>Open-source age-structured variant of a susceptible-exposed-infectious-recovered compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths.<h4>Setting</h4>SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.<h4>Participants</h4>Publicly available data on patients with COVID-19.<h4>Primary and secondary outcome measures</h4>The expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction ('R') number over time.<h4>Results</h4>SW model projections indicate that, as of 11 May 2020 (when 'lockdown' measures were eased), 5793 (95% credible interval (CrI) 2003 to 12 051) individuals were still infectious (0.10% of the total SW population, 95% CrI 0.04% to 0.22%), and a total of 189 048 (95% CrI 141 580 to 277 955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95% CrI 2.5% to 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on 11 May 2020 was predicted to be 701 (95% CrI 169 to 1543) and 110 (95% CrI 8 to 464), respectively. The R value in SW was predicted to be 2.6 (95% CrI 2.0 to 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95% CrI 1.8 to 2.9) and lockdown/school closures further reducing the R value to 0.6 (95% CrI 0.5 to 0.7).<h4>Conclusions</h4>The developed model has proved a valuable asset for regional healthcare services. The model will be used further in the SW as the pandemic evolves, and-as open-source software-is portable to healthcare systems in other geographies.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render
-36526319,https://doi.org/10.1136/bmjopen-2022-064910,Performance of scoring systems in selecting short stay medical admissions suitable for assessment in same day emergency care: an analysis of diagnostic accuracy in a UK hospital setting.,"Atkin C, Gallier S, Wallin E, Reddy-Kolanu V, Sapey E.",,BMJ open,2022,2022-12-16,Y,Internal Medicine; General Medicine (See Internal Medicine); Organisation Of Health Services,,,"<h4>Objectives</h4>To assess the performance of the Amb score and Glasgow Admission Prediction Score (GAPS) in identifying acute medical admissions suitable for same day emergency care (SDEC) in a large urban secondary centre.<h4>Design</h4>Retrospective assessment of routinely collected data from electronic healthcare records.<h4>Setting</h4>Single large urban tertiary care centre.<h4>Participants</h4>All unplanned admissions to general medicine on Monday-Friday, episodes starting 08:00-16:59 hours and lasting up to 48 hours, between 1 April 2019 and 9 March 2020.<h4>Main outcome measures</h4>Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.<h4>Results</h4>7365 episodes were assessed. 94.6% of episodes had an Amb score suggesting suitability for SDEC. The positive predictive value of the Amb score in identifying those discharged within 12 hours was 54.5% (95% CI 53.3% to 55.8%). The area under the receiver operating characteristic curve (AUROC) for the Amb score was 0.612 (95% CI 0.599 to 0.625).42.4% of episodes had a GAPS suggesting suitability for SDEC. The positive predictive value of the GAPS in identifying those discharged within 12 hours was 50.5% (95% CI 48.4% to 52.7%). The AUROC for the GAPS was 0.606 (95% CI 0.590 to 0.622).41.4% of the population had both an Amb and GAPS score suggestive of suitability for SDEC and 5.7% of the population had both and Amb and GAPS score suggestive of a lack of suitability for SDEC.<h4>Conclusions</h4>The Amb score and GAPS had poor discriminatory ability to identify acute medical admissions suitable for discharge within 12 hours, limiting their utility in selecting patients for assessment within SDEC services within this diverse patient population.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064910.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render
+37284234,https://doi.org/10.1140/epjds/s13688-023-00391-9,"The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.","Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",,EPJ data science,2023,2023-06-05,Y,Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19,,,"Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming ""digital residents."" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",,doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render
 35210898,https://doi.org/10.2147/por.s353400,Deriving a Standardised Recommended Respiratory Disease Codelist Repository for Future Research.,"MacRae C, Whittaker H, Mukherjee M, Daines L, Morgan A, Iwundu C, Alsallakh M, Vasileiou E, O'Rourke E, Williams AT, Stone PW, Sheikh A, Quint JK.",,Pragmatic and observational research,2022,2022-02-16,Y,Asthma; COPD; Respiratory Tract Infections; Electronic Healthcare Records,,,"<h4>Background</h4>Electronic health record (EHR) databases provide rich, longitudinal data on interactions with healthcare providers and can be used to advance research into respiratory conditions. However, since these data are primarily collected to support health care delivery, clinical coding can be inconsistent, resulting in inherent challenges in using these data for research purposes.<h4>Methods</h4>We systematically searched existing international literature and UK code repositories to find respiratory disease codelists for asthma from January 2018, and chronic obstructive pulmonary disease and respiratory tract infections from January 2020, based on prior searches. Medline searches using key terms provided in article lists. Full-text articles, supplementary files, and reference lists were examined for codelists, and codelists repositories were searched. A reproducible methodology for codelists creation was developed with recommended lists for each disease created based on multidisciplinary expert opinion and previously published literature.<h4>Results</h4>Medline searches returned 1126 asthma articles, 70 COPD articles, and 90 respiratory infection articles, with 3%, 22% and 5% including codelists, respectively. Repository searching returned 12 asthma, 23 COPD, and 64 respiratory infection codelists. We have systematically compiled respiratory disease codelists and from these derived recommended lists for use by researchers to find the most up-to-date and relevant respiratory disease codelists that can be tailored to individual research questions.<h4>Conclusion</h4>Few published papers include codelists, and where published diverse codelists were used, even when answering similar research questions. Whilst some advances have been made, greater consistency and transparency across studies using routine data to study respiratory diseases are needed.",,pdf:https://www.dovepress.com/getfile.php?fileID=78337; doi:https://doi.org/10.2147/POR.S353400; html:https://europepmc.org/articles/PMC8859726; pdf:https://europepmc.org/articles/PMC8859726?pdf=render
+36526319,https://doi.org/10.1136/bmjopen-2022-064910,Performance of scoring systems in selecting short stay medical admissions suitable for assessment in same day emergency care: an analysis of diagnostic accuracy in a UK hospital setting.,"Atkin C, Gallier S, Wallin E, Reddy-Kolanu V, Sapey E.",,BMJ open,2022,2022-12-16,Y,Internal Medicine; General Medicine (See Internal Medicine); Organisation Of Health Services,,,"<h4>Objectives</h4>To assess the performance of the Amb score and Glasgow Admission Prediction Score (GAPS) in identifying acute medical admissions suitable for same day emergency care (SDEC) in a large urban secondary centre.<h4>Design</h4>Retrospective assessment of routinely collected data from electronic healthcare records.<h4>Setting</h4>Single large urban tertiary care centre.<h4>Participants</h4>All unplanned admissions to general medicine on Monday-Friday, episodes starting 08:00-16:59 hours and lasting up to 48 hours, between 1 April 2019 and 9 March 2020.<h4>Main outcome measures</h4>Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.<h4>Results</h4>7365 episodes were assessed. 94.6% of episodes had an Amb score suggesting suitability for SDEC. The positive predictive value of the Amb score in identifying those discharged within 12 hours was 54.5% (95% CI 53.3% to 55.8%). The area under the receiver operating characteristic curve (AUROC) for the Amb score was 0.612 (95% CI 0.599 to 0.625).42.4% of episodes had a GAPS suggesting suitability for SDEC. The positive predictive value of the GAPS in identifying those discharged within 12 hours was 50.5% (95% CI 48.4% to 52.7%). The AUROC for the GAPS was 0.606 (95% CI 0.590 to 0.622).41.4% of the population had both an Amb and GAPS score suggestive of suitability for SDEC and 5.7% of the population had both and Amb and GAPS score suggestive of a lack of suitability for SDEC.<h4>Conclusions</h4>The Amb score and GAPS had poor discriminatory ability to identify acute medical admissions suitable for discharge within 12 hours, limiting their utility in selecting patients for assessment within SDEC services within this diverse patient population.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064910.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render
 32831176,https://doi.org/10.7554/elife.58699,The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship. ,"Emery JC, Russell TW, Liu Y, Hellewell J, Pearson CA, CMMID COVID-19 Working Group, Knight GM, Eggo RM, Kucharski AJ, Kucharski AJ, Funk S, Flasche S, Houben RM.",,eLife,2020,2020-08-24,Y,,,,"A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission.",,doi:https://doi.org/10.7554/elife.58699; doi:https://doi.org/10.7554/eLife.58699; html:https://europepmc.org/articles/PMC7527238; pdf:https://europepmc.org/articles/PMC7527238?pdf=render
 34661663,https://doi.org/10.1001/jamanetworkopen.2021.29639,Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.,"Izadi Z, Brenner EJ, Mahil SK, Dand N, Yiu ZZN, Yates M, Ungaro RC, Zhang X, Agrawal M, Colombel JF, Gianfrancesco MA, Hyrich KL, Strangfeld A, Carmona L, Mateus EF, Lawson-Tovey S, Klingberg E, Cuomo G, Caprioli M, Cruz-Machado AR, Mazeda Pereira AC, Hasseli R, Pfeil A, Lorenz HM, Hoyer BF, Trupin L, Rush S, Katz P, Schmajuk G, Jacobsohn L, Seet AM, Al Emadi S, Wise L, Gilbert EL, Duarte-García A, Valenzuela-Almada MO, Isnardi CA, Quintana R, Soriano ER, Hsu TY, D'Silva KM, Sparks JA, Patel NJ, Xavier RM, Marques CDL, Kakehasi AM, Flipo RM, Claudepierre P, Cantagrel A, Goupille P, Wallace ZS, Bhana S, Costello W, Grainger R, Hausmann JS, Liew JW, Sirotich E, Sufka P, Robinson PC, Machado PM, Griffiths CEM, Barker JN, Smith CH, Yazdany J, Kappelman MD, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Allianc, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Alliance (GRA).",,JAMA network open,2021,2021-10-01,Y,,,,"<h4>Importance</h4>Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood.<h4>Objective</h4>To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs.<h4>Design, setting, and participants</h4>This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included.<h4>Exposures</h4>Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy.<h4>Main outcomes and measures</h4>The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations.<h4>Results</h4>A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone.<h4>Conclusions and relevance</h4>In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.",,doi:https://doi.org/10.1001/jamanetworkopen.2021.29639; html:https://europepmc.org/articles/PMC8524310; pdf:https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2785080/izadi_2021_oi_210864_1633624160.94853.pdf
 37105743,https://doi.org/10.3399/bjgp.2022.0353,Impact of COVID-19 pandemic on incidence of long-term conditions in Wales: a population data linkage study using primary and secondary care health records.,"Qi C, Osborne T, Bailey R, Cooper A, Hollinghurst JP, Akbari A, Crowder R, Peters H, Law RJ, Lewis R, Smith D, Edwards A, Lyons RA.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-04-27,Y,Diagnosis; Chronic disease; Anxiety; Primary Health Care; Covid-19,,,"<h4>Background</h4>The COVID-19 pandemic has directly and indirectly had an impact on health service provision owing to surges and sustained pressures on the system. The effects of these pressures on the management of long-term or chronic conditions are not fully understood.<h4>Aim</h4>To explore the effects of COVID-19 on the recorded incidence of 17 long-term conditions.<h4>Design and setting</h4>This was an observational retrospective population data linkage study on the population of Wales using primary and secondary care data within the Secure Anonymised Information Linkage (SAIL) Databank.<h4>Method</h4>Monthly rates of new diagnosis between 2000 and 2021 are presented for each long-term condition. Incidence rates post-2020 were compared with expected rates predicted using time series modelling of pre-2020 trends. The proportion of annual incidence is presented by sociodemographic factors: age, sex, social deprivation, ethnicity, frailty, and learning disability.<h4>Results</h4>A total of 5 476 012 diagnoses from 2 257 992 individuals are included. Incidence rates from 2020 to 2021 were lower than mean expected rates across all conditions. The largest relative deficit in incidence was in chronic obstructive pulmonary disease corresponding to 343 (95% confidence interval = 230 to 456) undiagnosed patients per 100 000 population, followed by depression, type 2 diabetes, hypertension, anxiety disorders, and asthma. A GP practice of 10 000 patients might have over 400 undiagnosed long-term conditions. No notable differences between sociodemographic profiles of post- and pre-2020 incidences were observed.<h4>Conclusion</h4>There is a potential backlog of undiagnosed patients with multiple long-term conditions. Resources are required to tackle anticipated workload as part of COVID-19 recovery, particularly in primary care.",,pdf:https://bjgp.org/content/bjgp/early/2023/03/06/BJGP.2022.0353.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0353; html:https://europepmc.org/articles/PMC9997656; pdf:https://europepmc.org/articles/PMC9997656?pdf=render
@@ -523,8 +523,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 32518842,https://doi.org/10.12688/wellcomeopenres.15786.1,Inferring the number of COVID-19 cases from recently reported deaths.,"Jombart T, van Zandvoort K, Russell TW, Jarvis CI, Gimma A, Abbott S, Clifford S, Funk S, Gibbs H, Liu Y, Pearson CAB, Bosse NI, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Eggo RM, Kucharski AJ, Edmunds WJ.",,Wellcome open research,2020,2020-04-27,Y,Estimation; Statistics; epidemics; outbreak; Modelling; Covid-19; Sars-cov-2,,,"We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.",,doi:https://doi.org/10.12688/wellcomeopenres.15786.1; doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render
 35677101,https://doi.org/10.23889/ijpds.v5i4.1715,"Impact of COVID-19 pandemic on community medication dispensing: a national cohort analysis in Wales, UK.","Torabi F, Akbari A, Bedston S, Davies G, Abbasizanjani H, Gravenor M, Griffiths R, Harris D, Jenkins N, Lyons J, Morris A, North L, Halcox J, Lyons RA.",,International journal of population data science,2020,2020-01-01,Y,Public Health; Covid-19; Dispensed Medication; Community Dispensing; Interactive Dispensing Dashboard,,,"<h4>Background</h4>Population-level information on dispensed medication provides insight on the distribution of treated morbidities, particularly if linked to other population-scale data at an individual-level.<h4>Objective</h4>To evaluate the impact of COVID-19 on dispensing patterns of medications.<h4>Methods</h4>Retrospective observational study using population-scale, individual-level dispensing records in Wales, UK. Total dispensed drug items for the population between 1 <sup><i>st</i></sup> January 2016 and 31 <sup><i>st</i></sup> December 2019 (3-years, pre-COVID-19) were compared to 2020 with follow up until 27 <sup><i>th</i></sup> July 2021 (COVID-19 period). We compared trends across all years and British National Formulary (BNF) chapters and highlighted the trends in three major chapters for 2019-21: 1-Cardiovascular system (CVD); 2-Central Nervous System (CNS); 3-Immunological & Vaccine. We developed an interactive dashboard to enable monitoring of changes as the pandemic evolves.<h4>Result</h4>Amongst all BNF chapters, 73,410,543 items were dispensed in 2020 compared to 74,121,180 items in 2019 demonstrating -0.96% relative decrease in 2020. Comparison of monthly patterns showed average difference (D) of -59,220 and average Relative Change (RC) of -0.74% between the number of dispensed items in 2020 and 2019. Maximum RC was observed in March 2020 (D = +1,224,909 and RC = +20.62), followed by second peak in June 2020 (D = +257,920, RC = +4.50%). A third peak was observed in September 2020 (D = +264,138, RC = +4.35%). Large increases in March 2020 were observed for CVD and CNS medications across all age groups. The Immunological and Vaccine products dropped to very low levels across all age groups and all months (including the March dispensing peak).<h4>Conclusions</h4>Reconfiguration of routine clinical services during COVID-19 led to substantial changes in community pharmacy drug dispensing. This change may contribute to a long-term burden of COVID-19, raising the importance of a comprehensive and timely monitoring of changes for evaluation of the potential impact on clinical care and outcomes.",,pdf:https://ijpds.org/article/download/1715/3382; doi:https://doi.org/10.23889/ijpds.v5i4.1715; html:https://europepmc.org/articles/PMC9135049; pdf:https://europepmc.org/articles/PMC9135049?pdf=render
 33588321,https://doi.org/10.1016/j.retram.2021.103276,Biological responses to COVID-19: Insights from physiological and blood biomarker profiles.,"Zakeri R, Pickles A, Carr E, Bean DM, O'Gallagher K, Kraljewic Z, Searle T, Shek A, Galloway JB, Teo JTH, Shah AM, Dobson RJB, Bendayan R.",,Current research in translational medicine,2021,2021-02-03,Y,Inflammation; Biomarkers; Classes; Sars-cov-2,,,"<h4>Background</h4>Understanding the spectrum and course of biological responses to coronavirus disease 2019 (COVID-19) may have important therapeutic implications. We sought to characterise biological responses among patients hospitalised with severe COVID-19 based on serial, routinely collected, physiological and blood biomarker values.<h4>Methods and findings</h4>We performed a retrospective cohort study of 1335 patients hospitalised with laboratory-confirmed COVID-19 (median age 70 years, 56 % male), between 1st March and 30th April 2020. Latent profile analysis was performed on serial physiological and blood biomarkers. Patient characteristics, comorbidities and rates of death and admission to intensive care, were compared between the latent classes. A five class solution provided the best fit. Class 1 ""Typical response"" exhibited a moderately elevated and rising C-reactive protein (CRP), stable lymphopaenia, and the lowest rates of 14-day adverse outcomes. Class 2 ""Rapid hyperinflammatory response"" comprised older patients, with higher admission white cell and neutrophil counts, which declined over time, accompanied by a very high and rising CRP and platelet count, and exibited the highest mortality risk. Class 3 ""Progressive inflammatory response"" was similar to the typical response except for a higher and rising CRP, though similar mortality rate. Class 4 ""Inflammatory response with kidney injury"" had prominent lymphopaenia, moderately elevated (and rising) CRP, and severe renal failure. Class 5 ""Hyperinflammatory response with kidney injury"" comprised older patients, with a very high and rising CRP, and severe renal failure that attenuated over time. Physiological measures did not substantially vary between classes at baseline or early admission.<h4>Conclusions and relevance</h4>Our identification of five distinct classes of biomarker profiles provides empirical evidence for heterogeneous biological responses to COVID-19. Early hyperinflammatory responses and kidney injury may signify unique pathophysiology that requires targeted therapy.",,doi:https://doi.org/10.1016/j.retram.2021.103276; doi:https://doi.org/10.1016/j.retram.2021.103276; html:https://europepmc.org/articles/PMC7857048; pdf:https://europepmc.org/articles/PMC7857048?pdf=render
-37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"<h4>Background</h4>Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.<h4>Objective</h4>This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.<h4>Methods</h4>Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.<h4>Results</h4>A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.<h4>Conclusions</h4>Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627
 36093379,https://doi.org/10.1016/j.isci.2022.105079,Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.",,iScience,2022,2022-09-05,Y,Artificial intelligence; Virology; Machine Learning; Health Sciences,,,"Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.",,doi:https://doi.org/10.1016/j.isci.2022.105079; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render
+37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"<h4>Background</h4>Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.<h4>Objective</h4>This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.<h4>Methods</h4>Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.<h4>Results</h4>A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.<h4>Conclusions</h4>Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627
 33716109,https://doi.org/10.1016/j.jinf.2021.03.002,Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate.,"Chaudhry Z, Shawe-Taylor M, Rampling T, Cutfield T, Bidwell G, Chan XHS, Last A, Williams B, Logan S, Marks M, Esmail H.",,The Journal of infection,2021,2021-03-11,Y,Dexamethasone; Corticosteroids; Hospital; Readmissions; Covid-19,,,"<h4>Objective</h4>Our objective was to describe the characteristics of patients admitted, discharged and readmitted, due to COVID-19, to a central London acute-care hospital during the second peak, in particular in relation to corticosteroids use.<h4>Methods</h4>We reviewed patients admitted from the community to University College Hospital (UCH) with COVID-19 as their primary diagnosis between 1st-31st December 2020. Re-attendance and readmission data were collected for patients who re-presented within 10 days following discharge. Data were retrospectively collected.<h4>Results</h4>196 patients were admitted from the community with a diagnosis of COVID-19 and discharged alive in December 2020. Corticosteroids were prescribed in hospital for a median of 5 days (IQR 3-8). 20 patients (10.2%) were readmitted within 10 days. 11/20 received corticosteroids in the first admission of which 10 had received 1-3 days of corticosteroids. Readmission rate in those receiving 1-3 days of corticosteroids was 25%.<h4>Conclusions</h4>Most international guidelines have recommended providing up to 10 days of corticosteroids for severe COVID-19 but stopping on discharge. Our findings show shorter courses of corticosteroids during admission are associated with an increased risk of being readmitted and support continuing the course of corticosteroids after hospital discharge monitored in the virtual ward setting.",,pdf:http://www.journalofinfection.com/article/S0163445321001158/pdf; doi:https://doi.org/10.1016/j.jinf.2021.03.002; html:https://europepmc.org/articles/PMC7948670; pdf:https://europepmc.org/articles/PMC7948670?pdf=render
 33050951,https://doi.org/10.1186/s12916-020-01789-2,Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study.,"van Zandvoort K, Jarvis CI, Pearson CAB, Davies NG, CMMID COVID-19 working group, Ratnayake R, Russell TW, Kucharski AJ, Jit M, Flasche S, Eggo RM, Checchi F.",,BMC medicine,2020,2020-10-14,Y,Control; Response; Africa; Coronavirus; mathematical model; Low-income; Covid-19; Sars-cov-2,,,"<h4>Background</h4>The health impact of COVID-19 may differ in African settings as compared to countries in Europe or China due to demographic, epidemiological, environmental and socio-economic factors. We evaluated strategies to reduce SARS-CoV-2 burden in African countries, so as to support decisions that balance minimising mortality, protecting health services and safeguarding livelihoods.<h4>Methods</h4>We used a Susceptible-Exposed-Infectious-Recovered mathematical model, stratified by age, to predict the evolution of COVID-19 epidemics in three countries representing a range of age distributions in Africa (from oldest to youngest average age: Mauritius, Nigeria and Niger), under various effectiveness assumptions for combinations of different non-pharmaceutical interventions: self-isolation of symptomatic people, physical distancing and 'shielding' (physical isolation) of the high-risk population. We adapted model parameters to better represent uncertainty about what might be expected in African populations, in particular by shifting the distribution of severity risk towards younger ages and increasing the case-fatality ratio. We also present sensitivity analyses for key model parameters subject to uncertainty.<h4>Results</h4>We predicted median symptomatic attack rates over the first 12 months of 23% (Niger) to 42% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R<sub>0</sub>. The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Mitigation strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand and mortality by around 50%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature, and assumptions on transmissibility, infectiousness of asymptomatic cases and risk of severe disease or death by age.<h4>Conclusions</h4>In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding could achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01789-2; doi:https://doi.org/10.1186/s12916-020-01789-2; html:https://europepmc.org/articles/PMC7553800; pdf:https://europepmc.org/articles/PMC7553800?pdf=render
 32355555,https://doi.org/10.7189/jogh.10.010104,COVID-19 must catalyse key global natural experiments.,"Been JV, Sheikh A.",,Journal of global health,2020,2020-06-01,Y,,,,,"""Been and Sheikh’s editorial about COVID-19, outlines the importance of two natural experiments: a- how different countries responded to the pandemic and its effects and b- impact of improvements in air quality on human and planetary health.""",doi:https://doi.org/10.7189/jogh.10.010104; doi:https://doi.org/10.7189/jogh.10.010104; html:https://europepmc.org/articles/PMC7179980; pdf:https://europepmc.org/articles/PMC7179980?pdf=render
@@ -537,15 +537,15 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 36802769,https://doi.org/10.1259/bjr.20201465,Applying machine learning classifiers to automate quality assessment of paediatric dynamic susceptibility contrast (DSC-) MRI data.,"Powell SJ, Withey SB, Sun Y, Grist JT, Novak J, MacPherson L, Abernethy L, Pizer B, Grundy R, Morgan PS, Jaspan T, Bailey S, Mitra D, Auer DP, Avula S, Arvanitis TN, Peet A.",,The British journal of radiology,2023,2023-02-20,Y,,,,"<h4>Objective</h4>Investigate the performance of qualitative review (QR) for assessing dynamic susceptibility contrast (DSC-) MRI data quality in paediatric normal brain and develop an automated alternative to QR.<h4>Methods</h4>1027 signal-time courses were assessed by Reviewer 1 using QR. 243 were additionally assessed by Reviewer 2 and % disagreements and Cohen's κ (κ) were calculated. The signal drop-to-noise ratio (SDNR), root mean square error (RMSE), full width half maximum (FWHM) and percentage signal recovery (PSR) were calculated for the 1027 signal-time courses. Data quality thresholds for each measure were determined using QR results. The measures and QR results trained machine learning classifiers. Sensitivity, specificity, precision, classification error and area under the curve from a receiver operating characteristic curve were calculated for each threshold and classifier.<h4>Results</h4>Comparing reviewers gave 7% disagreements and κ = 0.83. Data quality thresholds of: 7.6 for SDNR; 0.019 for RMSE; 3 s and 19 s for FWHM; and 42.9 and 130.4% for PSR were produced. SDNR gave the best sensitivity, specificity, precision, classification error and area under the curve values of 0.86, 0.86, 0.93, 14.2% and 0.83. Random forest was the best machine learning classifier, giving sensitivity, specificity, precision, classification error and area under the curve of 0.94, 0.83, 0.93, 9.3% and 0.89.<h4>Conclusion</h4>The reviewers showed good agreement. Machine learning classifiers trained on signal-time course measures and QR can assess quality. Combining multiple measures reduces misclassification.<h4>Advances in knowledge</h4>A new automated quality control method was developed, which trained machine learning classifiers using QR results.",,doi:https://doi.org/10.1259/bjr.20201465; doi:https://doi.org/10.1259/bjr.20201465; html:https://europepmc.org/articles/PMC10161906; pdf:https://europepmc.org/articles/PMC10161906?pdf=render
 37311637,https://doi.org/10.1136/bmjopen-2023-071973,Number and timing of primary cleft lip and palate repair surgeries in England: whole nation study of electronic health records before and during the COVID-19 pandemic.,"Etoori D, Park MH, Blackburn RM, Fitzsimons KJ, Butterworth S, Medina J, Mc Grath-Lone L, Russell C, van der Meulen J.",,BMJ open,2023,2023-06-13,Y,epidemiology; Paediatric Surgery; Covid-19,,,"<h4>Objective</h4>To quantify differences in number and timing of first primary cleft lip and palate (CLP) repair procedures during the first year of the COVID-19 pandemic (1 April 2020 to 31 March 2021; 2020/2021) compared with the preceding year (1 April 2019 to 31 March 2020; 2019/2021).<h4>Design</h4>National observational study of administrative hospital data.<h4>Setting</h4>National Health Service hospitals in England.<h4>Study population</h4>Children <5 years undergoing primary repair for an orofacial cleft Population Consensus and Surveys Classification of Interventions and Procedures-fourth revisions (OPCS-4) codes F031, F291).<h4>Main exposure</h4>Procedure date (2020/2021 vs 2019/2020).<h4>Main outcomes</h4>Numbers and timing (age in months) of first primary CLP procedures.<h4>Results</h4>1716 CLP primary repair procedures were included in the analysis. In 2020/2021, 774 CLP procedures were carried out compared with 942 in 2019/2020, a reduction of 17.8% (95% CI 9.5% to 25.4%). The reduction varied over time in 2020/2021, with no surgeries at all during the first 2 months (April and May 2020). Compared with 2019/2020, first primary lip repair procedures performed in 2020/2021 were delayed by 1.6 months on average (95% CI 0.9 to 2.2 months). Delays in primary palate repairs were smaller on average but varied across the nine geographical regions.<h4>Conclusion</h4>There were significant reductions in the number and delays in timing of first primary CLP repair procedures in England during the first year of the pandemic, which may affect long-term outcomes.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e071973.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-071973; html:https://europepmc.org/articles/PMC10276964; pdf:https://europepmc.org/articles/PMC10276964?pdf=render
 34053260,https://doi.org/10.1098/rstb.2020.0283,Exploring surveillance data biases when estimating the reproduction number: with insights into subpopulation transmission of COVID-19 in England.,"Sherratt K, Abbott S, Meakin SR, Hellewell J, Munday JD, Bosse N, CMMID COVID-19 Working Group, Jit M, Funk S.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Transmission; Surveillance; Bias; Covid-19; Sars-cov-2; Time-varying Reproduction Number,,,"The time-varying reproduction number (<i>R<sub>t</sub></i>: the average number of secondary infections caused by each infected person) may be used to assess changes in transmission potential during an epidemic. While new infections are not usually observed directly, they can be estimated from data. However, data may be delayed and potentially biased. We investigated the sensitivity of <i>R<sub>t</sub></i> estimates to different data sources representing COVID-19 in England, and we explored how this sensitivity could track epidemic dynamics in population sub-groups. We sourced public data on test-positive cases, hospital admissions and deaths with confirmed COVID-19 in seven regions of England over March through August 2020. We estimated <i>R<sub>t</sub></i> using a model that mapped unobserved infections to each data source. We then compared differences in <i>R<sub>t</sub></i> with the demographic and social context of surveillance data over time. Our estimates of transmission potential varied for each data source, with the relative inconsistency of estimates varying across regions and over time. <i>R<sub>t</sub></i> estimates based on hospital admissions and deaths were more spatio-temporally synchronous than when compared to estimates from all test positives. We found these differences may be linked to biased representations of subpopulations in each data source. These included spatially clustered testing, and where outbreaks in hospitals, care homes, and young age groups reflected the link between age and severity of the disease. We highlight that policy makers could better target interventions by considering the source populations of <i>R<sub>t</sub></i> estimates. Further work should clarify the best way to combine and interpret <i>R<sub>t</sub></i> estimates from different data sources based on the desired use. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0283; doi:https://doi.org/10.1098/rstb.2020.0283; html:https://europepmc.org/articles/PMC8165604; pdf:https://europepmc.org/articles/PMC8165604?pdf=render
-36065116,https://doi.org/10.1093/brain/awac321,Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.,"Needham EJ, Ren AL, Digby RJ, Norton EJ, Ebrahimi S, Outtrim JG, Chatfield DA, Manktelow AE, Leibowitz MM, Newcombe VFJ, Doffinger R, Barcenas-Morales G, Fonseca C, Taussig MJ, Burnstein RM, Samanta RJ, Dunai C, Sithole N, Ashton NJ, Zetterberg H, Gisslén M, Edén A, Marklund E, Openshaw PJM, Dunning J, Griffiths MJ, Cavanagh J, Breen G, Irani SR, Elmer A, Kingston N, Summers C, Bradley JR, Taams LS, Michael BD, Bullmore ET, Smith KGC, Lyons PA, Coles AJ, Menon DK, Cambridge NeuroCOVID Group, CITIID-NIHR COVID-19 BioResource Collaboration, Cambridge NIHR Clinical Research Facility.",,Brain : a journal of neurology,2022,2022-11-01,Y,Autoantibodies; Brain injury; neuroinflammation; Covid-19,,,"COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible.",,pdf:https://academic.oup.com/brain/article-pdf/145/11/4097/47170622/awac321.pdf; doi:https://doi.org/10.1093/brain/awac321; html:https://europepmc.org/articles/PMC9494359; pdf:https://europepmc.org/articles/PMC9494359?pdf=render
 34261639,https://doi.org/10.1136/bmj.n1592,Risks of covid-19 hospital admission and death for people with learning disability: population based cohort study using the OpenSAFELY platform.,"Williamson EJ, McDonald HI, Bhaskaran K, Walker AJ, Bacon S, Davy S, Schultze A, Tomlinson L, Bates C, Ramsay M, Curtis HJ, Forbes H, Wing K, Minassian C, Tazare J, Morton CE, Nightingale E, Mehrkar A, Evans D, Inglesby P, MacKenna B, Cockburn J, Rentsch CT, Mathur R, Wong AYS, Eggo RM, Hulme W, Croker R, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Smeeth L, Goldacre B, Kuper H.",,BMJ (Clinical research ed.),2021,2021-07-14,Y,,,,"<h4>Objective</h4>To assess the association between learning disability and risk of hospital admission and death from covid-19 in England among adults and children.<h4>Design</h4>Population based cohort study on behalf of NHS England using the OpenSAFELY platform.<h4>Setting</h4>Patient level data were obtained for more than 17 million people registered with a general practice in England that uses TPP software. Electronic health records were linked with death data from the Office for National Statistics and hospital admission data from NHS Secondary Uses Service.<h4>Participants</h4>Adults (aged 16-105 years) and children (<16 years) from two cohorts: wave 1 (registered with a TPP practice as of 1 March 2020 and followed until 31 August 2020); and wave 2 (registered 1 September 2020 and followed until 8 February 2021). The main exposure group consisted of people on a general practice learning disability register; a subgroup was defined as those having profound or severe learning disability. People with Down's syndrome and cerebral palsy were identified (whether or not they were on the learning disability register).<h4>Main outcome measure</h4>Covid-19 related hospital admission and covid-19 related death. Non-covid-19 deaths were also explored.<h4>Results</h4>For wave 1, 14 312 023 adults aged ≥16 years were included, and 90 307 (0.63%) were on the learning disability register. Among adults on the register, 538 (0.6%) had a covid-19 related hospital admission; there were 222 (0.25%) covid-19 related deaths and 602 (0.7%) non-covid deaths. Among adults not on the register, 29 781 (0.2%) had a covid-19 related hospital admission; there were 13 737 (0.1%) covid-19 related deaths and 69 837 (0.5%) non-covid deaths. Wave 1 hazard ratios for adults on the learning disability register (adjusted for age, sex, ethnicity, and geographical location) were 5.3 (95% confidence interval 4.9 to 5.8) for covid-19 related hospital admission and 8.2 (7.2 to 9.4) for covid-19 related death. Wave 2 produced similar estimates. Associations were stronger among those classified as having severe to profound learning disability, and among those in residential care. For both waves, Down's syndrome and cerebral palsy were associated with increased hazards for both events; Down's syndrome to a greater extent. Hazard ratios for non-covid deaths followed similar patterns with weaker associations. Similar patterns of increased relative risk were seen for children, but covid-19 related deaths and hospital admissions were rare, reflecting low event rates among children.<h4>Conclusions</h4>People with learning disability have markedly increased risks of hospital admission and death from covid-19, over and above the risks observed for non-covid causes of death. Prompt access to covid-19 testing and healthcare is warranted for this vulnerable group, and prioritisation for covid-19 vaccination and other targeted preventive measures should be considered.",,pdf:https://www.bmj.com/content/bmj/374/bmj.n1592.full.pdf; doi:https://doi.org/10.1136/bmj.n1592; html:https://europepmc.org/articles/PMC8278652; pdf:https://europepmc.org/articles/PMC8278652?pdf=render
+36065116,https://doi.org/10.1093/brain/awac321,Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.,"Needham EJ, Ren AL, Digby RJ, Norton EJ, Ebrahimi S, Outtrim JG, Chatfield DA, Manktelow AE, Leibowitz MM, Newcombe VFJ, Doffinger R, Barcenas-Morales G, Fonseca C, Taussig MJ, Burnstein RM, Samanta RJ, Dunai C, Sithole N, Ashton NJ, Zetterberg H, Gisslén M, Edén A, Marklund E, Openshaw PJM, Dunning J, Griffiths MJ, Cavanagh J, Breen G, Irani SR, Elmer A, Kingston N, Summers C, Bradley JR, Taams LS, Michael BD, Bullmore ET, Smith KGC, Lyons PA, Coles AJ, Menon DK, Cambridge NeuroCOVID Group, CITIID-NIHR COVID-19 BioResource Collaboration, Cambridge NIHR Clinical Research Facility.",,Brain : a journal of neurology,2022,2022-11-01,Y,Autoantibodies; Brain injury; neuroinflammation; Covid-19,,,"COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible.",,pdf:https://academic.oup.com/brain/article-pdf/145/11/4097/47170622/awac321.pdf; doi:https://doi.org/10.1093/brain/awac321; html:https://europepmc.org/articles/PMC9494359; pdf:https://europepmc.org/articles/PMC9494359?pdf=render
 36629015,https://doi.org/10.1177/17407745221143449,Lack of transparent reporting of trial monitoring approaches in randomised controlled trials: A systematic review of contemporary protocol papers.,"Hsieh SF, Yorke-Edwards V, Murray ML, Diaz-Montana C, Love SB, Sydes MR.",,"Clinical trials (London, England)",2023,2023-01-11,Y,Systematic review; Randomised Controlled Trial; On-site Monitoring; Risk-based Monitoring; Protocol Paper; Central Monitoring; Trial Monitoring; Reporting Monitoring,,,"<h4>Background</h4>Monitoring is essential to ensure patient safety and data integrity in clinical trials as per Good Clinical Practice. The Standard Protocol Items: Recommendations for Interventional Trials Statement and its checklist guides authors to include monitoring in their protocols. We investigated how well monitoring was reported in published 'protocol papers' for contemporary randomised controlled trials.<h4>Methods</h4>A systematic search was conducted in PubMed to identify eligible protocol papers published in selected journals between 1 January 2020 and 31 May 2020. Protocol papers were classified by whether they reported monitoring and, if so, by the details of monitoring. Data were summarised descriptively.<h4>Results</h4>Of 811 protocol papers for randomised controlled trials, 386 (48%; 95% CI: 44%-51%) explicitly reported some monitoring information. Of these, 20% (77/386) reported monitoring information consistent with an on-site monitoring approach, and 39% (152/386) with central monitoring, 26% (101/386) with a mixed approach, while 14% (54/386) did not provide sufficient information to specify an approach. Only 8% (30/386) of randomised controlled trials reported complete details about all of scope, frequency and organisation of monitoring; frequency of monitoring was the least reported. However, 6% (25/386) of papers used the term 'audit' to describe 'monitoring'.<h4>Discussion</h4>Monitoring information was reported in only approximately half of the protocol papers. Suboptimal reporting of monitoring hinders the clinical community from having the full information on which to judge the validity of a trial and jeopardises the value of protocol papers and the credibility of the trial itself. Greater efforts are needed to promote the transparent reporting of monitoring to journal editors and authors.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/17407745221143449; doi:https://doi.org/10.1177/17407745221143449; html:https://europepmc.org/articles/PMC10021127; pdf:https://europepmc.org/articles/PMC10021127?pdf=render
 34053271,https://doi.org/10.1098/rstb.2020.0266,Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection.,"Jombart T, Ghozzi S, Schumacher D, Taylor TJ, Leclerc QJ, Jit M, Flasche S, Greaves F, Ward T, Eggo RM, Nightingale E, Meakin S, Brady OJ, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Medley GF, Höhle M, Edmunds WJ.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Algorithm; Surveillance; outbreak; Machine Learning; Asmodee; Trendbreaker,,,"As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package <i>trendbreaker</i>. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0266; doi:https://doi.org/10.1098/rstb.2020.0266; html:https://europepmc.org/articles/PMC8165581; pdf:https://europepmc.org/articles/PMC8165581?pdf=render
 37315048,https://doi.org/10.1371/journal.pone.0287091,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,PloS one,2023,2023-06-14,Y,,,,"<h4>Background</h4>Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.<h4>Methods</h4>Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.<h4>Results</h4>We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.<h4>Conclusion</h4>The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287091&type=printable; doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render
 36258219,https://doi.org/10.1186/s13063-022-06824-6,"Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.","Sandercock PAG, Darbyshire J, DeMets D, Fowler R, Lalloo DG, Munavvar M, Staplin N, Warris A, Wittes J, Emberson JR.",,Trials,2022,2022-10-18,Y,,,,"<h4>Aim</h4>To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.<h4>Methods and findings</h4>During the first 24 months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving > 45,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively 'competing' for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab + imdevimab, and tocilizumab.<h4>Conclusions</h4>RECOVERY's streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial's efficiency, without compromising the DMC's ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06824-6; doi:https://doi.org/10.1186/s13063-022-06824-6; html:https://europepmc.org/articles/PMC9579551; pdf:https://europepmc.org/articles/PMC9579551?pdf=render
 36446449,https://doi.org/10.1136/bmjopen-2022-061849,Effect of lifting COVID-19 restrictions on utilisation of primary care services in Nepal: a difference-in-differences analysis.,"Kapoor NR, Aryal A, Mehata S, Dulal M, Kruk ME, Bauhoff S, Arsenault C.",,BMJ open,2022,2022-11-29,Y,Primary Care; Health Policy; Covid-19,,,"<h4>Introduction</h4>An increasing number of studies have reported disruptions in health service utilisation due to the COVID-19 pandemic and its associated restrictions. However, little is known about the effect of lifting COVID-19 restrictions on health service utilisation. The objective of this study was to estimate the effect of lifting COVID-19 restrictions on primary care service utilisation in Nepal.<h4>Methods</h4>Data on utilisation of 10 primary care services were extracted from the Health Management Information System across all health facilities in Nepal. We used a difference-in-differences design and linear fixed effects regressions to estimate the effect of lifting COVID-19 restrictions. The treatment group included palikas that had lifted restrictions in place from 17 August 2020 to 16 September 2020 (Bhadra 2077) and the control group included palikas that had maintained restrictions during that period. The pre-period included the 4 months of national lockdown from 24 March 2020 to 22 July 2020 (Chaitra 2076 to Ashar 2077). Models included month and palika fixed effects and controlled for COVID-19 incidence.<h4>Results</h4>We found that lifting COVID-19 restrictions was associated with an average increase per palika of 57.5 contraceptive users (95% CI 14.6 to 100.5), 15.6 antenatal care visits (95% CI 5.3 to 25.9) and 1.6 child pneumonia visits (95% CI 0.2 to 2.9). This corresponded to a 9.4% increase in contraceptive users, 34.2% increase in antenatal care visits and 15.6% increase in child pneumonia visits. Utilisation of most other primary care services also increased after lifting restrictions, but coefficients were not statistically significant.<h4>Conclusions</h4>Despite the ongoing pandemic, lifting restrictions can lead to an increase in some primary care services. Our results point to a causal link between restrictions and health service utilisation and call for policy makers in low- and middle-income countries to carefully consider the trade-offs of strict lockdowns during future COVID-19 waves or future pandemics.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render
-37303488,https://doi.org/10.1136/bmjmed-2022-000392,"Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.","Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.",,BMJ medicine,2023,2023-05-11,Y,Primary Health Care; Medical Informatics; Covid-19,,,"<h4>Objective</h4>To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.<h4>Design</h4>Population based, retrospective cohort study using federated analytics.<h4>Setting</h4>Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.<h4>Participants</h4>NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.<h4>Main outcome measure</h4>Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.<h4>Results</h4>The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.<h4>Conclusion</h4>NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000392.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render
 32679111,https://doi.org/10.1016/s0140-6736(20)31356-8,COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England.,"Mafham MM, Spata E, Goldacre R, Gair D, Curnow P, Bray M, Hollings S, Roebuck C, Gale CP, Mamas MA, Deanfield JE, de Belder MA, Luescher TF, Denwood T, Landray MJ, Emberson JR, Collins R, Morris EJA, Casadei B, Baigent C.",,"Lancet (London, England)",2020,2020-07-14,Y,,,,"<h4>Background</h4>Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.<h4>Methods</h4>We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.<h4>Findings</h4>Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37-43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13-20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38-46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12-29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29-45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2-9) in 2019 to 3 days (1-5) by the end of March, 2020.<h4>Interpretation</h4>Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.<h4>Funding</h4>UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.",,doi:https://doi.org/10.1016/s0140-6736(20)31356-8; doi:https://doi.org/10.1016/S0140-6736(20)31356-8; html:https://europepmc.org/articles/PMC7429983; pdf:https://europepmc.org/articles/PMC7429983?pdf=render
+37303488,https://doi.org/10.1136/bmjmed-2022-000392,"Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.","Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.",,BMJ medicine,2023,2023-05-11,Y,Primary Health Care; Medical Informatics; Covid-19,,,"<h4>Objective</h4>To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.<h4>Design</h4>Population based, retrospective cohort study using federated analytics.<h4>Setting</h4>Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.<h4>Participants</h4>NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.<h4>Main outcome measure</h4>Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.<h4>Results</h4>The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.<h4>Conclusion</h4>NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000392.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render
 35605170,https://doi.org/10.2196/37668,Differences in Clinical Presentation With Long COVID After Community and Hospital Infection and Associations With All-Cause Mortality: English Sentinel Network Database Study.,"Meza-Torres B, Delanerolle G, Okusi C, Mayor N, Anand S, Macartney J, Gatenby P, Glampson B, Chapman M, Curcin V, Mayer E, Joy M, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-16,Y,Phenotype; Hospitalization; Social Class; General Practitioners; Ethnicity; Medical Record Systems; Systematized Nomenclature Of Medicine; Computerized; Biomedical Ontologies; Data Accuracy; Covid-19; Sars-cov-2; Long Covid; Post–covid-19 Syndrome; Post–acute Covid-19 Syndrome; Data Extracts,,,"<h4>Background</h4>Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records.<h4>Objective</h4>We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates.<h4>Methods</h4>We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs.<h4>Results</h4>In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001).<h4>Conclusions</h4>The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.",,pdf:https://publichealth.jmir.org/2022/8/e37668/PDF; doi:https://doi.org/10.2196/37668; html:https://europepmc.org/articles/PMC9384859
 36929968,https://doi.org/10.1016/s0140-6736(22)02235-8,Impact of the temporary suspension of the Bowel Screening Wales programme on inequalities during the COVID-19 pandemic: a retrospective register-based study.,"Bright D, Song J, Hillier S, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,"Lancet (London, England)",2022,2022-11-24,Y,,,,"<h4>Background</h4>Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention.<h4>Methods</h4>BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models.<h4>Findings</h4>Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60·4% vs 62·7%; p<0·001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard.<h4>Interpretation</h4>Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening.<h4>Funding</h4>Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691043; doi:https://doi.org/10.1016/S0140-6736(22)02235-8; html:https://europepmc.org/articles/PMC9691043; pdf:https://europepmc.org/articles/PMC9691043?pdf=render
 37606853,https://doi.org/10.1007/s00520-023-07944-8,"The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.","Han J, Rolles M, Torabi F, Griffiths R, Bedston S, Akbari A, Burnett B, Lyons J, Greene G, Thomas R, Long T, Arnold C, Huws DW, Lawler M, Lyons RA.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-08-22,Y,Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic,,,"<h4>Purpose</h4>Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care.<h4>Methods</h4>A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds.<h4>Results</h4>We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision.<h4>Conclusions</h4>We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf; doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render
@@ -623,8 +623,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 35301688,https://doi.org/10.1007/s12471-022-01670-2,Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning.,"van de Leur RR, Bleijendaal H, Taha K, Mast T, Gho JMIH, Linschoten M, van Rees B, Henkens MTHM, Heymans S, Sturkenboom N, Tio RA, Offerhaus JA, Bor WL, Maarse M, Haerkens-Arends HE, Kolk MZH, van der Lingen ACJ, Selder JJ, Wierda EE, van Bergen PFMM, Winter MM, Zwinderman AH, Doevendans PA, van der Harst P, Pinto YM, Asselbergs FW, van Es R, Tjong FVY, CAPACITY-COVID collaborative consortium.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2022,2022-03-17,Y,Mortality; Electrocardiogram; Arrhythmia; Machine Learning; Deep Learning; Covid-19,,,"<h4>Background and purpose</h4>The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients.<h4>Methods</h4>Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation.<h4>Results</h4>Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65-0.79), 0.76 (95% CI 0.68-0.82) and 0.77 (95% CI 0.70-0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block.<h4>Conclusion</h4>This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features.",,pdf:https://link.springer.com/content/pdf/10.1007/s12471-022-01670-2.pdf; doi:https://doi.org/10.1007/s12471-022-01670-2; html:https://europepmc.org/articles/PMC8929464; pdf:https://europepmc.org/articles/PMC8929464?pdf=render
 36706770,https://doi.org/10.1016/s2214-109x(23)00007-4,Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.,Global Burden of Disease 2021 Health Financing Collaborator Network.,,The Lancet. Global health,2023,2023-01-24,Y,,,,"<h4>Background</h4>The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.<h4>Methods</h4>In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.<h4>Findings</h4>In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1-9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2-7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3-25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.<h4>Interpretation</h4>There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.<h4>Funding</h4>Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S2214109X23000074/pdf; doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276
 34319235,https://doi.org/10.2196/28873,Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH): Protocol for a Prospective Observational Study.,"Ranjan Y, Althobiani M, Jacob J, Orini M, Dobson RJ, Porter J, Hurst J, Folarin AA.",,JMIR research protocols,2021,2021-10-07,Y,Lung diseases; Mental health; Remote Monitoring; Respiratory Health; Internet Of Things; Mhealth; Mobile Health; Wearables; Cardiopulmonary Diseases; Covid-19,,,"<h4>Background</h4>Chronic lung disorders like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by exacerbations. They are unpleasant for patients and sometimes severe enough to cause hospital admission and death. Moreover, due to the COVID-19 pandemic, vulnerable populations with these disorders are at high risk, and their routine care cannot be done properly. Remote monitoring offers a low cost and safe solution for gaining visibility into the health of people in their daily lives, making it useful for vulnerable populations.<h4>Objective</h4>The primary objective is to assess the feasibility and acceptability of remote monitoring using wearables and mobile phones in patients with pulmonary diseases. The secondary objective is to provide power calculations for future studies centered around understanding the number of exacerbations according to sample size and duration.<h4>Methods</h4>Twenty participants will be recruited in each of three cohorts (COPD, IPF, and posthospitalization COVID). Data collection will be done remotely using the RADAR-Base (Remote Assessment of Disease And Relapse) mobile health (mHealth) platform for different devices, including Garmin wearable devices and smart spirometers, mobile app questionnaires, surveys, and finger pulse oximeters. Passive data include wearable-derived continuous heart rate, oxygen saturation, respiration rate, activity, and sleep. Active data include disease-specific patient-reported outcome measures, mental health questionnaires, and symptom tracking to track disease trajectory. Analyses will assess the feasibility of lung disorder remote monitoring (including data quality, data completeness, system usability, and system acceptability). We will attempt to explore disease trajectory, patient stratification, and identification of acute clinical events such as exacerbations. A key aspect is understanding the potential of real-time data collection. We will simulate an intervention to acquire responses at the time of the event to assess model performance for exacerbation identification.<h4>Results</h4>The Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH) study provides a unique opportunity to assess the use of remote monitoring in the evaluation of lung disorders. The study started in the middle of June 2021. The data collection apparatus, questionnaires, and wearable integrations were setup and tested by the clinical teams prior to the start of recruitment. While recruitment is ongoing, real-time exacerbation identification models are currently being constructed. The models will be pretrained daily on data of previous days, but the inference will be run in real time.<h4>Conclusions</h4>The RALPMH study will provide a reference infrastructure for remote monitoring of lung diseases. It specifically involves information regarding the feasibility and acceptability of remote monitoring and the potential of real-time data collection and analysis in the context of chronic lung disorders. It will help plan and inform decisions in future studies in the area of respiratory health.<h4>Trial registration</h4>ISRCTN Registry ISRCTN16275601; https://www.isrctn.com/ISRCTN16275601.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/28873.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i10e28873_app2.pdf&filename=4dda9f18456291d5d5d6facee1b77a71.pdf; doi:https://doi.org/10.2196/28873; html:https://europepmc.org/articles/PMC8500349
-37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"<h4>Background</h4>During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.<h4>Methods</h4>A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.<h4>Results</h4>Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.<h4>Conclusion</h4>e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render
 35634533,https://doi.org/10.12688/wellcomeopenres.17360.1,A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.,"Rowan A, Bates C, Hulme W, Evans D, Davy S, A Kennedy N, Galloway J, E Mansfield K, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, J Walker A, E Morton C, Bhaskaran K, T Rentsch C, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Green A, Fisher L, J Curtis H, Tazare J, M Eggo R, Inglesby P, Cockburn J, I McDonald H, Mathur R, Ys Wong A, Forbes H, Parry J, Hester F, Harper S, J Douglas I, Smeeth L, A Tomlinson L, W Lees C, Evans S, Smith C, M Langan S, Mehkar A, MacKenna B, Goldacre B.",,Wellcome open research,2021,2021-12-22,Y,Medications; Biosimilars; Healthcare Administration; Opensafely,,,"<b>Background:</b> At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, ""high-cost drugs"" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. <b>Methods:</b> Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. <b>Results:</b> In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. <b>Conclusions:</b> We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.",,doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render
+37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"<h4>Background</h4>During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.<h4>Methods</h4>A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.<h4>Results</h4>Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.<h4>Conclusion</h4>e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render
 36777997,https://doi.org/10.1016/j.xgen.2022.100181,Leveraging global multi-ancestry meta-analysis in the study of idiopathic pulmonary fibrosis genetics.,"Partanen JJ, Häppölä P, Zhou W, Lehisto AA, Ainola M, Sutinen E, Allen RJ, Stockwell AD, Leavy OC, Oldham JM, Guillen-Guio B, Cox NJ, Hirbo JB, Schwartz DA, Fingerlin TE, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV, Ripatti S, Pirinen M, International IPF Genetics Consortium, Global Biobank Meta-Analysis Initiative (GBMI), Laitinen T, Kaarteenaho R, Myllärniemi M, Daly MJ, Koskela JT.",,Cell genomics,2022,2022-10-12,Y,Meta-analysis; idiopathic pulmonary fibrosis; Gwas; Ancestry; Muc5b; Fine-mapping; Cross-population Analysis; Covid-19; Global Biobank Meta-Analysis Initiative,,,"The research of rare and devastating orphan diseases, such as idiopathic pulmonary fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor-the prevalence of IPF is only approximately four times the incidence, limiting the recruitment of patients to trials and studies of the underlying biology. Global biobanking efforts can dramatically alter the future of IPF research. We describe a large-scale meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine this meta-analysis with the largest available meta-analysis of IPF, reaching 11,160 patients and 1,364,410 population controls. We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection and note an unexplained sex-heterogeneity effect at the strongest IPF locus <i>MUC5B</i>.",,pdf:https://helda.helsinki.fi/bitstream/10138/355828/1/Leveraging_global_multi_ancestry_meta_a...pdf; doi:https://doi.org/10.1016/j.xgen.2022.100181; html:https://europepmc.org/articles/PMC9903787; pdf:https://europepmc.org/articles/PMC9903787?pdf=render
 35802687,https://doi.org/10.1371/journal.pone.0270668,"Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.","Godolphin PJ, Fisher DJ, Berry LR, Derde LPG, Diaz JV, Gordon AC, Lorenzi E, Marshall JC, Murthy S, Shankar-Hari M, Sterne JAC, Tierney JF, Vale CL.",,PloS one,2022,2022-07-08,Y,,,,"<h4>Background</h4>A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence.<h4>Methods</h4>Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence.<h4>Findings</h4>One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71-0·95, p = 0·008]] and sarilumab [0·80 [0·61-1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81-1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28.<h4>Conclusions</h4>Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable; doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render
 36050271,https://doi.org/10.1016/s2589-7500(22)00151-0,CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Lumbers RT, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.",,The Lancet. Digital health,2022,2022-08-29,N,,,,"Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.",,doi:https://doi.org/10.1016/s2589-7500(22)00151-0; doi:https://doi.org/10.1016/S2589-7500(22)00151-0
@@ -703,12 +703,12 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 37381004,https://doi.org/10.1186/s12913-023-09545-x,A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.,"Ferrah N, Parker C, Ibrahim J, Gabbe B, Cameron P.",,BMC health services research,2023,2023-06-28,Y,Trauma; Rural; Interview; Older Adults,,,"<h4>Background</h4>For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.<h4>Method</h4>We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.<h4>Results</h4>Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.<h4>Conclusions</h4>Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09545-x; doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render
 35176022,https://doi.org/10.1371/journal.pmed.1003915,"Changes in household food and drink purchases following restrictions on the advertisement of high fat, salt, and sugar products across the Transport for London network: A controlled interrupted time series analysis.","Yau A, Berger N, Law C, Cornelsen L, Greener R, Adams J, Boyland EJ, Burgoine T, de Vocht F, Egan M, Er V, Lake AA, Lock K, Mytton O, Petticrew M, Thompson C, White M, Cummins S.",,PLoS medicine,2022,2022-02-17,Y,,,,"<h4>Background</h4>Restricting the advertisement of products with high fat, salt, and sugar (HFSS) content has been recommended as a policy tool to improve diet and tackle obesity, but the impact on HFSS purchasing is unknown. This study aimed to evaluate the impact of HFSS advertising restrictions, implemented across the London (UK) transport network in February 2019, on HFSS purchases.<h4>Methods and findings</h4>Over 5 million take-home food and drink purchases were recorded by 1,970 households (London [intervention], n = 977; North of England [control], n = 993) randomly selected from the Kantar Fast Moving Consumer Goods panel. The intervention and control samples were similar in household characteristics but had small differences in main food shopper sex, socioeconomic position, and body mass index. Using a controlled interrupted time series design, we estimated average weekly household purchases of energy and nutrients from HFSS products in the post-intervention period (44 weeks) compared to a counterfactual constructed from the control and pre-intervention (36 weeks) series. Energy purchased from HFSS products was 6.7% (1,001.0 kcal, 95% CI 456.0 to 1,546.0) lower among intervention households compared to the counterfactual. Relative reductions in purchases of fat (57.9 g, 95% CI 22.1 to 93.7), saturated fat (26.4 g, 95% CI 12.4 to 40.4), and sugar (80.7 g, 95% CI 41.4 to 120.1) from HFSS products were also observed. Energy from chocolate and confectionery purchases was 19.4% (317.9 kcal, 95% CI 200.0 to 435.8) lower among intervention households than for the counterfactual, with corresponding relative reductions in fat (13.1 g, 95% CI 7.5 to 18.8), saturated fat (8.7 g, 95% CI 5.7 to 11.7), sugar (41.4 g, 95% CI 27.4 to 55.4), and salt (0.2 g, 95% CI 0.1 to 0.2) purchased from chocolate and confectionery. Relative reductions are in the context of secular increases in HFSS purchases in both the intervention and control areas, so the policy was associated with attenuated growth of HFSS purchases rather than absolute reduction in HFSS purchases. Study limitations include the lack of out-of-home purchases in our analyses and not being able to assess the sustainability of observed changes beyond 44 weeks.<h4>Conclusions</h4>This study finds an association between the implementation of restrictions on outdoor HFSS advertising and relative reductions in energy, sugar, and fat purchased from HFSS products. These findings provide support for policies that restrict HFSS advertising as a tool to reduce purchases of HFSS products.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003915&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003915; html:https://europepmc.org/articles/PMC8853584; pdf:https://europepmc.org/articles/PMC8853584?pdf=render
 34903266,https://doi.org/10.1186/s13059-021-02561-2,CIDER: an interpretable meta-clustering framework for single-cell RNA-seq data integration and evaluation.,"Hu Z, Ahmed AA, Yau C.",,Genome biology,2021,2021-12-13,Y,Clustering; Confounding Factors; Single-cell Rna-seq,,,"Clustering of joint single-cell RNA-Seq (scRNA-Seq) data is often challenged by confounding factors, such as batch effects and biologically relevant variability. Existing batch effect removal methods typically require strong assumptions on the composition of cell populations being near identical across samples. Here, we present CIDER, a meta-clustering workflow based on inter-group similarity measures. We demonstrate that CIDER outperforms other scRNA-Seq clustering methods and integration approaches in both simulated and real datasets. Moreover, we show that CIDER can be used to assess the biological correctness of integration in real datasets, while it does not require the existence of prior cellular annotations.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-021-02561-2; doi:https://doi.org/10.1186/s13059-021-02561-2; html:https://europepmc.org/articles/PMC8667531; pdf:https://europepmc.org/articles/PMC8667531?pdf=render
-34781301,https://doi.org/10.1159/000520674,"Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.","Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.",,Cardiology,2022,2021-11-15,N,Data Sources; cardiovascular; Real-world Data; Real-world Evidence,,,"<h4>Background</h4>Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).<h4>Methods</h4>We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.<h4>Results</h4>Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.<h4>Conclusions</h4>This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.",,pdf:https://www.karger.com/Article/Pdf/520674; doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674
 34514354,https://doi.org/10.1093/jamiaopen/ooab001,Transforming and evaluating electronic health record disease phenotyping algorithms using the OMOP common data model: a case study in heart failure.,"Papez V, Moinat M, Payralbe S, Asselbergs FW, Lumbers RT, Hemingway H, Dobson R, Denaxas S.",,JAMIA open,2021,2021-02-04,Y,Phenotyping; Heart Failure; Algorithms; Ehr; Omop,,,"<h4>Objective</h4>The aim of the study was to transform a resource of linked electronic health records (EHR) to the OMOP common data model (CDM) and evaluate the process in terms of syntactic and semantic consistency and quality when implementing disease and risk factor phenotyping algorithms.<h4>Materials and methods</h4>Using heart failure (HF) as an exemplar, we represented three national EHR sources (Clinical Practice Research Datalink, Hospital Episode Statistics Admitted Patient Care, Office for National Statistics) into the OMOP CDM 5.2. We compared the original and CDM HF patient population by calculating and presenting descriptive statistics of demographics, related comorbidities, and relevant clinical biomarkers.<h4>Results</h4>We identified a cohort of 502 536 patients with the incident and prevalent HF and converted 1 099 195 384 rows of data from 216 581 914 encounters across three EHR sources to the OMOP CDM. The largest percentage (65%) of unmapped events was related to medication prescriptions in primary care. The average coverage of source vocabularies was >98% with the exception of laboratory tests recorded in primary care. The raw and transformed data were similar in terms of demographics and comorbidities with the largest difference observed being 3.78% in the prevalence of chronic obstructive pulmonary disease (COPD).<h4>Conclusion</h4>Our study demonstrated that the OMOP CDM can successfully be applied to convert EHR linked across multiple healthcare settings and represent phenotyping algorithms spanning multiple sources. Similar to previous research, challenges mapping primary care prescriptions and laboratory measurements still persist and require further work. The use of OMOP CDM in national UK EHR is a valuable research tool that can enable large-scale reproducible observational research.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/4/3/ooab001/40325375/ooab001.pdf; doi:https://doi.org/10.1093/jamiaopen/ooab001; html:https://europepmc.org/articles/PMC8423424; pdf:https://europepmc.org/articles/PMC8423424?pdf=render
+34781301,https://doi.org/10.1159/000520674,"Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.","Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.",,Cardiology,2022,2021-11-15,N,Data Sources; cardiovascular; Real-world Data; Real-world Evidence,,,"<h4>Background</h4>Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).<h4>Methods</h4>We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.<h4>Results</h4>Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.<h4>Conclusions</h4>This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.",,pdf:https://www.karger.com/Article/Pdf/520674; doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674
 36538350,https://doi.org/10.2196/41200,Identifying Patterns of Clinical Interest in Clinicians' Treatment Preferences: Hypothesis-free Data Science Approach to Prioritizing Prescribing Outliers for Clinical Review.,"MacKenna B, Curtis HJ, Hopcroft LEM, Walker AJ, Croker R, Macdonald O, Evans SJW, Inglesby P, Evans D, Morley J, Bacon SCJ, Goldacre B.",,JMIR medical informatics,2022,2022-12-20,Y,Prescribing; Clinical Audit; Antipsychotics; Pericyazine; Data Science; Nhs England; Promazine Hydrochloride,,,"<h4>Background</h4>Data analysis is used to identify signals suggestive of variation in treatment choice or clinical outcome. Analyses to date have generally focused on a hypothesis-driven approach.<h4>Objective</h4>This study aimed to develop a hypothesis-free approach to identify unusual prescribing behavior in primary care data. We aimed to apply this methodology to a national data set in a cross-sectional study to identify chemicals with significant variation in use across Clinical Commissioning Groups (CCGs) for further clinical review, thereby demonstrating proof of concept for prioritization approaches.<h4>Methods</h4>Here we report a new data-driven approach to identify unusual prescribing behaviour in primary care data. This approach first applies a set of filtering steps to identify chemicals with prescribing rate distributions likely to contain outliers, then applies two ranking approaches to identify the most extreme outliers amongst those candidates. This methodology has been applied to three months of national prescribing data (June-August 2017).<h4>Results</h4>Our methodology provides rankings for all chemicals by administrative region. We provide illustrative results for 2 antipsychotic drugs of particular clinical interest: promazine hydrochloride and pericyazine, which rank highly by outlier metrics. Specifically, our method identifies that, while promazine hydrochloride and pericyazine are barely used by most clinicians (with national prescribing rates of 11.1 and 6.2 per 1000 antipsychotic prescriptions, respectively), they make up a substantial proportion of antipsychotic prescribing in 2 small geographic regions in England during the study period (with maximum regional prescribing rates of 298.7 and 241.1 per 1000 antipsychotic prescriptions, respectively).<h4>Conclusions</h4>Our hypothesis-free approach is able to identify candidates for audit and review in clinical practice. To illustrate this, we provide 2 examples of 2 very unusual antipsychotics used disproportionately in 2 small geographic areas of England.",,pdf:https://medinform.jmir.org/2022/12/e41200/PDF; doi:https://doi.org/10.2196/41200; html:https://europepmc.org/articles/PMC9812268
 37293269,https://doi.org/10.1140/epjds/s13688-023-00394-6,Do poverty and wealth look the same the world over? A comparative study of 12 cities from five high-income countries using street images.,"Suel E, Muller E, Bennett JE, Blakely T, Doyle Y, Lynch J, Mackenbach JD, Middel A, Mizdrak A, Nathvani R, Brauer M, Ezzati M.",,EPJ data science,2023,2023-06-07,Y,Computer vision; Visual Similarity; Urban Inequalities; Street Images,,,"Urbanization and inequalities are two of the major policy themes of our time, intersecting in large cities where social and economic inequalities are particularly pronounced. Large scale street-level images are a source of city-wide visual information and allow for comparative analyses of multiple cities. Computer vision methods based on deep learning applied to street images have been shown to successfully measure inequalities in socioeconomic and environmental features, yet existing work has been within specific geographies and have not looked at how visual environments compare across different cities and countries. In this study, we aim to apply existing methods to understand whether, and to what extent, poor and wealthy groups live in visually similar neighborhoods across cities and countries. We present novel insights on similarity of neighborhoods using street-level images and deep learning methods. We analyzed 7.2 million images from 12 cities in five high-income countries, home to more than 85 million people: Auckland (New Zealand), Sydney (Australia), Toronto and Vancouver (Canada), Atlanta, Boston, Chicago, Los Angeles, New York, San Francisco, and Washington D.C. (United States of America), and London (United Kingdom). Visual features associated with neighborhood disadvantage are more distinct and unique to each city than those associated with affluence. For example, from what is visible from street images, high density poor neighborhoods located near the city center (e.g., in London) are visually distinct from poor suburban neighborhoods characterized by lower density and lower accessibility (e.g., in Atlanta). This suggests that differences between two cities is also driven by historical factors, policies, and local geography. Our results also have implications for image-based measures of inequality in cities especially when trained on data from cities that are visually distinct from target cities. We showed that these are more prone to errors for disadvantaged areas especially when transferring across cities, suggesting more attention needs to be paid to improving methods for capturing heterogeneity in poor environment across cities around the world.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00394-6.",,doi:https://doi.org/10.1140/epjds/s13688-023-00394-6; html:https://europepmc.org/articles/PMC10245348; pdf:https://europepmc.org/articles/PMC10245348?pdf=render
-36932161,https://doi.org/10.1038/s41433-023-02478-z,Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.,"Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.",,"Eye (London, England)",2023,2023-03-17,Y,,,,"<h4>Objective</h4>To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.<h4>Methods</h4>We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).<h4>Results</h4>From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.<h4>Conclusion</h4>There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.",,pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render
 34266851,https://doi.org/10.1136/bmjhci-2021-100356,Development of a core competency framework for clinical informatics. ,"Davies A, Mueller J, Hassey A, Moulton G.",,BMJ health & care informatics,2021,2021-07-01,Y,,,,"Until this point there was no national core competency framework for clinical informatics in the UK. We report on the final two iterations of work carried out in the formation of a national core competency framework. This follows an initial systematic literature review of existing skills and competencies and a job listing analysis.MethodsAn iterative approach was applied to framework development. Using a mixed-methods design we carried out semi-structured interviews with participants involved in informatics (n=15). The framework was updated based on the interview findings and was subsequently distributed as part of a bespoke online digital survey for wider participation (n=87). The final version of the framework is based on the findings of the survey. Over 102 people reviewed the framework as part of the interview or survey process. This led to a final core competency framework containing 6 primary domains with 36 subdomains containing 111 individual competencies. An iterative mixed-methods approach for competency development involving the target community was appropriate for development of the competency framework. There is some contention around the depth of technical competencies required. Care is also needed to avoid professional burnout, as clinicians and healthcare practitioners already have clinical competencies to maintain. Therefore, how the framework is applied in practice and how practitioners meet the competencies requires careful consideration.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100356.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render
+36932161,https://doi.org/10.1038/s41433-023-02478-z,Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.,"Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.",,"Eye (London, England)",2023,2023-03-17,Y,,,,"<h4>Objective</h4>To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.<h4>Methods</h4>We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).<h4>Results</h4>From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.<h4>Conclusion</h4>There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.",,pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render
 34038519,https://doi.org/10.1093/ageing/afab084,Developing a UK sarcopenia registry: recruitment and baseline characteristics of the SarcNet pilot.,"Witham MD, Heslop P, Dodds RM, Clegg AP, Hope SV, McDonald C, Smithard D, Storey B, Tan AL, Thornhill A, Sayer AA.",,Age and ageing,2021,2021-09-01,Y,Recruitment; Older People; Registry; Sarcopenia,,,"<h4>Background</h4>sarcopenia registries are a potential method to meet the challenge of recruitment to sarcopenia trials. We tested the feasibility of setting up a UK sarcopenia registry, the feasibility of recruitment methods and sought to characterise the pilot registry population.<h4>Methods</h4>six diverse UK sites took part, with potential participants aged 65 and over approached via mailshots from local primary care practices. Telephone pre-screening using the SARC-F score was followed by in-person screening and baseline visit. Co-morbidities, medications, grip strength, Short Physical Performance Battery, bioimpedance analysis, Geriatric Depression Score, Montreal Cognitive Assessment, Sarcopenia Quality of Life score were performed and permission sought for future recontact. Descriptive statistics for recruitment rates and baseline measures were generated; an embedded randomised trial examined the effect of a University logo on the primary care mailshot on recruitment rates.<h4>Results</h4>sixteen practices contributed a total of 3,508 letters. In total, 428 replies were received (12% response rate); 380 underwent telephone pre-screening of whom 215 (57%) were eligible to attend a screening visit; 150 participants were recruited (40% of those pre-screened) with 147 contributing baseline data. No significant difference was seen in response rates between mailshots with and without the logo (between-group difference 1.1% [95% confidence interval -1.0% to 3.4%], P = 0.31). The mean age of enrollees was 78 years; 72 (49%) were women. In total, 138/147 (94%) had probable sarcopenia on European Working Group on Sarcopenia 2019 criteria and 145/147 (98%) agreed to be recontacted about future studies.<h4>Conclusion</h4>recruitment to a multisite UK sarcopenia registry is feasible, with high levels of consent for recontact.",,pdf:https://academic.oup.com/ageing/article-pdf/50/5/1762/40349116/afab084.pdf; doi:https://doi.org/10.1093/ageing/afab084; html:https://europepmc.org/articles/PMC8437066; pdf:https://europepmc.org/articles/PMC8437066?pdf=render
 35143670,https://doi.org/10.1093/molbev/msac034,The Carbon Footprint of Bioinformatics.,"Grealey J, Lannelongue L, Saw WY, Marten J, Méric G, Ruiz-Carmona S, Inouye M.",,Molecular biology and evolution,2022,2022-03-01,Y,Bioinformatics; Genomics; Carbon Footprint; Green Algorithms,,,"Bioinformatic research relies on large-scale computational infrastructures which have a nonzero carbon footprint but so far, no study has quantified the environmental costs of bioinformatic tools and commonly run analyses. In this work, we estimate the carbon footprint of bioinformatics (in kilograms of CO2 equivalent units, kgCO2e) using the freely available Green Algorithms calculator (www.green-algorithms.org, last accessed 2022). We assessed 1) bioinformatic approaches in genome-wide association studies (GWAS), RNA sequencing, genome assembly, metagenomics, phylogenetics, and molecular simulations, as well as 2) computation strategies, such as parallelization, CPU (central processing unit) versus GPU (graphics processing unit), cloud versus local computing infrastructure, and geography. In particular, we found that biobank-scale GWAS emitted substantial kgCO2e and simple software upgrades could make it greener, for example, upgrading from BOLT-LMM v1 to v2.3 reduced carbon footprint by 73%. Moreover, switching from the average data center to a more efficient one can reduce carbon footprint by approximately 34%. Memory over-allocation can also be a substantial contributor to an algorithm's greenhouse gas emissions. The use of faster processors or greater parallelization reduces running time but can lead to greater carbon footprint. Finally, we provide guidance on how researchers can reduce power consumption and minimize kgCO2e. Overall, this work elucidates the carbon footprint of common analyses in bioinformatics and provides solutions which empower a move toward greener research.",,pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf; doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?pdf=render
 36654802,https://doi.org/10.1002/lrh2.10315,"A framework for understanding, designing, developing and evaluating learning health systems.","Foley T, Vale L.",,Learning health systems,2023,2022-05-20,Y,Quality improvement; Informatics; Implementation Science; Learning Health Systems; Learning Healthcare Systems,,,"<h4>Introduction</h4>A Learning Health System is not a technical project. It is the evolution of an existing health system into one capable of learning from every patient. This paper outlines a recently published framework intended to aid the understanding, design, development and evaluation of Learning Health Systems.<h4>Methods</h4>This work extended an existing repository of Learning Health System evidence, adding five more workshops. The total was subjected to thematic analysis, yielding a framework of elements important to understanding, designing, developing and evaluating Learning Health Systems. Purposeful literature reviews were conducted on each element. The findings were revised following a review by a group of international experts.<h4>Results</h4>The resulting framework was arranged around four questions:What is our rationale for developing a Learning Health System?There can be many reasons for developing a Learning Health System. Understanding these will guide its development.What sources of complexity exist at the system and the intervention level?An understanding of complexity is central to making Learning Health Systems work. The non-adoption, abandonment, scale-up, spread and sustainability framework was utilised to help understand and manage it.What strategic approaches to change do we need to consider?A range of strategic issues must be addressed to enable successful change in a Learning Health System. These include, strategy, organisational structure, culture, workforce, implementation science, behaviour change, co-design and evaluation.What technical building blocks will we need?A Learning Health System must capture data from practice, turn it into knowledge and apply it back into practice. There are many methods to achieve this and a range of platforms to help.<h4>Discussion</h4>The results form a framework for understanding, designing, developing and evaluating Learning Health Systems at any scale.<h4>Conclusion</h4>It is hoped that this framework will evolve with use and feedback.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835047; doi:https://doi.org/10.1002/lrh2.10315; html:https://europepmc.org/articles/PMC9835047; pdf:https://europepmc.org/articles/PMC9835047?pdf=render
@@ -754,9 +754,9 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34970633,https://doi.org/10.23889/ijpds.v6i1.1674,Evaluation of the ASSIGN open-source deterministic address-matching algorithm for allocating unique property reference numbers to general practitioner-recorded patient addresses.,"Harper G, Stables D, Simon P, Ahmed Z, Smith K, Robson J, Dezateux C.",,International journal of population data science,2021,2021-12-08,Y,Quality assurance; Data Linkage; Population Health; Electronic Health Record; Addresses; Address-matching; Place-based Health,,,"<h4>Introduction</h4>Linking places to people is a core element of the UK government's geospatial strategy. Matching patient addresses in electronic health records to their Unique Property Reference Numbers (UPRNs) enables spatial linkage for research, innovation and public benefit. Available algorithms are not transparent or evaluated for use with addresses recorded by health care providers.<h4>Objectives</h4>To describe and quality assure the open-source deterministic ASSIGN address-matching algorithm applied to general practitioner-recorded patient addresses.<h4>Methods</h4>Best practice standards were used to report the ASSIGN algorithm match rate, sensitivity and positive predictive value using gold-standard datasets from London and Wales. We applied the ASSIGN algorithm to the recorded addresses of a sample of 1,757,018 patients registered with all general practices in north east London. We examined bias in match results for the study population using multivariable analyses to estimate the likelihood of an address-matched UPRN by demographic, registration, and organisational variables.<h4>Results</h4>We found a 99.5% and 99.6% match rate with high sensitivity (0.999,0.998) and positive predictive value (0.996,0.998) for the Welsh and London gold standard datasets respectively, and a 98.6% match rate for the study population.The 1.4% of the study population without a UPRN match were more likely to have changed registered address in the last 12 months (match rate: 95.4%), be from a Chinese ethnic background (95.5%), or registered with a general practice using the SystmOne clinical record system (94.4%). Conversely, people registered for more than 6.5 years with their general practitioner were more likely to have a match (99.4%) than those with shorter registration durations.<h4>Conclusions</h4>ASSIGN is a highly accurate open-source address-matching algorithm with a high match rate and minimal biases when evaluated against a large sample of general practice-recorded patient addresses. ASSIGN has potential to be used in other address-based datasets including those with information relevant to the wider determinants of health.",,pdf:https://ijpds.org/article/download/1674/3300; doi:https://doi.org/10.23889/ijpds.v6i1.1674; html:https://europepmc.org/articles/PMC8678979; pdf:https://europepmc.org/articles/PMC8678979?pdf=render
 34328441,https://doi.org/10.2196/29840,Predicting Depressive Symptom Severity Through Individuals' Nearby Bluetooth Device Count Data Collected by Mobile Phones: Preliminary Longitudinal Study.,"Zhang Y, Folarin AA, Sun S, Cummins N, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Matcham F, Oetzmann C, Lamers F, Siddi S, Simblett S, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Narayan VA, Annas P, Hotopf M, Dobson RJB.",,JMIR mHealth and uHealth,2021,2021-07-30,Y,Monitoring; Depression; Mental health; Hierarchical Bayesian Model; Bluetooth; Mhealth; Mobile Health; Digital Health; Digital Biomarkers; Digital Phenotyping,,,"<h4>Background</h4>Research in mental health has found associations between depression and individuals' behaviors and statuses, such as social connections and interactions, working status, mobility, and social isolation and loneliness. These behaviors and statuses can be approximated by the nearby Bluetooth device count (NBDC) detected by Bluetooth sensors in mobile phones.<h4>Objective</h4>This study aimed to explore the value of the NBDC data in predicting depressive symptom severity as measured via the 8-item Patient Health Questionnaire (PHQ-8).<h4>Methods</h4>The data used in this paper included 2886 biweekly PHQ-8 records collected from 316 participants recruited from three study sites in the Netherlands, Spain, and the United Kingdom as part of the EU Remote Assessment of Disease and Relapse-Central Nervous System (RADAR-CNS) study. From the NBDC data 2 weeks prior to each PHQ-8 score, we extracted 49 Bluetooth features, including statistical features and nonlinear features for measuring the periodicity and regularity of individuals' life rhythms. Linear mixed-effect models were used to explore associations between Bluetooth features and the PHQ-8 score. We then applied hierarchical Bayesian linear regression models to predict the PHQ-8 score from the extracted Bluetooth features.<h4>Results</h4>A number of significant associations were found between Bluetooth features and depressive symptom severity. Generally speaking, along with depressive symptom worsening, one or more of the following changes were found in the preceding 2 weeks of the NBDC data: (1) the amount decreased, (2) the variance decreased, (3) the periodicity (especially the circadian rhythm) decreased, and (4) the NBDC sequence became more irregular. Compared with commonly used machine learning models, the proposed hierarchical Bayesian linear regression model achieved the best prediction metrics (R<sup>2</sup>=0.526) and a root mean squared error (RMSE) of 3.891. Bluetooth features can explain an extra 18.8% of the variance in the PHQ-8 score relative to the baseline model without Bluetooth features (R<sup>2</sup>=0.338, RMSE=4.547).<h4>Conclusions</h4>Our statistical results indicate that the NBDC data have the potential to reflect changes in individuals' behaviors and statuses concurrent with the changes in the depressive state. The prediction results demonstrate that the NBDC data have a significant value in predicting depressive symptom severity. These findings may have utility for the mental health monitoring practice in real-world settings.",,pdf:https://mhealth.jmir.org/2021/7/e29840/PDF; doi:https://doi.org/10.2196/29840; html:https://europepmc.org/articles/PMC8367113
 36692937,https://doi.org/10.2196/42866,The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.,"de Angel V, Adeleye F, Zhang Y, Cummins N, Munir S, Lewis S, Laporta Puyal E, Matcham F, Sun S, Folarin AA, Ranjan Y, Conde P, Rashid Z, Dobson R, Hotopf M.",,JMIR mental health,2023,2023-01-24,Y,Depression; Mobile phone; Anxiety; Smartphone; Mhealth; Mobile Health; Wearable Devices; Digital Health; Digital Phenotyping; Passive Sensing,,,"<h4>Background</h4>Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment.<h4>Objective</h4>A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement.<h4>Methods</h4>A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device.<h4>Results</h4>The overall retention rate was 60%. Higher-intensity treatment (χ<sup>2</sup><sub>1</sub>=4.6; P=.03) and higher baseline anxiety (t<sub>56.28</sub>=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t<sub>50.4</sub>=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list.<h4>Conclusions</h4>Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.",,pdf:https://mental.jmir.org/2023/1/e42866/PDF; doi:https://doi.org/10.2196/42866; html:https://europepmc.org/articles/PMC9906314
-37477803,https://doi.org/10.1007/s11897-023-00615-z,Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.,"Meijs C, Handoko ML, Savarese G, Vernooij RWM, Vaartjes I, Banerjee A, Koudstaal S, Brugts JJ, Asselbergs FW, Uijl A.",,Current heart failure reports,2023,2023-07-21,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Precision Medicine,,,"<h4>Review purpose</h4>This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice.<h4>Findings</h4>34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render
 34244270,https://doi.org/10.1136/bmjopen-2020-048008,Protocol for development of a reporting guideline (TRIPOD-AI) and risk of bias tool (PROBAST-AI) for diagnostic and prognostic prediction model studies based on artificial intelligence.,"Collins GS, Dhiman P, Andaur Navarro CL, Ma J, Hooft L, Reitsma JB, Logullo P, Beam AL, Peng L, Van Calster B, van Smeden M, Riley RD, Moons KG.",,BMJ open,2021,2021-07-09,Y,epidemiology; Statistics & Research Methods; General Medicine (See Internal Medicine),,,"<h4>Introduction</h4>The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) were both published to improve the reporting and critical appraisal of prediction model studies for diagnosis and prognosis. This paper describes the processes and methods that will be used to develop an extension to the TRIPOD statement (TRIPOD-artificial intelligence, AI) and the PROBAST (PROBAST-AI) tool for prediction model studies that applied machine learning techniques.<h4>Methods and analysis</h4>TRIPOD-AI and PROBAST-AI will be developed following published guidance from the EQUATOR Network, and will comprise five stages. Stage 1 will comprise two systematic reviews (across all medical fields and specifically in oncology) to examine the quality of reporting in published machine-learning-based prediction model studies. In stage 2, we will consult a diverse group of key stakeholders using a Delphi process to identify items to be considered for inclusion in TRIPOD-AI and PROBAST-AI. Stage 3 will be virtual consensus meetings to consolidate and prioritise key items to be included in TRIPOD-AI and PROBAST-AI. Stage 4 will involve developing the TRIPOD-AI checklist and the PROBAST-AI tool, and writing the accompanying explanation and elaboration papers. In the final stage, stage 5, we will disseminate TRIPOD-AI and PROBAST-AI via journals, conferences, blogs, websites (including TRIPOD, PROBAST and EQUATOR Network) and social media. TRIPOD-AI will provide researchers working on prediction model studies based on machine learning with a reporting guideline that can help them report key details that readers need to evaluate the study quality and interpret its findings, potentially reducing research waste. We anticipate PROBAST-AI will help researchers, clinicians, systematic reviewers and policymakers critically appraise the design, conduct and analysis of machine learning based prediction model studies, with a robust standardised tool for bias evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been granted by the Central University Research Ethics Committee, University of Oxford on 10-December-2020 (R73034/RE001). Findings from this study will be disseminated through peer-review publications.<h4>Prospero registration number</h4>CRD42019140361 and CRD42019161764.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e048008.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048008; html:https://europepmc.org/articles/PMC8273461; pdf:https://europepmc.org/articles/PMC8273461?pdf=render
 36082306,https://doi.org/10.1016/j.xgen.2021.100004,Workshop proceedings: GWAS summary statistics standards and sharing.,"MacArthur JAL, Buniello A, Harris LW, Hayhurst J, McMahon A, Sollis E, Cerezo M, Hall P, Lewis E, Whetzel PL, Bahcall OG, Barroso I, Carroll RJ, Inouye M, Manolio TA, Rich SS, Hindorff LA, Wiley K, Parkinson H.",,Cell genomics,2021,2021-10-01,Y,,,,"Genome-wide association studies (GWASs) have enabled robust mapping of complex traits in humans. The open sharing of GWAS summary statistics (SumStats) is essential in facilitating the larger meta-analyses needed for increased power in resolving the genetic basis of disease. However, most GWAS SumStats are not readily accessible because of limited sharing and a lack of defined standards. With the aim of increasing the availability, quality, and utility of GWAS SumStats, the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) GWAS Catalog organized a community workshop to address the standards, infrastructure, and incentives required to promote and enable sharing. We evaluated the barriers to SumStats sharing, both technological and sociological, and developed an action plan to address those challenges and ensure that SumStats and study metadata are findable, accessible, interoperable, and reusable (FAIR). We encourage early deposition of datasets in the GWAS Catalog as the recognized central repository. We recommend standard requirements for reporting elements and formats for SumStats and accompanying metadata as guidelines for community standards and a basis for submission to the GWAS Catalog. Finally, we provide recommendations to enable, promote, and incentivize broader data sharing, standards and FAIRness in order to advance genomic medicine.",,doi:https://doi.org/10.1016/j.xgen.2021.100004; doi:https://doi.org/10.1016/j.xgen.2021.100004; html:https://europepmc.org/articles/PMC9451133; pdf:https://europepmc.org/articles/PMC9451133?pdf=render
+37477803,https://doi.org/10.1007/s11897-023-00615-z,Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.,"Meijs C, Handoko ML, Savarese G, Vernooij RWM, Vaartjes I, Banerjee A, Koudstaal S, Brugts JJ, Asselbergs FW, Uijl A.",,Current heart failure reports,2023,2023-07-21,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Precision Medicine,,,"<h4>Review purpose</h4>This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice.<h4>Findings</h4>34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render
 36346654,https://doi.org/10.2196/38168,Developing an Automated Assessment of In-session Patient Activation for Psychological Therapy: Codevelopment Approach.,"Malins S, Figueredo G, Jilani T, Long Y, Andrews J, Rawsthorne M, Manolescu C, Clos J, Higton F, Waldram D, Hunt D, Perez Vallejos E, Moghaddam N.",,JMIR medical informatics,2022,2022-11-08,Y,Mental health; Machine Learning; Cognitive Behavioral Therapy; Natural Language Processing; Multimorbidity; Responsible Artificial Intelligence,,,"<h4>Background</h4>Patient activation is defined as a patient's confidence and perceived ability to manage their own health. Patient activation has been a consistent predictor of long-term health and care costs, particularly for people with multiple long-term health conditions. However, there is currently no means of measuring patient activation from what is said in health care consultations. This may be particularly important for psychological therapy because most current methods for evaluating therapy content cannot be used routinely due to time and cost restraints. Natural language processing (NLP) has been used increasingly to classify and evaluate the contents of psychological therapy. This aims to make the routine, systematic evaluation of psychological therapy contents more accessible in terms of time and cost restraints. However, comparatively little attention has been paid to algorithmic trust and interpretability, with few studies in the field involving end users or stakeholders in algorithm development.<h4>Objective</h4>This study applied a responsible design to use NLP in the development of an artificial intelligence model to automate the ratings assigned by a psychological therapy process measure: the consultation interactions coding scheme (CICS). The CICS assesses the level of patient activation observable from turn-by-turn psychological therapy interactions.<h4>Methods</h4>With consent, 128 sessions of remotely delivered cognitive behavioral therapy from 53 participants experiencing multiple physical and mental health problems were anonymously transcribed and rated by trained human CICS coders. Using participatory methodology, a multidisciplinary team proposed candidate language features that they thought would discriminate between high and low patient activation. The team included service-user researchers, psychological therapists, applied linguists, digital research experts, artificial intelligence ethics researchers, and NLP researchers. Identified language features were extracted from the transcripts alongside demographic features, and machine learning was applied using k-nearest neighbors and bagged trees algorithms to assess whether in-session patient activation and interaction types could be accurately classified.<h4>Results</h4>The k-nearest neighbors classifier obtained 73% accuracy (82% precision and 80% recall) in a test data set. The bagged trees classifier obtained 81% accuracy for test data (87% precision and 75% recall) in differentiating between interactions rated high in patient activation and those rated low or neutral.<h4>Conclusions</h4>Coproduced language features identified through a multidisciplinary collaboration can be used to discriminate among psychological therapy session contents based on patient activation among patients experiencing multiple long-term physical and mental health conditions.",,pdf:https://medinform.jmir.org/2022/11/e38168/PDF; doi:https://doi.org/10.2196/38168; html:https://europepmc.org/articles/PMC9682451
 37649471,https://doi.org/10.23889/ijpds.v6i3.1705,Data linkage can reduce the burden and increase the opportunities in the implementation of Value-Based Health Care policy: a study in patients with ulcerative colitis (PROUD-UC Study).,"Walshe J, Akbari A, Hawthorne AB, Laing H.",,International journal of population data science,2021,2021-01-01,Y,"Colitis, ulcerative; Health Policy; Patient Reported Outcome Measure; Routinely Collected Health Data; Data Science; Value-based Health Care",,,"<h4>Introduction</h4>Healthcare systems face rising demand and unsustainable cost pressures. In response, health policymakers are adopting Value-Based Health Care (VBHC), targeting available resources to achieve the best possible patient outcomes at the lowest possible cost and actively disinvesting in care of low-value. This requires the evaluation of longitudinal clinical and patient reported outcome measures (PROMs) at an individual-level and population-scale, which can create significant data challenges. Achieving this through routinely collected electronic health record (EHR) data-linkage could facilitate the implementation of VBHC without an unacceptable data burden on patients or health systems and release time for higher-value activities.<h4>Objectives</h4>Our study tested the ability to report an international, patient-centred outcome dataset (ICHOM-IBD) using only anonymised individual-level population-scale linked electronic health record (EHR) data sources, including clinical and patient-reported outcomes, in a cohort of patients with moderate-to-severe ulcerative colitis (UC), receiving biopharmaceutical therapies (""biologics"") in a single, publicly funded, healthcare system.<h4>Results</h4>We identified a cohort of 17,632 patients with UC in Wales and a cohort from two Health Boards of 447 patients with UC receiving biologics. 112 of these patients had completed 866 condition-specific PROMs during their biologics treatment. 44 out of 59 (74.6%) items in the ICHOM-IBD could be derived from routinely collected data of which a primary care source was essential for eight items and desirable for 21.<h4>Conclusions</h4>We demonstrated that it is possible to report most but not all the ICHOM-IBD outcomes using routinely collected data from multiple sources without additional system burden, potentially supporting Value-Based Health Care implementation with population data science. As digital collection of PROMs and use of condition-specific registries grow, greater utility of this approach can be anticipated. We have identified that the availability of longitudinal primary and secondary care data linked with PROMs is essential for this to be possible.",,doi:https://doi.org/10.23889/ijpds.v6i3.1705; html:https://europepmc.org/articles/PMC10464864; pdf:https://europepmc.org/articles/PMC10464864?pdf=render
 35300523,https://doi.org/10.1161/circulationaha.121.056663,Therapeutic Targets for Heart Failure Identified Using Proteomics and Mendelian Randomization.,"Henry A, Gordillo-Marañón M, Finan C, Schmidt AF, Ferreira JP, Karra R, Sundström J, Lind L, Ärnlöv J, Zannad F, Mälarstig A, Hingorani AD, Lumbers RT, HERMES and SCALLOP Consortia.",,Circulation,2022,2022-03-18,Y,Proteomics; Heart Failure; Drug Target Prediction; Mendelian Randomization Analysis,,,"<h4>Background</h4>Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets.<h4>Methods</h4>We investigated the observational and causal associations of 90 cardiovascular proteins, which were measured using affinity-based proteomic assays. First, we estimated the associations of 90 cardiovascular proteins with incident heart failure by means of a fixed-effect meta-analysis of 4 population-based studies, composed of a total of 3019 participants with 732 HF events. The causal effects of HF-associated proteins were then investigated by Mendelian randomization, using <i>cis</i>-protein quantitative loci genetic instruments identified from genomewide association studies in more than 30 000 individuals. To improve the precision of causal estimates, we implemented an Mendelian randomization model that accounted for linkage disequilibrium between instruments and tested the robustness of causal estimates through a multiverse sensitivity analysis that included up to 120 combinations of instrument selection parameters and Mendelian randomization models per protein. The druggability of candidate proteins was surveyed, and mechanism of action and potential on-target side effects were explored with cross-trait Mendelian randomization analysis.<h4>Results</h4>Forty-four of ninety proteins were positively associated with risk of incident HF (<i>P</i><6.0×10<sup>-4</sup>). Among these, 8 proteins had evidence of a causal association with HF that was robust to multiverse sensitivity analysis: higher CSF-1 (macrophage colony-stimulating factor 1), Gal-3 (galectin-3) and KIM-1 (kidney injury molecule 1) were positively associated with risk of HF, whereas higher ADM (adrenomedullin), CHI3L1 (chitinase-3-like protein 1), CTSL1 (cathepsin L1), FGF-23 (fibroblast growth factor 23), and MMP-12 (matrix metalloproteinase-12) were protective. Therapeutics targeting ADM and Gal-3 are currently under evaluation in clinical trials, and all the remaining proteins were considered druggable, except KIM-1.<h4>Conclusions</h4>We identified 44 circulating proteins that were associated with incident HF, of which 8 showed evidence of a causal relationship and 7 were druggable, including adrenomedullin, which represents a particularly promising drug target. Our approach demonstrates a tractable roadmap for the triangulation of population genomic and proteomic data for the prioritization of therapeutic targets for complex human diseases.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.056663; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.056663; html:https://europepmc.org/articles/PMC9010023; pdf:https://europepmc.org/articles/PMC9010023?pdf=render
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@@ -66,8 +66,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 36083213,https://doi.org/10.1093/jamia/ocac158,Translating and evaluating historic phenotyping algorithms using SNOMED CT.,"Elkheder M, Gonzalez-Izquierdo A, Qummer Ul Arfeen M, Kuan V, Lumbers RT, Denaxas S, Shah AD.",,Journal of the American Medical Informatics Association : JAMIA,2023,2023-01-01,Y,Terminology; Phenotype; Ontology; Electronic Health Records; Snomed Ct,,,"<h4>Objective</h4>Patient phenotype definitions based on terminologies are required for the computational use of electronic health records. Within UK primary care research databases, such definitions have typically been represented as flat lists of Read terms, but Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) (a widely employed international reference terminology) enables the use of relationships between concepts, which could facilitate the phenotyping process. We implemented SNOMED CT-based phenotyping approaches and investigated their performance in the CPRD Aurum primary care database.<h4>Materials and methods</h4>We developed SNOMED CT phenotype definitions for 3 exemplar diseases: diabetes mellitus, asthma, and heart failure, using 3 methods: ""primary"" (primary concept and its descendants), ""extended"" (primary concept, descendants, and additional relations), and ""value set"" (based on text searches of term descriptions). We also derived SNOMED CT codelists in a semiautomated manner for 276 disease phenotypes used in a study of health across the lifecourse. Cohorts selected using each codelist were compared to ""gold standard"" manually curated Read codelists in a sample of 500 000 patients from CPRD Aurum.<h4>Results</h4>SNOMED CT codelists selected a similar set of patients to Read, with F1 scores exceeding 0.93, and age and sex distributions were similar. The ""value set"" and ""extended"" codelists had slightly greater recall but lower precision than ""primary"" codelists. We were able to represent 257 of the 276 phenotypes by a single concept hierarchy, and for 135 phenotypes, the F1 score was greater than 0.9.<h4>Conclusions</h4>SNOMED CT provides an efficient way to define disease phenotypes, resulting in similar patient populations to manually curated codelists.",,pdf:https://discovery.ucl.ac.uk/id/eprint/10155637/1/ocac158.pdf; doi:https://doi.org/10.1093/jamia/ocac158; html:https://europepmc.org/articles/PMC9846670; pdf:https://europepmc.org/articles/PMC9846670?pdf=render
 37309989,https://doi.org/10.1002/pds.5656,Prevalent new user designs: A literature review of current implementation practice.,"Tazare J, Gibbons DC, Bokern M, Williamson EJ, Gillespie IA, Cunnington M, Logie J, Douglas IJ.",,Pharmacoepidemiology and drug safety,2023,2023-06-22,N,Literature review; Database Research; Prevalent New User Designs,,,"<h4>Purpose</h4>Prevalent new user (PNU) designs extend the active comparator new user design by allowing for the inclusion of initiators of the study drug who were previously on a comparator treatment. We performed a literature review summarising current practice.<h4>Methods</h4>PubMed was searched for studies applying the PNU design since its proposal in 2017. The review focused on three components. First, we extracted information on the overall study design, including the database used. We summarised information on implementation of the PNU design, including key decisions relating to exposure set definition and estimation of time-conditional propensity scores. Finally, we reviewed the analysis strategy of the matched cohort.<h4>Results</h4>Nineteen studies met the criteria for inclusion. Most studies (73%) implemented the PNU design in electronic health record or registry databases, with the remaining using insurance claims databases. Of 15 studies including a class of prevalent users, 40% deviated from the original exposure set definition proposals in favour of a more complex definition. Four studies did not include prevalent new users but used other aspects of the PNU framework. Several studies lacked details on exposure set definition (n = 2), time-conditional propensity score model (n = 2) or integration of complex analytical techniques, such as the high-dimensional propensity score algorithm (n = 3).<h4>Conclusion</h4>PNU designs have been applied in a range of therapeutic and disease areas. However, to encourage more widespread use of this design and help shape best practice, there is a need for improved accessibility, specifically through the provision of analytical code alongside guidance to support implementation and transparent reporting.",,doi:https://doi.org/10.1002/pds.5656; doi:https://doi.org/10.1002/pds.5656
 37227368,https://doi.org/10.1097/ede.0000000000001626,Evaluating Metformin Strategies for Cancer Prevention: A Target Trial Emulation Using Electronic Health Records.,"Dickerman BA, García-Albéniz X, Logan RW, Denaxas S, Hernán MA.",,"Epidemiology (Cambridge, Mass.)",2023,2023-05-23,N,,,,"<h4>Background</h4>Metformin users appear to have a substantially lower risk of cancer than nonusers in many observational studies. These inverse associations may be explained by common flaws in observational analyses that can be avoided by explicitly emulating a target trial.<h4>Methods</h4>We emulated target trials of metformin therapy and cancer risk using population-based linked electronic health records from the UK (2009-2016). We included individuals with diabetes, no history of cancer, no recent prescription for metformin or other glucose-lowering medication, and hemoglobin A1c (HbA1c) <64 mmol/mol (<8.0%). Outcomes included total cancer and 4 site-specific cancers (breast, colorectal, lung, and prostate). We estimated risks using pooled logistic regression with adjustment for risk factors via inverse-probability weighting. We emulated a second target trial among individuals regardless of diabetes status. We compared our estimates with those obtained using previously applied analytic approaches.<h4>Results</h4>Among individuals with diabetes, the estimated 6-year risk differences (metformin - no metformin) were -0.2% (95% CI = -1.6%, 1.3%) in the intention-to-treat analysis and 0.0% (95% CI = -2.1%, 2.3%) in the per-protocol analysis. The corresponding estimates for all site-specific cancers were close to zero. Among individuals regardless of diabetes status, these estimates were also close to zero and more precise. By contrast, previous analytic approaches yielded estimates that appeared strongly protective.<h4>Conclusions</h4>Our findings are consistent with the hypothesis that metformin therapy does not meaningfully influence cancer incidence. The findings highlight the importance of explicitly emulating a target trial to reduce bias in the effect estimates derived from observational analyses.",,doi:https://doi.org/10.1097/EDE.0000000000001626
-37562853,https://doi.org/10.1136/bmjment-2023-300842,Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.,"McElroy E, Herrett E, Patel K, Piehlmaier DM, Gessa GD, Huggins C, Green MJ, Kwong ASF, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, OpenSAFELY Collaborative, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson LA, Patalay P, Longitudinal Health and Wellbeing Collaborative.",,BMJ mental health,2023,2023-08-01,Y,Psychiatry; Anxiety Disorders; Covid-19,,,"<h4>Background</h4>People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic.<h4>Objective</h4>To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic.<h4>Methods</h4>Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP.<h4>Findings</h4>In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic.<h4>Conclusions</h4>People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use.<h4>Clinical implications</h4>Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.",,doi:https://doi.org/10.1136/bmjment-2023-300842; html:https://europepmc.org/articles/PMC10577768; pdf:https://europepmc.org/articles/PMC10577768?pdf=render
 35501391,https://doi.org/10.1038/s41416-022-01830-6,"Impact of the SARS-CoV-2 pandemic on female breast, colorectal and non-small cell lung cancer incidence, stage and healthcare pathway to diagnosis during 2020 in Wales, UK, using a national cancer clinical record system.","Greene G, Griffiths R, Han J, Akbari A, Jones M, Lyons J, Lyons RA, Rolles M, Torabi F, Warlow J, Morris ERA, Lawler M, Huws DW.",,British journal of cancer,2022,2022-05-02,Y,,,,"<h4>Background</h4>COVID-19 pandemic responses impacted behaviour and health services. We estimated the impact on incidence, stage and healthcare pathway to diagnosis for female breast, colorectal and non-small cell lung cancers at population level in Wales.<h4>Methods</h4>Cancer e-record and hospital admission data linkage identified adult cases, stage and healthcare pathway to diagnosis (population ~2.5 million). Using multivariate Poisson regressions, we compared 2019 and 2020 counts and estimated incidence rate ratios (IRR).<h4>Results</h4>Cases decreased 15.2% (n = -1011) overall. Female breast annual IRR was 0.81 (95% CI: 0.76-0.86, p < 0.001), colorectal 0.80 (95% CI: 0.79-0.81, p < 0.001) and non-small cell lung 0.91 (95% CI: 0.90-0.92, p < 0.001). Decreases were largest in 50-69 year olds for female breast and 80+ year olds for all cancers. Stage I female breast cancer declined 41.6%, but unknown stage increased 55.8%. Colorectal stages I-IV declined (range 26.6-29.9%), while unknown stage increased 803.6%. Colorectal Q2-2020 GP-urgent suspected cancer diagnoses decreased 50.0%, and 53.9% for non-small cell lung cancer. Annual screen-detected female breast and colorectal cancers fell 47.8% and 13.3%, respectively. Non-smal -cell lung cancer emergency presentation diagnoses increased 9.5% (Q2-2020) and 16.3% (Q3-2020).<h4>Conclusion</h4>Significantly fewer cases of three common cancers were diagnosed in 2020. Detrimental impacts on outcomes varied between cancers. Ongoing surveillance with health service optimisation will be needed to mitigate impacts.",,pdf:https://www.nature.com/articles/s41416-022-01830-6.pdf; doi:https://doi.org/10.1038/s41416-022-01830-6; html:https://europepmc.org/articles/PMC9060409; pdf:https://europepmc.org/articles/PMC9060409?pdf=render
+37562853,https://doi.org/10.1136/bmjment-2023-300842,Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.,"McElroy E, Herrett E, Patel K, Piehlmaier DM, Gessa GD, Huggins C, Green MJ, Kwong ASF, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, OpenSAFELY Collaborative, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson LA, Patalay P, Longitudinal Health and Wellbeing Collaborative.",,BMJ mental health,2023,2023-08-01,Y,Psychiatry; Anxiety Disorders; Covid-19,,,"<h4>Background</h4>People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic.<h4>Objective</h4>To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic.<h4>Methods</h4>Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP.<h4>Findings</h4>In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic.<h4>Conclusions</h4>People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use.<h4>Clinical implications</h4>Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.",,doi:https://doi.org/10.1136/bmjment-2023-300842; html:https://europepmc.org/articles/PMC10577768; pdf:https://europepmc.org/articles/PMC10577768?pdf=render
 36469089,https://doi.org/10.1093/ageing/afac250,"The impact of dementia, frailty and care home characteristics on SARS-CoV-2 incidence in a national cohort of Welsh care home residents during a period of high community prevalence. ","Emmerson C, Hollinghurst J, North L, Fry R, Akbari A, Humphreys C, Gravenor MB, Lyons RA.",,Age and ageing,2022,2022-12-01,Y,,,,"dementia may increase care home residents' risk of COVID-19, but there is a lack of evidence on this effect and on interactions with individual and care home-level factors. we created a national cross-sectional retrospective cohort of care home residents in Wales for 1 September to 31 December 2020. Risk factors were analysed using multi-level logistic regression to model the likelihood of SARS-CoV-2 infection and mortality. the cohort included 9,571 individuals in 673 homes. Dementia was diagnosed in 5,647 individuals (59%); 1,488 (15.5%) individuals tested positive for SARS-CoV-2. We estimated the effects of age, dementia, frailty, care home size, proportion of residents with dementia, nursing and dementia services, communal space and region. The final model included the proportion of residents with dementia (OR for positive test 4.54 (95% CIs 1.55-13.27) where 75% of residents had dementia compared to no residents with dementia) and frailty (OR 1.29 (95% CIs 1.05-1.59) for severe frailty compared with no frailty). Analysis suggested 76% of the variation was due to setting rather than individual factors. Additional analysis suggested severe frailty and proportion of residents with dementia was associated with all-cause mortality, as was dementia diagnosis. Mortality analyses were challenging to interpret. whilst individual frailty increased the risk of COVID-19 infection, dementia was a risk factor at care home but not individual level. These findings suggest whole-setting interventions, particularly in homes with high proportions of residents with dementia and including those with low/no individual risk factors may reduce the impact of COVID-19.",,doi:https://doi.org/10.1093/ageing/afac250; doi:https://doi.org/10.1093/ageing/afac250; html:https://europepmc.org/articles/PMC9721242; pdf:https://europepmc.org/articles/PMC9721242?pdf=render
 34130677,https://doi.org/10.1186/s12911-021-01556-0,Developing automated methods for disease subtyping in UK Biobank: an exemplar study on stroke.,"Rannikmäe K, Wu H, Tominey S, Whiteley W, Allen N, Sudlow C, UK Biobank.",,BMC medical informatics and decision making,2021,2021-06-15,Y,Cerebral hemorrhage; Stroke; Natural Language Processing; Brain Scan; Disease Subtyping,,,"<h4>Background</h4>Better phenotyping of routinely collected coded data would be useful for research and health improvement. For example, the precision of coded data for hemorrhagic stroke (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]) may be as poor as < 50%. This work aimed to investigate the feasibility and added value of automated methods applied to clinical radiology reports to improve stroke subtyping.<h4>Methods</h4>From a sub-population of 17,249 Scottish UK Biobank participants, we ascertained those with an incident stroke code in hospital, death record or primary care administrative data by September 2015, and ≥ 1 clinical brain scan report. We used a combination of natural language processing and clinical knowledge inference on brain scan reports to assign a stroke subtype (ischemic vs ICH vs SAH) for each participant and assessed performance by precision and recall at entity and patient levels.<h4>Results</h4>Of 225 participants with an incident stroke code, 207 had a relevant brain scan report and were included in this study. Entity level precision and recall ranged from 78 to 100%. Automated methods showed precision and recall at patient level that were very good for ICH (both 89%), good for SAH (both 82%), but, as expected, lower for ischemic stroke (73%, and 64%, respectively), suggesting coded data remains the preferred method for identifying the latter stroke subtype.<h4>Conclusions</h4>Our automated method applied to radiology reports provides a feasible, scalable and accurate solution to improve disease subtyping when used in conjunction with administrative coded health data. Future research should validate these findings in a different population setting.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-021-01556-0; doi:https://doi.org/10.1186/s12911-021-01556-0; html:https://europepmc.org/articles/PMC8204419; pdf:https://europepmc.org/articles/PMC8204419?pdf=render
 35918098,https://doi.org/10.1136/bmj-2022-070695,Risk of covid-19 related deaths for SARS-CoV-2 omicron (B.1.1.529) compared with delta (B.1.617.2): retrospective cohort study.,"Ward IL, Bermingham C, Ayoubkhani D, Gethings OJ, Pouwels KB, Yates T, Khunti K, Hippisley-Cox J, Banerjee A, Walker AS, Nafilyan V.",,BMJ (Clinical research ed.),2022,2022-08-02,Y,,,,"<h4>Objective</h4>To assess the risk of covid-19 death after infection with omicron BA.1 compared with delta (B.1.617.2).<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>England, United Kingdom, from 1 December 2021 to 30 December 2021.<h4>Participants</h4>1 035 149 people aged 18-100 years who tested positive for SARS-CoV-2 under the national surveillance programme and had an infection identified as omicron BA.1 or delta compatible.<h4>Main outcome measures</h4>The main outcome measure was covid-19 death as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause specific Cox proportional hazard regression models (censoring non-covid-19 deaths) were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, index of multiple deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Interactions between variant and sex, age, vaccination status, and comorbidities were also investigated.<h4>Results</h4>The risk of covid-19 death was 66% lower (95% confidence interval 54% to 75%) for omicron BA.1 compared with delta after adjusting for a wide range of potential confounders. The reduction in the risk of covid-19 death for omicron compared with delta was more pronounced in people aged 18-59 years (number of deaths: delta=46, omicron=11; hazard ratio 0.14, 95% confidence interval 0.07 to 0.27) than in those aged ≥70 years (number of deaths: delta=113, omicron=135; hazard ratio 0.44, 95% confidence interval 0.32 to 0.61, P<0.0001). No evidence of a difference in risk was found between variant and number of comorbidities.<h4>Conclusions</h4>The results support earlier studies showing a reduction in severity of infection with omicron BA.1 compared with delta in terms of hospital admission. This study extends the research to also show a reduction in the risk of covid-19 death for the omicron variant compared with the delta variant.",,pdf:https://www.bmj.com/content/bmj/378/bmj-2022-070695.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070695; html:https://europepmc.org/articles/PMC9344192; pdf:https://europepmc.org/articles/PMC9344192?pdf=render
@@ -80,9 +80,9 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 35275994,https://doi.org/10.2337/dc21-1709,Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19.,"Norris T, Razieh C, Yates T, Zaccardi F, Gillies CL, Chudasama YV, Rowlands A, Davies MJ, McCann GP, Banerjee A, Docherty AB, Openshaw PJM, Baillie JK, Semple MG, Lawson CA, Khunti K.",,Diabetes care,2022,2022-05-01,N,,,,"<h4>Objective</h4>To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications.<h4>Research design and methods</h4>In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors.<h4>Results</h4>Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication.<h4>Conclusions</h4>Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.",,pdf:https://diabetesjournals.org/care/article-pdf/45/5/1132/678515/dc211709.pdf; doi:https://doi.org/10.2337/dc21-1709; html:https://europepmc.org/articles/PMC9174963; pdf:https://europepmc.org/articles/PMC9174963?pdf=render; doi:https://doi.org/10.2337/dc21-1709
 34706900,https://doi.org/10.1136/emermed-2021-211706,Comparative analysis of major incident triage tools in children: a UK population-based analysis.,"Vassallo J, Chernbumroong S, Malik N, Xu Y, Keene D, Gkoutos G, Lyttle MD, Smith J, in collaboration with PERUKI (Paediatric Emergency Research in the UK and Ireland).",,Emergency medicine journal : EMJ,2021,2021-10-27,Y,Planning; Paediatrics; Major Incident; Clinical Care; Triage; Major Incidents,,,"<h4>Introduction</h4>Triage is a key principle in the effective management of major incidents. There is currently a paucity of evidence to guide the triage of children. The aim of this study was to perform a comparative analysis of nine adult and paediatric triage tools, including the novel 'Sheffield Paediatric Triage Tool' (SPTT), assessing their ability in identifying patients needing life-saving interventions (LSIs).<h4>Methods</h4>A 10-year (2008-2017) retrospective database review of the Trauma Audit Research Network (TARN) Database for paediatric patients (<16 years) was performed. Primary outcome was identification of patients receiving one or more LSIs from a previously defined list. Secondary outcomes included mortality and prediction of Injury Severity Score (ISS) >15. Primary analysis was conducted on patients with complete prehospital physiological data with planned secondary analyses using first recorded data. Performance characteristics were evaluated using sensitivity, specificity, undertriage and overtriage.<h4>Results</h4>15 133 patients met TARN inclusion criteria. 4962 (32.8%) had complete prehospital physiological data and 8255 (54.5%) had complete first recorded physiological data. The majority of patients were male (69.5%), with a median age of 11.9 years. The overwhelming majority of patients (95.4%) sustained blunt trauma, yielding a median ISS of 9 and overall, 875 patients (17.6%) received at least one LSI. The SPTT demonstrated the greatest sensitivity of all triage tools at identifying need for LSI (92.2%) but was associated with the highest rate of overtriage (75.0%). Both the Paediatric Triage Tape (sensitivity 34.1%) and JumpSTART (sensitivity 45.0%) performed less well at identifying LSI. By contrast, the adult Modified Physiological Triage Tool-24 (MPTT-24) triage tool had the second highest sensitivity (80.8%) with tolerable rates of overtriage (70.2%).<h4>Conclusion</h4>The SPTT and MPTT-24 outperform existing paediatric triage tools at identifying those patients requiring LSIs. This may necessitate a change in recommended practice. Further work is needed to determine the optimum method of paediatric major incident triage, but consideration should be given to simplifying major incident triage by the use of one generic tool (the MPTT-24) for adults and children.",,pdf:https://emj.bmj.com/content/emermed/early/2022/04/27/emermed-2021-211706.full.pdf; doi:https://doi.org/10.1136/emermed-2021-211706; html:https://europepmc.org/articles/PMC9510399; pdf:https://europepmc.org/articles/PMC9510399?pdf=render
 33484944,https://doi.org/10.1016/j.compbiomed.2021.104216,"A fast, accurate, and generalisable heuristic-based negation detection algorithm for clinical text.","Slater LT, Bradlow W, Motti DF, Hoehndorf R, Ball S, Gkoutos GV.",,Computers in biology and medicine,2021,2021-01-16,Y,Text Mining Negation Detection Context Disambiguation Clinical Information Extraction,,,"Negation detection is an important task in biomedical text mining. Particularly in clinical settings, it is of critical importance to determine whether findings mentioned in text are present or absent. Rule-based negation detection algorithms are a common approach to the task, and more recent investigations have resulted in the development of rule-based systems utilising the rich grammatical information afforded by typed dependency graphs. However, interacting with these complex representations inevitably necessitates complex rules, which are time-consuming to develop and do not generalise well. We hypothesise that a heuristic approach to determining negation via dependency graphs could offer a powerful alternative. We describe and implement an algorithm for negation detection based on grammatical distance from a negatory construct in a typed dependency graph. To evaluate the algorithm, we develop two testing corpora comprised of sentences of clinical text extracted from the MIMIC-III database and documents related to hypertrophic cardiomyopathy patients routinely collected at University Hospitals Birmingham NHS trust. Gold-standard validation datasets were built by a combination of human annotation and examination of algorithm error. Finally, we compare the performance of our approach with four other rule-based algorithms on both gold-standard corpora. The presented algorithm exhibits the best performance by f-measure over the MIMIC-III dataset, and a similar performance to the syntactic negation detection systems over the HCM dataset. It is also the fastest of the dependency-based negation systems explored in this study. Our results show that while a single heuristic approach to dependency-based negation detection is ignorant to certain advanced cases, it nevertheless forms a powerful and stable method, requiring minimal training and adaptation between datasets. As such, it could present a drop-in replacement or augmentation for many-rule negation approaches in clinical text-mining pipelines, particularly for cases where adaptation and rule development is not required or possible.",,doi:https://doi.org/10.1016/j.compbiomed.2021.104216; doi:https://doi.org/10.1016/j.compbiomed.2021.104216; html:https://europepmc.org/articles/PMC7910278
+36332519,https://doi.org/10.1016/j.ijmedinf.2022.104905,Creation of a core competency framework for clinical informatics: From genesis to maintaining relevance.,"Davies A, Hassey A, Williams J, Moulton G.",,International journal of medical informatics,2022,2022-10-30,N,Informatics; Core Competencies; Competency Framework; Healthcare Workforce; Informaticians,,,"<h4>Background</h4>The United Kingdom's Faculty of Clinical Informatics (FCI) embarked on the creation of a core competency framework in response to the need to provide support to those working in clinical and health and social care that also hold informatics roles.<h4>Methods</h4>The work spanned several phases and utilised a mixed-methods approach consisting of interviews, surveys, job listing analysis, expert discussions and a systematic literature review. The work presented here explores the lessons learnt from the process of creating the framework and the next steps for ensuring its use and continued relevance.<h4>Results</h4>A core competency framework was generated with six domains, 36 sub-domains and 111 individual competency statements. A discussion and eight key recommendations are presented based on the development of this framework.<h4>Conclusion</h4>Definition of the target audience is important to manage scope and define purpose. The use of robust reproducible methods helps to establish a strong evidence base. Competency frameworks should be living documents, ideally presented in an accessible digital form to enable easy use and embedding in other tools (e.g. for accreditation or to search competencies).",,doi:https://doi.org/10.1016/j.ijmedinf.2022.104905
 36860174,https://doi.org/10.1093/ije/dyad022,Proxy gene-by-environment Mendelian randomization study of the association between cigarette smoking during pregnancy and offspring mental health.,"Sallis HM, Wootton RE, Davey Smith G, Munafò MR.",,International journal of epidemiology,2023,2023-10-01,Y,Schizophrenia; Depression; Smoking; Mendelian Randomization,,,"<h4>Background</h4>Smoking prevalence is higher among individuals with schizophrenia or depression, and previous work has suggested this relationship is causal. However, this may be due to dynastic effects, for example reflecting maternal smoking during pregnancy rather than a direct effect of smoking. We used a proxy gene-by-environment Mendelian randomization approach to investigate whether there is a causal effect of maternal heaviness of smoking during pregnancy on offspring mental health.<h4>Methods</h4>Analyses were performed in the UK Biobank cohort. Individuals with data on smoking status, maternal smoking during pregnancy, a diagnosis of schizophrenia or depression, and genetic data were included. We used participants' genotype (rs16969968 in the CHRNA5 gene) as a proxy for their mothers' genotype. Analyses were stratified on participants' own smoking status in order to estimate the effect of maternal smoking heaviness during pregnancy independently of offspring smoking.<h4>Results</h4>The effect of maternal smoking on offspring schizophrenia was in opposing directions when stratifying on offspring smoking status. Among offspring of never smokers, each additional risk allele for maternal smoking heaviness appeared to have a protective effect [odds ratio (OR) = 0.77, 95% confidence interval (CI) 0.62 to 0.95, P = 0.015], whereas among ever smokers the effect of maternal smoking was in the reverse direction (OR = 1.23, 95% CI 1.05 to 1.45, P = 0.011, Pinteraction <0.001). There was no clear evidence of an association between maternal smoking heaviness and offspring depression.<h4>Conclusions</h4>These findings do not provide clear evidence of an effect of maternal smoking during pregnancy on offspring schizophrenia or depression, which implies that any causal effect of smoking on schizophrenia or depression is direct.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyad022/49393500/dyad022.pdf; doi:https://doi.org/10.1093/ije/dyad022; html:https://europepmc.org/articles/PMC10555861; pdf:https://europepmc.org/articles/PMC10555861?pdf=render
 37263685,https://doi.org/10.1136/bmjopen-2022-070637,"Impact of the COVID-19 pandemic on domiciliary care workers in Wales, UK: a data linkage cohort study using the SAIL Databank.","Cannings-John R, Schoenbuchner S, Jones H, Lugg-Widger FV, Akbari A, Brookes-Howell L, Hood K, John A, Thomas DR, Prout H, Robling M.",,BMJ open,2023,2023-06-01,Y,Mental health; Social Medicine; Covid-19,,,"<h4>Objectives</h4>To quantify population health risks for domiciliary care workers (DCWs) in Wales, UK, working during the COVID-19 pandemic.<h4>Design</h4>A population-level retrospective study linking occupational registration data to anonymised electronic health records maintained by the Secure Anonymised Information Linkage Databank in a privacy-protecting trusted research environment.<h4>Setting</h4>Registered DCW population in Wales.<h4>Participants</h4>Records for all linked DCWs from 1 March 2020 to 30 November 2021.<h4>Primary and secondary outcome measures</h4>Our primary outcome was confirmed COVID-19 infection; secondary outcomes included contacts for suspected COVID-19, mental health including self-harm, fit notes, respiratory infections not necessarily recorded as COVID-19, deaths involving COVID-19 and all-cause mortality.<h4>Results</h4>Confirmed and suspected COVID-19 infection rates increased over the study period to 24% by 30 November 2021. Confirmed COVID-19 varied by sex (males: 19% vs females: 24%) and age (>55 years: 19% vs <35 years: 26%) and were higher for care workers employed by local authority social services departments compared with the private sector (27% and 23%, respectively). 34% of DCWs required support for a mental health condition, with mental health-related prescribing increasing in frequency when compared with the prepandemic period. Events for self-harm increased from 0.2% to 0.4% over the study period as did the issuing of fit notes. There was no evidence to suggest a miscoding of COVID-19 infection with non-COVID-19 respiratory conditions. COVID-19-related and all-cause mortality were no greater than for the general population aged 15-64 years in Wales (0.1% and 0.034%, respectively). A comparable DCW workforce in Scotland and England would result in a comparable rate of COVID-19 infection, while the younger workforce in Northern Ireland may result in a greater infection rate.<h4>Conclusions</h4>While initial concerns about excess mortality are alleviated, the substantial pre-existing and increased mental health burden for DCWs will require investment to provide long-term support to the sector's workforce.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e070637.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070637; html:https://europepmc.org/articles/PMC10255029; pdf:https://europepmc.org/articles/PMC10255029?pdf=render
-36332519,https://doi.org/10.1016/j.ijmedinf.2022.104905,Creation of a core competency framework for clinical informatics: From genesis to maintaining relevance.,"Davies A, Hassey A, Williams J, Moulton G.",,International journal of medical informatics,2022,2022-10-30,N,Informatics; Core Competencies; Competency Framework; Healthcare Workforce; Informaticians,,,"<h4>Background</h4>The United Kingdom's Faculty of Clinical Informatics (FCI) embarked on the creation of a core competency framework in response to the need to provide support to those working in clinical and health and social care that also hold informatics roles.<h4>Methods</h4>The work spanned several phases and utilised a mixed-methods approach consisting of interviews, surveys, job listing analysis, expert discussions and a systematic literature review. The work presented here explores the lessons learnt from the process of creating the framework and the next steps for ensuring its use and continued relevance.<h4>Results</h4>A core competency framework was generated with six domains, 36 sub-domains and 111 individual competency statements. A discussion and eight key recommendations are presented based on the development of this framework.<h4>Conclusion</h4>Definition of the target audience is important to manage scope and define purpose. The use of robust reproducible methods helps to establish a strong evidence base. Competency frameworks should be living documents, ideally presented in an accessible digital form to enable easy use and embedding in other tools (e.g. for accreditation or to search competencies).",,doi:https://doi.org/10.1016/j.ijmedinf.2022.104905
 35273122,https://doi.org/10.1136/heartjnl-2021-320325,Evaluation of antithrombotic use and COVID-19 outcomes in a nationwide atrial fibrillation cohort.,"Handy A, Banerjee A, Wood AM, Dale C, Sudlow CLM, Tomlinson C, Bean D, Thygesen JH, Mizani MA, Katsoulis M, Takhar R, Hollings S, Denaxas S, Walker V, Dobson R, Sofat R, CVD-COVID-UK Consortium.",,Heart (British Cardiac Society),2022,2022-05-25,Y,Atrial fibrillation; epidemiology; Electronic Health Records; drug monitoring; Covid-19,,,"<h4>Objective</h4>To evaluate antithrombotic (AT) use in individuals with atrial fibrillation (AF) and at high risk of stroke (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥2) and investigate whether pre-existing AT use may improve COVID-19 outcomes.<h4>Methods</h4>Individuals with AF and CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥2 on 1 January 2020 were identified using electronic health records for 56 million people in England and were followed up until 1 May 2021. Factors associated with pre-existing AT use were analysed using logistic regression. Differences in COVID-19-related hospitalisation and death were analysed using logistic and Cox regression in individuals with pre-existing AT use versus no AT use, anticoagulants (AC) versus antiplatelets (AP), and direct oral anticoagulants (DOACs) versus warfarin.<h4>Results</h4>From 972 971 individuals with AF (age 79 (±9.3), female 46.2%) and CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥2, 88.0% (n=856 336) had pre-existing AT use, 3.8% (n=37 418) had a COVID-19 hospitalisation and 2.2% (n=21 116) died, followed up to 1 May 2021. Factors associated with no AT use included comorbidities that may contraindicate AT use (liver disease and history of falls) and demographics (socioeconomic status and ethnicity). Pre-existing AT use was associated with lower odds of death (OR=0.92, 95% CI 0.87 to 0.96), but higher odds of hospitalisation (OR=1.20, 95% CI 1.15 to 1.26). AC versus AP was associated with lower odds of death (OR=0.93, 95% CI 0.87 to 0.98) and higher hospitalisation (OR=1.17, 95% CI 1.11 to 1.24). For DOACs versus warfarin, lower odds were observed for hospitalisation (OR=0.86, 95% CI 0.82 to 0.89) but not for death (OR=1.00, 95% CI 0.95 to 1.05).<h4>Conclusions</h4>Pre-existing AT use may be associated with lower odds of COVID-19 death and, while not evidence of causality, provides further incentive to improve AT coverage for eligible individuals with AF.",,pdf:https://heart.bmj.com/content/heartjnl/108/12/923.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-320325; html:https://europepmc.org/articles/PMC8931797; pdf:https://europepmc.org/articles/PMC8931797?pdf=render
 36647111,https://doi.org/10.1186/s12911-022-02093-0,"Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration.","Abbasizanjani H, Torabi F, Bedston S, Bolton T, Davies G, Denaxas S, Griffiths R, Herbert L, Hollings S, Keene S, Khunti K, Lowthian E, Lyons J, Mizani MA, Nolan J, Sudlow C, Walker V, Whiteley W, Wood A, Akbari A, CVD-COVID-UK/COVID-IMPACT Consortium.",,BMC medical informatics and decision making,2023,2023-01-16,Y,Population Health; Electronic Health Record; Reproducible Research; Common Data Model; Covid-19; Nhs Digital Tre For England; Sail Databank; Trusted Research Environments; Data Harmonisation,,,"<h4>Background</h4>The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enable analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt.<h4>Methods</h4>Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer.<h4>Results</h4>Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information.<h4>Conclusions</h4>We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02093-0; doi:https://doi.org/10.1186/s12911-022-02093-0; html:https://europepmc.org/articles/PMC9842203; pdf:https://europepmc.org/articles/PMC9842203?pdf=render
 36749628,https://doi.org/10.2196/42449,Charting a Course for Smartphones and Wearables to Transform Population Health Research.,"Dixon WG, van der Veer SN, Ali SM, Laidlaw L, Dobson RJB, Sudlow C, Chico T, MacArthur JAL, Doherty A.",,Journal of medical Internet research,2023,2023-02-07,Y,Research; Health; Clinical; Data; Digital; Devices; Wearable; Mhealth; Mobile Health; Person-generated Health Data; Population Health Research,,,"The use of data from smartphones and wearable devices has huge potential for population health research, given the high level of device ownership; the range of novel health-relevant data types available from consumer devices; and the frequency and duration with which data are, or could be, collected. Yet, the uptake and success of large-scale mobile health research in the last decade have not met this intensely promoted opportunity. We make the argument that digital person-generated health data are required and necessary to answer many top priority research questions, using illustrative examples taken from the James Lind Alliance Priority Setting Partnerships. We then summarize the findings from 2 UK initiatives that considered the challenges and possible solutions for what needs to be done and how such solutions can be implemented to realize the future opportunities of digital person-generated health data for clinically important population health research. Examples of important areas that must be addressed to advance the field include digital inequality and possible selection bias; easy access for researchers to the appropriate data collection tools, including how best to harmonize data items; analysis methodologies for time series data; patient and public involvement and engagement methods for optimizing recruitment, retention, and public trust; and methods for providing research participants with greater control over their data. There is also a major opportunity, provided through the linkage of digital person-generated health data to routinely collected data, to support novel population health research, bringing together clinician-reported and patient-reported measures. We recognize that well-conducted studies need a wide range of diverse challenges to be skillfully addressed in unison (eg, challenges regarding epidemiology, data science and biostatistics, psychometrics, behavioral and social science, software engineering, user interface design, information governance, data management, and patient and public involvement and engagement). Consequently, progress would be accelerated by the establishment of a new interdisciplinary community where all relevant and necessary skills are brought together to allow for excellence throughout the life cycle of a research study. This will require a partnership of diverse people, methods, and technologies. If done right, the synergy of such a partnership has the potential to transform many millions of people's lives for the better.",,pdf:https://www.jmir.org/2023/1/e42449/PDF; doi:https://doi.org/10.2196/42449; html:https://europepmc.org/articles/PMC7614184; pdf:https://europepmc.org/articles/PMC7614184?pdf=render
@@ -126,20 +126,20 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 34713086,https://doi.org/10.3389/fdgth.2021.598916,Markup: A Web-Based Annotation Tool Powered by Active Learning.,"Dobbie S, Strafford H, Pickrell WO, Fonferko-Shadrach B, Jones C, Akbari A, Thompson S, Lacey A.",,Frontiers in digital health,2021,2021-07-26,Y,Active Learning; Annotation; Natural Language Processing; Unstructured Text; Sequence-to-sequence Learning,,,"Across various domains, such as health and social care, law, news, and social media, there are increasing quantities of unstructured texts being produced. These potential data sources often contain rich information that could be used for domain-specific and research purposes. However, the unstructured nature of free-text data poses a significant challenge for its utilisation due to the necessity of substantial manual intervention from domain-experts to label embedded information. Annotation tools can assist with this process by providing functionality that enables the accurate capture and transformation of unstructured texts into structured annotations, which can be used individually, or as part of larger Natural Language Processing (NLP) pipelines. We present Markup (https://www.getmarkup.com/) an open-source, web-based annotation tool that is undergoing continued development for use across all domains. Markup incorporates NLP and Active Learning (AL) technologies to enable rapid and accurate annotation using custom user configurations, predictive annotation suggestions, and automated mapping suggestions to both domain-specific ontologies, such as the Unified Medical Language System (UMLS), and custom, user-defined ontologies. We demonstrate a real-world use case of how Markup has been used in a healthcare setting to annotate structured information from unstructured clinic letters, where captured annotations were used to build and test NLP applications.",,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2021.598916/pdf; doi:https://doi.org/10.3389/fdgth.2021.598916; html:https://europepmc.org/articles/PMC8521860; pdf:https://europepmc.org/articles/PMC8521860?pdf=render
 36385522,https://doi.org/10.1093/ehjqcco/qcac077,Effects of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries.,"Wright FL, Cheema K, Goldacre R, Hall N, Herz N, Islam N, Karim Z, Moreno-Martos D, Morales DR, O'Connell D, Spata E, Akbari A, Ashworth M, Barber M, Briffa N, Canoy D, Denaxas S, Khunti K, Kurdi A, Mamas M, Priedon R, Sudlow C, Morris EJA, Lacey B, Banerjee A.",,European heart journal. Quality of care & clinical outcomes,2023,2023-06-01,Y,,,,"<h4>Background</h4>Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described.<h4>Methods and results</h4>Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions.<h4>Conclusion</h4>The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62054/Download/62054__26063__5453b00901174a7d9a0797547f023fba.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac077; html:https://europepmc.org/articles/PMC10284263; pdf:https://europepmc.org/articles/PMC10284263?pdf=render
 36244382,https://doi.org/10.1016/s0140-6736(22)01656-7,"Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales.","Agrawal U, Bedston S, McCowan C, Oke J, Patterson L, Robertson C, Akbari A, Azcoaga-Lorenzo A, Bradley DT, Fagbamigbe AF, Grange Z, Hall ECR, Joy M, Katikireddi SV, Kerr S, Ritchie L, Murphy S, Owen RK, Rudan I, Shah SA, Simpson CR, Torabi F, Tsang RSM, de Lusignan S, Lyons RA, O'Reilly D, Sheikh A.",,"Lancet (London, England)",2022,2022-10-01,Y,,,,"<h4>Background</h4>Current UK vaccination policy is to offer future COVID-19 booster doses to individuals at high risk of serious illness from COVID-19, but it is still uncertain which groups of the population could benefit most. In response to an urgent request from the UK Joint Committee on Vaccination and Immunisation, we aimed to identify risk factors for severe COVID-19 outcomes (ie, COVID-19-related hospitalisation or death) in individuals who had completed their primary COVID-19 vaccination schedule and had received the first booster vaccine.<h4>Methods</h4>We constructed prospective cohorts across all four UK nations through linkages of primary care, RT-PCR testing, vaccination, hospitalisation, and mortality data on 30 million people. We included individuals who received primary vaccine doses of BNT162b2 (tozinameran; Pfizer-BioNTech) or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in our initial analyses. We then restricted analyses to those given a BNT162b2 or mRNA-1273 (elasomeran; Moderna) booster and had a severe COVID-19 outcome between Dec 20, 2021, and Feb 28, 2022 (when the omicron (B.1.1.529) variant was dominant). We fitted time-dependent Poisson regression models and calculated adjusted rate ratios (aRRs) and 95% CIs for the associations between risk factors and COVID-19-related hospitalisation or death. We adjusted for a range of potential covariates, including age, sex, comorbidities, and previous SARS-CoV-2 infection. Stratified analyses were conducted by vaccine type. We then did pooled analyses across UK nations using fixed-effect meta-analyses.<h4>Findings</h4>Between Dec 8, 2020, and Feb 28, 2022, 16 208 600 individuals completed their primary vaccine schedule and 13 836 390 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59 510 (0·4%) of the primary vaccine group and 26 100 (0·2%) of those who received their booster had severe COVID-19 outcomes. The risk of severe COVID-19 outcomes reduced after receiving the booster (rate change: 8·8 events per 1000 person-years to 7·6 events per 1000 person-years). Older adults (≥80 years vs 18-49 years; aRR 3·60 [95% CI 3·45-3·75]), those with comorbidities (≥5 comorbidities vs none; 9·51 [9·07-9·97]), being male (male vs female; 1·23 [1·20-1·26]), and those with certain underlying health conditions-in particular, individuals receiving immunosuppressants (yes vs no; 5·80 [5·53-6·09])-and those with chronic kidney disease (stage 5 vs no; 3·71 [2·90-4·74]) remained at high risk despite the initial booster. Individuals with a history of COVID-19 infection were at reduced risk (infected ≥9 months before booster dose vs no previous infection; aRR 0·41 [95% CI 0·29-0·58]).<h4>Interpretation</h4>Older people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics.<h4>Funding</h4>National Core Studies-Immunity, UK Research and Innovation (Medical Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.",,doi:https://doi.org/10.1016/s0140-6736(22)01656-7; doi:https://doi.org/10.1016/S0140-6736(22)01656-7; html:https://europepmc.org/articles/PMC9560746; pdf:https://europepmc.org/articles/PMC9560746?pdf=render
-37368983,https://doi.org/10.2337/dc23-0294,"Relationship Among Diabetes, Obesity, and Cardiovascular Disease Phenotypes: A UK Biobank Cohort Study.","Brown OI, Drozd M, McGowan H, Giannoudi M, Conning-Rowland M, Gierula J, Straw S, Wheatcroft SB, Bridge K, Roberts LD, Levelt E, Ajjan R, Griffin KJ, Bailey MA, Kearney MT, Cubbon RM.",,Diabetes care,2023,2023-08-01,Y,,,,"<h4>Objective</h4>Obesity and diabetes frequently coexist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events, and mortality in the UK Biobank stratified by BMI and diabetes.<h4>Research design and methods</h4>A total of 451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including carotid intima-media thickness (CIMT), arterial stiffness, left ventricular ejection fraction (LVEF), and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRRs) for myocardial infarction, ischemic stroke, and cardiovascular death, with normal-weight nondiabetes as comparator.<h4>Results</h4>Five percent of participants had diabetes (10% normal weight, 34% overweight, and 55% obese vs. 34%, 43%, and 23%, respectively, without diabetes). In the nondiabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness, and CCI and lower LVEF (P < 0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (P < 0.005), particularly in the normal-weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke, and cardiovascular mortality rose across increasing BMI categories without diabetes (P < 0.005); this was comparable in the diabetes groups (P-interaction > 0.05). Normal-weight diabetes had comparable adjusted cardiovascular mortality to obese nondiabetes (IRR 1.22 [95% CI 0.96-1.56]; P = 0.1).<h4>Conclusions</h4>Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. While adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting that other factors underpin the high cardiovascular risk of normal-weight diabetes.",,doi:https://doi.org/10.2337/dc23-0294; html:https://europepmc.org/articles/PMC10369123; pdf:https://europepmc.org/articles/PMC10369123?pdf=render
 37254630,https://doi.org/10.1111/acel.13808,"Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants.","Liu R, Xiang M, Pilling LC, Melzer D, Wang L, Manning KJ, Steffens DC, Bowden J, Fortinsky RH, Kuchel GA, Rhee TG, Diniz BS, Kuo CL.",,Aging cell,2023,2023-05-30,Y,Cognition; Alzheimer's disease; Vascular dementia; Brain Magnetic Resonance Imaging; Hallmarks Of Biological Aging,,,"Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90-0.96, p = 3.37 × 10<sup>-7</sup> ). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.",,doi:https://doi.org/10.1111/acel.13808; doi:https://doi.org/10.1111/acel.13808; html:https://europepmc.org/articles/PMC10352557; pdf:https://europepmc.org/articles/PMC10352557?pdf=render
+37368983,https://doi.org/10.2337/dc23-0294,"Relationship Among Diabetes, Obesity, and Cardiovascular Disease Phenotypes: A UK Biobank Cohort Study.","Brown OI, Drozd M, McGowan H, Giannoudi M, Conning-Rowland M, Gierula J, Straw S, Wheatcroft SB, Bridge K, Roberts LD, Levelt E, Ajjan R, Griffin KJ, Bailey MA, Kearney MT, Cubbon RM.",,Diabetes care,2023,2023-08-01,Y,,,,"<h4>Objective</h4>Obesity and diabetes frequently coexist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events, and mortality in the UK Biobank stratified by BMI and diabetes.<h4>Research design and methods</h4>A total of 451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including carotid intima-media thickness (CIMT), arterial stiffness, left ventricular ejection fraction (LVEF), and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRRs) for myocardial infarction, ischemic stroke, and cardiovascular death, with normal-weight nondiabetes as comparator.<h4>Results</h4>Five percent of participants had diabetes (10% normal weight, 34% overweight, and 55% obese vs. 34%, 43%, and 23%, respectively, without diabetes). In the nondiabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness, and CCI and lower LVEF (P < 0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (P < 0.005), particularly in the normal-weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke, and cardiovascular mortality rose across increasing BMI categories without diabetes (P < 0.005); this was comparable in the diabetes groups (P-interaction > 0.05). Normal-weight diabetes had comparable adjusted cardiovascular mortality to obese nondiabetes (IRR 1.22 [95% CI 0.96-1.56]; P = 0.1).<h4>Conclusions</h4>Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. While adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting that other factors underpin the high cardiovascular risk of normal-weight diabetes.",,doi:https://doi.org/10.2337/dc23-0294; html:https://europepmc.org/articles/PMC10369123; pdf:https://europepmc.org/articles/PMC10369123?pdf=render
 36638616,https://doi.org/10.1016/j.compbiomed.2022.106425,Klarigi: Characteristic explanations for semantic biomedical data.,"Slater LT, Williams JA, Schofield PN, Russell S, Pendleton SC, Karwath A, Fanning H, Ball S, Hoehndorf R, Gkoutos GV.",,Computers in biology and medicine,2023,2022-12-22,N,Phenotypes; Ontology; Enrichment Analysis; Semantic Analysis; Explicability; Phenotype Profiles; Semantic Explanation,,,"Annotation of biomedical entities with ontology classes provides for formal semantic analysis and mobilisation of background knowledge in determining their relationships. To date, enrichment analysis has been routinely employed to identify classes that are over-represented in annotations across sets of groups, such as biosample gene expression profiles or patient phenotypes, and is useful for a range of tasks including differential diagnosis and causative variant prioritisation. These approaches, however, usually consider only univariate relationships, make limited use of the semantic features of ontologies, and provide limited information and evaluation of the explanatory power of both singular and grouped candidate classes. Moreover, they are not designed to solve the problem of deriving cohesive, characteristic, and discriminatory sets of classes for entity groups. We have developed a new tool, called Klarigi, which introduces multiple scoring heuristics for identification of classes that are both compositional and discriminatory for groups of entities annotated with ontology classes. The tool includes a novel algorithm for derivation of multivariable semantic explanations for entity groups, makes use of semantic inference through live use of an ontology reasoner, and includes a classification method for identifying the discriminatory power of candidate sets, in addition to significance testing apposite to traditional enrichment approaches. We describe the design and implementation of Klarigi, including its scoring and explanation determination methods, and evaluate its use in application to two test cases with clinical significance, comparing and contrasting methods and results with literature-based and enrichment analysis methods. We demonstrate that Klarigi produces characteristic and discriminatory explanations for groups of biomedical entities in two settings. We also show that these explanations recapitulate and extend the knowledge held in existing biomedical databases and literature for several diseases. We conclude that Klarigi provides a distinct and valuable perspective on biomedical datasets when compared with traditional enrichment methods, and therefore constitutes a new method by which biomedical datasets can be explored, contributing to improved insight into semantic data.",,doi:https://doi.org/10.1016/j.compbiomed.2022.106425; doi:https://doi.org/10.1016/j.compbiomed.2022.106425
 35381005,https://doi.org/10.1371/journal.pone.0264828,Reproducible disease phenotyping at scale: Example of coronary artery disease in UK Biobank.,"Patel RS, Denaxas S, Howe LJ, Eggo RM, Shah AD, Allen NE, Danesh J, Hingorani A, Sudlow C, Hemingway H.",,PloS one,2022,2022-04-05,Y,,,,"<h4>Importance</h4>A lack of internationally agreed standards for combining available data sources at scale risks inconsistent disease phenotyping limiting research reproducibility.<h4>Objective</h4>To develop and then evaluate if a rules-based algorithm can identify coronary artery disease (CAD) sub-phenotypes using electronic health records (EHR) and questionnaire data from UK Biobank (UKB).<h4>Design</h4>Case-control and cohort study.<h4>Setting</h4>Prospective cohort study of 502K individuals aged 40-69 years recruited between 2006-2010 into the UK Biobank with linked hospitalization and mortality data and genotyping.<h4>Participants</h4>We included all individuals for phenotyping into 6 predefined CAD phenotypes using hospital admission and procedure codes, mortality records and baseline survey data. Of these, 408,470 unrelated individuals of European descent had a polygenic risk score (PRS) for CAD estimated.<h4>Exposure</h4>CAD Phenotypes.<h4>Main outcomes and measures</h4>Association with baseline risk factors, mortality (n = 14,419 over 7.8 years median f/u), and a PRS for CAD.<h4>Results</h4>The algorithm classified individuals with CAD into prevalent MI (n = 4,900); incident MI (n = 4,621), prevalent CAD without MI (n = 10,910), incident CAD without MI (n = 8,668), prevalent self-reported MI (n = 2,754); prevalent self-reported CAD without MI (n = 5,623), yielding 37,476 individuals with any type of CAD. Risk factors were similar across the six CAD phenotypes, except for fewer men in the self-reported CAD without MI group (46.7% v 70.1% for the overall group). In age- and sex- adjusted survival analyses, mortality was highest following incident MI (HR 6.66, 95% CI 6.07-7.31) and lowest for prevalent self-reported CAD without MI at baseline (HR 1.31, 95% CI 1.15-1.50) compared to disease-free controls. There were similar graded associations across the six phenotypes per SD increase in PRS, with the strongest association for prevalent MI (OR 1.50, 95% CI 1.46-1.55) and the weakest for prevalent self-reported CAD without MI (OR 1.08, 95% CI 1.05-1.12). The algorithm is available in the open phenotype HDR UK phenotype library (https://portal.caliberresearch.org/).<h4>Conclusions</h4>An algorithmic, EHR-based approach distinguished six phenotypes of CAD with distinct survival and PRS associations, supporting adoption of open approaches to help standardize CAD phenotyping and its wider potential value for reproducible research in other conditions.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264828&type=printable; doi:https://doi.org/10.1371/journal.pone.0264828; html:https://europepmc.org/articles/PMC8982857; pdf:https://europepmc.org/articles/PMC8982857?pdf=render
-36719907,https://doi.org/10.1371/journal.pmed.1004086,Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study.,"Turtle L, Thorpe M, Drake TM, Swets M, Palmieri C, Russell CD, Ho A, Aston S, Wootton DG, Richter A, de Silva TI, Hardwick HE, Leeming G, Law A, Openshaw PJM, Harrison EM, ISARIC4C investigators, Baillie JK, Semple MG, Docherty AB.",,PLoS medicine,2023,2023-01-31,Y,,,,"<h4>Background</h4>Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic.<h4>Methods and findings</h4>We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent.<h4>Conclusions</h4>Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group.<h4>Trial registration</h4>ISRCTN 66726260.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004086&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004086; html:https://europepmc.org/articles/PMC9928075; pdf:https://europepmc.org/articles/PMC9928075?pdf=render
 36195871,https://doi.org/10.1186/s12916-022-02533-8,Post-mortem examination of high mortality in patients with heart failure and atrial fibrillation.,"Țica O, Țica O, Bunting KV, deBono J, Gkoutos GV, Popescu MI, Kotecha D.",,BMC medicine,2022,2022-10-05,Y,Mortality; Atrial fibrillation; Autopsy; Heart Failure; Post-mortem,,,"<h4>Background</h4>The prevalence of combined heart failure (HF) and atrial fibrillation (AF) is rising, and these patients suffer from high rates of mortality. This study aims to provide robust data on factors associated with death, uniquely supported by post-mortem examination.<h4>Methods</h4>A retrospective cohort study of hospitalized adults with a clinical diagnosis of HF and AF at a tertiary centre in Romania between 2014 and 2017. A standardized post-mortem examination was performed where death occurred within 24 h of admission, when the cause of death was not clear or by physician request. National records were used to collect mortality data, subsequently categorized and analysed as HF-related death, vascular death and non-cardiovascular death using Cox proportional hazards regression.<h4>Results</h4>A total of 1009 consecutive patients with a mean age of 73 ± 11 years, 47% women, NYHA class 3.0 ± 0.9, left ventricular ejection fraction (LVEF) 40.1 ± 11.0% and 100% anticoagulated were followed up for 1.5 ± 0.9 years. A total of 291 (29%) died, with post-mortems performed on 186 (64%). Baseline factors associated with mortality were dependent on the cause of death. HF-related death in 136 (47%) was associated with higher NYHA class (hazard ratio [HR] 2.45 per one class increase, 95% CI 1.73-3.46; p < 0.001) and lower LVEF (0.95 per 1% increase, 0.93-0.97; p < 0.001). Vascular death occurred in 75 (26%) and was associated with hypertension (HR 2.83, 1.36-5.90; p = 0.005) and higher LVEF (1.08 per 1% increase, 1.05-1.11; p < 0.001). Non-cardiovascular death in 80 (28%) was associated with clinical obesity (HR 2.20, 1.21-4.00; p = 0.010) and higher LVEF (1.10 per 1% increase, 1.06-1.13; p < 0.001). Across all causes, there was no relationship between mortality and AF type (p = 0.77), HF type (p = 0.85) or LVEF (p = 0.58).<h4>Conclusions</h4>Supported by post-mortem data, the cause of death in HF and AF patients is heterogeneous, and the relationships with typical markers of mortality are critically dependent on the mode of death. The poor prognosis in this group demands further attention to improve management beyond anticoagulation.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02533-8; doi:https://doi.org/10.1186/s12916-022-02533-8; html:https://europepmc.org/articles/PMC9533594; pdf:https://europepmc.org/articles/PMC9533594?pdf=render
+36719907,https://doi.org/10.1371/journal.pmed.1004086,Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study.,"Turtle L, Thorpe M, Drake TM, Swets M, Palmieri C, Russell CD, Ho A, Aston S, Wootton DG, Richter A, de Silva TI, Hardwick HE, Leeming G, Law A, Openshaw PJM, Harrison EM, ISARIC4C investigators, Baillie JK, Semple MG, Docherty AB.",,PLoS medicine,2023,2023-01-31,Y,,,,"<h4>Background</h4>Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic.<h4>Methods and findings</h4>We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent.<h4>Conclusions</h4>Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group.<h4>Trial registration</h4>ISRCTN 66726260.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004086&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004086; html:https://europepmc.org/articles/PMC9928075; pdf:https://europepmc.org/articles/PMC9928075?pdf=render
 37468507,https://doi.org/10.1038/s41598-023-37580-5,Biobank-scale methods and projections for sparse polygenic prediction from machine learning.,"Raben TG, Lello L, Widen E, Hsu SDH.",,Scientific reports,2023,2023-07-19,Y,,,,"In this paper we characterize the performance of linear models trained via widely-used sparse machine learning algorithms. We build polygenic scores and examine performance as a function of training set size, genetic ancestral background, and training method. We show that predictor performance is most strongly dependent on size of training data, with smaller gains from algorithmic improvements. We find that LASSO generally performs as well as the best methods, judged by a variety of metrics. We also investigate performance characteristics of predictors trained on one genetic ancestry group when applied to another. Using LASSO, we develop a novel method for projecting AUC and correlation as a function of data size (i.e., for new biobanks) and characterize the asymptotic limit of performance. Additionally, for LASSO (compressed sensing) we show that performance metrics and predictor sparsity are in agreement with theoretical predictions from the Donoho-Tanner phase transition. Specifically, a future predictor trained in the Taiwan Precision Medicine Initiative for asthma can achieve an AUC of [Formula: see text] and for height a correlation of [Formula: see text] for a Taiwanese population. This is above the measured values of [Formula: see text] and [Formula: see text], respectively, for UK Biobank trained predictors applied to a European population.",,doi:https://doi.org/10.1038/s41598-023-37580-5; html:https://europepmc.org/articles/PMC10356957; pdf:https://europepmc.org/articles/PMC10356957?pdf=render
 36807005,https://doi.org/10.1055/a-2038-0541,Long-term outcomes of pouch surveillance and risk of neoplasia in familial adenomatous polyposis.,"Patel RV, Curtius K, Man R, Fletcher J, Cuthill V, Clark SK, von Roon AC, Latchford A.",,Endoscopy,2023,2023-02-17,Y,,,,"<h4>Background</h4>Long-term pouch surveillance outcomes for familial adenomatous polyposis (FAP) are unknown. We aimed to quantify surveillance outcomes and to determine which of selected possible predictive factors are associated with pouch dysplasia.<h4>Methods</h4>Retrospective analysis of collected data on 249 patients was performed, analyzing potential risk factors for the development of adenomas or advanced lesions ( ≥ 10 mm/high grade dysplasia (HGD)/cancer) in the pouch body and cuff using Cox proportional hazards models. Kaplan-Meier analyses included landmark time-point analyses at 10 years after surgery to predict the future risk of advanced lesions.<h4>Results</h4>Of 249 patients, 76 % developed at least one pouch body adenoma, with 16 % developing an advanced pouch body lesion; 18 % developed an advanced cuff lesion. Kaplan-Meier analysis showed a 10-year lag before most advanced lesions developed; cumulative incidence of 2.8 % and 6.4 % at 10 years in the pouch body and cuff, respectively. Landmark analysis suggested the presence of adenomas prior to the 10-year point was associated with subsequent development of advanced lesions in the pouch body (hazard ratio [HR] 4.8, 95 %CI 1.6-14.1; <i>P</i> = 0.004) and cuff (HR 6.8, 95 %CI 2.5-18.3; <i>P</i> < 0.001). There were two HGD and four cancer cases in the cuff and one pouch body cancer; all cases of cancer/HGD that had prior surveillance were preceded by ≥ 10-mm adenomas.<h4>Conclusions</h4>Pouch adenoma progression is slow and most advanced lesions occur after 10 years. HGD and cancer were rare events. Pouch phenotype in the first decade is associated with the future risk of developing advanced lesions and may guide personalized surveillance beyond 10 years.",,pdf:http://www.thieme-connect.de/products/ejournals/pdf/10.1055/a-2038-0541.pdf; doi:https://doi.org/10.1055/a-2038-0541; html:https://europepmc.org/articles/PMC10465241; pdf:https://europepmc.org/articles/PMC10465241?pdf=render
 33980500,https://doi.org/10.1136/bmjhci-2020-100303,Development of a data utility framework to support effective health data curation. ,"Gordon B, Barrett J, Fennessy C, Cake C, Milward A, Irwin C, Jones M, Sebire N.",,BMJ health & care informatics,2021,2021-05-01,Y,,,,"The value of healthcare data is being increasingly recognised, including the need to improve health dataset utility. There is no established mechanism for evaluating healthcare dataset utility making it difficult to evaluate the effectiveness of activities improving the data. To describe the method for generating and involving the user community in developing a proposed framework for evaluation and communication of healthcare dataset utility for given research areas. Aninitial version of a matrix to review datasets across a range of dimensions wasdeveloped based on previous published findings regarding healthcare data. Thiswas used to initiate a design process through interviews and surveys with datausers representing a broad range of user types and use cases, to help develop afocused framework for characterising datasets. Following 21 interviews, 31 survey responses and testing on 43 datasets, five major categories and 13 subcategories were identified as useful for a dataset, including Data Model, Completeness and Linkage. Each sub-category was graded to facilitate rapid and reproducible evaluation of dataset utility for specific use-cases. Testing of applicability to >40 existing datasets demonstrated potential usefulness for subsequent evaluation in real-world practice. Theresearch has developed an evidenced-based initial approach for a framework tounderstand the utility of a healthcare dataset. It likely to require further refinementfollowing wider application and additional categories may be required. The process has resulted in a user-centred designed framework for objectively evaluating the likely utility of specific healthcare datasets, and therefore, should be of value both for potential users of health data, and for data custodians to identify the areas to provide the optimal value for data curation investment.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100303.full.pdf; doi:https://doi.org/10.1136/bmjhci-2020-100303; html:https://europepmc.org/articles/PMC8117992; pdf:https://europepmc.org/articles/PMC8117992?pdf=render
 36891499,https://doi.org/10.1016/j.ssmph.2023.101370,How does the local area deprivation influence life chances for children in poverty in Wales: A record linkage cohort study.,"Bandyopadhyay A, Whiffen T, Fry R, Brophy S.",,SSM - population health,2023,2023-02-23,Y,Resilience; Cohort study; Education; Deprivation; Child Poverty; Record Linkage; Local Area,,,"<h4>Objectives</h4>Children growing up in poverty are less likely to achieve in school and more likely to experience mental health problems. This study examined factors in the local area that can help a child overcome the negative impact of poverty.<h4>Design</h4>A longitudinal record linkage retrospective cohort study.<h4>Participants</h4>This study included 159,131 children who lived in Wales and completed their age 16 exams (Key Stage 4 (KS4)) between 2009 and 2016. Free School Meal (FSM) provision was used as an indicator of household-level deprivation. Area-level deprivation was measured using the Welsh Index of Multiple Deprivation (WIMD) 2011. An encrypted unique Anonymous Linking Field was used to link the children with their health- and educational records.<h4>Outcome measures</h4>The outcome variable 'Profile to Leave Poverty' (PLP) was constructed based on successful completion of age 16 exams, no mental health condition, no substance and alcohol misuse records in routine data. Logistic regression with stepwise model selection was used to investigate the association between local area deprivation and the outcome variable.<h4>Results</h4>22% of children on FSM achieved PLP compared to 54.9% of non-FSM children. FSM Children from least deprived areas were significantly more likely to achieve PLP (adjusted odds ratio (aOR) - 2.20 (1.93, 2.51)) than FSM children from most deprived areas. FSM children, living in areas with higher community safety, higher relative income, higher access to services, were more likely to achieve PLP than their peers.<h4>Conclusion</h4>The findings indicate that community-level improvements such as increasing safety, connectivity and employment might help in child's education attainment, mental health and reduce risk taking behaviours.",,doi:https://doi.org/10.1016/j.ssmph.2023.101370; doi:https://doi.org/10.1016/j.ssmph.2023.101370; html:https://europepmc.org/articles/PMC9986621; pdf:https://europepmc.org/articles/PMC9986621?pdf=render
 36035235,https://doi.org/10.1212/nxg.0000000000200015,"Frequency and Phenotype Associations of Rare Variants in 5 Monogenic Cerebral Small Vessel Disease Genes in 200,000 UK Biobank Participants.","Ferguson AC, Thrippleton S, Henshall D, Whittaker E, Conway B, MacLeod M, Malik R, Rawlik K, Tenesa A, Sudlow C, Rannikmae K.",,Neurology. Genetics,2022,2022-08-24,Y,,,,"<h4>Background and objectives</h4>Based on previous case reports and disease-based cohorts, a minority of patients with cerebral small vessel disease (cSVD) have a monogenic cause, with many also manifesting extracerebral phenotypes. We investigated the frequency, penetrance, and phenotype associations of putative pathogenic variants in cSVD genes in the UK Biobank (UKB), a large population-based study.<h4>Methods</h4>We used a systematic review of previous literature and ClinVar to identify putative pathogenic rare variants in <i>CTSA</i>, <i>TREX1</i>, <i>HTRA1</i>, and <i>COL4A1/2</i>. We mapped phenotypes previously attributed to these variants (phenotypes-of-interest) to disease coding systems used in the UKB's linked health data from UK hospital admissions, death records, and primary care. Among 199,313 exome-sequenced UKB participants, we assessed the following: the proportion of participants carrying ≥1 variant(s); phenotype-of-interest penetrance; and the association between variant carrier status and phenotypes-of-interest using a binary (any phenotype present/absent) and phenotype burden (linear score of the number of phenotypes a participant possessed) approach.<h4>Results</h4>Among UKB participants, 0.5% had ≥1 variant(s) in studied genes. Using hospital admission and death records, 4%-20% of variant carriers per gene had an associated phenotype. This increased to 7%-55% when including primary care records. Only <i>COL4A1</i> variant carrier status was significantly associated with having ≥1 phenotype-of-interest and a higher phenotype score (OR = 1.29, <i>p</i> = 0.006).<h4>Discussion</h4>While putative pathogenic rare variants in monogenic cSVD genes occur in 1:200 people in the UKB population, only approximately half of variant carriers have a relevant disease phenotype recorded in their linked health data. We could not replicate most previously reported gene-phenotype associations, suggesting lower penetrance rates, overestimated pathogenicity, and/or limited statistical power.",,pdf:https://ng.neurology.org/content/nng/8/5/e200015.full.pdf; doi:https://doi.org/10.1212/NXG.0000000000200015; html:https://europepmc.org/articles/PMC9403885; pdf:https://europepmc.org/articles/PMC9403885?pdf=render
 34497074,https://doi.org/10.1136/bmjopen-2020-042483,Modelling the impact of lockdown-easing measures on cumulative COVID-19 cases and deaths in England.,"Ziauddeen H, Subramaniam N, Gurdasani D.",,BMJ open,2021,2021-09-08,Y,Infection control; epidemiology; Public Health; Health Policy,,,"<h4>Objectives</h4>To assess the potential impacts of successive lockdown-easing measures in England, at a point in the COVID-19 pandemic when community transmission levels were relatively high.<h4>Design</h4>We developed a Bayesian model to infer incident cases and reproduction number (<i>R</i>) in England, from incident death data. We then used this to forecast excess cases and deaths in multiple plausible scenarios in which <i>R</i> increases at one or more time points.<h4>Setting</h4>England.<h4>Participants</h4>Publicly available national incident death data for COVID-19 were examined.<h4>Primary outcome</h4>Excess cumulative cases and deaths forecast at 90 days, in simulated scenarios of plausible increases in <i>R</i> after successive easing of lockdown in England, compared with a baseline scenario where <i>R</i> remained constant.<h4>Results</h4>Our model inferred an <i>R</i> of 0.75 on 13 May when England first started easing lockdown. In the most conservative scenario modelled where <i>R</i> increased to 0.80 as lockdown was eased further on 1 June and then remained constant, the model predicted an excess 257 (95% CI 108 to 492) deaths and 26 447 (95% CI 11 105 to 50 549) cumulative cases over 90 days. In the scenario with maximal increases in <i>R</i> (but staying ≤1), the model predicts 3174 (95% CI 1334 to 6060) excess cumulative deaths and 421 310 (95% CI 177 012 to 804 811) cases. Observed data from the forecasting period aligned most closely to the scenario in which <i>R</i> increased to 0.85 on 1 June, and 0.9 on 4 July.<h4>Conclusions</h4>When levels of transmission are high, even small changes in <i>R</i> with easing of lockdown can have significant impacts on expected cases and deaths, even if <i>R</i> remains ≤1. This will have a major impact on population health, tracing systems and healthcare services in England. Following an elimination strategy rather than one of maintenance of <i>R</i> ≤1 would substantially mitigate the impact of the COVID-19 epidemic within England.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/9/e042483.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042483; html:https://europepmc.org/articles/PMC8438582; pdf:https://europepmc.org/articles/PMC8438582?pdf=render
-34799365,https://doi.org/10.1136/bmjopen-2021-054861,Retrospective cohort study to evaluate medication use in patients hospitalised with COVID-19 in Scotland: protocol for a national observational study.,"Mueller T, Kerr S, McTaggart S, Kurdi A, Vasileiou E, Docherty A, Fraser K, Shi T, Simpson CR, Bennie M, Sheikh A.",,BMJ open,2021,2021-11-19,Y,Therapeutics; clinical pharmacology; Covid-19,,,"<h4>Introduction</h4>COVID-19 has caused millions of hospitalisations and deaths globally. A range of vaccines have been developed and are being deployed at scale in the UK to prevent SARS-CoV-2 infection, which have reduced risk of infection and severe COVID-19 outcomes. Those with COVID-19 are now being treated with several repurposed drugs based on evidence emerging from recent clinical trials. However, there is currently limited real-world data available related to the use of these drugs in routine clinical practice. The purpose of this study is to address the prevailing knowledge gaps regarding the use of dexamethasone, remdesivir and tocilizumab by conducting an exploratory drug utilisation study, aimed at providing in-depth descriptions of patients receiving these drugs as well as the treatment patterns observed in Scotland.<h4>Methods and analysis</h4>Retrospective cohort study, comprising adult patients admitted to hospital with confirmed or suspected COVID-19 across five Scottish Health Boards using data from in-hospital ePrescribing linked to the Early Estimation of Vaccine and Anti-Viral Effectiveness (EAVE II) COVID-19 surveillance platform. The primary outcome will be exposure to the medicines of interest (dexamethasone, remdesivir, tocilizumab), either alone or in combination; exposure will be described in terms of drug(s) of choice; prescribed and administered dose; treatment duration; and any changes in treatment, for example, dose escalation and/or switching to an alternative drug. Analyses will primarily be descriptive in nature.<h4>Ethics and dissemination</h4>Ethical and information governance approvals have been obtained by the National Research Ethics Service Committee, South East Scotland 02 and the Public Benefit and Privacy Panel for Health and Social Care, respectively. Findings from this study will be presented at academic and clinical conferences, and to the funders and other interested parties as appropriate; study findings will also be published in peer-reviewed journals. Publications will be available on the EAVE II website (https://www.ed.ac.uk/usher/eave-ii/key-outputs/our-publications), alongside lay summaries and infographics aimed at the general public. Press releases will also be considered, if appropriate.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e054861.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054861; html:https://europepmc.org/articles/PMC8609490; pdf:https://europepmc.org/articles/PMC8609490?pdf=render
 32741245,https://doi.org/10.1177/0954411920946526,Artificial intelligence approaches to predict coronary stenosis severity using non-invasive fractional flow reserve.,"Carson JM, Chakshu NK, Sazonov I, Nithiarasu P.",,"Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine",2020,2020-08-03,Y,Artificial intelligence; Biomedical engineering; Coronary Heart Disease; Fractional Flow Reserve; Computational Mechanics; Haemodynamic Modelling,,,"Fractional flow reserve is the current reference standard in the assessment of the functional impact of a stenosis in coronary heart disease. In this study, three models of artificial intelligence of varying degrees of complexity were compared to fractional flow reserve measurements. The three models are the multivariate polynomial regression, which is a statistical method used primarily for correlation; the feed-forward neural network; and the long short-term memory, which is a type of recurrent neural network that is suited to modelling sequences. The models were initially trained using a virtual patient database that was generated from a validated one-dimensional physics-based model. The feed-forward neural network performed the best for all test cases considered, which were a single vessel case from a virtual patient database, a multi-vessel network from a virtual patient database, and 25 clinically invasive fractional flow reserve measurements from real patients. The feed-forward neural network model achieved around 99% diagnostic accuracy in both tests involving virtual patients, and a respectable 72% diagnostic accuracy when compared to the invasive fractional flow reserve measurements. The multivariate polynomial regression model performed well in the single vessel case, but struggled on network cases as the variation of input features was much larger. The long short-term memory performed well for the single vessel cases, but tended to have a bias towards a positive fractional flow reserve prediction for the virtual multi-vessel case, and for the patient cases. Overall, the feed-forward neural network shows promise in successfully predicting fractional flow reserve in real patients, and could be a viable option if trained using a large enough data set of real patients.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0954411920946526; doi:https://doi.org/10.1177/0954411920946526; html:https://europepmc.org/articles/PMC7675765; pdf:https://europepmc.org/articles/PMC7675765?pdf=render
+34799365,https://doi.org/10.1136/bmjopen-2021-054861,Retrospective cohort study to evaluate medication use in patients hospitalised with COVID-19 in Scotland: protocol for a national observational study.,"Mueller T, Kerr S, McTaggart S, Kurdi A, Vasileiou E, Docherty A, Fraser K, Shi T, Simpson CR, Bennie M, Sheikh A.",,BMJ open,2021,2021-11-19,Y,Therapeutics; clinical pharmacology; Covid-19,,,"<h4>Introduction</h4>COVID-19 has caused millions of hospitalisations and deaths globally. A range of vaccines have been developed and are being deployed at scale in the UK to prevent SARS-CoV-2 infection, which have reduced risk of infection and severe COVID-19 outcomes. Those with COVID-19 are now being treated with several repurposed drugs based on evidence emerging from recent clinical trials. However, there is currently limited real-world data available related to the use of these drugs in routine clinical practice. The purpose of this study is to address the prevailing knowledge gaps regarding the use of dexamethasone, remdesivir and tocilizumab by conducting an exploratory drug utilisation study, aimed at providing in-depth descriptions of patients receiving these drugs as well as the treatment patterns observed in Scotland.<h4>Methods and analysis</h4>Retrospective cohort study, comprising adult patients admitted to hospital with confirmed or suspected COVID-19 across five Scottish Health Boards using data from in-hospital ePrescribing linked to the Early Estimation of Vaccine and Anti-Viral Effectiveness (EAVE II) COVID-19 surveillance platform. The primary outcome will be exposure to the medicines of interest (dexamethasone, remdesivir, tocilizumab), either alone or in combination; exposure will be described in terms of drug(s) of choice; prescribed and administered dose; treatment duration; and any changes in treatment, for example, dose escalation and/or switching to an alternative drug. Analyses will primarily be descriptive in nature.<h4>Ethics and dissemination</h4>Ethical and information governance approvals have been obtained by the National Research Ethics Service Committee, South East Scotland 02 and the Public Benefit and Privacy Panel for Health and Social Care, respectively. Findings from this study will be presented at academic and clinical conferences, and to the funders and other interested parties as appropriate; study findings will also be published in peer-reviewed journals. Publications will be available on the EAVE II website (https://www.ed.ac.uk/usher/eave-ii/key-outputs/our-publications), alongside lay summaries and infographics aimed at the general public. Press releases will also be considered, if appropriate.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e054861.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054861; html:https://europepmc.org/articles/PMC8609490; pdf:https://europepmc.org/articles/PMC8609490?pdf=render
 36000189,https://doi.org/10.1515/dx-2022-0052,The diagnostic potential and barriers of microbiome based therapeutics.,"Acharjee A, Singh U, Choudhury SP, Gkoutos GV.",,"Diagnosis (Berlin, Germany)",2022,2022-08-25,N,Microbiota; Biomarker; Diagnostics; Machine Learning,,,"High throughput technological innovations in the past decade have accelerated research into the trillions of commensal microbes in the gut. The 'omics' technologies used for microbiome analysis are constantly evolving, and large-scale datasets are being produced. Despite of the fact that much of the research is still in its early stages, specific microbial signatures have been associated with the promotion of cancer, as well as other diseases such as inflammatory bowel disease, neurogenerative diareses etc. It has been also reported that the diversity of the gut microbiome influences the safety and efficacy of medicines. The availability and declining sequencing costs has rendered the employment of RNA-based diagnostics more common in the microbiome field necessitating improved data-analytical techniques so as to fully exploit all the resulting rich biological datasets, while accounting for their unique characteristics, such as their compositional nature as well their heterogeneity and sparsity. As a result, the gut microbiome is increasingly being demonstrating as an important component of personalised medicine since it not only plays a role in inter-individual variability in health and disease, but it also represents a potentially modifiable entity or feature that may be addressed by treatments in a personalised way. In this context, machine learning and artificial intelligence-based methods may be able to unveil new insights into biomedical analyses through the generation of models that may be used to predict category labels, and continuous values. Furthermore, diagnostic aspects will add value in the identification of the non invasive markers in the critical diseases like cancer.",,pdf:https://www.degruyter.com/document/doi/10.1515/dx-2022-0052/pdf; doi:https://doi.org/10.1515/dx-2022-0052
 34911741,https://doi.org/10.1136/heartjnl-2021-320047,Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19.,"Norris T, Razieh C, Zaccardi F, Yates T, Islam N, Gillies CL, Chudasama YV, Rowlands AV, Davies MJ, McCann GP, Banerjee A, Lam CSP, Docherty AB, Openshaw PJ, Baillie JK, Semple MG, Lawson CA, Khunti K, ISARIC4C investigators.",,Heart (British Cardiac Society),2022,2022-07-13,Y,epidemiology; risk factors; Covid-19,,,"<h4>Objective</h4>Using a large national database of people hospitalised with COVID-19, we investigated the contribution of cardio-metabolic conditions, multi-morbidity and ethnicity on the risk of in-hospital cardiovascular complications and death.<h4>Methods</h4>A multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 6 February 2020 and 16 March 2021. Logistic models were used to explore associations between baseline patient ethnicity, cardiometabolic conditions and multimorbidity (0, 1, 2, >2 conditions), and in-hospital cardiovascular complications (heart failure, arrhythmia, cardiac ischaemia, cardiac arrest, coagulation complications, stroke), renal injury and death.<h4>Results</h4>Of 65 624 patients hospitalised with COVID-19, 44 598 (68.0%) reported at least one cardiometabolic condition on admission. Cardiovascular/renal complications or death occurred in 24 609 (38.0%) patients. Baseline cardiometabolic conditions were independently associated with increased odds of in-hospital complications and this risk increased in the presence of cardiometabolic multimorbidity. For example, compared with having no cardiometabolic conditions, 1, 2 or ≥3 conditions was associated with 1.46 (95% CI 1.39 to 1.54), 2.04 (95% CI 1.93 to 2.15) and 3.10 (95% CI 2.92 to 3.29) times higher odds of any cardiovascular/renal complication, respectively. A similar pattern was observed for all-cause death. Compared with the white group, the South Asian (OR 1.19, 95% CI 1.10 to 1.29) and black (OR 1.53 to 95% CI 1.37 to 1.72) ethnic groups had higher risk of any cardiovascular/renal complication.<h4>Conclusions</h4>In hospitalised patients with COVID-19, cardiovascular complications or death impacts just under half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidity.",,pdf:https://heart.bmj.com/content/heartjnl/108/15/1200.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-320047; html:https://europepmc.org/articles/PMC8678560; pdf:https://europepmc.org/articles/PMC8678560?pdf=render
 35140406,https://doi.org/10.1038/s41591-022-01701-w,Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil.,"Cerqueira-Silva T, Katikireddi SV, de Araujo Oliveira V, Flores-Ortiz R, Júnior JB, Paixão ES, Robertson C, Penna GO, Werneck GL, Barreto ML, Pearce N, Sheikh A, Barral-Netto M, Boaventura VS.",,Nature medicine,2022,2022-02-09,Y,,,,"There is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14-30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3-55.7) against confirmed infection and 82.1% (95% CI: 81.4-82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1-36.2) against infection and 72.5% (95% CI: 70.9-74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0-94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1-98.1) 14-30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly.",,pdf:https://www.nature.com/articles/s41591-022-01701-w.pdf; doi:https://doi.org/10.1038/s41591-022-01701-w; html:https://europepmc.org/articles/PMC9018414; pdf:https://europepmc.org/articles/PMC9018414?pdf=render
@@ -163,8 +163,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 36178783,https://doi.org/10.1167/tvst.11.9.34,Phenotyping of ABCA4 Retinopathy by Machine Learning Analysis of Full-Field Electroretinography.,"Glinton SL, Calcagni A, Lilaonitkul W, Pontikos N, Vermeirsch S, Zhang G, Arno G, Wagner SK, Michaelides M, Keane PA, Webster AR, Mahroo OA, Robson AG.",,Translational vision science & technology,2022,2022-09-01,Y,,,,"<h4>Purpose</h4>Biallelic pathogenic variants in ABCA4 are the commonest cause of monogenic retinal disease. The full-field electroretinogram (ERG) quantifies severity of retinal dysfunction. We explored application of machine learning in ERG interpretation and in genotype-phenotype correlations.<h4>Methods</h4>International standard ERGs in 597 cases of ABCA4 retinopathy were classified into three functional phenotypes by human experts: macular dysfunction alone (group 1), or with additional generalized cone dysfunction (group 2), or both cone and rod dysfunction (group 3). Algorithms were developed for automatic selection and measurement of ERG components and for classification of ERG phenotype. Elastic-net regression was used to quantify severity of specific ABCA4 variants based on effect on retinal function.<h4>Results</h4>Of the cohort, 57.6%, 7.4%, and 35.0% fell into groups 1, 2, and 3 respectively. Compared with human experts, automated classification showed overall accuracy of 91.8% (SE, 0.169), and 96.7%, 39.3%, and 93.8% for groups 1, 2, and 3. When groups 2 and 3 were combined, the average holdout group accuracy was 93.6% (SE, 0.142). A regression model yielded phenotypic severity scores for the 47 commonest ABCA4 variants.<h4>Conclusions</h4>This study quantifies prevalence of phenotypic groups based on retinal function in a uniquely large single-center cohort of patients with electrophysiologically characterized ABCA4 retinopathy and shows applicability of machine learning. Novel regression-based analyses of ABCA4 variant severity could identify individuals predisposed to severe disease.<h4>Translational relevance</h4>Machine learning can yield meaningful classifications of ERG data, and data-driven scoring of genetic variants can identify patients likely to benefit most from future therapies.",,doi:https://doi.org/10.1167/tvst.11.9.34; doi:https://doi.org/10.1167/tvst.11.9.34; html:https://europepmc.org/articles/PMC9527330; pdf:https://europepmc.org/articles/PMC9527330?pdf=render
 36441117,https://doi.org/10.1111/acps.13523,Predictors of hospital readmission for patients diagnosed with delirium: An electronic health record data analysis.,"Friedrich ME, Perera G, Leutgeb L, Haardt D, Frey R, Stewart R, Mueller C.",,Acta psychiatrica Scandinavica,2023,2022-12-28,Y,Dementia; risk factors; Delirium; Readmission,,,"<h4>Introduction</h4>Delirium is an acute and fluctuating change in attention and cognition that increases the risk of functional decline, institutionalisation and death in hospitalised patients. After delirium, patients have a significantly higher risk of readmission to hospital. Our aim was to investigate factors associated with hospital readmission in people with delirium.<h4>Methods</h4>We carried out an observational retrospective cohort study using linked mental health care and hospitalisation records from South London. Logistic regression models were used to predict the odds of 30-day readmission and Cox proportional hazard models to calculate readmission risks when not restricting follow-up time.<h4>Results</h4>Of 2814 patients (mean age 78.9 years SD ±11.8) discharged from hospital after an episode of delirium, 823 (29.3%) were readmitted within 30 days. Depressed mood (odds ratio (OR) 1.34 (95% confidence interval (CI) 1.08-1.66)), moderate-to-severe physical health problems (OR 1.67 (95% CI 1.18-2.2.36)) and a history of serious circulatory disease (OR 1.29 (95% CI 1.07-1.55)) were associated with higher odds of hospital readmission, whereas a diagnosis of delirium superimposed on dementia (OR 0.67 (95% CI 0.53-0.84)) and problematic alcohol/substance (OR 0.54 (95% CI 0.33-0.89)) use were associated with lower odds. Cox proportionate hazard models showed similar results.<h4>Conclusion</h4>Almost one-third of patients with delirium were readmitted within a short period of time, a more detailed understanding of the underlying risk factors could help prevent readmissions. Our findings indicate that the aetiology (as alcohol-related delirium), the recognition that delirium occurred in the context of dementia, as well as potentially modifiable factors, as depressed mood affect readmission risk, and should be assessed in clinical settings.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acps.13523; doi:https://doi.org/10.1111/acps.13523; html:https://europepmc.org/articles/PMC10463092; pdf:https://europepmc.org/articles/PMC10463092?pdf=render
 36369151,https://doi.org/10.1038/s41467-022-34244-2,"Variant-specific symptoms of COVID-19 in a study of 1,542,510 adults in England.","Whitaker M, Elliott J, Bodinier B, Barclay W, Ward H, Cooke G, Donnelly CA, Chadeau-Hyam M, Elliott P.",,Nature communications,2022,2022-11-11,Y,,,,"Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study monitored the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell or taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and effects on daily activities will become increasingly important.",,pdf:https://www.nature.com/articles/s41467-022-34244-2.pdf; doi:https://doi.org/10.1038/s41467-022-34244-2; html:https://europepmc.org/articles/PMC9651890; pdf:https://europepmc.org/articles/PMC9651890?pdf=render
-36997856,https://doi.org/10.1186/s12882-023-03126-0,A clinical frailty scale obtained from MDT discussion performs poorly in assessing frailty in haemodialysis recipients.,"Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,BMC nephrology,2023,2023-03-30,Y,Mortality; Frailty; Haemodialysis; Hospitalisation; Clinical Frailty Scale,,,"<h4>Background</h4>The Clinical Frailty Scale (CFS) is a commonly utilised frailty screening tool that has been associated with hospitalisation and mortality in haemodialysis recipients, but is subject to heterogenous methodologies including subjective clinician opinion. The aims of this study were to (i) examine the accuracy of a subjective, multidisciplinary assessment of CFS at haemodialysis Quality Assurance (QA) meetings (CFS-MDT), compared with a standard CFS score via clinical interview, and (ii) ascertain the associations of these scores with hospitalisation and mortality.<h4>Methods</h4>We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalisation. Frailty was assessed using the CFS after structured clinical interview. The CFS-MDT was derived from consensus at haemodialysis QA meetings, involving dialysis nurses, dietitians, and nephrologists.<h4>Results</h4>453 participants were followed-up for a median of 685 days (IQR 544-812), during which there were 96 (21.2%) deaths and 1136 hospitalisations shared between 327 (72.1%) participants. Frailty was identified in 246 (54.3%) participants via CFS, but only 120 (26.5%) via CFS-MDT. There was weak correlation (Spearman Rho 0.485, P < 0.001) on raw frailty scores and minimal agreement (Cohen's κ = 0.274, P < 0.001) on categorisation of frail, vulnerable and robust between the CFS and CFS-MDT. Increasing frailty was associated with higher rates of hospitalisation for the CFS (IRR 1.26, 95% C.I. 1.17-1.36, P = 0.016) and CFS-MDT (IRR 1.10, 1.02-1.19, P = 0.02), but only the CFS-MDT was associated with nights spent in hospital (IRR 1.22, 95% C.I. 1.08-1.38, P = 0.001). Both scores were associated with mortality (CFS HR 1.31, 95% C.I. 1.09-1.57, P = 0.004; CFS-MDT HR 1.36, 95% C.I. 1.16-1.59, P < 0.001).<h4>Conclusions</h4>Assessment of CFS is deeply affected by the underlying methodology, with the potential to profoundly affect decision-making. The CFS-MDT appears to be a weak alternative to conventional CFS. Standardisation of CFS use is of paramount importance in clinical and research practice in haemodialysis.<h4>Trial registration</h4>Clinicaltrials.gov : NCT03071107 registered 06/03/2017.",,pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-023-03126-0; doi:https://doi.org/10.1186/s12882-023-03126-0; html:https://europepmc.org/articles/PMC10062243; pdf:https://europepmc.org/articles/PMC10062243?pdf=render
 36426419,https://doi.org/10.1111/hsc.14109,"""I don't mean to be rude, but could you put a mask on while I'm here?"" A qualitative study of risks experienced by domiciliary care workers in Wales during the COVID-19 pandemic. ","Prout H, Lugg-Widger FV, Brookes-Howell L, Cannings-John R, Akbari A, John A, Thomas DR, Robling M.",,Health & social care in the community,2022,2022-11-24,Y,,,,"Domiciliary care workers (DCWs) continued to provide care to adults in their own homes throughout the COVID-19 pandemic. The evidence of the impact of COVID-19 on health outcomes of DCWs is currently mixed. The OSCAR study will quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, explore causes of variation and extrapolate to the rest of the UK DCW population. An embedded qualitative study aimed to explore DCW experiences during the pandemic, including factors that may have varied risk of exposure to COVID-19 and adverse health and wellbeing outcomes. Registered DCWs working throughout Wales were invited to participate in a semi-structured telephone interview. 24 DCWs were interviewed between February and July 2021. Themes were identified through inductive analysis using thematic coding. Several themes emerged relating to risk of exposure to COVID-19. First, general changes to the role of the DCW during the pandemic were identified. Second, practical challenges for DCWs in the workplace were reported, including staff shortages, clients and families not following safety procedures, initial shortages of personal protective equipment (PPE), DCW criticism of standard use PPE, client difficulty with PPE and management of rapid antigen testing. Third, lack of government/employer preparation for a pandemic was described, including the reorganisation of staff clients and services, inadequate or confusing information for many DCWs, COVID-19 training and the need for improved practical instruction and limited official standard risk assessments for DCWs. Pressure to attend work and perceptions of COVID-19 risk and vaccination was also reported. In summary, this paper describes the risk factors associated with working during the pandemic. We have mapped recommendations for each problem using these qualitative findings including tailored training and better support for isolated team members and identified the required changes at several socio-ecological levels.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/hsc.14109; doi:https://doi.org/10.1111/hsc.14109; html:https://europepmc.org/articles/PMC10100139; pdf:https://europepmc.org/articles/PMC10100139?pdf=render
+36997856,https://doi.org/10.1186/s12882-023-03126-0,A clinical frailty scale obtained from MDT discussion performs poorly in assessing frailty in haemodialysis recipients.,"Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,BMC nephrology,2023,2023-03-30,Y,Mortality; Frailty; Haemodialysis; Hospitalisation; Clinical Frailty Scale,,,"<h4>Background</h4>The Clinical Frailty Scale (CFS) is a commonly utilised frailty screening tool that has been associated with hospitalisation and mortality in haemodialysis recipients, but is subject to heterogenous methodologies including subjective clinician opinion. The aims of this study were to (i) examine the accuracy of a subjective, multidisciplinary assessment of CFS at haemodialysis Quality Assurance (QA) meetings (CFS-MDT), compared with a standard CFS score via clinical interview, and (ii) ascertain the associations of these scores with hospitalisation and mortality.<h4>Methods</h4>We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalisation. Frailty was assessed using the CFS after structured clinical interview. The CFS-MDT was derived from consensus at haemodialysis QA meetings, involving dialysis nurses, dietitians, and nephrologists.<h4>Results</h4>453 participants were followed-up for a median of 685 days (IQR 544-812), during which there were 96 (21.2%) deaths and 1136 hospitalisations shared between 327 (72.1%) participants. Frailty was identified in 246 (54.3%) participants via CFS, but only 120 (26.5%) via CFS-MDT. There was weak correlation (Spearman Rho 0.485, P < 0.001) on raw frailty scores and minimal agreement (Cohen's κ = 0.274, P < 0.001) on categorisation of frail, vulnerable and robust between the CFS and CFS-MDT. Increasing frailty was associated with higher rates of hospitalisation for the CFS (IRR 1.26, 95% C.I. 1.17-1.36, P = 0.016) and CFS-MDT (IRR 1.10, 1.02-1.19, P = 0.02), but only the CFS-MDT was associated with nights spent in hospital (IRR 1.22, 95% C.I. 1.08-1.38, P = 0.001). Both scores were associated with mortality (CFS HR 1.31, 95% C.I. 1.09-1.57, P = 0.004; CFS-MDT HR 1.36, 95% C.I. 1.16-1.59, P < 0.001).<h4>Conclusions</h4>Assessment of CFS is deeply affected by the underlying methodology, with the potential to profoundly affect decision-making. The CFS-MDT appears to be a weak alternative to conventional CFS. Standardisation of CFS use is of paramount importance in clinical and research practice in haemodialysis.<h4>Trial registration</h4>Clinicaltrials.gov : NCT03071107 registered 06/03/2017.",,pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-023-03126-0; doi:https://doi.org/10.1186/s12882-023-03126-0; html:https://europepmc.org/articles/PMC10062243; pdf:https://europepmc.org/articles/PMC10062243?pdf=render
 35024157,https://doi.org/10.1177/20552076211059350,Digitally enabled flash glucose monitoring for inpatients with COVID-19: Feasibility and pilot implementation in a teaching NHS Hospital in the UK.,"Robbins T, Hopper A, Brophy J, Pearson E, Suthantirakumar R, Vankad M, Igharo N, Baitule S, Clark CC, Arvanitis TN, Sankar S, Kyrou I, Randeva H.",,Digital health,2022,2022-01-07,Y,Diabetes; Inpatient Care; Digital Health; Covid-19; Flash Glucose Monitoring,,,"<h4>Background</h4>COVID-19 placed significant challenges on healthcare systems. People with diabetes are at high risk of severe COVID-19 with poor outcomes. We describe the first reported use of inpatient digital flash glucose monitoring devices in a UK NHS hospital to support management of people with diabetes hospitalized for COVID-19.<h4>Methods</h4>Inpatients at University Hospitals Coventry & Warwickshire (UHCW) NHS Trust with COVID-19 and diabetes were considered for digitally enabled flash glucose monitoring during their hospitalization. Glucose monitoring data were analysed, and potential associations were explored between relevant parameters, including time in hypoglycaemia, hyperglycaemia, and in range, glycated haemoglobin (HbA1c), average glucose, body mass index (BMI), and length of stay.<h4>Results</h4>During this pilot, digital flash glucose monitoring devices were offered to 25 inpatients, of whom 20 (type 2/type 1: 19/1; mean age: 70.6 years; mean HbA1c: 68.2 mmol/mol; mean BMI: 28.2 kg/m<sup>2</sup>) accepted and used these (80% uptake). In total, over 2788 h of flash glucose monitoring were recorded for these inpatients with COVID-19 and diabetes. Length of stay was not associated with any of the studied variables (all p-values >0.05). Percentage of time in hyperglycaemia exhibited significant associations with both percentage of time in hypoglycaemia and percentage of time in range, as well as with HbA1c (all p-values <0.05). The average glucose was significantly associated with percentage of time in hypoglycaemia, percentage of time in range, and HbA1c (all p-values <0.05).<h4>Discussion</h4>We report the first pilot inpatient use of digital flash glucose monitors in an NHS hospital to support care of inpatients with diabetes and COVID-19. Overall, there are strong arguments for the inpatient use of these devices in the COVID-19 setting, and the findings of this pilot demonstrate feasibility of this digitally enabled approach and support wider use for inpatients with diabetes and COVID-19.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/20552076211059350; doi:https://doi.org/10.1177/20552076211059350; html:https://europepmc.org/articles/PMC8744149; pdf:https://europepmc.org/articles/PMC8744149?pdf=render
 36139476,https://doi.org/10.3390/cells11182901,Dysregulated Neutrophil Phenotype and Function in Hospitalised Non-ICU COVID-19 Pneumonia.,"Belchamber KBR, Thein OS, Hazeldine J, Grudzinska FS, Faniyi AA, Hughes MJ, Jasper AE, Yip KP, Crowley LE, Lugg ST, Sapey E, Parekh D, Thickett DR, Scott A.",,Cells,2022,2022-09-16,Y,Inflammation; neutrophil; innate immunity; Covid-19,,,"<b>Rationale</b>: Infection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based on transcriptomics or single functional assays. Cell functions are interwoven pathways, and understanding the effect across the spectrum of neutrophil function may identify therapeutic targets. <b>Objectives</b>: Examine neutrophil phenotype and function in 41 hospitalised, non-ICU COVID-19 patients versus 23 age-matched controls (AMC) and 26 community acquired pneumonia patients (CAP). <b>Methods</b>: Isolated neutrophils underwent ex vivo analyses for migration, bacterial phagocytosis, ROS generation, NETosis and receptor expression. Circulating DNAse 1 activity, levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI were measured and correlated to clinical outcome. Serial sampling on day three to five post hospitalization were also measured. The effect of ex vivo PI3K inhibition was measured in a further cohort of 18 COVID-19 patients. <b>Results</b>: Compared to AMC and CAP, COVID-19 neutrophils demonstrated elevated transmigration (<i>p</i> = 0.0397) and NETosis (<i>p</i> = 0.0332), and impaired phagocytosis (<i>p</i> = 0.0036) associated with impaired ROS generation (<i>p</i> < 0.0001). The percentage of CD54+ neutrophils (<i>p</i> < 0.001) was significantly increased, while surface expression of CD11b (<i>p</i> = 0.0014) and PD-L1 (<i>p</i> = 0.006) were significantly decreased in COVID-19. COVID-19 and CAP patients showed increased systemic markers of NETosis including increased cfDNA (<i>p</i> = 0.0396) and impaired DNAse activity (<i>p</i> < 0.0001). The ex vivo inhibition of PI3K γ and δ reduced NET release by COVID-19 neutrophils (<i>p</i> = 0.0129). <b>Conclusions</b>: COVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration and NETosis, and impaired antimicrobial responses. These changes highlight that targeting neutrophil function may help modulate COVID-19 severity.",,pdf:https://www.mdpi.com/2073-4409/11/18/2901/pdf?version=1663743438; doi:https://doi.org/10.3390/cells11182901; html:https://europepmc.org/articles/PMC9496854; pdf:https://europepmc.org/articles/PMC9496854?pdf=render
 34430954,https://doi.org/10.1016/s2666-7568(21)00168-9,Profile of humoral and cellular immune responses to single doses of BNT162b2 or ChAdOx1 nCoV-19 vaccines in residents and staff within residential care homes (VIVALDI): an observational study.,"Tut G, Lancaster T, Krutikov M, Sylla P, Bone D, Kaur N, Spalkova E, Bentley C, Amin U, Jadir AT, Hulme S, Butler MS, Ayodele M, Bruton R, Shrotri M, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,The lancet. Healthy longevity,2021,2021-08-19,Y,,,,"<h4>Background</h4>Residents of long-term care facilities (LTCFs) have been prioritised for COVID-19 vaccination because of the high COVID-19 mortality in this population. Several countries have implemented an extended interval of up to 12 weeks between the first and second vaccine doses to increase population coverage of single-dose vaccination. We aimed to assess the magnitude and quality of adaptive immune responses following a single dose of COVID-19 vaccine in LTCF residents and staff.<h4>Methods</h4>From the LTCFs participating in the ongoing VIVALDI study (ISRCTN14447421), staff and residents who had received a first dose of COVID-19 vaccine (BNT162b2 [tozinameran] or ChAdOx1 nCoV-19), had pre-vaccination and post-vaccination blood samples (collected between Dec 11, 2020, and Feb 16, 2021), and could be linked to a pseudoidentifier in the COVID-19 Data Store were included in our cohort. Past infection with SARS-CoV-2 was defined on the basis of nucleocapsid-specific IgG antibodies being detected through a semiquantitative immunoassay, and participants who tested positive on this assay after but not before vaccination were excluded from the study. Processed blood samples were assessed for spike-specific immune responses, including spike-specific IgG antibody titres, T-cell responses to spike protein peptide mixes, and inhibition of ACE2 binding by spike protein from four variants of SARS-CoV-2 (the original strain as well as the B.1.1.7, B.1.351, and P.1 variants). Responses before and after vaccination were compared on the basis of age, previous infection status, role (staff or resident), and time since vaccination.<h4>Findings</h4>Our cohort comprised 124 participants from 14 LTCFs: 89 (72%) staff (median age 48 years [IQR 35·5-56]) and 35 (28%) residents (87 years [77-90]). Blood samples were collected a median 40 days (IQR 25-47; range 6-52) after vaccination. 30 (24%) participants (18 [20%] staff and 12 [34%] residents) had serological evidence of previous SARS-CoV-2 infection. All participants with previous infection had high antibody titres following vaccination that were independent of age (<i>r</i> <sub>s</sub>=0·076, p=0·70). In participants without evidence of previous infection, titres were negatively correlated with age (<i>r</i> <sub>s</sub>=-0·434, p<0·0001) and were 8·2-times lower in residents than in staff. This effect appeared to result from a kinetic delay antibody generation in older infection-naive participants, with the negative age correlation disappearing only in samples taken more than 42 days post-vaccination (<i>r</i> <sub>s</sub>=-0·207, p=0·20; n=40), in contrast to samples taken after 0-21 days (<i>r</i> <sub>s</sub>=-0·774, p=0·0043; n=12) or 22-42 days (<i>r</i> <sub>s</sub>=-0·437, p=0·0034; n=43). Spike-specific cellular responses were similar between older and younger participants. In infection-naive participants, antibody inhibition of ACE2 binding by spike protein from the original SARS-CoV-2 strain was negatively correlated with age (<i>r</i> <sub>s</sub>=-0·439, p<0·0001), and was significantly lower against spike protein from the B.1.351 variant (median inhibition 31% [14-100], p=0·010) and the P.1 variant (23% [14-97], p<0·0001) than against the original strain (58% [27-100]). By contrast, a single dose of vaccine resulted in around 100% inhibition of the spike-ACE2 interaction against all variants in people with a history of infection.<h4>Interpretation</h4>History of SARS-CoV-2 infection impacts the magnitude and quality of antibody response after a single dose of COVID-19 vaccine in LTCF residents. Residents who are infection-naive have delayed antibody responses to the first dose of vaccine and should be considered for an early second dose where possible.<h4>Funding</h4>UK Government Department of Health and Social Care.",,pdf:https://discovery.ucl.ac.uk/10133388/1/1-s2.0-S2666756821001689-main.pdf; doi:https://doi.org/10.1016/S2666-7568(21)00168-9; html:https://europepmc.org/articles/PMC8376213
@@ -181,11 +181,11 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 37429634,https://doi.org/10.3399/bjgpo.2023.0057,UK research data resources based on primary care electronic health records: review and summary for potential users.,"Edwards L, Pickett J, Ashcroft DM, Dambha-Miller H, Majeed A, Mallen C, Petersen I, Qureshi N, van Staa T, Abel G, Carvalho C, Denholm R, Kontopantelis E, Macaulay A, Macleod J.",,BJGP open,2023,2023-09-19,N,Population; Primary Health Care; Electronic Health Records; Primary Care Databases; Population Level Linked Data,,,"<h4>Background</h4>The range and scope of electronic health record (EHR) data assets in the UK has recently increased, which has been mainly in response to the COVID-19 pandemic. Summarising and comparing the large primary care resources will help researchers to choose the data resources most suited to their needs.<h4>Aim</h4>To describe the current landscape of UK EHR databases and considerations of access and use of these resources relevant to researchers.<h4>Design & setting</h4>Narrative review of EHR databases in the UK.<h4>Method</h4>Information was collected from the Health Data Research Innovation Gateway, publicly available websites and other published data, and from key informants. The eligibility criteria were population-based open-access databases sampling EHRs across the whole population of one or more countries in the UK. Published database characteristics were extracted and summarised, and these were corroborated with resource providers. Results were synthesised narratively.<h4>Results</h4>Nine large national primary care EHR data resources were identified and summarised. These resources are enhanced by linkage to other administrative data to a varying extent. Resources are mainly intended to support observational research, although some can support experimental studies. There is considerable overlap of populations covered. While all resources are accessible to bona fide researchers, access mechanisms, costs, timescales, and other considerations vary across databases.<h4>Conclusion</h4>Researchers are currently able to access primary care EHR data from several sources. Choice of data resource is likely to be driven by project needs and access considerations. The landscape of data resources based on primary care EHRs in the UK continues to evolve.",,doi:https://doi.org/10.3399/bjgpo.2023.0057; doi:https://doi.org/10.3399/BJGPO.2023.0057
 37363696,https://doi.org/10.1155/2023/5885059,Gender Disparity in Expression of Sarcopenia in Haemodialysis Recipients: Analysis from the FITNESS Cohort.,"Anderson BM, Wilson DV, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,International journal of nephrology,2023,2023-06-17,Y,,,,"<h4>Background</h4>There has been little exploration of the interplay between sarcopenia and frailty in haemodialysis, particularly regarding gender difference. We aimed to (1) assess whether ultrasound-derived low muscle mass (LMM) and sarcopenia are more common in male or female haemodialysis recipients; (2) assess whether age influences any observed gender difference, and (3) explore the interplay between sarcopenia, frailty, and gender in haemodialysis recipients.<h4>Methods</h4>This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis with frailty phenotype (FP) scores. Bilateral anterior thigh thickness (BATT) was obtained according to an established ultrasound protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, LMM, and sarcopenia with a priori covariables, stratified by gender.<h4>Results</h4>In total of 223 studies, participants had ultrasound measurements. Males showed greater prevalence of LMM. On adjusted analyses, LMM was associated with lower hand grip strength in males (<i>β</i> = -4.17; 95% C.I. -7.57 to -0.77; <i>P</i>=0.02), but not females (<i>β</i> = -1.88; 95% C.I. -5.41 to 1.64; <i>P</i>=0.29). LMM was also associated with slower walking speed in both males (<i>β</i> = -0.115; 95% C.I. -0.258 to -0.013; <i>P</i>=0.03) and females (<i>β</i> = -0.152; 95% C.I. -0.300 to -0.005; <i>P</i>=0.04). Sarcopenia was associated with greater odds of frailty on adjusted models in males (OR = 9.86; 95% C.I. 1.8 to 54.0; <i>P</i>=0.01), but not females (OR = 5.16; 95% C.I. 0.22 to 124; <i>P</i>=0.31).<h4>Conclusions</h4>The clinical expression and significance of sarcopenia differ substantially between males and females on haemodialysis. Further work is required to elucidate underlying mechanisms and guide tailored treatment.",,doi:https://doi.org/10.1155/2023/5885059; html:https://europepmc.org/articles/PMC10290558; pdf:https://europepmc.org/articles/PMC10290558?pdf=render
 37586846,https://doi.org/10.1136/openhrt-2023-002378,Cardiovascular imaging research priorities.,"MacArthur JAL, Yong GL, Dweck MR, Fairbairn TA, Weir-McCall J, Puyol-Antón E, Meldrum J, Blakelock P, Khan S, Morrice L, Sudlow CLM, Williams MC.",,Open heart,2023,2023-08-01,Y,Health Services; Research Design; Diagnostic Imaging,,,"<h4>Objectives</h4>Two interlinked surveys were organised by the British Heart Foundation Data Science Centre, which aimed to establish national priorities for cardiovascular imaging research.<h4>Methods</h4>First a single time point public survey explored their views of cardiovascular imaging research. Subsequently, a three-phase modified Delphi prioritisation exercise was performed by researchers and healthcare professionals. Research questions were submitted by a diverse range of stakeholders to the question 'What are the most important research questions that cardiovascular imaging should be used to address?'. Of these, 100 research questions were prioritised based on their positive impact for patients. The 32 highest rated questions were further prioritised based on three domains: positive impact for patients, potential to reduce inequalities in healthcare and ability to be implemented into UK healthcare practice in a timely manner.<h4>Results</h4>The public survey was completed by 354 individuals, with the highest rated areas relating to improving treatment, quality of life and diagnosis. In the second survey, 506 research questions were submitted by diverse stakeholders. Prioritisation was performed by 90 researchers or healthcare professionals in the first round and 64 in the second round. The highest rated questions were 'How do we ensure patients have equal access to cardiovascular imaging when it is needed?' and 'How can we use cardiovascular imaging to avoid invasive procedures'. There was general agreement between healthcare professionals and researchers regarding priorities for the positive impact for patients and least agreement for their ability to be implemented into UK healthcare practice in a timely manner. There was broad overlap between the prioritised research questions and the results of the public survey.<h4>Conclusions</h4>We have identified priorities for cardiovascular imaging research, incorporating the views of diverse stakeholders. These priorities will be useful for researchers, funders and other organisations planning future research.",,doi:https://doi.org/10.1136/openhrt-2023-002378; html:https://europepmc.org/articles/PMC10432634; pdf:https://europepmc.org/articles/PMC10432634?pdf=render
-36417468,https://doi.org/10.1371/journal.pcbi.1010724,"Trends in SARS-CoV-2 infection prevalence during England's roadmap out of lockdown, January to July 2021.","Eales O, Wang H, Haw D, Ainslie KEC, Walters CE, Atchison C, Cooke G, Barclay W, Ward H, Darzi A, Ashby D, Donnelly CA, Elliott P, Riley S.",,PLoS computational biology,2022,2022-11-23,Y,,,,"<h4>Background</h4>Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards.<h4>Aim</h4>We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence.<h4>Methods</h4>On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions.<h4>Results</h4>Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was offset by the effects of vaccination and also affected by the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups.<h4>Conclusion</h4>High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was effective at reducing risk of infection with school holidays/closures playing a significant part.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010724&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010724; html:https://europepmc.org/articles/PMC9728904; pdf:https://europepmc.org/articles/PMC9728904?pdf=render
 35155637,https://doi.org/10.3389/fcvm.2022.822269,Generalizable Framework for Atrial Volume Estimation for Cardiac CT Images Using Deep Learning With Quality Control Assessment.,"Abdulkareem M, Brahier MS, Zou F, Taylor A, Thomaides A, Bergquist PJ, Srichai MB, Lee AM, Vargas JD, Petersen SE.",,Frontiers in cardiovascular medicine,2022,2022-01-28,Y,Quality control; CT; Left Atrial Volume; Left Atrium; Deep Learning,,,"<h4>Objectives</h4>Cardiac computed tomography (CCT) is a common pre-operative imaging modality to evaluate pulmonary vein anatomy and left atrial appendage thrombus in patients undergoing catheter ablation (CA) for atrial fibrillation (AF). These images also allow for full volumetric left atrium (LA) measurement for recurrence risk stratification, as larger LA volume (LAV) is associated with higher recurrence rates. Our objective is to apply deep learning (DL) techniques to fully automate the computation of LAV and assess the quality of the computed LAV values.<h4>Methods</h4>Using a dataset of 85,477 CCT images from 337 patients, we proposed a framework that consists of several processes that perform a combination of tasks including the selection of images with LA from all other images using a ResNet50 classification model, the segmentation of images with LA using a UNet image segmentation model, the assessment of the quality of the image segmentation task, the estimation of LAV, and quality control (QC) assessment.<h4>Results</h4>Overall, the proposed LAV estimation framework achieved accuracies of 98% (precision, recall, and F1 score metrics) in the image classification task, 88.5% (mean dice score) in the image segmentation task, 82% (mean dice score) in the segmentation quality prediction task, and <i>R</i> <sup>2</sup> (the coefficient of determination) value of 0.968 in the volume estimation task. It correctly identified 9 out of 10 poor LAV estimations from a total of 337 patients as poor-quality estimates.<h4>Conclusions</h4>We proposed a generalizable framework that consists of DL models and computational methods for LAV estimation. The framework provides an efficient and robust strategy for QC assessment of the accuracy for DL-based image segmentation and volume estimation tasks, allowing high-throughput extraction of reproducible LAV measurements to be possible.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.822269/pdf; doi:https://doi.org/10.3389/fcvm.2022.822269; html:https://europepmc.org/articles/PMC8831539; pdf:https://europepmc.org/articles/PMC8831539?pdf=render
+36417468,https://doi.org/10.1371/journal.pcbi.1010724,"Trends in SARS-CoV-2 infection prevalence during England's roadmap out of lockdown, January to July 2021.","Eales O, Wang H, Haw D, Ainslie KEC, Walters CE, Atchison C, Cooke G, Barclay W, Ward H, Darzi A, Ashby D, Donnelly CA, Elliott P, Riley S.",,PLoS computational biology,2022,2022-11-23,Y,,,,"<h4>Background</h4>Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards.<h4>Aim</h4>We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence.<h4>Methods</h4>On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions.<h4>Results</h4>Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was offset by the effects of vaccination and also affected by the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups.<h4>Conclusion</h4>High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was effective at reducing risk of infection with school holidays/closures playing a significant part.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010724&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010724; html:https://europepmc.org/articles/PMC9728904; pdf:https://europepmc.org/articles/PMC9728904?pdf=render
 37120260,https://doi.org/10.1016/s2468-2667(23)00079-8,Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: a retrospective cohort study using the OpenSAFELY platform.,"Nab L, Parker EPK, Andrews CD, Hulme WJ, Fisher L, Morley J, Mehrkar A, MacKenna B, Inglesby P, Morton CE, Bacon SCJ, Hickman G, Evans D, Ward T, Smith RM, Davy S, Dillingham I, Maude S, Butler-Cole BFC, O'Dwyer T, Stables CL, Bridges L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Zheng B, Williamson EJ, Eggo RM, Evans SJW, Goldacre B, Tomlinson LA, Walker AJ, OpenSAFELY Collaborative.",,The Lancet. Public health,2023,2023-05-01,Y,,,,"<h4>Background</h4>COVID-19 has been shown to differently affect various demographic and clinical population subgroups. We aimed to describe trends in absolute and relative COVID-19-related mortality risks across clinical and demographic population subgroups during successive SARS-CoV-2 pandemic waves.<h4>Methods</h4>We did a retrospective cohort study in England using the OpenSAFELY platform with the approval of National Health Service England, covering the first five SARS-CoV-2 pandemic waves (wave one [wild-type] from March 23 to May 30, 2020; wave two [alpha (B.1.1.7)] from Sept 7, 2020, to April 24, 2021; wave three [delta (B.1.617.2)] from May 28 to Dec 14, 2021; wave four [omicron (B.1.1.529)] from Dec 15, 2021, to April 29, 2022; and wave five [omicron] from June 24 to Aug 3, 2022). In each wave, we included people aged 18-110 years who were registered with a general practice on the first day of the wave and who had at least 3 months of continuous general practice registration up to this date. We estimated crude and sex-standardised and age-standardised wave-specific COVID-19-related death rates and relative risks of COVID-19-related death in population subgroups.<h4>Findings</h4>18 895 870 adults were included in wave one, 19 014 720 in wave two, 18 932 050 in wave three, 19 097 970 in wave four, and 19 226 475 in wave five. Crude COVID-19-related death rates per 1000 person-years decreased from 4·48 deaths (95% CI 4·41-4·55) in wave one to 2·69 (2·66-2·72) in wave two, 0·64 (0·63-0·66) in wave three, 1·01 (0·99-1·03) in wave four, and 0·67 (0·64-0·71) in wave five. In wave one, the standardised COVID-19-related death rates were highest in people aged 80 years or older, people with chronic kidney disease stage 5 or 4, people receiving dialysis, people with dementia or learning disability, and people who had received a kidney transplant (ranging from 19·85 deaths per 1000 person-years to 44·41 deaths per 1000 person-years, compared with from 0·05 deaths per 1000 person-years to 15·93 deaths per 1000 person-years in other subgroups). In wave two compared with wave one, in a largely unvaccinated population, the decrease in COVID-19-related mortality was evenly distributed across population subgroups. In wave three compared with wave one, larger decreases in COVID-19-related death rates were seen in groups prioritised for primary SARS-CoV-2 vaccination, including people aged 80 years or older and people with neurological disease, learning disability, or severe mental illness (90-91% decrease). Conversely, smaller decreases in COVID-19-related death rates were observed in younger age groups, people who had received organ transplants, and people with chronic kidney disease, haematological malignancies, or immunosuppressive conditions (0-25% decrease). In wave four compared with wave one, the decrease in COVID-19-related death rates was smaller in groups with lower vaccination coverage (including younger age groups) and conditions associated with impaired vaccine response, including people who had received organ transplants and people with immunosuppressive conditions (26-61% decrease).<h4>Interpretation</h4>There was a substantial decrease in absolute COVID-19-related death rates over time in the overall population, but demographic and clinical relative risk profiles persisted and worsened for people with lower vaccination coverage or impaired immune response. Our findings provide an evidence base to inform UK public health policy for protecting these vulnerable population subgroups.<h4>Funding</h4>UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139026; doi:https://doi.org/10.1016/S2468-2667(23)00079-8; html:https://europepmc.org/articles/PMC10139026; pdf:https://europepmc.org/articles/PMC10139026?pdf=render
-37388527,https://doi.org/10.1155/2023/4518843,Somatic Symptoms of Depression Lose Association with Mortality upon Adjustment for Frailty: Analysis from the Fitness Haemodialysis Cohort.,"Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,International journal of nephrology,2023,2023-06-21,Y,,,,"<h4>Introduction</h4>The somatic symptom component of depression is associated with increased hospitalisation and mortality and poorer health-related quality of life (HRQOL). However, the relationship of subsets of depression symptoms with frailty and outcomes is not known. This study aimed to (1) explore the relationship between the Clinical Frailty Scale (CFS) and components of depression and (2) their association with mortality, hospitalisation, and HRQOL in haemodialysis recipients.<h4>Methods</h4>We conducted a prospective cohort study of prevalent haemodialysis recipients, with deep bio-clinical phenotyping including CFS and PHQ-9 somatic (fatigue, poor appetite, and poor sleep) and cognitive component scores. EuroQol EQ-5D summary index assessed HRQOL at the baseline. Electronic linkage to English national administration datasets ensured robust follow-up data for hospitalisation and mortality events. <i>Findings</i>. Somatic (<i>β</i> = 0.067; 95% C.I. 0.029 to 0.104; <i>P</i> < 0.001) and cognitive (<i>β</i> = 0.062; 95% C.I. 0.034 to 0.089; <i>P</i><0.001) components were associated with increased CFS scores. Both somatic (<i>β</i> = -0.062; 95% C.I. -0.104 to -0.021; <i>P</i><0.001) and cognitive (<i>β</i> = 0.052; 95% C.I. -0.081 to -0.024; <i>P</i> < 0.001) scores were associated with lower HRQOL. Somatic scores lost mortality association on addition of CFS to the multivariable model (HR1.06; 95% C.I. 0.977 to 1.14; <i>P</i>=0.173). Cognitive symptoms were not associated with mortality. Neither the component score was associated with hospitalisation on multivariable analyses.<h4>Conclusions</h4>Both somatic and cognitive depression symptoms are associated with frailty and poorer HRQOL in haemodialysis recipients but were not associated with mortality or hospitalisation when adjusted for frailty. The risk profile of depression somatic scores may be related to overlap with symptoms of frailty.",,doi:https://doi.org/10.1155/2023/4518843; html:https://europepmc.org/articles/PMC10307017; pdf:https://europepmc.org/articles/PMC10307017?pdf=render
 34217220,https://doi.org/10.1186/s12872-021-02137-9,Pre-existing cardiovascular disease rather than cardiovascular risk factors drives mortality in COVID-19.,"O'Gallagher K, Shek A, Bean DM, Bendayan R, Papachristidis A, Teo JTH, Dobson RJB, Shah AM, Zakeri R.",,BMC cardiovascular disorders,2021,2021-07-03,Y,Hypertension; Diabetes; Cardiovascular disease; Cardiovascular risk factors; Covid-19,,,"<h4>Background</h4>The relative association between cardiovascular (CV) risk factors, such as diabetes and hypertension, established CV disease (CVD), and susceptibility to CV complications or mortality in COVID-19 remains unclear.<h4>Methods</h4>We conducted a cohort study of consecutive adults hospitalised for severe COVID-19 between 1st March and 30th June 2020. Pre-existing CVD, CV risk factors and associations with mortality and CV complications were ascertained.<h4>Results</h4>Among 1721 patients (median age 71 years, 57% male), 349 (20.3%) had pre-existing CVD (CVD), 888 (51.6%) had CV risk factors without CVD (RF-CVD), 484 (28.1%) had neither. Patients with CVD were older with a higher burden of non-CV comorbidities. During follow-up, 438 (25.5%) patients died: 37% with CVD, 25.7% with RF-CVD and 16.5% with neither. CVD was independently associated with in-hospital mortality among patients < 70 years of age (adjusted HR 2.43 [95% CI 1.16-5.07]), but not in those ≥ 70 years (aHR 1.14 [95% CI 0.77-1.69]). RF-CVD were not independently associated with mortality in either age group (< 70 y aHR 1.21 [95% CI 0.72-2.01], ≥ 70 y aHR 1.07 [95% CI 0.76-1.52]). Most CV complications occurred in patients with CVD (66%) versus RF-CVD (17%) or neither (11%; p < 0.001). 213 [12.4%] patients developed venous thromboembolism (VTE). CVD was not an independent predictor of VTE.<h4>Conclusions</h4>In patients hospitalised with COVID-19, pre-existing established CVD appears to be a more important contributor to mortality than CV risk factors in the absence of CVD. CVD-related hazard may be mediated, in part, by new CV complications. Optimal care and vigilance for destabilised CVD are essential in this patient group. Trial registration n/a.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-021-02137-9; doi:https://doi.org/10.1186/s12872-021-02137-9; html:https://europepmc.org/articles/PMC8254437; pdf:https://europepmc.org/articles/PMC8254437?pdf=render
+37388527,https://doi.org/10.1155/2023/4518843,Somatic Symptoms of Depression Lose Association with Mortality upon Adjustment for Frailty: Analysis from the Fitness Haemodialysis Cohort.,"Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,International journal of nephrology,2023,2023-06-21,Y,,,,"<h4>Introduction</h4>The somatic symptom component of depression is associated with increased hospitalisation and mortality and poorer health-related quality of life (HRQOL). However, the relationship of subsets of depression symptoms with frailty and outcomes is not known. This study aimed to (1) explore the relationship between the Clinical Frailty Scale (CFS) and components of depression and (2) their association with mortality, hospitalisation, and HRQOL in haemodialysis recipients.<h4>Methods</h4>We conducted a prospective cohort study of prevalent haemodialysis recipients, with deep bio-clinical phenotyping including CFS and PHQ-9 somatic (fatigue, poor appetite, and poor sleep) and cognitive component scores. EuroQol EQ-5D summary index assessed HRQOL at the baseline. Electronic linkage to English national administration datasets ensured robust follow-up data for hospitalisation and mortality events. <i>Findings</i>. Somatic (<i>β</i> = 0.067; 95% C.I. 0.029 to 0.104; <i>P</i> < 0.001) and cognitive (<i>β</i> = 0.062; 95% C.I. 0.034 to 0.089; <i>P</i><0.001) components were associated with increased CFS scores. Both somatic (<i>β</i> = -0.062; 95% C.I. -0.104 to -0.021; <i>P</i><0.001) and cognitive (<i>β</i> = 0.052; 95% C.I. -0.081 to -0.024; <i>P</i> < 0.001) scores were associated with lower HRQOL. Somatic scores lost mortality association on addition of CFS to the multivariable model (HR1.06; 95% C.I. 0.977 to 1.14; <i>P</i>=0.173). Cognitive symptoms were not associated with mortality. Neither the component score was associated with hospitalisation on multivariable analyses.<h4>Conclusions</h4>Both somatic and cognitive depression symptoms are associated with frailty and poorer HRQOL in haemodialysis recipients but were not associated with mortality or hospitalisation when adjusted for frailty. The risk profile of depression somatic scores may be related to overlap with symptoms of frailty.",,doi:https://doi.org/10.1155/2023/4518843; html:https://europepmc.org/articles/PMC10307017; pdf:https://europepmc.org/articles/PMC10307017?pdf=render
 35027756,https://doi.org/10.1038/s41591-021-01666-2,SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland.,"Stock SJ, Carruthers J, Calvert C, Denny C, Donaghy J, Goulding A, Hopcroft LEM, Hopkins L, McLaughlin T, Pan J, Shi T, Taylor B, Agrawal U, Auyeung B, Katikireddi SV, McCowan C, Murray J, Simpson CR, Robertson C, Vasileiou E, Sheikh A, Wood R.",,Nature medicine,2022,2022-01-13,Y,,,,"Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18-44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9-38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1-6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2-78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7-92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5-99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.",,pdf:https://www.nature.com/articles/s41591-021-01666-2.pdf; doi:https://doi.org/10.1038/s41591-021-01666-2; html:https://europepmc.org/articles/PMC8938271; pdf:https://europepmc.org/articles/PMC8938271?pdf=render
 36798088,https://doi.org/10.1177/26335565221148616,Classification of long-term condition patterns in rheumatoid arthritis and associations with adverse health events: a UK Biobank cohort study.,"McLoone P, Jani BD, Siebert S, Morton FR, Canning J, Macdonald S, Mair FS, Nicholl BI.",,Journal of multimorbidity and comorbidity,2023,2023-01-01,Y,Rheumatoid arthritis; Mortality; Comorbidity; Latent Class Analysis; Multimorbidity,,,"<h4>Purpose</h4>We aimed to classify individuals with RA and ≥2 additional long-term conditions (LTCs) and describe the association between different LTC classes, number of LTCs and adverse health outcomes.<h4>Methods</h4>We used UK Biobank participants who reported RA (n=5,625) and employed latent class analysis (LCA) to create classes of LTC combinations for those with ≥2 additional LTCs. Cox-proportional hazard and negative binomial regression were used to compare the risk of all-cause mortality, major adverse cardiac events (MACE), and number of emergency hospitalisations over an 11-year follow-up across the different LTC classes and in those with RA plus one additional LTC. Persons with RA without LTCs were the reference group. Analyses were adjusted for demographic characteristics, smoking, BMI, alcohol consumption and physical activity.<h4>Results</h4>A total of 2,566 (46%) participants reported ≥2 LTCs in addition to RA. This involved 1,138 distinct LTC combinations of which 86% were reported by ≤2 individuals. LCA identified 5 morbidity-classes. The distinctive condition in the class with the highest mortality was cancer (class 5; HR 2.66 95%CI (1.91-3.70)). The highest MACE (HR 2.95 95%CI (2.11-4.14)) and emergency hospitalisations (rate ratio 3.01 (2.56-3.54)) were observed in class 3 which comprised asthma, COPD & CHD. There was an increase in mortality, MACE and emergency hospital admissions within each class as the number of LTCs increased.<h4>Conclusions</h4>The risk of adverse health outcomes in RA varied with different patterns of multimorbidity. The pattern of multimorbidity should be considered in risk assessment and formulating management plans in patients with RA.",,doi:https://doi.org/10.1177/26335565221148616; doi:https://doi.org/10.1177/26335565221148616; html:https://europepmc.org/articles/PMC9926377; pdf:https://europepmc.org/articles/PMC9926377?pdf=render
 35756853,https://doi.org/10.1016/j.lanepe.2022.100428,"Impact of COVID-19 pandemic on asthma exacerbations: Retrospective cohort study of over 500,000 patients in a national English primary care database.","Shah SA, Quint JK, Sheikh A.",,The Lancet regional health. Europe,2022,2022-06-15,Y,Asthma; Pandemic; Asthma Exacerbations; Covid-19,,,"<h4>Background</h4>Several countries reported a substantial reduction in asthma exacerbations associated with COVID-19 pandemic-related restrictions. However, it is not known if these early reported declines were short-term and if these have rebounded to pre-pandemic levels following easing of lockdown restrictions.<h4>Methods</h4>We undertook a retrospective, cohort study of all asthma patients in a national primary care database of almost 10 million patients, Optimum Patient Care Database (OPCRD), identified from January 1, 2010, to December 31, 2015, using a previously validated algorithm. We subsequently followed the identified cohort of asthma patients from January 1, 2016, to October 3, 2021, and identified every asthma exacerbation episode with a validated algorithm. To quantify any pandemic-related change in exacerbations, we created a control time-series (mean of 2016-2019) and then compared the change in exacerbation rate in 2020-2021 over quarterly periods when compared with the control period (the pre-pandemic period). We undertook overall and stratified analyses by age group, sex, and English region.<h4>Findings</h4>We identified 100,362 asthma patients (502,669 patient-years) from across England who experienced at least one exacerbation episode (298,390 exacerbation episodes during the entire follow-up). Except for the first quarter of 2020, the exacerbation rates were substantially lower (>25%) during all quarters in 2020-2021 when compared with the rates during 2016-2019 (39.7% (95% Confidence Interval (CI): 34.6, 44.9) in quarter-2, 2020; 46.5% (95%CI: 36.7, 56.4) in quarter-3, 2020; 56.3% (95%CI: 48.7, 63.9) in quarter-4, 2020; 63.2% (95%CI: 53.9, 72.5) in quarter-1, 2021; 57.7% (95%CI: 52.9, 62.4) in quarter-2, 2021; 53.3% (95%CI: 43.8, 62.8) in quarter-3, 2021).<h4>Interpretation</h4>There was a substantial and persistent reduction in asthma exacerbations across England over the first 18 months after the first lockdown. This is unlikely to be adequately explained by changes in health-seeking behaviour, pandemic-related healthcare service disruption, or any air-quality improvements.<h4>Funding</h4>Asthma UK, Health Data Research UK (HDR UK), Medical Research Council (MRC), National Institute for Health Research (NIHR).",,doi:https://doi.org/10.1016/j.lanepe.2022.100428; doi:https://doi.org/10.1016/j.lanepe.2022.100428; html:https://europepmc.org/articles/PMC9213032; pdf:https://europepmc.org/articles/PMC9213032?pdf=render
@@ -200,8 +200,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 34056579,https://doi.org/10.3389/frai.2021.652669,"The Promise of AI in Detection, Diagnosis, and Epidemiology for Combating COVID-19: Beyond the Hype.","Abdulkareem M, Petersen SE.",,Frontiers in artificial intelligence,2021,2021-05-14,Y,Artificial intelligence; Detection; Diagnosis; Medical imaging; epidemiology; Contact tracing; Social Control; Covid-19,,,"COVID-19 has created enormous suffering, affecting lives, and causing deaths. The ease with which this type of coronavirus can spread has exposed weaknesses of many healthcare systems around the world. Since its emergence, many governments, research communities, commercial enterprises, and other institutions and stakeholders around the world have been fighting in various ways to curb the spread of the disease. Science and technology have helped in the implementation of policies of many governments that are directed toward mitigating the impacts of the pandemic and in diagnosing and providing care for the disease. Recent technological tools, artificial intelligence (AI) tools in particular, have also been explored to track the spread of the coronavirus, identify patients with high mortality risk and diagnose patients for the disease. In this paper, areas where AI techniques are being used in the detection, diagnosis and epidemiological predictions, forecasting and social control for combating COVID-19 are discussed, highlighting areas of successful applications and underscoring issues that need to be addressed to achieve significant progress in battling COVID-19 and future pandemics. Several AI systems have been developed for diagnosing COVID-19 using medical imaging modalities such as chest CT and X-ray images. These AI systems mainly differ in their choices of the algorithms for image segmentation, classification and disease diagnosis. Other AI-based systems have focused on predicting mortality rate, long-term patient hospitalization and patient outcomes for COVID-19. AI has huge potential in the battle against the COVID-19 pandemic but successful practical deployments of these AI-based tools have so far been limited due to challenges such as limited data accessibility, the need for external evaluation of AI models, the lack of awareness of AI experts of the regulatory landscape governing the deployment of AI tools in healthcare, the need for clinicians and other experts to work with AI experts in a multidisciplinary context and the need to address public concerns over data collection, privacy, and protection. Having a dedicated team with expertise in medical data collection, privacy, access and sharing, using federated learning whereby AI scientists hand over training algorithms to the healthcare institutions to train models locally, and taking full advantage of biomedical data stored in biobanks can alleviate some of problems posed by these challenges. Addressing these challenges will ultimately accelerate the translation of AI research into practical and useful solutions for combating pandemics.",,pdf:https://www.frontiersin.org/articles/10.3389/frai.2021.652669/pdf; doi:https://doi.org/10.3389/frai.2021.652669; html:https://europepmc.org/articles/PMC8160471; pdf:https://europepmc.org/articles/PMC8160471?pdf=render
 34011491,https://doi.org/10.1136/bmj.n1137,Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries.,"Islam N, Shkolnikov VM, Acosta RJ, Klimkin I, Kawachi I, Irizarry RA, Alicandro G, Khunti K, Yates T, Jdanov DA, White M, Lewington S, Lacey B.",,BMJ (Clinical research ed.),2021,2021-05-19,Y,,,,"<h4>Objective</h4>To estimate the direct and indirect effects of the covid-19 pandemic on mortality in 2020 in 29 high income countries with reliable and complete age and sex disaggregated mortality data.<h4>Design</h4>Time series study of high income countries.<h4>Setting</h4>Austria, Belgium, Czech Republic, Denmark, England and Wales, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, the Netherlands, New Zealand, Northern Ireland, Norway, Poland, Portugal, Scotland, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, and United States.<h4>Participants</h4>Mortality data from the Short-term Mortality Fluctuations data series of the Human Mortality Database for 2016-20, harmonised and disaggregated by age and sex.<h4>Interventions</h4>Covid-19 pandemic and associated policy measures.<h4>Main outcome measures</h4>Weekly excess deaths (observed deaths versus expected deaths predicted by model) in 2020, by sex and age (0-14, 15-64, 65-74, 75-84, and ≥85 years), estimated using an over-dispersed Poisson regression model that accounts for temporal trends and seasonal variability in mortality.<h4>Results</h4>An estimated 979 000 (95% confidence interval 954 000 to 1 001 000) excess deaths occurred in 2020 in the 29 high income countries analysed. All countries had excess deaths in 2020, except New Zealand, Norway, and Denmark. The five countries with the highest absolute number of excess deaths were the US (458 000, 454 000 to 461 000), Italy (89 100, 87 500 to 90 700), England and Wales (85 400, 83 900 to 86 800), Spain (84 100, 82 800 to 85 300), and Poland (60 100, 58 800 to 61 300). New Zealand had lower overall mortality than expected (-2500, -2900 to -2100). In many countries, the estimated number of excess deaths substantially exceeded the number of reported deaths from covid-19. The highest excess death rates (per 100 000) in men were in Lithuania (285, 259 to 311), Poland (191, 184 to 197), Spain (179, 174 to 184), Hungary (174, 161 to 188), and Italy (168, 163 to 173); the highest rates in women were in Lithuania (210, 185 to 234), Spain (180, 175 to 185), Hungary (169, 156 to 182), Slovenia (158, 132 to 184), and Belgium (151, 141 to 162). Little evidence was found of subsequent compensatory reductions following excess mortality.<h4>Conclusion</h4>Approximately one million excess deaths occurred in 2020 in these 29 high income countries. Age standardised excess death rates were higher in men than women in almost all countries. Excess deaths substantially exceeded reported deaths from covid-19 in many countries, indicating that determining the full impact of the pandemic on mortality requires assessment of excess deaths. Many countries had lower deaths than expected in children <15 years. Sex inequality in mortality widened further in most countries in 2020.",,pdf:https://www.bmj.com/content/bmj/373/bmj.n1137.full.pdf; doi:https://doi.org/10.1136/bmj.n1137; html:https://europepmc.org/articles/PMC8132017; pdf:https://europepmc.org/articles/PMC8132017?pdf=render
 31783849,https://doi.org/10.1186/s12911-019-0953-2,Developing a standardised approach to the aggregation of inpatient episodes into person-based spells in all specialties and psychiatric specialties.,"Rees S, Akbari A, Collins H, Lee SC, Marchant A, Rees A, Thayer D, Wang T, Wood S, John A.",,BMC medical informatics and decision making,2019,2019-11-29,Y,Data Quality; Data Linkage; Electronic Healthcare Record; Spells; Hospital Inpatient Episodes; Routine Health Data,Improving Public Health,,"<h4>Background</h4>Electronic health record (EHR) data are available for research in all UK nations and cross-nation comparative studies are becoming more common. All UK inpatient EHRs are based around episodes, but episode-based analysis may not sufficiently capture the patient journey. There is no UK-wide method for aggregating episodes into standardised person-based spells. This study identifies two data quality issues affecting the creation of person-based spells, and tests four methods to create these spells, for implementation across all UK nations.<h4>Methods</h4>Welsh inpatient EHRs from 2013 to 2017 were analysed. Phase one described two data quality issues; transfers of care and episode sequencing. Phase two compared four methods for creating person spells. Measures were mean length of stay (LOS, expressed in days) and number of episodes per person spell for each method.<h4>Results</h4>3.5% of total admissions were transfers-in and 3.1% of total discharges were transfers-out. 68.7% of total transfers-in and 48.7% of psychiatric transfers-in had an identifiable preceding transfer-out, and 78.2% of total transfers-out and 59.0% of psychiatric transfers-out had an identifiable subsequent transfer-in. 0.2% of total episodes and 4.0% of psychiatric episodes overlapped with at least one other episode of any specialty. Method one (no evidence of transfer required; overlapping episodes grouped together) resulted in the longest mean LOS (4.0 days for all specialties; 48.5 days for psychiatric specialties) and the fewest single episode person spells (82.4% of all specialties; 69.7% for psychiatric specialties). Method three (evidence of transfer required; overlapping episodes separated) resulted in the shortest mean LOS (3.7 days for all specialties; 45.8 days for psychiatric specialties) and the most single episode person spells; (86.9% for all specialties; 86.3% for psychiatric specialties).<h4>Conclusions</h4>Transfers-in appear better recorded than transfers-out. Transfer coding is incomplete, particularly for psychiatric specialties. The proportion of episodes that overlap is small but psychiatric episodes are disproportionately affected. The most successful method for grouping episodes into person spells aggregated overlapping episodes and required no evidence of transfer from admission source/method or discharge destination codes. The least successful method treated overlapping episodes as distinct and required transfer coding. The impact of all four methods was greater for psychiatric specialties.","Rees et al used a Welsh database to examine inpatient episode/transfer coding coding for psychiatric patients. They identified deficiencies in the existing coding system for psychitatrics transfers and unexplained coding mistakes/problems, then they presesnt several different methods for constructing the inpatient spell to improve coding and avoid misclassification.",pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0953-2; doi:https://doi.org/10.1186/s12911-019-0953-2; html:https://europepmc.org/articles/PMC6884917; pdf:https://europepmc.org/articles/PMC6884917?pdf=render
-37147628,https://doi.org/10.1186/s12911-023-02181-9,Ontology-driven and weakly supervised rare disease identification from clinical notes.,"Dong H, Suárez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.",,BMC medical informatics and decision making,2023,2023-05-05,Y,Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision,,,"<h4>Background</h4>Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.<h4>Methods</h4>We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.<h4>Results</h4>The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).<h4>Conclusion</h4>The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02181-9; doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render
 34942103,https://doi.org/10.1016/s0140-6736(21)02754-9,"Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil.","Katikireddi SV, Cerqueira-Silva T, Vasileiou E, Robertson C, Amele S, Pan J, Taylor B, Boaventura V, Werneck GL, Flores-Ortiz R, Agrawal U, Docherty AB, McCowan C, McMenamin J, Moore E, Ritchie LD, Rudan I, Shah SA, Shi T, Simpson CR, Barreto ML, Oliveira VA, Barral-Netto M, Sheikh A.",,"Lancet (London, England)",2022,2021-12-20,Y,,,,"<h4>Background</h4>Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants-especially delta (B.1.617.2)-is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon).<h4>Methods</h4>In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2-3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs.<h4>Findings</h4>1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54-2·62) at 10-11 weeks, 3·01 (2·26-3·99) at 14-15 weeks, and 5·43 (4·00-7·38) at 18-19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01-2·61) at 10-11 weeks, 3·10 (2·63-3·64) at 14-15 weeks, and 4·71 (3·83-5·78) at 18-19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7-87·0) at 2-3 weeks, to 75·9% (72·9-78·6) at 14-15 weeks, and 63·7% (59·6-67·4) at 18-19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4-87·3) at 2-3 weeks, to 59·7% (54·6-64·2) at 14-15 weeks, and 42·2% (32·4-50·6) at 18-19 weeks.<h4>Interpretation</h4>We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19.<h4>Funding</h4>UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.<h4>Translation</h4>For the Portuguese translation of the abstract see Supplementary Materials section.",,pdf:http://www.thelancet.com/article/S0140673621027549/pdf; doi:https://doi.org/10.1016/S0140-6736(21)02754-9; html:https://europepmc.org/articles/PMC8687670
+37147628,https://doi.org/10.1186/s12911-023-02181-9,Ontology-driven and weakly supervised rare disease identification from clinical notes.,"Dong H, Suárez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.",,BMC medical informatics and decision making,2023,2023-05-05,Y,Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision,,,"<h4>Background</h4>Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.<h4>Methods</h4>We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.<h4>Results</h4>The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).<h4>Conclusion</h4>The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02181-9; doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render
 36174228,https://doi.org/10.1093/ije/dyac189,Cohort Profile: Longitudinal population-based study of COVID-19 in UK adults (COVIDENCE UK).,"Holt H, Relton C, Talaei M, Symons J, Davies MR, Jolliffe DA, Vivaldi G, Tydeman F, Williamson AE, Pfeffer PE, Orton C, Ford DV, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Breen G, Shaheen SO, Martineau AR.",,International journal of epidemiology,2023,2023-02-01,N,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e46/49127271/dyac189.pdf; doi:https://doi.org/10.1093/ije/dyac189; html:https://europepmc.org/articles/PMC9620716; pdf:https://europepmc.org/articles/PMC9620716?pdf=render; doi:https://doi.org/10.1093/ije/dyac189
 37463814,https://doi.org/10.1136/bmjopen-2022-069635,HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.,"Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.",,BMJ open,2023,2023-07-18,Y,Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care,,,"<h4>Objectives</h4>To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.<h4>Design</h4>The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.<h4>Settings</h4>A large mental healthcare provider, the South London and Maudsley National Health Service Trust.<h4>Participants</h4>Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.<h4>Outcome measures</h4>Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.<h4>Results</h4>Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).<h4>Conclusions</h4>Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/7/e069635.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render
 34104901,https://doi.org/10.1016/s2666-7568(21)00093-3,Incidence of SARS-CoV-2 infection according to baseline antibody status in staff and residents of 100 long-term care facilities (VIVALDI): a prospective cohort study.,"Krutikov M, Palmer T, Tut G, Fuller C, Shrotri M, Williams H, Davies D, Irwin-Singer A, Robson J, Hayward A, Moss P, Copas A, Shallcross L.",,The lancet. Healthy longevity,2021,2021-06-03,Y,,,,"<h4>Background</h4>SARS-CoV-2 infection represents a major challenge for long-term care facilities (LTCFs) and many residents and staff are seropositive following persistent outbreaks. We aimed to investigate the association between the SARS-CoV-2 antibody status at baseline and subsequent infection in this population.<h4>Methods</h4>We did a prospective cohort study of SARS-CoV-2 infection in staff (aged <65 years) and residents (aged >65 years) at 100 LTCFs in England between Oct 1, 2020, and Feb 1, 2021. Blood samples were collected between June and November, 2020, at baseline, and 2 and 4 months thereafter and tested for IgG antibodies to SARS-CoV-2 nucleocapsid and spike proteins. PCR testing for SARS-CoV-2 was done weekly in staff and monthly in residents. Cox regression was used to estimate hazard ratios (HRs) of a PCR-positive test by baseline antibody status, adjusted for age and sex, and stratified by LTCF.<h4>Findings</h4>682 residents from 86 LCTFs and 1429 staff members from 97 LTCFs met study inclusion criteria. At baseline, IgG antibodies to nucleocapsid were detected in 226 (33%) of 682 residents and 408 (29%) of 1429 staff members. 93 (20%) of 456 residents who were antibody-negative at baseline had a PCR-positive test (infection rate 0·054 per month at risk) compared with four (2%) of 226 residents who were antibody-positive at baseline (0·007 per month at risk). 111 (11%) of 1021 staff members who were antibody-negative at baseline had PCR-positive tests (0·042 per month at risk) compared with ten (2%) of 408 staff members who were antibody-positive staff at baseline (0·009 per month at risk). The risk of PCR-positive infection was higher for residents who were antibody-negative at baseline than residents who were antibody-positive at baseline (adjusted HR [aHR] 0·15, 95% CI 0·05-0·44, p=0·0006), and the risk of a PCR-positive infection was also higher for staff who were antibody-negative at baseline compared with staff who were antibody-positive at baseline (aHR 0·39, 0·19-0·82; p=0·012). 12 of 14 reinfected participants had available data on symptoms, and 11 of these participants were symptomatic. Antibody titres to spike and nucleocapsid proteins were comparable in PCR-positive and PCR-negative cases.<h4>Interpretation</h4>The presence of IgG antibodies to nucleocapsid protein was associated with substantially reduced risk of reinfection in staff and residents for up to 10 months after primary infection.<h4>Funding</h4>UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/S2666-7568(21)00093-3; html:https://europepmc.org/articles/PMC8175048; pdf:https://europepmc.org/articles/PMC8175048?pdf=render; doi:https://doi.org/10.1016/s2666-7568(21)00093-3
@@ -217,8 +217,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 36629015,https://doi.org/10.1177/17407745221143449,Lack of transparent reporting of trial monitoring approaches in randomised controlled trials: A systematic review of contemporary protocol papers.,"Hsieh SF, Yorke-Edwards V, Murray ML, Diaz-Montana C, Love SB, Sydes MR.",,"Clinical trials (London, England)",2023,2023-01-11,Y,Systematic review; Randomised Controlled Trial; On-site Monitoring; Risk-based Monitoring; Protocol Paper; Central Monitoring; Trial Monitoring; Reporting Monitoring,,,"<h4>Background</h4>Monitoring is essential to ensure patient safety and data integrity in clinical trials as per Good Clinical Practice. The Standard Protocol Items: Recommendations for Interventional Trials Statement and its checklist guides authors to include monitoring in their protocols. We investigated how well monitoring was reported in published 'protocol papers' for contemporary randomised controlled trials.<h4>Methods</h4>A systematic search was conducted in PubMed to identify eligible protocol papers published in selected journals between 1 January 2020 and 31 May 2020. Protocol papers were classified by whether they reported monitoring and, if so, by the details of monitoring. Data were summarised descriptively.<h4>Results</h4>Of 811 protocol papers for randomised controlled trials, 386 (48%; 95% CI: 44%-51%) explicitly reported some monitoring information. Of these, 20% (77/386) reported monitoring information consistent with an on-site monitoring approach, and 39% (152/386) with central monitoring, 26% (101/386) with a mixed approach, while 14% (54/386) did not provide sufficient information to specify an approach. Only 8% (30/386) of randomised controlled trials reported complete details about all of scope, frequency and organisation of monitoring; frequency of monitoring was the least reported. However, 6% (25/386) of papers used the term 'audit' to describe 'monitoring'.<h4>Discussion</h4>Monitoring information was reported in only approximately half of the protocol papers. Suboptimal reporting of monitoring hinders the clinical community from having the full information on which to judge the validity of a trial and jeopardises the value of protocol papers and the credibility of the trial itself. Greater efforts are needed to promote the transparent reporting of monitoring to journal editors and authors.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/17407745221143449; doi:https://doi.org/10.1177/17407745221143449; html:https://europepmc.org/articles/PMC10021127; pdf:https://europepmc.org/articles/PMC10021127?pdf=render
 33893241,https://doi.org/10.1126/science.abf0874,Resurgence of SARS-CoV-2: Detection by community viral surveillance.,"Riley S, Ainslie KEC, Eales O, Walters CE, Wang H, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,"Science (New York, N.Y.)",2021,2021-04-23,Y,,,,"Surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has mainly relied on case reporting, which is biased by health service performance, test availability, and test-seeking behaviors. We report a community-wide national representative surveillance program in England based on self-administered swab results from ~594,000 individuals tested for SARS-CoV-2, regardless of symptoms, between May and the beginning of September 2020. The epidemic declined between May and July 2020 but then increased gradually from mid-August, accelerating into early September 2020 at the start of the second wave. When compared with cases detected through routine surveillance, we report here a longer period of decline and a younger age distribution. Representative community sampling for SARS-CoV-2 can substantially improve situational awareness and feed into the public health response even at low prevalence.",,pdf:https://www.science.org/cms/asset/00326f17-60ca-4c01-8814-727df6504005/pap.pdf; doi:https://doi.org/10.1126/science.abf0874; html:https://europepmc.org/articles/PMC8158959; pdf:https://europepmc.org/articles/PMC8158959?pdf=render
 37358897,https://doi.org/10.2196/45849,Development of a Corpus Annotated With Mentions of Pain in Mental Health Records: Natural Language Processing Approach.,"Chaturvedi J, Chance N, Mirza L, Vernugopan V, Velupillai S, Stewart R, Roberts A.",,JMIR formative research,2023,2023-06-26,Y,Pain; Mental health; Annotation; Information Extraction; Natural Language Processing,,,"<h4>Background</h4>Pain is a widespread issue, with 20% of adults (1 in 5) experiencing it globally. A strong association has been demonstrated between pain and mental health conditions, and this association is known to exacerbate disability and impairment. Pain is also known to be strongly related to emotions, which can lead to damaging consequences. As pain is a common reason for people to access health care facilities, electronic health records (EHRs) are a potential source of information on this pain. Mental health EHRs could be particularly beneficial since they can show the overlap of pain with mental health. Most mental health EHRs contain the majority of their information within the free-text sections of the records. However, it is challenging to extract information from free text. Natural language processing (NLP) methods are therefore required to extract this information from the text.<h4>Objective</h4>This research describes the development of a corpus of manually labeled mentions of pain and pain-related entities from the documents of a mental health EHR database, for use in the development and evaluation of future NLP methods.<h4>Methods</h4>The EHR database used, Clinical Record Interactive Search, consists of anonymized patient records from The South London and Maudsley National Health Service Foundation Trust in the United Kingdom. The corpus was developed through a process of manual annotation where pain mentions were marked as relevant (ie, referring to physical pain afflicting the patient), negated (ie, indicating absence of pain), or not relevant (ie, referring to pain affecting someone other than the patient, or metaphorical and hypothetical mentions). Relevant mentions were also annotated with additional attributes such as anatomical location affected by pain, pain character, and pain management measures, if mentioned.<h4>Results</h4>A total of 5644 annotations were collected from 1985 documents (723 patients). Over 70% (n=4028) of the mentions found within the documents were annotated as relevant, and about half of these mentions also included the anatomical location affected by the pain. The most common pain character was chronic pain, and the most commonly mentioned anatomical location was the chest. Most annotations (n=1857, 33%) were from patients who had a primary diagnosis of mood disorders (International Classification of Diseases-10th edition, chapter F30-39).<h4>Conclusions</h4>This research has helped better understand how pain is mentioned within the context of mental health EHRs and provided insight into the kind of information that is typically mentioned around pain in such a data source. In future work, the extracted information will be used to develop and evaluate a machine learning-based NLP application to automatically extract relevant pain information from EHR databases.",,pdf:https://formative.jmir.org/2023/1/e45849/PDF; doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render
-37346822,https://doi.org/10.12688/wellcomeopenres.18735.2,First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY.,"Hopcroft LE, Curtis HJ, Brown AD, Hulme WJ, Andrews CD, Morton CE, Inglesby P, Morley J, Mehrkar A, Bacon SC, Eggo RM, Mahalingasivam V, Parker EPK, Tomlinson LA, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, Walker AJ, MacKenna B.",,Wellcome open research,2023,2023-06-09,Y,Vaccine; Primary Health Care; Public Health; Covid-19,,,"<b>Background:</b> The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. <b>Methods:</b> With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,  <i>in situ</i> and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. <b>Results:</b> Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. <b>Conclusion:</b> First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.",,doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render
 36369736,https://doi.org/10.1080/19490976.2022.2139979,"Integration of stool microbiota, proteome and amino acid profiles to discriminate patients with adenomas and colorectal cancer.","Bosch S, Acharjee A, Quraishi MN, Bijnsdorp IV, Rojas P, Bakkali A, Jansen EE, Stokkers P, Kuijvenhoven J, Pham TV, Beggs AD, Jimenez CR, Struys EA, Gkoutos GV, de Meij TG, de Boer NK.",,Gut microbes,2022,2022-01-01,Y,Screening; Biomarker; Adenoma; Colon cancer; Data integration; stool; Multi Omics,,,"<h4>Background</h4>Screening for colorectal cancer (CRC) reduces its mortality but has limited sensitivity and specificity. Aims We aimed to explore potential biomarker panels for CRC and adenoma detection and to gain insight into the interaction between gut microbiota and human metabolism in the presence of these lesions.<h4>Methods</h4>This multicenter case-control cohort was performed between February 2016 and November 2019. Consecutive patients ≥18 years with a scheduled colonoscopy were asked to participate and divided into three age, gender, body-mass index and smoking status-matched subgroups: CRC (n = 12), adenomas (n = 21) and controls (n = 20). Participants collected fecal samples prior to bowel preparation on which proteome (LC-MS/MS), microbiota (16S rRNA profiling) and amino acid (HPLC) composition were assessed. Best predictive markers were combined to create diagnostic biomarker panels. Pearson correlation-based analysis on selected markers was performed to create networks of all platforms.<h4>Results</h4>Combining omics platforms provided new panels which outperformed hemoglobin in this cohort, currently used for screening (AUC 0.98, 0.95 and 0.87 for CRC vs controls, adenoma vs controls and CRC vs adenoma, respectively). Integration of data sets revealed markers associated with increased blood excretion, stress- and inflammatory responses and pointed toward downregulation of epithelial integrity.<h4>Conclusions</h4>Integrating fecal microbiota, proteome and amino acids platforms provides for new biomarker panels that may improve noninvasive screening for adenomas and CRC, and may subsequently lead to lower incidence and mortality of colon cancer.",,doi:https://doi.org/10.1080/19490976.2022.2139979; doi:https://doi.org/10.1080/19490976.2022.2139979; html:https://europepmc.org/articles/PMC9662191; pdf:https://europepmc.org/articles/PMC9662191?pdf=render
+37346822,https://doi.org/10.12688/wellcomeopenres.18735.2,First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY.,"Hopcroft LE, Curtis HJ, Brown AD, Hulme WJ, Andrews CD, Morton CE, Inglesby P, Morley J, Mehrkar A, Bacon SC, Eggo RM, Mahalingasivam V, Parker EPK, Tomlinson LA, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, Walker AJ, MacKenna B.",,Wellcome open research,2023,2023-06-09,Y,Vaccine; Primary Health Care; Public Health; Covid-19,,,"<b>Background:</b> The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. <b>Methods:</b> With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,  <i>in situ</i> and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. <b>Results:</b> Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. <b>Conclusion:</b> First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.",,doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render
 35858698,https://doi.org/10.1136/bmj-2022-071249,Waning effectiveness of BNT162b2 and ChAdOx1 covid-19 vaccines over six months since second dose: OpenSAFELY cohort study using linked electronic health records.,"Horne EMF, Hulme WJ, Keogh RH, Palmer TM, Williamson EJ, Parker EPK, Green A, Walker V, Walker AJ, Curtis H, Fisher L, MacKenna B, Croker R, Hopcroft L, Park RY, Massey J, Morley J, Mehrkar A, Bacon S, Evans D, Inglesby P, Morton CE, Hickman G, Davy S, Ward T, Dillingham I, Goldacre B, Hernán MA, Sterne JAC.",,BMJ (Clinical research ed.),2022,2022-07-20,Y,,,,"<h4>Objective</h4>To estimate waning of covid-19 vaccine effectiveness over six months after second dose.<h4>Design</h4>Cohort study, approved by NHS England.<h4>Setting</h4>Linked primary care, hospital, and covid-19 records within the OpenSAFELY-TPP database.<h4>Participants</h4>Adults without previous SARS-CoV-2 infection were eligible, excluding care home residents and healthcare professionals.<h4>Exposures</h4>People who had received two doses of BNT162b2 or ChAdOx1 (administered during the national vaccine rollout) were compared with unvaccinated people during six consecutive comparison periods, each of four weeks.<h4>Main outcome measures</h4>Adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, positive SARS-CoV-2 test, and non-covid-19 related death comparing vaccinated with unvaccinated people. Waning vaccine effectiveness was quantified as ratios of adjusted hazard ratios per four week period, separately for subgroups aged ≥65 years, 18-64 years and clinically vulnerable, 40-64 years, and 18-39 years.<h4>Results</h4>1 951 866 and 3 219 349 eligible adults received two doses of BNT162b2 and ChAdOx1, respectively, and 2 422 980 remained unvaccinated. Waning of vaccine effectiveness was estimated to be similar across outcomes and vaccine brands. In the ≥65 years subgroup, ratios of adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test ranged from 1.19 (95% confidence interval 1.14 to 1.24)to 1.34 (1.09 to 1.64) per four weeks. Despite waning vaccine effectiveness, rates of covid-19 related hospital admission and death were substantially lower among vaccinated than unvaccinated adults up to 26 weeks after the second dose, with estimated vaccine effectiveness ≥80% for BNT162b2, and ≥75% for ChAdOx1. By weeks 23-26, rates of positive SARS-CoV-2 test in vaccinated people were similar to or higher than in unvaccinated people (adjusted hazard ratios up to 1.72 (1.11 to 2.68) for BNT162b2 and 1.86 (1.79 to 1.93) for ChAdOx1).<h4>Conclusions</h4>The rate at which estimated vaccine effectiveness waned was consistent for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test and was similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination.",,pdf:https://www.bmj.com/content/bmj/378/bmj-2022-071249.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071249; html:https://europepmc.org/articles/PMC10441183
 35918110,https://doi.org/10.1136/bmjopen-2021-057433,"Investigating the relationship between thought interference, somatic passivity and outcomes in patients with psychosis: a natural language processing approach using a clinical records search platform in south London.","Magrangeas TT, Kolliakou A, Sanyal J, Patel R, Stewart R.",,BMJ open,2022,2022-08-02,Y,Health Informatics; Adult Psychiatry; Schizophrenia & Psychotic Disorders,,,"<h4>Objectives</h4>We aimed to apply natural language processing algorithms in routine healthcare records to identify reported somatic passivity (external control of sensations, actions and impulses) and thought interference symptoms (thought broadcasting, insertion, withdrawal), first-rank symptoms traditionally central to diagnosing schizophrenia, and determine associations with prognosis by analysing routine outcomes.<h4>Design</h4>Four algorithms were developed on deidentified mental healthcare data and applied to ascertain recorded symptoms over the 3 months following first presentation to a mental healthcare provider in a cohort of patients with a primary schizophreniform disorder (ICD-10 F20-F29) diagnosis.<h4>Setting and participants</h4>From the electronic health records of a large secondary mental healthcare provider in south London, 9323 patients were ascertained from 2007 to the data extraction date (25 February 2020).<h4>Outcomes</h4>The primary binary dependent variable for logistic regression analyses was any negative outcome (Mental Health Act section, >2 antipsychotics prescribed, >22 days spent in crisis care) over the subsequent 2 years.<h4>Results</h4>Final adjusted models indicated significant associations of this composite outcome with baseline somatic passivity (prevalence 4.9%; adjusted OR 1.61, 95% CI 1.37 to 1.88), thought insertion (10.7%; 1.24, 95% CI 1.15 to 1.55) and thought withdrawal (4.9%; 1.36, 95% CI 1.10 to 1.69), but not independently with thought broadcast (10.3%; 1.05, 95% CI 0.91 to 1.22).<h4>Conclusions</h4>Symptoms traditionally central to the diagnosis of schizophrenia, but under-represented in current diagnostic frameworks, were thus identified as important predictors of short-term to medium-term prognosis in schizophreniform disorders.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/8/e057433.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057433; html:https://europepmc.org/articles/PMC9351333; pdf:https://europepmc.org/articles/PMC9351333?pdf=render
 35290489,https://doi.org/10.1007/s00247-021-05266-7,Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study.,"Withey SB, MacPherson L, Oates A, Powell S, Novak J, Abernethy L, Pizer B, Grundy R, Morgan PS, Bailey S, Mitra D, Arvanitis TN, Auer DP, Avula S, Peet AC.",,Pediatric radiology,2022,2022-03-15,Y,Brain; Tumor; Children; Perfusion; Magnetic Resonance Imaging; Blood volume; Multicenter; Leakage Correction; Dynamic Susceptibility-contrast Magnetic Resonance Imaging,,,"<h4>Background</h4>Relative cerebral blood volume (rCBV) measured using dynamic susceptibility-contrast MRI can differentiate between low- and high-grade pediatric brain tumors. Multicenter studies are required for translation into clinical practice.<h4>Objective</h4>We compared leakage-corrected dynamic susceptibility-contrast MRI perfusion parameters acquired at multiple centers in low- and high-grade pediatric brain tumors.<h4>Materials and methods</h4>Eighty-five pediatric patients underwent pre-treatment dynamic susceptibility-contrast MRI scans at four centers. MRI protocols were variable. We analyzed data using the Boxerman leakage-correction method producing pixel-by-pixel estimates of leakage-uncorrected (rCBV<sub>uncorr</sub>) and corrected (rCBV<sub>corr</sub>) relative cerebral blood volume, and the leakage parameter, K<sub>2</sub>. Histological diagnoses were obtained. Tumors were classified by high-grade tumor. We compared whole-tumor median perfusion parameters between low- and high-grade tumors and across tumor types.<h4>Results</h4>Forty tumors were classified as low grade, 45 as high grade. Mean whole-tumor median rCBV<sub>uncorr</sub> was higher in high-grade tumors than low-grade tumors (mean ± standard deviation [SD] = 2.37±2.61 vs. -0.14±5.55; P<0.01). Average median rCBV increased following leakage correction (2.54±1.63 vs. 1.68±1.36; P=0.010), remaining higher in high-grade tumors than low grade-tumors. Low-grade tumors, particularly pilocytic astrocytomas, showed T1-dominant leakage effects; high-grade tumors showed T2*-dominance (mean K<sub>2</sub>=0.017±0.049 vs. 0.002±0.017). Parameters varied with tumor type but not center. Median rCBV<sub>uncorr</sub> was higher (mean = 1.49 vs. 0.49; P=0.015) and K<sub>2</sub> lower (mean = 0.005 vs. 0.016; P=0.013) in children who received a pre-bolus of contrast agent compared to those who did not. Leakage correction removed the difference.<h4>Conclusion</h4>Dynamic susceptibility-contrast MRI acquired at multiple centers helped distinguish between children's brain tumors. Relative cerebral blood volume was significantly higher in high-grade compared to low-grade tumors and differed among common tumor types. Vessel leakage correction is required to provide accurate rCBV, particularly in low-grade enhancing tumors.",,pdf:https://link.springer.com/content/pdf/10.1007/s00247-021-05266-7.pdf; doi:https://doi.org/10.1007/s00247-021-05266-7; html:https://europepmc.org/articles/PMC9107460; pdf:https://europepmc.org/articles/PMC9107460?pdf=render
@@ -239,8 +239,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 36526319,https://doi.org/10.1136/bmjopen-2022-064910,Performance of scoring systems in selecting short stay medical admissions suitable for assessment in same day emergency care: an analysis of diagnostic accuracy in a UK hospital setting.,"Atkin C, Gallier S, Wallin E, Reddy-Kolanu V, Sapey E.",,BMJ open,2022,2022-12-16,Y,Internal Medicine; General Medicine (See Internal Medicine); Organisation Of Health Services,,,"<h4>Objectives</h4>To assess the performance of the Amb score and Glasgow Admission Prediction Score (GAPS) in identifying acute medical admissions suitable for same day emergency care (SDEC) in a large urban secondary centre.<h4>Design</h4>Retrospective assessment of routinely collected data from electronic healthcare records.<h4>Setting</h4>Single large urban tertiary care centre.<h4>Participants</h4>All unplanned admissions to general medicine on Monday-Friday, episodes starting 08:00-16:59 hours and lasting up to 48 hours, between 1 April 2019 and 9 March 2020.<h4>Main outcome measures</h4>Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.<h4>Results</h4>7365 episodes were assessed. 94.6% of episodes had an Amb score suggesting suitability for SDEC. The positive predictive value of the Amb score in identifying those discharged within 12 hours was 54.5% (95% CI 53.3% to 55.8%). The area under the receiver operating characteristic curve (AUROC) for the Amb score was 0.612 (95% CI 0.599 to 0.625).42.4% of episodes had a GAPS suggesting suitability for SDEC. The positive predictive value of the GAPS in identifying those discharged within 12 hours was 50.5% (95% CI 48.4% to 52.7%). The AUROC for the GAPS was 0.606 (95% CI 0.590 to 0.622).41.4% of the population had both an Amb and GAPS score suggestive of suitability for SDEC and 5.7% of the population had both and Amb and GAPS score suggestive of a lack of suitability for SDEC.<h4>Conclusions</h4>The Amb score and GAPS had poor discriminatory ability to identify acute medical admissions suitable for discharge within 12 hours, limiting their utility in selecting patients for assessment within SDEC services within this diverse patient population.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064910.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render
 35473737,https://doi.org/10.1136/bmjopen-2021-060413,"Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).","Haroon S, Nirantharakumar K, Hughes SE, Subramanian A, Aiyegbusi OL, Davies EH, Myles P, Williams T, Turner G, Chandan JS, McMullan C, Lord J, Wraith DC, McGee K, Denniston AK, Taverner T, Jackson LJ, Sapey E, Gkoutos G, Gokhale K, Leggett E, Iles C, Frost C, McNamara G, Bamford A, Marshall T, Zemedikun DT, Price G, Marwaha S, Simms-Williams N, Brown K, Walker A, Jones K, Matthews K, Camaradou J, Saint-Cricq M, Kumar S, Alder Y, Stanton DE, Agyen L, Baber M, Blaize H, Calvert M.",,BMJ open,2022,2022-04-26,Y,Therapeutics; immunology; Public Health; Covid-19,,,"<h4>Introduction</h4>Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.<h4>Methods and analysis</h4>A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.<h4>Ethics and dissemination</h4>Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.<h4>Trial registration number</h4>1567490.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e060413.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060413; html:https://europepmc.org/articles/PMC9044550; pdf:https://europepmc.org/articles/PMC9044550?pdf=render
 34977922,https://doi.org/10.1093/ije/dyab243,Cohort Profile: The COVID-19 in Pregnancy in Scotland (COPS) dynamic cohort of pregnant women to assess effects of viral and vaccine exposures on pregnancy.,"Stock SJ, Carruthers J, Denny C, Donaghy J, Goulding A, Hopcroft LEM, Hopkins L, Mulholland R, Agrawal U, Auyeung B, Katikireddi SV, McCowan C, Murray J, Robertson C, Sheikh A, Shi T, Simpson CR, Vasileiou E, Wood R.",,International journal of epidemiology,2022,2022-10-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/51/5/e245/46495259/dyab243.pdf; doi:https://doi.org/10.1093/ije/dyab243; html:https://europepmc.org/articles/PMC9557859; pdf:https://europepmc.org/articles/PMC9557859?pdf=render
-37678881,https://doi.org/10.1093/ageing/afad157,Survival and critical care use among people with dementia in a large English cohort.,"Yorganci E, Sleeman KE, Sampson EL, Stewart R, EMBED-Care Programme.",,Age and ageing,2023,2023-09-01,Y,Survival; Dementia; Intensive Care; Older People; Critical Care; Routine Data,,,"<h4>Background</h4>Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England.<h4>Objective</h4>To investigate critical care use and survival among people with dementia in a large London catchment area.<h4>Methods</h4>A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends.<h4>Results</h4>Of 19,787 people diagnosed with dementia, 726 (3.7%) had ≥1 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n = 345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (β = -0.05; 95% CI = -0.01, -0.0003; P = 0.03), while critical care admissions occurring during the last year of life increased (β = 0.11, 95% CI = 0.01, 0.20, P = 0.03).<h4>Conclusions</h4>In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.",,doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?pdf=render
 33228632,https://doi.org/10.1186/s12920-020-00826-6,A random forest based biomarker discovery and power analysis framework for diagnostics research.,"Acharjee A, Larkman J, Xu Y, Cardoso VR, Gkoutos GV.",,BMC medical genomics,2020,2020-11-23,Y,Biomarker; Feature Selection; Random Forest; Power Study,,,"<h4>Background</h4>Biomarker identification is one of the major and important goal of functional genomics and translational medicine studies. Large scale -omics data are increasingly being accumulated and can provide vital means for the identification of biomarkers for the early diagnosis of complex disease and/or for advanced patient/diseases stratification. These tasks are clearly interlinked, and it is essential that an unbiased and stable methodology is applied in order to address them. Although, recently, many, primarily machine learning based, biomarker identification approaches have been developed, the exploration of potential associations between biomarker identification and the design of future experiments remains a challenge.<h4>Methods</h4>In this study, using both simulated and published experimentally derived datasets, we assessed the performance of several state-of-the-art Random Forest (RF) based decision approaches, namely the Boruta method, the permutation based feature selection without correction method, the permutation based feature selection with correction method, and the backward elimination based feature selection method. Moreover, we conducted a power analysis to estimate the number of samples required for potential future studies.<h4>Results</h4>We present a number of different RF based stable feature selection methods and compare their performances using simulated, as well as published, experimentally derived, datasets. Across all of the scenarios considered, we found the Boruta method to be the most stable methodology, whilst the Permutation (Raw) approach offered the largest number of relevant features, when allowed to stabilise over a number of iterations. Finally, we developed and made available a web interface ( https://joelarkman.shinyapps.io/PowerTools/ ) to streamline power calculations thereby aiding the design of potential future studies within a translational medicine context.<h4>Conclusions</h4>We developed a RF-based biomarker discovery framework and provide a web interface for our framework, termed PowerTools, that caters the design of appropriate and cost-effective subsequent future omics study.",,pdf:https://bmcmedgenomics.biomedcentral.com/track/pdf/10.1186/s12920-020-00826-6; doi:https://doi.org/10.1186/s12920-020-00826-6; html:https://europepmc.org/articles/PMC7685541; pdf:https://europepmc.org/articles/PMC7685541?pdf=render
+37678881,https://doi.org/10.1093/ageing/afad157,Survival and critical care use among people with dementia in a large English cohort.,"Yorganci E, Sleeman KE, Sampson EL, Stewart R, EMBED-Care Programme.",,Age and ageing,2023,2023-09-01,Y,Survival; Dementia; Intensive Care; Older People; Critical Care; Routine Data,,,"<h4>Background</h4>Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England.<h4>Objective</h4>To investigate critical care use and survival among people with dementia in a large London catchment area.<h4>Methods</h4>A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends.<h4>Results</h4>Of 19,787 people diagnosed with dementia, 726 (3.7%) had ≥1 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n = 345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (β = -0.05; 95% CI = -0.01, -0.0003; P = 0.03), while critical care admissions occurring during the last year of life increased (β = 0.11, 95% CI = 0.01, 0.20, P = 0.03).<h4>Conclusions</h4>In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.",,doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?pdf=render
 37480048,https://doi.org/10.1186/s12872-023-03394-6,"Associations of circulating fatty acids with incident coronary heart disease: a prospective study of 89,242 individuals in UK Biobank.","Jin D, Trichia E, Islam N, Lewington S, Lacey B.",,BMC cardiovascular disorders,2023,2023-07-21,Y,Fatty acids; Lipids; Nuclear magnetic resonance; Coronary Heart Disease; Uk Biobank,,,"<h4>Background</h4>The role of fatty acids in coronary heart disease (CHD) remains uncertain. There is little evidence from large-scale epidemiological studies on the relevance of circulating fatty acids levels to CHD risk. This study aims to examine the independent associations of the major circulating types of fatty acids with CHD risk.<h4>Methods</h4>UK Biobank is a prospective study of adults aged 40-69 in 2006-2010; in 2012-2013, a subset of the participants were resurveyed. Analyses were restricted to 89,242 participants with baseline plasma fatty acids (measured using nuclear magnetic resonance spectroscopy) and without prior CHD. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the associations with incidence CHD, defined as the first-ever myocardial infarction, unstable angina pectoris, coronary-related death, or relevant procedure. And the major types of fatty acids were mutually adjusted to examine the independent associations. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey fatty acids measures.<h4>Results</h4>During a median follow-up of 11.8 years, 3,815 incident cases of CHD occurred. Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA), inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HR per standard deviation higher were 1.14 (95% CI, 1.09-1.20), 1.15 (1.10-1.21), 0.91 (0.87-0.94), and 1.04 (0.99-1.09) respectively. Independently of triglycerides and cholesterol, the inverse association with omega-3 PUFA was not materially changed, but the positive associations with SFA and MUFA attenuated to null after adjusting for triglycerides levels.<h4>Conclusions</h4>This large-scale study has quantitated the independent associations of circulating fatty acids with CHD risk. Omega-3 PUFA was inversely related to CHD risk, independently of other fatty acids and major lipid fractions. By contrast, independently of other fatty acids, the positive associations of circulating SFA and MUFA with CHD risk were mostly attributed to their relationship with triglycerides.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-023-03394-6; doi:https://doi.org/10.1186/s12872-023-03394-6; html:https://europepmc.org/articles/PMC10362581; pdf:https://europepmc.org/articles/PMC10362581?pdf=render
 37674175,https://doi.org/10.1186/s12884-023-05958-y,Using the COM-B framework to elucidate facilitators and barriers to COVID-19 vaccine uptake in pregnant women: a qualitative study.,"Patterson L, Berry E, Parsons C, Clarke B, Little A, Beggs J, Chuter A, Jackson T, Hsia Y, McGrath H, Millman C, Murphy S, Bradley DT, Milligan S.",,BMC pregnancy and childbirth,2023,2023-09-06,Y,Pregnancy; Qualitative; Barriers; Facilitators; Com-b; Covid-19 Vaccination,,,"Since April 2021, COVID-19 vaccines have been recommended for pregnant women. Despite this, COVID-19 vaccine uptake in this group is low compared to the non-pregnant population of childbearing age. Our aim was to understand barriers and facilitators to COVID-19 vaccine uptake among pregnant women in Northern Ireland using the COM-B framework, and so to make recommendations for public health interventions. The COM-B proposes that human behaviour is influenced by the extent to which a person has the capability, opportunity, and motivation to enact that behaviour. Understanding the factors underpinning behaviour through this lens helps discern what needs to change to change behaviour, therefore supporting the development of targeted interventions.This study consisted of eight semi-structured interviews with new/expectant mothers who did not receive a COVID-19 vaccine dose while pregnant since April 2021, and a focus group with five participants who received at least one COVID-19 vaccine dose while pregnant. Interview and focus group data were analysed using semi-deductive reflexive thematic analysis framed by a subtle realist approach. The COM-B was used to categorise codes and subthemes were developed within each COM-B construct.Within Psychological Capability, subthemes captured the need for consistent and reliable COVID-19 vaccine information and access to balanced and jargon-free, risk-benefit information that is tailored to the pregnant individual. The behaviour/opinions of family, friends, and local healthcare providers had a powerful influence on COVID-19 vaccine decisions (Social Opportunity). Integrating the COVID-19 vaccine as part of routine antenatal pathways was believed to support access and sense of familiarity (Physical Opportunity). Participants valued health autonomy, however experienced internal conflict driven by concerns about long-term side effects for their baby (Reflective Motivation). Feelings of fear, lack of empathy from healthcare providers, and anticipated guilt commonly underpinned indecision as to whether to get the vaccine (Automatic Motivation).Our study highlighted that the choice to accept a vaccine during pregnancy generates internal conflict and worry. Several participants cited their concern was primarily around the safety for their baby. Healthcare professionals (HCPs) play a significant part when it comes to decision making about COVID-19 vaccines among pregnant women. HCPs and pregnant women should be involved in the development of interventions to improve the delivery and communication of information.",,pdf:https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-023-05958-y; doi:https://doi.org/10.1186/s12884-023-05958-y; html:https://europepmc.org/articles/PMC10481472; pdf:https://europepmc.org/articles/PMC10481472?pdf=render
 37181393,https://doi.org/10.1016/j.jacasi.2022.12.006,Ambient Temperature and Myocardial Infarction: Who Is at Risk?,"Lowry MTH, Mills NL, Kimenai DM.",,JACC. Asia,2023,2023-03-14,Y,Myocardial infarction; Ambient temperature; risk factors,,,,,doi:https://doi.org/10.1016/j.jacasi.2022.12.006; doi:https://doi.org/10.1016/j.jacasi.2022.12.006; html:https://europepmc.org/articles/PMC10167505; pdf:https://europepmc.org/articles/PMC10167505?pdf=render
@@ -249,9 +249,9 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 36941845,https://doi.org/10.1016/j.xkme.2023.100613,"Cognitive Impairment, Frailty, and Adverse Outcomes Among Prevalent Hemodialysis Recipients: Results From a Large Prospective Cohort Study in the United Kingdom.","Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,Kidney medicine,2023,2023-02-09,Y,Mortality; Frailty; Dementia; Cognitive impairment; epidemiology; hemodialysis; Hospitalization; End-stage Kidney Disease,,,"<h4>Rationale & objective</h4>Frailty and cognitive impairment are common in hemodialysis recipients and have been associated with high mortality. There is considerable heterogeneity in frailty reporting, with little comparison between commonly used frailty tools and little exploration of the interplay between cognition and frailty. The aims were to explore the relationship between frailty scores and cognition and their associations with hospitalization and mortality.<h4>Study design</h4>Prospective cohort study.<h4>Setting & population</h4>Prevalent hemodialysis recipients linked to national datasets for hospitalization and mortality.<h4>Predictors</h4>Montreal Cognitive Assessment (MoCA), Frailty Phenotype, Frailty Index (FI), Edmonton Frailty Scale, and Clinical Frailty Scale (CFS) were performed at baseline. Cognitive impairment was defined as MoCA scores of <26, or <21 in dexterity impairment, <18 in visual impairment.<h4>Outcomes</h4>Mortality, hospitalization.<h4>Analytical approach</h4>Cox proportional hazards model for mortality, censored for end of follow-up. Negative binomial regression for admission rates, censored for death/end of follow-up.<h4>Results</h4>In total, 448 participants were recruited with valid MoCAs and followed up for a median of 685 days. There were 103 (23%) deaths and 1,120 admissions of at least one night. Cognitive impairment was identified in 346 (77.2%) participants. Increasing frailty by all definitions was associated with poorer cognition. Cognition was not associated with mortality (HR, 0.99; 95% CI, 0.95-1.03; <i>P</i> = 0.41) or hospitalization (IRR, 1.01; 95% CI, 0.99-1.04; <i>P</i> = 0.39) on multivariable analyses. There were interactions between MoCA scores and increasing frailty by FI (<i>P</i> = 0.002) and Clinical Frailty Scale (<i>P</i> = 0.005); admissions were highest when both MoCA and frailty scores were high, and when both scores were low.<h4>Limitations</h4>As frailty is a dynamic state, a single cross-sectional assessment may not accurately reflect its year-to-year variability. In addition, these findings are in maintenance dialysis and may not be transferable to incident hemodialysis. There were small variations in application of frailty tool criteria from other studies, which may have influenced the results.<h4>Conclusions</h4>Cognitive impairment is highly prevalent in this hemodialysis cohort. The interaction between cognition and frailty on rates of admission suggests the MoCA offers value in identifying higher risk hemodialysis populations with both high and low degrees of frailty.",,doi:https://doi.org/10.1016/j.xkme.2023.100613; doi:https://doi.org/10.1016/j.xkme.2023.100613; html:https://europepmc.org/articles/PMC10024232; pdf:https://europepmc.org/articles/PMC10024232?pdf=render
 34445233,https://doi.org/10.3390/ijms22168527,The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers. ,"Jahangiri L, Pucci P, Ishola T, Trigg RM, Williams JA, Pereira J, Cavanagh ML, Turner SD, Gkoutos GV, Tsaprouni L.",,International journal of molecular sciences,2021,2021-08-08,Y,,,,"MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.",,pdf:https://www.mdpi.com/1422-0067/22/16/8527/pdf?version=1628431894; doi:https://doi.org/10.3390/ijms22168527; html:https://europepmc.org/articles/PMC8395220; pdf:https://europepmc.org/articles/PMC8395220?pdf=render
 34879829,https://doi.org/10.1186/s12911-021-01693-6,Identifying and evaluating clinical subtypes of Alzheimer's disease in care electronic health records using unsupervised machine learning.,"Alexander N, Alexander DC, Barkhof F, Denaxas S.",,BMC medical informatics and decision making,2021,2021-12-08,Y,Alzheimer's disease; Clustering; Subtyping; Ehr; K-means,,,"<h4>Background</h4>Alzheimer's disease (AD) is a highly heterogeneous disease with diverse trajectories and outcomes observed in clinical populations. Understanding this heterogeneity can enable better treatment, prognosis and disease management. Studies to date have mainly used imaging or cognition data and have been limited in terms of data breadth and sample size. Here we examine the clinical heterogeneity of Alzheimer's disease patients using electronic health records (EHR) to identify and characterise disease subgroups using multiple clustering methods, identifying clusters which are clinically actionable.<h4>Methods</h4>We identified AD patients in primary care EHR from the Clinical Practice Research Datalink (CPRD) using a previously validated rule-based phenotyping algorithm. We extracted and included a range of comorbidities, symptoms and demographic features as patient features. We evaluated four different clustering methods (k-means, kernel k-means, affinity propagation and latent class analysis) to cluster Alzheimer's disease patients. We compared clusters on clinically relevant outcomes and evaluated each method using measures of cluster structure, stability, efficiency of outcome prediction and replicability in external data sets.<h4>Results</h4>We identified 7,913 AD patients, with a mean age of 82 and 66.2% female. We included 21 features in our analysis. We observed 5, 2, 5 and 6 clusters in k-means, kernel k-means, affinity propagation and latent class analysis respectively. K-means was found to produce the most consistent results based on four evaluative measures. We discovered a consistent cluster found in three of the four methods composed of predominantly female, younger disease onset (43% between ages 42-73) diagnosed with depression and anxiety, with a quicker rate of progression compared to the average across other clusters.<h4>Conclusion</h4>Each clustering approach produced substantially different clusters and K-Means performed the best out of the four methods based on the four evaluative criteria. However, the consistent appearance of one particular cluster across three of the four methods potentially suggests the presence of a distinct disease subtype that merits further exploration. Our study underlines the variability of the results obtained from different clustering approaches and the importance of systematically evaluating different approaches for identifying disease subtypes in complex EHR.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-021-01693-6; doi:https://doi.org/10.1186/s12911-021-01693-6; html:https://europepmc.org/articles/PMC8653614; pdf:https://europepmc.org/articles/PMC8653614?pdf=render
-37363797,https://doi.org/10.1016/j.lanepe.2023.100653,Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SC, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Lancet regional health. Europe,2023,2023-05-16,Y,Antimicrobial resistance; Primary Care; Broad-spectrum Antibiotics; Covid-19 Pandemic,,,"<h4>Background</h4>The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started.<h4>Methods</h4>With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models.<h4>Findings</h4>Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13).<h4>Interpretation</h4>An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation.<h4>Funding</h4>This work was supported by Health Data Research UK and by National Institute for Health Research.",,doi:https://doi.org/10.1016/j.lanepe.2023.100653; doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render
-35910710,https://doi.org/10.1093/rap/rkac056,Real-world use of an etanercept biosimilar including selective <i>versus</i> automatic substitution in inflammatory arthritis patients: a UK-based electronic health records study.,"Cooksey R, Brophy S, Kennedy J, Seaborne M, Choy E.",,Rheumatology advances in practice,2022,2022-07-27,Y,RA; As; PSA; Etanercept; Biosimilars,,,"<h4>Objective</h4>Biosimilars are approved as an alternative treatment to their originators. We compared the clinical outcomes of etanercept (ETN) biosimilar compared with ETN originator in real-world practice, from two local health boards in Wales with different policies on switching: automatic <i>vs</i> selective.<h4>Methods</h4>Data from the Secure Anonymised Information Linkage (SAIL) databank in Wales were used to create a retrospective cohort study using linked primary and secondary care data. Patients aged ≥18 years with diagnosis codes for RA, PsA or AS were included. Outcomes included treatment failure and DAS-28 score (for RA). The local health board with a policy of automatic switching (i.e. clinician/nurse involvement not mandated) is labelled as automatic switch area, and the other, which required clinician/nurse supervision, as selective switch.<h4>Results</h4>Of 8925 individuals with inflammatory arthritis, 13.3% (365) received ETN biosimilar and 31.5% (863) ETN originator. The treatment discontinuation rate was similar for ETN biosimilar and originator by Kaplan-Meier analysis. More biosimilar failure patients were treated in the automatic switch area (15 <i>vs</i> 4.8%). In the automatic switch area, 28.8% (75 of 260) of patients switched automatically from ETN originator to biosimilar compared with 10.5% (11 of 105) in the selective switch area. ETN biosimilar reduced DAS-28 by 1.6 ± 1.8 in the selective switch area <i>vs</i> 0.4 ± 0.6 in the automatic switch area.<h4>Conclusion</h4>The ETN biosimilar was well tolerated. Fewer people were switched using selective policy, but this was associated with lower failure rates. Automatic switch policy led to more patients being switched and did not lead to significant worsening of disease.",,pdf:https://academic.oup.com/rheumap/advance-article-pdf/doi/10.1093/rap/rkac056/45095148/rkac056.pdf; doi:https://doi.org/10.1093/rap/rkac056; html:https://europepmc.org/articles/PMC9336562; pdf:https://europepmc.org/articles/PMC9336562?pdf=render
 33683514,https://doi.org/10.1007/s10237-021-01437-5,A framework for incorporating 3D hyperelastic vascular wall models in 1D blood flow simulations.,"Coccarelli A, Carson JM, Aggarwal A, Pant S.",,Biomechanics and modeling in mechanobiology,2021,2021-03-08,Y,Pulse wave velocity; Common carotid artery; Hyperelasticity; Tube Law; Axial Stretching; One-dimensional Blood Flow Modelling,,,"We present a novel framework for investigating the role of vascular structure on arterial haemodynamics in large vessels, with a special focus on the human common carotid artery (CCA). The analysis is carried out by adopting a three-dimensional (3D) derived, fibre-reinforced, hyperelastic structural model, which is coupled with an axisymmetric, reduced order model describing blood flow. The vessel transmural pressure and lumen area are related via a Holzapfel-Ogden type of law, and the residual stresses along the thickness and length of the vessel are also accounted for. After a structural characterization of the adopted hyperelastic model, we investigate the link underlying the vascular wall response and blood-flow dynamics by comparing the proposed framework results against a popular tube law. The comparison shows that the behaviour of the model can be captured by the simpler linear surrogate only if a representative value of compliance is applied. Sobol's multi-variable sensitivity analysis is then carried out in order to identify the extent to which the structural parameters have an impact on the CCA haemodynamics. In this case, the local pulse wave velocity (PWV) is used as index for representing the arterial transmission capacity of blood pressure waveforms. The sensitivity analysis suggests that some geometrical factors, such as the stress-free inner radius and opening angle, play a major role on the system's haemodynamics. Subsequently, we quantified the differences in haemodynamic variables obtained from different virtual CCAs, tube laws and flow conditions. Although each artery presents a distinct vascular response, the differences obtained across different flow regimes are not significant. As expected, the linear tube law is unable to accurately capture all the haemodynamic features characterizing the current model. The findings from the sensitivity analysis are further confirmed by investigating the axial stretching effect on the CCA fluid dynamics. This factor does not seem to alter the pressure and flow waveforms. On the contrary, it is shown that, for an axially stretched vessel, the vascular wall exhibits an attenuation in absolute distension and an increase in circumferential stress, corroborating the findings of previous studies. This analysis shows that the new model offers a good balance between computational complexity and physics captured, making it an ideal framework for studies aiming to investigate the profound link between vascular mechanobiology and blood flow.",,pdf:https://link.springer.com/content/pdf/10.1007/s10237-021-01437-5.pdf; doi:https://doi.org/10.1007/s10237-021-01437-5; html:https://europepmc.org/articles/PMC8298378; pdf:https://europepmc.org/articles/PMC8298378?pdf=render
+35910710,https://doi.org/10.1093/rap/rkac056,Real-world use of an etanercept biosimilar including selective <i>versus</i> automatic substitution in inflammatory arthritis patients: a UK-based electronic health records study.,"Cooksey R, Brophy S, Kennedy J, Seaborne M, Choy E.",,Rheumatology advances in practice,2022,2022-07-27,Y,RA; As; PSA; Etanercept; Biosimilars,,,"<h4>Objective</h4>Biosimilars are approved as an alternative treatment to their originators. We compared the clinical outcomes of etanercept (ETN) biosimilar compared with ETN originator in real-world practice, from two local health boards in Wales with different policies on switching: automatic <i>vs</i> selective.<h4>Methods</h4>Data from the Secure Anonymised Information Linkage (SAIL) databank in Wales were used to create a retrospective cohort study using linked primary and secondary care data. Patients aged ≥18 years with diagnosis codes for RA, PsA or AS were included. Outcomes included treatment failure and DAS-28 score (for RA). The local health board with a policy of automatic switching (i.e. clinician/nurse involvement not mandated) is labelled as automatic switch area, and the other, which required clinician/nurse supervision, as selective switch.<h4>Results</h4>Of 8925 individuals with inflammatory arthritis, 13.3% (365) received ETN biosimilar and 31.5% (863) ETN originator. The treatment discontinuation rate was similar for ETN biosimilar and originator by Kaplan-Meier analysis. More biosimilar failure patients were treated in the automatic switch area (15 <i>vs</i> 4.8%). In the automatic switch area, 28.8% (75 of 260) of patients switched automatically from ETN originator to biosimilar compared with 10.5% (11 of 105) in the selective switch area. ETN biosimilar reduced DAS-28 by 1.6 ± 1.8 in the selective switch area <i>vs</i> 0.4 ± 0.6 in the automatic switch area.<h4>Conclusion</h4>The ETN biosimilar was well tolerated. Fewer people were switched using selective policy, but this was associated with lower failure rates. Automatic switch policy led to more patients being switched and did not lead to significant worsening of disease.",,pdf:https://academic.oup.com/rheumap/advance-article-pdf/doi/10.1093/rap/rkac056/45095148/rkac056.pdf; doi:https://doi.org/10.1093/rap/rkac056; html:https://europepmc.org/articles/PMC9336562; pdf:https://europepmc.org/articles/PMC9336562?pdf=render
+37363797,https://doi.org/10.1016/j.lanepe.2023.100653,Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SC, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Lancet regional health. Europe,2023,2023-05-16,Y,Antimicrobial resistance; Primary Care; Broad-spectrum Antibiotics; Covid-19 Pandemic,,,"<h4>Background</h4>The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started.<h4>Methods</h4>With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models.<h4>Findings</h4>Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13).<h4>Interpretation</h4>An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation.<h4>Funding</h4>This work was supported by Health Data Research UK and by National Institute for Health Research.",,doi:https://doi.org/10.1016/j.lanepe.2023.100653; doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render
 34829865,https://doi.org/10.3390/biomedicines9111636,Machine Learning-Based Identification of Potentially Novel Non-Alcoholic Fatty Liver Disease Biomarkers. ,"Shafiha R, Bahcivanci B, Gkoutos GV, Acharjee A.",,Biomedicines,2021,2021-11-07,Y,,,,"Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that presents a great challenge for treatment and prevention.. This study aims to implement a machine learning approach that employs such datasets to identify potential biomarker targets. We developed a pipeline to identify potential biomarkers for NAFLD that includes five major processes, namely, a pre-processing step, a feature selection and a generation of a random forest model and, finally, a downstream feature analysis and a provision of a potential biological interpretation. The pre-processing step includes data normalising and variable extraction accompanied by appropriate annotations. A feature selection based on a differential gene expression analysis is then conducted to identify significant features and then employ them to generate a random forest model whose performance is assessed based on a receiver operating characteristic curve. Next, the features are subjected to a downstream analysis, such as univariate analysis, a pathway enrichment analysis, a network analysis and a generation of correlation plots, boxplots and heatmaps. Once the results are obtained, the biological interpretation and the literature validation is conducted over the identified features and results. We applied this pipeline to transcriptomics and lipidomic datasets and concluded that the C4BPA gene could play a role in the development of NAFLD. The activation of the complement pathway, due to the downregulation of the C4BPA gene, leads to an increase in triglyceride content, which might further render the lipid metabolism. This approach identified the C4BPA gene, an inhibitor of the complement pathway, as a potential biomarker for the development of NAFLD.",,pdf:https://www.mdpi.com/2227-9059/9/11/1636/pdf?version=1637024773; doi:https://doi.org/10.3390/biomedicines9111636; html:https://europepmc.org/articles/PMC8615894; pdf:https://europepmc.org/articles/PMC8615894?pdf=render
 36460578,https://doi.org/10.1016/s2589-7500(22)00187-x,Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study.,"Kuan V, Denaxas S, Patalay P, Nitsch D, Mathur R, Gonzalez-Izquierdo A, Sofat R, Partridge L, Roberts A, Wong ICK, Hingorani M, Chaturvedi N, Hemingway H, Hingorani AD, Multimorbidity Mechanism and Therapeutic Research Collaborative (MMTRC).",,The Lancet. Digital health,2023,2022-11-29,N,,,,"<h4>Background</h4>Globally, there is a paucity of multimorbidity and comorbidity data, especially for minority ethnic groups and younger people. We estimated the frequency of common disease combinations and identified non-random disease associations for all ages in a multiethnic population.<h4>Methods</h4>In this population-based study, we examined multimorbidity and comorbidity patterns stratified by ethnicity or race, sex, and age for 308 health conditions using electronic health records from individuals included on the Clinical Practice Research Datalink linked with the Hospital Episode Statistics admitted patient care dataset in England. We included individuals who were older than 1 year and who had been registered for at least 1 year in a participating general practice during the study period (between April 1, 2010, and March 31, 2015). We identified the most common combinations of conditions and comorbidities for index conditions. We defined comorbidity as the accumulation of additional conditions to an index condition over an individual's lifetime. We used network analysis to identify conditions that co-occurred more often than expected by chance. We developed online interactive tools to explore multimorbidity and comorbidity patterns overall and by subgroup based on ethnicity, sex, and age.<h4>Findings</h4>We collected data for 3 872 451 eligible patients, of whom 1 955 700 (50·5%) were women and girls, 1 916 751 (49·5%) were men and boys, 2 666 234 (68·9%) were White, 155 435 (4·0%) were south Asian, and 98 815 (2·6%) were Black. We found that a higher proportion of boys aged 1-9 years (132 506 [47·8%] of 277 158) had two or more diagnosed conditions than did girls in the same age group (106 982 [40·3%] of 265 179), but more women and girls were diagnosed with multimorbidity than were boys aged 10 years and older and men (1 361 232 [80·5%] of 1 690 521 vs 1 161 308 [70·8%] of 1 639 593). White individuals (2 097 536 [78·7%] of 2 666 234) were more likely to be diagnosed with two or more conditions than were Black (59 339 [60·1%] of 98 815) or south Asian individuals (93 617 [60·2%] of 155 435). Depression commonly co-occurred with anxiety, migraine, obesity, atopic conditions, deafness, soft-tissue disorders, and gastrointestinal disorders across all subgroups. Heart failure often co-occurred with hypertension, atrial fibrillation, osteoarthritis, stable angina, myocardial infarction, chronic kidney disease, type 2 diabetes, and chronic obstructive pulmonary disease. Spinal fractures were most strongly non-randomly associated with malignancy in Black individuals, but with osteoporosis in White individuals. Hypertension was most strongly associated with kidney disorders in those aged 20-29 years, but with dyslipidaemia, obesity, and type 2 diabetes in individuals aged 40 years and older. Breast cancer was associated with different comorbidities in individuals from different ethnic groups. Asthma was associated with different comorbidities between males and females. Bipolar disorder was associated with different comorbidities in younger age groups compared with older age groups.<h4>Interpretation</h4>Our findings and interactive online tools are a resource for: patients and their clinicians, to prevent and detect comorbid conditions; research funders and policy makers, to redesign service provision, training priorities, and guideline development; and biomedical researchers and manufacturers of medicines, to provide leads for research into common or sequential pathways of disease and inform the design of clinical trials.<h4>Funding</h4>UK Research and Innovation, Medical Research Council, National Institute for Health and Care Research, Department of Health and Social Care, Wellcome Trust, British Heart Foundation, and The Alan Turing Institute.",,pdf:http://www.thelancet.com/article/S258975002200187X/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00187-X
 32634370,https://doi.org/10.1098/rsob.200121,Core regulatory circuitries in defining cancer cell identity across the malignant spectrum.,"Jahangiri L, Tsaprouni L, Trigg RM, Williams JA, Gkoutos GV, Turner SD, Pereira J.",,Open biology,2020,2020-07-08,Y,Cell Identity; Super-enhancers; Core Regulatory Circuitry; Liquid And Solid Cancers,,,"Gene expression programmes driving cell identity are established by tightly regulated transcription factors that auto- and cross-regulate in a feed-forward manner, forming core regulatory circuitries (CRCs). CRC transcription factors create and engage super-enhancers by recruiting acetylation writers depositing permissive H3K27ac chromatin marks. These super-enhancers are largely associated with BET proteins, including BRD4, that influence higher-order chromatin structure. The orchestration of these events triggers accessibility of RNA polymerase machinery and the imposition of lineage-specific gene expression. In cancers, CRCs drive cell identity by superimposing developmental programmes on a background of genetic alterations. Further, the establishment and maintenance of oncogenic states are reliant on CRCs that drive factors involved in tumour development. Hence, the molecular dissection of CRC components driving cell identity and cancer state can contribute to elucidating mechanisms of diversion from pre-determined developmental programmes and highlight cancer dependencies. These insights can provide valuable opportunities for identifying and re-purposing drug targets. In this article, we review the current understanding of CRCs across solid and liquid malignancies and avenues of investigation for drug development efforts. We also review techniques used to understand CRCs and elaborate the indication of discussed CRC transcription factors in the wider context of cancer CRC models.",,pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.200121; doi:https://doi.org/10.1098/rsob.200121; html:https://europepmc.org/articles/PMC7574545; pdf:https://europepmc.org/articles/PMC7574545?pdf=render
@@ -272,13 +272,13 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 36530697,https://doi.org/10.3389/fpubh.2022.1035415,Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study.,"Ronaldson A, Arias de la Torre J, Ashworth M, Hansell AL, Hotopf M, Mudway I, Stewart R, Dregan A, Bakolis I.",,Frontiers in public health,2022,2022-12-02,Y,Air pollution; Nitrogen dioxide; particulate matter; Health Status; Exploratory Factor Analysis; Multimorbidity,,,"<h4>Background</h4>Long-term exposure to air pollution concentrations is known to be adversely associated with a broad range of single non-communicable diseases, but its role in multimorbidity has not been investigated in the UK. We aimed to assess associations between long-term air pollution exposure and multimorbidity status, severity, and patterns using the UK Biobank cohort.<h4>Methods</h4>Multimorbidity status was calculated based on 41 physical and mental conditions. We assessed cross-sectional associations between annual modeled particulate matter (PM)<sub>2.5</sub>, PM<sub>coarse</sub>, PM<sub>10</sub>, and nitrogen dioxide (NO<sub>2</sub>) concentrations (μg/m<sup>3</sup>-modeled to residential address) and multimorbidity status at the baseline assessment (2006-2010) in 364,144 people (mean age: 52.2 ± 8.1 years, 52.6% female). Air pollutants were categorized into quartiles to assess dose-response associations. Among those with multimorbidity (≥2 conditions; <i>n</i> = 156,395) we assessed associations between air pollutant exposure levels and multimorbidity severity and multimorbidity patterns, which were identified using exploratory factor analysis. Associations were explored using generalized linear models adjusted for sociodemographic, behavioral, and environmental indicators.<h4>Results</h4>Higher exposures to PM<sub>2.5</sub>, and NO<sub>2</sub> were associated with multimorbidity status in a dose-dependent manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) [PM<sub>2.5</sub>: adjusted odds ratio (adjOR) = 1.21 (95% CI = 1.18, 1.24); NO<sub>2</sub>: adjOR = 1.19 (95 % CI = 1.16, 1.23)]. We also observed dose-response associations between air pollutant exposures and multimorbidity severity scores. We identified 11 multimorbidity patterns. Air pollution was associated with several multimorbidity patterns with strongest associations (Q4 vs. Q1) observed for neurological (stroke, epilepsy, alcohol/substance dependency) [PM<sub>2.5</sub>: adjOR = 1.31 (95% CI = 1.14, 1.51); NO<sub>2</sub>: adjOR = 1.33 (95% CI = 1.11, 1.60)] and respiratory patterns (COPD, asthma) [PM<sub>2.5</sub>: adjOR = 1.24 (95% CI = 1.16, 1.33); NO<sub>2</sub>: adjOR = 1.26 (95% CI = 1.15, 1.38)].<h4>Conclusions</h4>This cross-sectional study provides evidence that exposure to air pollution might be associated with having multimorbid, multi-organ conditions. Longitudinal studies are needed to further explore these associations.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1035415/pdf; doi:https://doi.org/10.3389/fpubh.2022.1035415; html:https://europepmc.org/articles/PMC9755180; pdf:https://europepmc.org/articles/PMC9755180?pdf=render
 37528841,https://doi.org/10.1016/j.eclinm.2023.102064,Repeated antibiotic exposure and risk of hospitalisation and death following COVID-19 infection (OpenSAFELY): a matched case-control study.,"Yang YT, Wong D, Ashcroft DM, Massey J, MacKenna B, Fisher L, Mehrkar A, Bacon SC, OpenSAFELY collaborative, Hand K, Zhong X, Fahmi A, Goldacre B, van Staa T, Palin V.",,EClinicalMedicine,2023,2023-07-05,Y,Antibiotics; Primary Care; Severe Outcome; Covid-19,,,"<h4>Background</h4>Identifying potential risk factors related to severe COVID-19 outcomes is important. Repeated intermittent antibiotic use is known be associated with adverse outcomes. This study aims to examine whether prior frequent antibiotic exposure is associated with severe COVID-19 outcomes.<h4>Methods</h4>With the approval of NHS England, we used the OpenSAFELY platform, which integrated primary and secondary care, COVID-19 test, and death registration data. This matched case-control study included 0.67 million patients (aged 18-110 years) from an eligible 2.47 million patients with incident COVID-19 by matching with replacement. Inclusion criteria included registration within one general practice for at least 3 years and infection with incident COVID-19. Cases were identified according to different severity of COVID-19 outcomes. Cases and eligible controls were 1:6 matched on age, sex, region of GP practice, and index year and month of COVID-19 infection. Five quintile groups, based on the number of previous 3-year antibiotic prescriptions, were created to indicate the frequency of prior antibiotic exposure. Conditional logistic regression used to compare the differences between case and control groups, adjusting for ethnicity, body mass index, comorbidities, vaccination history, deprivation, and care home status. Sensitivity analyses were done to explore potential confounding and the effects of missing data.<h4>Findings</h4>Based on our inclusion criteria, between February 1, 2020 and December 31, 2021, 98,420 patients were admitted to hospitals and 22,660 died. 55 unique antibiotics were prescribed. A dose-response relationship between number of antibiotic prescriptions and risk of severe COVID-19 outcome was observed. Patients in the highest quintile with history of prior antibiotic exposure had 1.80 times greater odds of hospitalisation compared to patients without antibiotic exposure (adjusted odds ratio [OR] 1.80, 95% Confidence Interval [CI] 1.75-1.84). Similarly, the adjusted OR for hospitalised patients with death outcomes was 1.34 (95% CI 1.28-1.41). Larger number of prior antibiotic type was also associated with more severe COVID-19 related hospital admission. The adjusted OR of quintile 5 exposure (the most frequent) with more than 3 antibiotic types was around 2 times larger than quintile 1 (only 1 type; OR 1.80, 95% CI 1.75-1.84 vs. OR 1.03, 95% CI 1.01-1.05).<h4>Interpretation</h4>Our observational study has provided evidence that antibiotic exposure frequency and diversity may be associated with COVID-19 severity, potentially suggesting adverse effects of repeated intermittent antibiotic use. Future work could work to elucidate causal links and potential mechanisms. Antibiotic stewardship should put more emphasis on long-term antibiotic exposure and its adverse outcome to increase the awareness of appropriate antibiotics use.<h4>Funding</h4>Health Data Research UK and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102064; html:https://europepmc.org/articles/PMC10388579; pdf:https://europepmc.org/articles/PMC10388579?pdf=render
 35336739,https://doi.org/10.3390/biology11030365,Machine Learning-Based Identification of Colon Cancer Candidate Diagnostics Genes. ,"Koppad S, Basava A, Nash K, Gkoutos GV, Acharjee A.",,Biology,2022,2022-02-25,Y,,,,"Colorectal cancer (CRC) is the third leading cause of cancer-related death and the fourth most commonly diagnosed cancer worldwide. Due to a lack of diagnostic biomarkers and understanding of the underlying molecular mechanisms, CRC's mortality rate continues to grow. CRC occurrence and progression are dynamic processes. The expression levels of specific molecules vary at various stages of CRC, rendering its early detection and diagnosis challenging and the need for identifying accurate and meaningful CRC biomarkers more pressing. The advances in high-throughput sequencing technologies have been used to explore novel gene expression, targeted treatments, and colon cancer pathogenesis. Such approaches are routinely being applied and result in large datasets whose analysis is increasingly becoming dependent on machine learning (ML) algorithms that have been demonstrated to be computationally efficient platforms for the identification of variables across such high-dimensional datasets. We developed a novel ML-based experimental design to study CRC gene associations. Six different machine learning methods were employed as classifiers to identify genes that can be used as diagnostics for CRC using gene expression and clinical datasets. The accuracy, sensitivity, specificity, F1 score, and area under receiver operating characteristic (AUROC) curve were derived to explore the differentially expressed genes (DEGs) for CRC diagnosis. Gene ontology enrichment analyses of these DEGs were performed and predicted gene signatures were linked with miRNAs. We evaluated six machine learning classification methods (Adaboost, ExtraTrees, logistic regression, naïve Bayes classifier, random forest, and XGBoost) across different combinations of training and test datasets over GEO datasets. The accuracy and the AUROC of each combination of training and test data with different algorithms were used as comparison metrics. Random forest (RF) models consistently performed better than other models. In total, 34 genes were identified and used for pathway and gene set enrichment analysis. Further mapping of the 34 genes with miRNA identified interesting miRNA hubs genes. We identified 34 genes with high accuracy that can be used as a diagnostics panel for CRC.",,pdf:https://www.mdpi.com/2079-7737/11/3/365/pdf?version=1645777713; doi:https://doi.org/10.3390/biology11030365; html:https://europepmc.org/articles/PMC8944988; pdf:https://europepmc.org/articles/PMC8944988?pdf=render
-36944118,https://doi.org/10.2337/dc22-1238,Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.,"Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J, Sattar N, MacDonald T, McCrimmon RJ, Morales DR, Pearson ER, Scottish Diabetes Research Network Epidemiology Group.",,Diabetes care,2023,2023-05-01,Y,,,,"<h4>Objective</h4>To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.<h4>Research design and methods</h4>A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.<h4>Results</h4>Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17).<h4>Conclusions</h4>Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.",,pdf:https://diabetesjournals.org/care/article-pdf/46/5/967/702262/dc221238.pdf; doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?pdf=render
 32851419,https://doi.org/10.1007/s00394-020-02372-4,Vitamin D and COVID-19 infection and mortality in UK Biobank.,"Hastie CE, Pell JP, Sattar N.",,European journal of nutrition,2021,2020-08-26,Y,Vitamin D; Mortality; Covid-19,,,"<h4>Purpose</h4>Low blood 25-hydroxyvitamin D (25(OH)D) concentration has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether baseline serum 25(OH)D concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants.<h4>Methods</h4>UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including serum 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and Poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection.<h4>Results</h4>Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. 25(OH)D concentration was associated with severe COVID-19 infection and mortality univariably (mortality per 10 nmol/L 25(OH)D HR  0.92; 95% CI 0.86-0.98; p = 0.016), but not after adjustment for confounders (mortality per 10 nmol/L 25(OH)D HR 0.98; 95% CI = 0.91-1.06; p = 0.696). Vitamin D insufficiency or deficiency was also not independently associated with either COVID-19 infection or linked mortality.<h4>Conclusions</h4>Our findings do not support a potential link between 25(OH)D concentrations and risk of severe COVID-19 infection and mortality. Randomised trials are needed to prove a beneficial role for vitamin D in the prevention of severe COVID-19 reactions or death.",,pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02372-4.pdf; doi:https://doi.org/10.1007/s00394-020-02372-4; html:https://europepmc.org/articles/PMC7449523; pdf:https://europepmc.org/articles/PMC7449523?pdf=render
+36944118,https://doi.org/10.2337/dc22-1238,Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.,"Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J, Sattar N, MacDonald T, McCrimmon RJ, Morales DR, Pearson ER, Scottish Diabetes Research Network Epidemiology Group.",,Diabetes care,2023,2023-05-01,Y,,,,"<h4>Objective</h4>To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.<h4>Research design and methods</h4>A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.<h4>Results</h4>Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17).<h4>Conclusions</h4>Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.",,pdf:https://diabetesjournals.org/care/article-pdf/46/5/967/702262/dc221238.pdf; doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?pdf=render
 37558806,https://doi.org/10.1038/s41598-023-40215-4,"Associations of the serotonin transporter gene polymorphism, 5-HTTLPR, and adverse life events with late life depression in the elderly Lithuanian population.","Simonyte S, Grabauskyte I, Macijauskiene J, Lesauskaite V, Lesauskaite V, Kvaal KS, Stewart R.",,Scientific reports,2023,2023-08-09,Y,,,,"Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65 years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6 months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression.",,doi:https://doi.org/10.1038/s41598-023-40215-4; html:https://europepmc.org/articles/PMC10412533; pdf:https://europepmc.org/articles/PMC10412533?pdf=render
+33114263,https://doi.org/10.3390/ijms21217886,Biomarker Prioritisation and Power Estimation Using Ensemble Gene Regulatory Network Inference.,"Aziz F, Acharjee A, Williams JA, Russ D, Bravo-Merodio L, Gkoutos GV.",,International journal of molecular sciences,2020,2020-10-23,Y,Experimental design; Gene Regulatory Network; Causal Modelling; Omics Integration,,,"Inferring the topology of a gene regulatory network (GRN) from gene expression data is a challenging but important undertaking for gaining a better understanding of gene regulation. Key challenges include working with noisy data and dealing with a higher number of genes than samples. Although a number of different methods have been proposed to infer the structure of a GRN, there are large discrepancies among the different inference algorithms they adopt, rendering their meaningful comparison challenging. In this study, we used two methods, namely the MIDER (Mutual Information Distance and Entropy Reduction) and the PLSNET (Partial least square based feature selection) methods, to infer the structure of a GRN directly from data and computationally validated our results. Both methods were applied to different gene expression datasets resulting from inflammatory bowel disease (IBD), pancreatic ductal adenocarcinoma (PDAC), and acute myeloid leukaemia (AML) studies. For each case, gene regulators were successfully identified. For example, for the case of the IBD dataset, the <i>UGT1A</i> family genes were identified as key regulators while upon analysing the PDAC dataset, the <i>SULF1</i> and <i>THBS2</i> genes were depicted. We further demonstrate that an ensemble-based approach, that combines the output of the MIDER and PLSNET algorithms, can infer the structure of a GRN from data with higher accuracy. We have also estimated the number of the samples required for potential future validation studies. Here, we presented our proposed analysis framework that caters not only to candidate regulator genes prediction for potential validation experiments but also an estimation of the number of samples required for these experiments.",,pdf:https://www.mdpi.com/1422-0067/21/21/7886/pdf?version=1604329387; doi:https://doi.org/10.3390/ijms21217886; html:https://europepmc.org/articles/PMC7660606; pdf:https://europepmc.org/articles/PMC7660606?pdf=render
 36217535,https://doi.org/10.1038/s43856-022-00185-6,"Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity.","Penney NC, Yeung DKT, Garcia-Perez I, Posma JM, Kopytek A, Garratt B, Ashrafian H, Frost G, Marchesi JR, Purkayastha S, Hoyles L, Darzi A, Holmes E.",,Communications medicine,2022,2022-10-07,Y,Obesity; Type 2 diabetes; Dynamical Systems; Microbiome,,,"<h4>Background</h4>Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated.<h4>Methods</h4>To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D (<i>n</i> = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; <i>n</i> = 27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level.<h4>Results</h4>Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control.<h4>Conclusion</h4>We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality.",,pdf:https://www.nature.com/articles/s43856-022-00185-6.pdf; doi:https://doi.org/10.1038/s43856-022-00185-6; html:https://europepmc.org/articles/PMC9546886; pdf:https://europepmc.org/articles/PMC9546886?pdf=render
 37795045,https://doi.org/10.1177/26320843221147855,Monitoring metrics over time: Why clinical trialists need to systematically collect site performance metrics.,"Yorke-Edwards V, Diaz-Montana C, Murray ML, Sydes MR, Love SB.",,Research methods in medicine & health sciences,2023,2022-12-21,N,Clinical Trials; Risk-based Monitoring; Central Monitoring; Centralised Monitoring; Study-Within-A-Trial (Swat),,,"<h4>Background</h4>Over the last decade, there has been an increasing interest in risk-based monitoring (RBM) in clinical trials, resulting in a number of guidelines from regulators and its inclusion in ICH GCP. However, there is a lack of detail on how to approach RBM from a practical perspective, and insufficient understanding of best practice.<h4>Purpose</h4>We present a method for clinical trials units to track their metrics within clinical trials using descriptive statistics and visualisations.<h4>Research design</h4>We suggest descriptive statistics and visualisations within a SWAT methodology.<h4>Study sample</h4>We illustrate this method using the metrics from TEMPER, a monitoring study carried out in three trials at the MRC Clinical Trials Unit at UCL.<h4>Data collection</h4>The data collection for TEMPER is described in <i>DOI: 10.1177/1740774518793379</i>.<h4>Results</h4>We show the results and discuss a protocol for a Study-Within-A-Trial (SWAT 167) for those wishing to use the method.<h4>Conclusions</h4>The potential benefits metric tracking brings to clinical trials include enhanced assessment of sites for potential corrective action, improved evaluation and contextualisation of the influence of metrics and their thresholds, and the establishment of best practice in RBM. The standardisation of the collection of such monitoring data would benefit both individual trials and the clinical trials community.",,doi:https://doi.org/10.1177/26320843221147855; html:https://europepmc.org/articles/PMC7615148; pdf:https://europepmc.org/articles/PMC7615148?pdf=render; doi:https://doi.org/10.1177/26320843221147855
 36701357,https://doi.org/10.1371/journal.pone.0280943,Awareness and perceptions of Long COVID among people in the REACT programme: Early insights from a pilot interview study.,"Cooper E, Lound A, Atchison CJ, Whitaker M, Eccles C, Cooke GS, Elliott P, Ward H.",,PloS one,2023,2023-01-26,Y,,,,"<h4>Background</h4>Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID.<h4>Methods</h4>People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis.<h4>Results</h4>We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID.<h4>Conclusion</h4>This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0280943&type=printable; doi:https://doi.org/10.1371/journal.pone.0280943; html:https://europepmc.org/articles/PMC9879384; pdf:https://europepmc.org/articles/PMC9879384?pdf=render
-33114263,https://doi.org/10.3390/ijms21217886,Biomarker Prioritisation and Power Estimation Using Ensemble Gene Regulatory Network Inference.,"Aziz F, Acharjee A, Williams JA, Russ D, Bravo-Merodio L, Gkoutos GV.",,International journal of molecular sciences,2020,2020-10-23,Y,Experimental design; Gene Regulatory Network; Causal Modelling; Omics Integration,,,"Inferring the topology of a gene regulatory network (GRN) from gene expression data is a challenging but important undertaking for gaining a better understanding of gene regulation. Key challenges include working with noisy data and dealing with a higher number of genes than samples. Although a number of different methods have been proposed to infer the structure of a GRN, there are large discrepancies among the different inference algorithms they adopt, rendering their meaningful comparison challenging. In this study, we used two methods, namely the MIDER (Mutual Information Distance and Entropy Reduction) and the PLSNET (Partial least square based feature selection) methods, to infer the structure of a GRN directly from data and computationally validated our results. Both methods were applied to different gene expression datasets resulting from inflammatory bowel disease (IBD), pancreatic ductal adenocarcinoma (PDAC), and acute myeloid leukaemia (AML) studies. For each case, gene regulators were successfully identified. For example, for the case of the IBD dataset, the <i>UGT1A</i> family genes were identified as key regulators while upon analysing the PDAC dataset, the <i>SULF1</i> and <i>THBS2</i> genes were depicted. We further demonstrate that an ensemble-based approach, that combines the output of the MIDER and PLSNET algorithms, can infer the structure of a GRN from data with higher accuracy. We have also estimated the number of the samples required for potential future validation studies. Here, we presented our proposed analysis framework that caters not only to candidate regulator genes prediction for potential validation experiments but also an estimation of the number of samples required for these experiments.",,pdf:https://www.mdpi.com/1422-0067/21/21/7886/pdf?version=1604329387; doi:https://doi.org/10.3390/ijms21217886; html:https://europepmc.org/articles/PMC7660606; pdf:https://europepmc.org/articles/PMC7660606?pdf=render
 37798357,https://doi.org/10.1038/s41598-023-42331-7,"An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions.","Chua W, Cardoso VR, Guasch E, Sinner MF, Al-Taie C, Brady P, Casadei B, Crijns HJGM, Dudink EAMP, Hatem SN, Kääb S, Kastner P, Mont L, Nehaj F, Purmah Y, Reyat JS, Schotten U, Sommerfeld LC, Zeemering S, Ziegler A, Gkoutos GV, Kirchhof P, Fabritz L.",,Scientific reports,2023,2023-10-05,Y,,,,"Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.",,pdf:https://www.nature.com/articles/s41598-023-42331-7.pdf; doi:https://doi.org/10.1038/s41598-023-42331-7; html:https://europepmc.org/articles/PMC10556075; pdf:https://europepmc.org/articles/PMC10556075?pdf=render
 31799783,https://doi.org/10.1002/cnm.3267,Personalising cardiovascular network models in pregnancy: A two-tiered parameter estimation approach.,"Carson J, Warrander L, Johnstone E, van Loon R.",,International journal for numerical methods in biomedical engineering,2021,2020-01-13,Y,Pregnancy; Parameter estimation; Pre-eclampsia; Personalised Haemodynamic Model; Uterine Artery Waveform,,,"Uterine artery Doppler waveforms are often studied to determine whether a patient is at risk of developing pathologies such as pre-eclampsia. Many uterine waveform indices have been developed, which attempt to relate characteristics of the waveform with the physiological adaptation of the maternal cardiovascular system, and are often suggested to be an indicator of increased placenta resistance and arterial stiffness. Doppler waveforms of four patients, two of whom developed pre-eclampsia, are compared with a comprehensive closed-loop model of pregnancy. The closed-loop model has been previously validated but has been extended to include an improved parameter estimation technique that utilises systolic and diastolic blood pressure, cardiac output, heart rate, and pulse wave velocity measurements to adapt model resistances, compliances, blood volume, and the mean vessel areas in the main systemic arteries. The shape of the model-predicted uterine artery velocity waveforms showed good agreement with the characteristics observed in the patient Doppler waveforms. The personalised models obtained now allow a prediction of the uterine pressure waveforms in addition to the uterine velocity. This allows for a more detailed mechanistic analysis of the waveforms, eg, wave intensity analysis, to study existing clinical indices. The findings indicate that to accurately estimate arterial stiffness, both pulse pressure and pulse wave velocities are required. In addition, the results predict that patients who developed pre-eclampsia later in pregnancy have larger vessel areas in the main systemic arteries compared with the two patients who had normal pregnancy outcomes.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3267; doi:https://doi.org/10.1002/cnm.3267; html:https://europepmc.org/articles/PMC9286682; pdf:https://europepmc.org/articles/PMC9286682?pdf=render
 34007894,https://doi.org/10.23889/ijpds.v6i1.1373,Visualisation and optimisation of alcohol-related hospital admissions ICD-10 codes in Welsh e-cohort data.,"Trefan L, Akbari A, Morgan JS, Farewell DM, Fone D, Lyons RA, Jones Hywel M, Moore SC.",,International journal of population data science,2021,2021-03-24,Y,Alcohol; Hospital Admission; Optimisation; Icd-10 Codes; E-Cohort Data,,,"<h4>Introduction</h4>The excessive consumption of alcohol is detrimental to long term health and increases the likelihood of hospital admission. However, definitions of alcohol-related hospital admission vary, giving rise to uncertainty in the effect of alcohol on alcohol-related health care utilization.<h4>Objectives</h4>To compare diagnostic codes on hospital admission and discharge and to determine the ideal combination of codes necessary for an accurate determination of alcohol-related hospital admission.<h4>Methods</h4>Routine population-linked e-cohort data were extracted from the Secure Anonymised Information Linkage (SAIL) Databank containing all alcohol-related hospital admissions (n,= 92,553) from 2006 to 2011 in Wales, United Kingdom. The distributions of the diagnostic codes recorded at admission and discharge were compared. By calculating a misclassification rate (sensitivity-like measure) the appropriate number of coding fields to examine for alcohol-codes was established.<h4>Results</h4>There was agreement between admission and discharge codes. When more than ten coding fields were used the misclassification rate was less than 1%.<h4>Conclusion</h4>With the data at present and alcohol-related codes used, codes recorded at admission and discharge can be used equivalently to identify alcohol-related admissions. The appropriate number of coding fields to examine was established: fewer than ten is likely to lead to under-reporting of alcohol-related admissions. The methods developed here can be applied to other medical conditions that can be described using a certain set of diagnostic codes, each of which can be a known sole cause of the condition and recorded in multiple positions in e-cohort data.",,pdf:https://ijpds.org/article/download/1373/3264; doi:https://doi.org/10.23889/ijpds.v6i1.1373; html:https://europepmc.org/articles/PMC8103565; pdf:https://europepmc.org/articles/PMC8103565?pdf=render
@@ -300,12 +300,12 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc
 32405103,https://doi.org/10.1016/s0140-6736(20)30854-0,Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study.,"Banerjee A, Pasea L, Harris S, Gonzalez-Izquierdo A, Torralbo A, Shallcross L, Noursadeghi M, Pillay D, Sebire N, Holmes C, Pagel C, Wong WK, Langenberg C, Williams B, Denaxas S, Hemingway H.",,"Lancet (London, England)",2020,2020-05-12,Y,,,,"<h4>Background</h4>The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease.<h4>Methods</h4>In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK-CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1·5, 2·0, and 3·0 at differing infection rate scenarios, including full suppression (0·001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation.<h4>Findings</h4>We included 3 862 012 individuals (1 957 935 [50·7%] women and 1 904 077 [49·3%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13·7% were older than 70 years and 6·3% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4·46% (95% CI 4·41-4·51). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1·5, four with an RR of 2·0, and seven with an RR of 3·0. In a mitigation scenario, we estimated 18 374 excess deaths with an RR of 1·5, 36 749 with an RR of 2·0, and 73 498 with an RR of 3·0. In a do nothing scenario, we estimated 146 996 excess deaths with an RR of 1·5, 293 991 with an RR of 2·0, and 587 982 with an RR of 3·0.<h4>Interpretation</h4>We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality.<h4>Funding</h4>National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.","This paper aims to estimate the excess number of deaths over 1 year associated with covid-19, based on age and underlying conditions. They found that age, sex and underlying conditions do influence background risk, and support the need for sustained stringent suppression measures. They have also developed an online risk calculator prototype which is openly available for anyone to use.",pdf:https://discovery.ucl.ac.uk/10097486/1/Lancet%20final%201%20year%20mortality.pdf; doi:https://doi.org/10.1016/S0140-6736(20)30854-0; html:https://europepmc.org/articles/PMC7217641
 PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform,"Zheng B, Tazare J, Nab L, Green A, Curtis H, Mahalingasivam V, Herrett E, Costello R, Eggo R, Speed V, Bacon S, Bates C, Parry J, Cockburn J, Hester F, Harper S, Schaffer A, Hulme W, Mehrkar A, Evans S, MacKenna B, Goldacre B, Douglas I, Tomlinson L.",,The Lancet regional health. Europe,2023,2023-10-08,Y,Comparative Effectiveness; Real-world Data; Covid-19; Sotrovimab; Paxlovid,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624988/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624988/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?pdf=render
 36992188,https://doi.org/10.3390/vaccines11030604,"Household Composition and Inequalities in COVID-19 Vaccination in Wales, UK.","Lench A, Perry M, Johnson RD, Fry R, Richardson G, Lyons RA, Akbari A, Edwards A, Collins B, Joseph-Williams N, Cooper A, Cottrell S.",,Vaccines,2023,2023-03-07,Y,Vaccines; Vaccination; Households; Inequalities; Immunisation; Household Composition; Inequities; Covid-19,,,"The uptake of COVID-19 vaccination in Wales is high at a population level but many inequalities exist. Household composition may be an important factor in COVID-19 vaccination uptake due to the practical, social, and psychological implications associated with different living arrangements. In this study, the role of household composition in the uptake of COVID-19 vaccination in Wales was examined with the aim of identifying areas for intervention to address inequalities. Records within the Wales Immunisation System (WIS) COVID-19 vaccination register were linked to the Welsh Demographic Service Dataset (WDSD; a population register for Wales) held within the Secure Anonymised Information Linkage (SAIL) databank. Eight household types were defined based on household size, the presence or absence of children, and the presence of single or multiple generations. Uptake of the second dose of any COVID-19 vaccine was analysed using logistic regression. Gender, age group, health board, rural/urban residential classification, ethnic group, and deprivation quintile were included as covariates for multivariable regression. Compared to two-adult households, all other household types were associated with lower uptake. The most significantly reduced uptake was observed for large, multigenerational, adult group households (aOR 0.45, 95%CI 0.43-0.46). Comparing multivariable regression with and without incorporation of household composition as a variable produced significant differences in odds of vaccination for health board, age group, and ethnic group categories. These results indicate that household composition is an important factor for the uptake of COVID-19 vaccination and consideration of differences in household composition is necessary to mitigate vaccination inequalities.",,pdf:https://www.mdpi.com/2076-393X/11/3/604/pdf?version=1678670919; doi:https://doi.org/10.3390/vaccines11030604; html:https://europepmc.org/articles/PMC10055803; pdf:https://europepmc.org/articles/PMC10055803?pdf=render
-37340474,https://doi.org/10.1186/s12916-023-02877-9,Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.,"Glebov OO, Mueller C, Stewart R, Aarsland D, Perera G.",,BMC medicine,2023,2023-06-21,Y,Antidepressants; Ssri; respiratory infection; Drug Repurposing; Covid-19; Sars-cov-2,,,"<h4>Background</h4>Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention.<h4>Methods</h4>Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3 months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure.<h4>Results</h4>AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class.<h4>Conclusions</h4>This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02877-9; doi:https://doi.org/10.1186/s12916-023-02877-9; html:https://europepmc.org/articles/PMC10283271; pdf:https://europepmc.org/articles/PMC10283271?pdf=render
 32565483,https://doi.org/10.1136/bmjopen-2020-039097,Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II): protocol for an observational study using linked Scottish national data.,"Simpson CR, Robertson C, Vasileiou E, McMenamin J, Gunson R, Ritchie LD, Woolhouse M, Morrice L, Kelly D, Stagg HR, Marques D, Murray J, Sheikh A.",,BMJ open,2020,2020-06-21,Y,epidemiology; Public Health; Respiratory Medicine (See Thoracic Medicine),,,"<h4>Introduction</h4>Following the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 and the ensuing COVID-19 pandemic, population-level surveillance and rapid assessment of the effectiveness of existing or new therapeutic or preventive interventions are required to ensure that interventions are targeted to those at highest risk of serious illness or death from COVID-19. We aim to repurpose and expand an existing pandemic reporting platform to determine the attack rate of SARS-CoV-2, the uptake and effectiveness of any new pandemic vaccine (once available) and any protective effect conferred by existing or new antimicrobial drugs and other therapies.<h4>Methods and analysis</h4>A prospective observational cohort will be used to monitor daily/weekly the progress of the COVID-19 epidemic and to evaluate the effectiveness of therapeutic interventions in approximately 5.4 million individuals registered in general practices across Scotland. A national linked dataset of patient-level primary care data, out-of-hours, hospitalisation, mortality and laboratory data will be assembled. The primary outcomes will measure association between: (A) laboratory confirmed SARS-CoV-2 infection, morbidity and mortality, and demographic, socioeconomic and clinical population characteristics; and (B) healthcare burden of COVID-19 and demographic, socioeconomic and clinical population characteristics. The secondary outcomes will estimate: (A) the uptake (for vaccines only); (B) effectiveness; and (C) safety of new or existing therapies, vaccines and antimicrobials against SARS-CoV-2 infection. The association between population characteristics and primary outcomes will be assessed via multivariate logistic regression models. The effectiveness of therapies, vaccines and antimicrobials will be assessed from time-dependent Cox models or Poisson regression models. Self-controlled study designs will be explored to estimate the risk of therapeutic and prophylactic-related adverse events.<h4>Ethics and dissemination</h4>We obtained approval from the National Research Ethics Service Committee, Southeast Scotland 02. The study findings will be presented at international conferences and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/6/e039097.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-039097; html:https://europepmc.org/articles/PMC7311023; pdf:https://europepmc.org/articles/PMC7311023?pdf=render
+37340474,https://doi.org/10.1186/s12916-023-02877-9,Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.,"Glebov OO, Mueller C, Stewart R, Aarsland D, Perera G.",,BMC medicine,2023,2023-06-21,Y,Antidepressants; Ssri; respiratory infection; Drug Repurposing; Covid-19; Sars-cov-2,,,"<h4>Background</h4>Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention.<h4>Methods</h4>Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3 months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure.<h4>Results</h4>AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class.<h4>Conclusions</h4>This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02877-9; doi:https://doi.org/10.1186/s12916-023-02877-9; html:https://europepmc.org/articles/PMC10283271; pdf:https://europepmc.org/articles/PMC10283271?pdf=render
 35567479,https://doi.org/10.1093/rheumatology/keac283,Shielding reduced incidence of COVID-19 in patients with inflammatory arthritis but vulnerability is associated with increased mortality.,"Cooksey R, Underwood J, Brophy S, Atkinson M, Kennedy J, Choy E.",,"Rheumatology (Oxford, England)",2022,2022-06-01,Y,RA; As; PSA; Electronic Health Records; Covid-19; Inflammatory Arthritis,,,"<h4>Objectives</h4>Investigate whether individuals with inflammatory arthritis (IA), their treatments and shielding status affect the risk of adverse outcomes from COVID-19 for the entire population of Wales, UK.<h4>Methods</h4>Retrospective, population-based cohort study using linked, anonymized electronic health data from SAIL Databank, including primary/secondary care, rheumatology, Office for National Statistics Mortality and COVID-19 laboratory data. Individuals aged 18 years and over testing positive for COVID-19 between March 2020 and May 2021 with READ Codes present for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis formed the study cases.<h4>Results</h4>A total of 1966 people with IA and 166 602 without tested positive for COVID-19. The incidence rate was 3.5% (1966/56 914) in IA, vs 6% in the general population (166 602/2 760 442), (difference: 2.5%, 95% CI: 2.4%, 2.7%, P ≤0.001). In an adjusted Cox proportional hazard model, IA was not associated with higher mortality (HR: 0.56, 95% CI: 0.18, 1.64, P=0.286). Significant risk factors included shielding (HR: 1.52, 95% CI: 1.40, 1.64, P ≤0.001), hospitalization for previous infections (HR: 1.20, 95% CI: 1.12, 1.28, P ≤0.001), hospitalizations one year pre-pandemic (HR: 1.34, 95% CI: 1.25, 1.44, P ≤0.001) and glucocorticoid use (HR: 1.17, 95% CI: 1.09, 1.25, P ≤0.001).<h4>Conclusions</h4>Individuals with IA had a lower incidence of COVID-19, probably due to shielding. IA was not associated with increased mortality following COVID-19 infection; being vulnerable (shielded), comorbidities and other factors were associated with increased risk. These key risk factors can identify individuals with IA at greater risk from COVID-19 and advised to shield during high community prevalence.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62372/Download/62372__26337__5539f4f995224d80a2156218d11a03cb.pdf; doi:https://doi.org/10.1093/rheumatology/keac283; html:https://europepmc.org/articles/PMC9248059; pdf:https://europepmc.org/articles/PMC9248059?pdf=render
 36529825,https://doi.org/10.1007/s40258-022-00777-2,The False Economy of Seeking to Eliminate Delayed Transfers of Care: Some Lessons from Queueing Theory.,"Wood RM, Harper AL, Onen-Dumlu Z, Forte PG, Pitt M, Vasilakis C.",,Applied health economics and health policy,2023,2022-12-18,Y,,,,"<h4>Background</h4>It is a stated ambition of many healthcare systems to eliminate delayed transfers of care (DTOCs) between acute and step-down community services.<h4>Objective</h4>This study aims to demonstrate how, counter to intuition, pursual of such a policy is likely to be uneconomical, as it would require large amounts of community capacity to accommodate even the rarest of demand peaks, leaving much capacity unused for much of the time.<h4>Methods</h4>Some standard results from queueing theory-a mathematical discipline for considering the dynamics of queues and queueing systems-are used to provide a model of patient flow from the acute to community setting. While queueing models have a track record of application in healthcare, they have not before been used to address this question.<h4>Results</h4>Results show that 'eliminating' DTOCs is a false economy: the additional community costs required are greater than the possible acute cost saving. While a substantial proportion of DTOCs can be attributed to inefficient use of resources, the remainder can be considered economically essential to ensuring cost-efficient service operation. For England's National Health Service (NHS), our modelling estimates annual cost savings of £117m if DTOCs are reduced to the 12% of current levels that can be regarded as economically essential.<h4>Conclusion</h4>This study discourages the use of 'zero DTOC' targets and instead supports an assessment based on the specific characteristics of the healthcare system considered.",,doi:https://doi.org/10.1007/s40258-022-00777-2; html:https://europepmc.org/articles/PMC9760184; pdf:https://europepmc.org/articles/PMC9760184?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s40258-022-00777-2.pdf
-36857859,https://doi.org/10.1016/j.ebiom.2023.104489,"Identifying subtypes of chronic kidney disease with machine learning: development, internal validation and prognostic validation using linked electronic health records in 350,067 individuals.","Dashtban A, Mizani MA, Pasea L, Denaxas S, Corbett R, Mamza JB, Gao H, Morris T, Hemingway H, Banerjee A.",,EBioMedicine,2023,2023-02-27,Y,Cluster analysis; Survival analysis; Machine Learning; Unsupervised Clustering; Ckd Subtype,,,"<h4>Background</h4>Although chronic kidney disease (CKD) is associated with high multimorbidity, polypharmacy, morbidity and mortality, existing classification systems (mild to severe, usually based on estimated glomerular filtration rate, proteinuria or urine albumin-creatinine ratio) and risk prediction models largely ignore the complexity of CKD, its risk factors and its outcomes. Improved subtype definition could improve prediction of outcomes and inform effective interventions.<h4>Methods</h4>We analysed individuals ≥18 years with incident and prevalent CKD (n = 350,067 and 195,422 respectively) from a population-based electronic health record resource (2006-2020; Clinical Practice Research Datalink, CPRD). We included factors (n = 264 with 2670 derived variables), e.g. demography, history, examination, blood laboratory values and medications. Using a published framework, we identified subtypes through seven unsupervised machine learning (ML) methods (K-means, Diana, HC, Fanny, PAM, Clara, Model-based) with 66 (of 2670) variables in each dataset. We evaluated subtypes for: (i) internal validity (within dataset, across methods); (ii) prognostic validity (predictive accuracy for 5-year all-cause mortality and admissions); and (iii) medications (new and existing by British National Formulary chapter).<h4>Findings</h4>After identifying five clusters across seven approaches, we labelled CKD subtypes: 1. Early-onset, 2. Late-onset, 3. Cancer, 4. Metabolic, and 5. Cardiometabolic. Internal validity: We trained a high performing model (using XGBoost) that could predict disease subtypes with 95% accuracy for incident and prevalent CKD (Sensitivity: 0.81-0.98, F1 score:0.84-0.97). Prognostic validity: 5-year all-cause mortality, hospital admissions, and incidence of new chronic diseases differed across CKD subtypes. The 5-year risk of mortality and admissions in the overall incident CKD population were highest in cardiometabolic subtype: 43.3% (42.3-42.8%) and 29.5% (29.1-30.0%), respectively, and lowest in the early-onset subtype: 5.7% (5.5-5.9%) and 18.7% (18.4-19.1%).<h4>Medications</h4>Across CKD subtypes, the distribution of prescription medication classes at baseline varied, with highest medication burden in cardiometabolic and metabolic subtypes, and higher burden in prevalent than incident CKD.<h4>Interpretation</h4>In the largest CKD study using ML, to-date, we identified five distinct subtypes in individuals with incident and prevalent CKD. These subtypes have relevance to study of aetiology, therapeutics and risk prediction.<h4>Funding</h4>AstraZeneca UK Ltd, Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2352396423000543/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104489; html:https://europepmc.org/articles/PMC9989643; pdf:https://europepmc.org/articles/PMC9989643?pdf=render
 35413949,https://doi.org/10.1038/s41467-022-29521-z,"Persistent COVID-19 symptoms in a community study of 606,434 people in England.","Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P.",,Nature communications,2022,2022-04-12,Y,,,,"Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3-5 of the REACT-2 study (n = 508,707; September 2020 - February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3-5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3-5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.",,pdf:https://www.nature.com/articles/s41467-022-29521-z.pdf; doi:https://doi.org/10.1038/s41467-022-29521-z; html:https://europepmc.org/articles/PMC9005552; pdf:https://europepmc.org/articles/PMC9005552?pdf=render
+36857859,https://doi.org/10.1016/j.ebiom.2023.104489,"Identifying subtypes of chronic kidney disease with machine learning: development, internal validation and prognostic validation using linked electronic health records in 350,067 individuals.","Dashtban A, Mizani MA, Pasea L, Denaxas S, Corbett R, Mamza JB, Gao H, Morris T, Hemingway H, Banerjee A.",,EBioMedicine,2023,2023-02-27,Y,Cluster analysis; Survival analysis; Machine Learning; Unsupervised Clustering; Ckd Subtype,,,"<h4>Background</h4>Although chronic kidney disease (CKD) is associated with high multimorbidity, polypharmacy, morbidity and mortality, existing classification systems (mild to severe, usually based on estimated glomerular filtration rate, proteinuria or urine albumin-creatinine ratio) and risk prediction models largely ignore the complexity of CKD, its risk factors and its outcomes. Improved subtype definition could improve prediction of outcomes and inform effective interventions.<h4>Methods</h4>We analysed individuals ≥18 years with incident and prevalent CKD (n = 350,067 and 195,422 respectively) from a population-based electronic health record resource (2006-2020; Clinical Practice Research Datalink, CPRD). We included factors (n = 264 with 2670 derived variables), e.g. demography, history, examination, blood laboratory values and medications. Using a published framework, we identified subtypes through seven unsupervised machine learning (ML) methods (K-means, Diana, HC, Fanny, PAM, Clara, Model-based) with 66 (of 2670) variables in each dataset. We evaluated subtypes for: (i) internal validity (within dataset, across methods); (ii) prognostic validity (predictive accuracy for 5-year all-cause mortality and admissions); and (iii) medications (new and existing by British National Formulary chapter).<h4>Findings</h4>After identifying five clusters across seven approaches, we labelled CKD subtypes: 1. Early-onset, 2. Late-onset, 3. Cancer, 4. Metabolic, and 5. Cardiometabolic. Internal validity: We trained a high performing model (using XGBoost) that could predict disease subtypes with 95% accuracy for incident and prevalent CKD (Sensitivity: 0.81-0.98, F1 score:0.84-0.97). Prognostic validity: 5-year all-cause mortality, hospital admissions, and incidence of new chronic diseases differed across CKD subtypes. The 5-year risk of mortality and admissions in the overall incident CKD population were highest in cardiometabolic subtype: 43.3% (42.3-42.8%) and 29.5% (29.1-30.0%), respectively, and lowest in the early-onset subtype: 5.7% (5.5-5.9%) and 18.7% (18.4-19.1%).<h4>Medications</h4>Across CKD subtypes, the distribution of prescription medication classes at baseline varied, with highest medication burden in cardiometabolic and metabolic subtypes, and higher burden in prevalent than incident CKD.<h4>Interpretation</h4>In the largest CKD study using ML, to-date, we identified five distinct subtypes in individuals with incident and prevalent CKD. These subtypes have relevance to study of aetiology, therapeutics and risk prediction.<h4>Funding</h4>AstraZeneca UK Ltd, Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2352396423000543/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104489; html:https://europepmc.org/articles/PMC9989643; pdf:https://europepmc.org/articles/PMC9989643?pdf=render
 34598993,https://doi.org/10.1136/bmjopen-2021-054410,"Changes in neonatal admissions, care processes and outcomes in England and Wales during the COVID-19 pandemic: a whole population cohort study.","Greenbury SF, Longford N, Ougham K, Angelini ED, Battersby C, Uthaya S, Modi N.",,BMJ open,2021,2021-10-01,Y,Public Health; Neonatology; Neonatal Intensive & Critical Care,,,"<h4>Objectives</h4>The COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes and outcomes.<h4>Design</h4>Observational cohort study using the UK National Neonatal Research Database.<h4>Setting</h4>England and Wales.<h4>Participants</h4>Admissions to National Health Service neonatal units from 2012 to 2020.<h4>Main outcome measures</h4>Admissions by gestational age, ethnicity and Index of Multiple Deprivation, and key care processes and outcomes.<h4>Methods</h4>We calculated differences in numbers and rates between April and June 2020 (spring), the first 3 months of national lockdown (COVID-19 period), and December 2019-February 2020 (winter), prior to introduction of mitigation measures, and compared them with the corresponding differences in the previous 7 years. We considered the COVID-19 period highly unusual if the spring-winter difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion.<h4>Results</h4>Marked fluctuations occurred in all measures over the 8 years with several highly unusual changes during the COVID-19 period. Total admissions fell, having risen over all previous years (COVID-19 difference: -1492; previous 7-year difference range: +100, +1617; p<0.001); full-term black admissions rose (+66; -64, +35; p<0.001) whereas Asian (-137; -14, +101; p<0.001) and white (-319; -235, +643: p<0.001) admissions fell. Transfers to higher and lower designation neonatal units increased (+129; -4, +88; p<0.001) and decreased (-47; -25, +12; p<0.001), respectively. Total preterm admissions decreased (-350; -26, +479; p<0.001). The fall in extremely preterm admissions was most marked in the two lowest socioeconomic quintiles.<h4>Conclusions</h4>Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e054410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054410; html:https://europepmc.org/articles/PMC8488283; pdf:https://europepmc.org/articles/PMC8488283?pdf=render
 34340970,https://doi.org/10.3399/bjgp.2021.0301,Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records <i>in situ</i> using OpenSAFELY.,"Walker AJ, MacKenna B, Inglesby P, Tomlinson L, Rentsch CT, Curtis HJ, Morton CE, Morley J, Mehrkar A, Bacon S, Hickman G, Bates C, Croker R, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Williamson EJ, Hulme WJ, McDonald HI, Mathur R, Eggo RM, Wing K, Wong AY, Forbes H, Tazare J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Douglas IJ, Evans SJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-10-28,Y,Primary Health Care; General Practice; Electronic Health Records; Covid-19; Long Covid,,,"<h4>Background</h4>Long COVID describes new or persistent symptoms at least 4 weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were recently created.<h4>Aim</h4>To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time.<h4>Design and setting</h4>Population-based cohort study in English primary care.<h4>Method</h4>Working on behalf of NHS England, OpenSAFELY data were used encompassing 96% of the English population between 1 February 2020 and 25 May 2021. The proportion of people with a recorded code for long COVID was measured overall and by demographic factors, electronic health record software system (EMIS or TPP), and week.<h4>Results</h4>Long COVID was recorded for 23 273 people. Coding was unevenly distributed among practices, with 26.7% of practices having never used the codes. Regional variation ranged between 20.3 per 100 000 people for East of England (95% confidence interval [CI] = 19.3 to 21.4) and 55.6 per 100 000 people in London (95% CI = 54.1 to 57.1). Coding was higher among females (52.1, 95% CI = 51.3 to 52.9) than males (28.1, 95% CI = 27.5 to 28.7), and higher among practices using EMIS (53.7, 95% CI = 52.9 to 54.4) than those using TPP (20.9, 95% CI = 20.3 to 21.4).<h4>Conclusion</h4>Current recording of long COVID in primary care is very low, and variable between practices. This may reflect patients not presenting; clinicians and patients holding different diagnostic thresholds; or challenges with the design and communication of diagnostic codes. Increased awareness of diagnostic codes is recommended to facilitate research and planning of services, and also surveys with qualitative work to better evaluate clinicians' understanding of the diagnosis.",,pdf:https://bjgp.org/content/bjgp/71/712/e806.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0301; html:https://europepmc.org/articles/PMC8340730; pdf:https://europepmc.org/articles/PMC8340730?pdf=render
 32990744,https://doi.org/10.1093/gigascience/giaa095,An extensible big data software architecture managing a research resource of real-world clinical radiology data linked to other health data from the whole Scottish population.,"Nind T, Sutherland J, McAllister G, Hardy D, Hume A, MacLeod R, Caldwell J, Krueger S, Tramma L, Teviotdale R, Abdelatif M, Gillen K, Ward J, Scobbie D, Baillie I, Brooks A, Prodan B, Kerr W, Sloan-Murphy D, Herrera JFR, McManus D, Morris C, Sinclair C, Baxter R, Parsons M, Morris A, Jefferson E.",,GigaScience,2020,2020-09-01,Y,ML; AI; Radiology; Big Data,,,"<h4>Aim</h4>To enable a world-leading research dataset of routinely collected clinical images linked to other routinely collected data from the whole Scottish national population. This includes more than 30 million different radiological examinations from a population of 5.4 million and >2 PB of data collected since 2010.<h4>Methods</h4>Scotland has a central archive of radiological data used to directly provide clinical care to patients. We have developed an architecture and platform to securely extract a copy of those data, link it to other clinical or social datasets, remove personal data to protect privacy, and make the resulting data available to researchers in a controlled Safe Haven environment.<h4>Results</h4>An extensive software platform has been developed to host, extract, and link data from cohorts to answer research questions. The platform has been tested on 5 different test cases and is currently being further enhanced to support 3 exemplar research projects.<h4>Conclusions</h4>The data available are from a range of radiological modalities and scanner types and were collected under different environmental conditions. These real-world, heterogenous data are valuable for training algorithms to support clinical decision making, especially for deep learning where large data volumes are required. The resource is now available for international research access. The platform and data can support new health research using artificial intelligence and machine learning technologies, as well as enabling discovery science.",,pdf:https://academic.oup.com/gigascience/article-pdf/9/10/giaa095/33802377/giaa095.pdf; doi:https://doi.org/10.1093/gigascience/giaa095; html:https://europepmc.org/articles/PMC7523405; pdf:https://europepmc.org/articles/PMC7523405?pdf=render
@@ -315,8 +315,8 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 36333839,https://doi.org/10.1002/gps.5834,The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.,"Simkin L, Yung P, Greig F, Perera G, Tsamakis K, Rizos E, Stewart R, Velayudhan L, Mueller C.",,International journal of geriatric psychiatry,2022,2022-10-24,Y,Dementia; Hallucinations; Delusions; Psychosis; Older Adults; Lockdown; Covid-19; Non-white Ethnicity,,,"<h4>Objectives</h4>Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period.<h4>Methods</h4>In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period.<h4>Results</h4>1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period.<h4>Conclusions</h4>During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5834; doi:https://doi.org/10.1002/gps.5834; html:https://europepmc.org/articles/PMC9828419; pdf:https://europepmc.org/articles/PMC9828419?pdf=render
 37006328,https://doi.org/10.1093/braincomms/fcad065,"Infections among individuals with multiple sclerosis, Alzheimer's disease and Parkinson's disease.","Hu Y, Hu K, Song H, Pawitan Y, Piehl F, Fang F.",,Brain communications,2023,2023-03-16,Y,Multiple sclerosis; Alzheimer’s disease; Infections; Parkinson’s Disease,,,"A link between neurodegenerative diseases and infections has been previously reported. However, it is not clear to what extent such link is caused by confounding factors or to what extent it is intimately connected with the underlying conditions. Further, studies on the impact of infections on mortality risk following neurodegenerative diseases are rare. We analysed two data sets with different characteristics: (i) a community-based cohort from the UK Biobank with 2023 patients with multiple sclerosis, 2200 patients with Alzheimer's disease, 3050 patients with Parkinson's disease diagnosed before 1 March 2020 and 5 controls per case who were randomly selected and individually matched to the case; (ii) a Swedish Twin Registry cohort with 230 patients with multiple sclerosis, 885 patients with Alzheimer's disease and 626 patients with Parkinson's disease diagnosed before 31 December 2016 and their disease-free co-twins. The relative risk of infections after a diagnosis of neurodegenerative disease was estimated using stratified Cox models, with adjustment for differences in baseline characteristics. Causal mediation analyses of survival outcomes based on Cox models were performed to assess the impact of infections on mortality. Compared with matched controls or unaffected co-twins, we observed an elevated infection risk after diagnosis of neurodegenerative diseases, with a fully adjusted hazard ratio (95% confidence interval) of 2.45 (2.24-2.69) for multiple sclerosis, 5.06 (4.58-5.59) for Alzheimer's disease and 3.72 (3.44-4.01) for Parkinson's disease in the UK Biobank cohort, and 1.78 (1.21-2.62) for multiple sclerosis, 1.50 (1.19-1.88) for Alzheimer's disease and 2.30 (1.79-2.95) for Parkinson's disease in the twin cohort. Similar risk increases were observed when we analysed infections during the 5 years before diagnosis of the respective disease. Occurrence of infections after diagnosis had, however, relatively little impact on mortality, as mediation of infections on mortality (95% confidence interval) was estimated as 31.89% (26.83-37.11%) for multiple sclerosis, 13.38% (11.49-15.29%) for Alzheimer's disease and 18.85% (16.95-20.97%) for Parkinson's disease in the UK Biobank cohort, whereas it was 6.56% (-3.59 to 16.88%) for multiple sclerosis, -2.21% (-0.21 to 4.65%) for Parkinson's disease and -3.89% (-7.27 to -0.51%) for Alzheimer's disease in the twin cohort. Individuals with studied neurodegenerative diseases display an increased risk of infections independently of genetic and familial environment factors. A similar magnitude of risk increase is present prior to confirmed diagnosis, which may indicate a modulating effect of the studied neurological conditions on immune defences.",,pdf:https://academic.oup.com/braincomms/advance-article-pdf/doi/10.1093/braincomms/fcad065/49588224/fcad065.pdf; doi:https://doi.org/10.1093/braincomms/fcad065; html:https://europepmc.org/articles/PMC10053639; pdf:https://europepmc.org/articles/PMC10053639?pdf=render
 32635913,https://doi.org/10.1186/s12911-020-01169-z,Application of standardised effect sizes to hospital discharge outcomes for people with diabetes.,"Robbins T, Lim Choi Keung SN, Sankar S, Randeva H, Arvanitis TN.",,BMC medical informatics and decision making,2020,2020-07-07,Y,Mortality; Diabetes; Readmission; Effect Size,,,"<h4>Background</h4>Patients with diabetes are at an increased risk of readmission and mortality when discharged from hospital. Existing research identifies statistically significant risk factors that are thought to underpin these outcomes. Increasingly, these risk factors are being used to create risk prediction models, and target risk modifying interventions. These risk factors are typically reported in the literature accompanied by unstandardized effect sizes, which makes comparisons difficult. We demonstrate an assessment of variation between standardised effect sizes for such risk factors across care outcomes and patient cohorts. Such an approach will support development of more rigorous risk stratification tools and better targeting of intervention measures.<h4>Methods</h4>Data was extracted from the electronic health record of a major tertiary referral centre, over a 3-year period, for all patients discharged from hospital with a concurrent diagnosis of diabetes mellitus. Risk factors selected for extraction were pre-specified according to a systematic review of the research literature. Standardised effect sizes were calculated for all statistically significant risk factors, and compared across patient cohorts and both readmission & mortality outcome measures.<h4>Results</h4>Data was extracted for 46,357 distinct admissions patients, creating a large dataset of approximately 10,281,400 data points. The calculation of standardized effect size measures allowed direct comparison. Effect sizes were noted to be larger for mortality compared to readmission, as well as for being larger for surgical and type 1 diabetes cohorts of patients.<h4>Conclusions</h4>The calculation of standardised effect sizes is an important step in evaluating risk factors for healthcare events. This will improve our understanding of risk and support the development of more effective risk stratification tools to support patients to make better informed decisions at discharge from hospital.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-020-01169-z; doi:https://doi.org/10.1186/s12911-020-01169-z; html:https://europepmc.org/articles/PMC7339522; pdf:https://europepmc.org/articles/PMC7339522?pdf=render
-37408471,https://doi.org/10.1093/eurheartj/ehad424,The CODE-EHR global framework: lifting the veil on health record data.,"Asselbergs FW, Kotecha D.",,European heart journal,2023,2023-09-01,N,,,,,,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad424/50827856/ehad424.pdf; doi:https://doi.org/10.1093/eurheartj/ehad424
 35192611,https://doi.org/10.1371/journal.pmed.1003916,Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.,"McQuaid F, Mulholland R, Sangpang Rai Y, Agrawal U, Bedford H, Cameron JC, Gibbons C, Roy P, Sheikh A, Shi T, Simpson CR, Tait J, Tessier E, Turner S, Villacampa Ortega J, White J, Wood R.",,PLoS medicine,2022,2022-02-22,Y,,,,"<h4>Background</h4>In 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates.<h4>Methods and findings</h4>We conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK ""lockdown"". Data were obtained for Scotland from the Public Health Scotland ""COVID19 wider impacts on the health care system"" dashboard and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; 3 doses of ""6-in-1"" diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age. We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels. In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86- to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83). The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake.<h4>Conclusions</h4>In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003916&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003916; html:https://europepmc.org/articles/PMC8863286; pdf:https://europepmc.org/articles/PMC8863286?pdf=render
+37408471,https://doi.org/10.1093/eurheartj/ehad424,The CODE-EHR global framework: lifting the veil on health record data.,"Asselbergs FW, Kotecha D.",,European heart journal,2023,2023-09-01,N,,,,,,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad424/50827856/ehad424.pdf; doi:https://doi.org/10.1093/eurheartj/ehad424
 35289755,https://doi.org/10.2196/31021,Concept Libraries for Repeatable and Reusable Research: Qualitative Study Exploring the Needs of Users.,"Almowil Z, Zhou SM, Brophy S, Croxall J.",,JMIR human factors,2022,2022-03-15,Y,Electronic Health Records; Record Linkage; Reproducible Research; Clinical Codes; Concept Libraries,,,"<h4>Background</h4>Big data research in the field of health sciences is hindered by a lack of agreement on how to identify and define different conditions and their medications. This means that researchers and health professionals often have different phenotype definitions for the same condition. This lack of agreement makes it difficult to compare different study findings and hinders the ability to conduct repeatable and reusable research.<h4>Objective</h4>This study aims to examine the requirements of various users, such as researchers, clinicians, machine learning experts, and managers, in the development of a data portal for phenotypes (a concept library).<h4>Methods</h4>This was a qualitative study using interviews and focus group discussion. One-to-one interviews were conducted with researchers, clinicians, machine learning experts, and senior research managers in health data science (N=6) to explore their specific needs in the development of a concept library. In addition, a focus group discussion with researchers (N=14) working with the Secured Anonymized Information Linkage databank, a national eHealth data linkage infrastructure, was held to perform a SWOT (strengths, weaknesses, opportunities, and threats) analysis for the phenotyping system and the proposed concept library. The interviews and focus group discussion were transcribed verbatim, and 2 thematic analyses were performed.<h4>Results</h4>Most of the participants thought that the prototype concept library would be a very helpful resource for conducting repeatable research, but they specified that many requirements are needed before its development. Although all the participants stated that they were aware of some existing concept libraries, most of them expressed negative perceptions about them. The participants mentioned several facilitators that would stimulate them to share their work and reuse the work of others, and they pointed out several barriers that could inhibit them from sharing their work and reusing the work of others. The participants suggested some developments that they would like to see to improve reproducible research output using routine data.<h4>Conclusions</h4>The study indicated that most interviewees valued a concept library for phenotypes. However, only half of the participants felt that they would contribute by providing definitions for the concept library, and they reported many barriers regarding sharing their work on a publicly accessible platform. Analysis of interviews and the focus group discussion revealed that different stakeholders have different requirements, facilitators, barriers, and concerns about a prototype concept library.",,doi:https://doi.org/10.2196/31021; doi:https://doi.org/10.2196/31021; html:https://europepmc.org/articles/PMC8965669
 33087383,https://doi.org/10.1136/bmjopen-2020-043010,Understanding and responding to COVID-19 in Wales: protocol for a privacy-protecting data platform for enhanced epidemiology and evaluation of interventions. ,"Lyons J, Akbari A, Torabi F, Davies GI, North L, Griffiths R, Bailey R, Hollinghurst J, Fry R, Turner SL, Thompson D, Rafferty J, Mizen A, Orton C, Thompson S, Au-Yeung L, Cross L, Gravenor MB, Brophy S, Lucini B, John A, Szakmany T, Davies J, Davies C, Thomas DR, Williams C, Emmerson C, Cottrell S, Connor TR, Taylor C, Pugh RJ, Diggle P, John G, Scourfield S, Hunt J, Cunningham AM, Helliwell K, Lyons R.",,BMJ open,2020,2020-10-21,Y,,,,"The emergence of the novel respiratory SARS-CoV-2 and subsequent COVID-19 pandemic have required rapid assimilation of population-level data to understand and control the spread of infection in the general and vulnerable populations. Rapid analyses are needed to inform policy development and target interventions to at-risk groups to prevent serious health outcomes. We aim to provide an accessible research platform to determine demographic, socioeconomic and clinical risk factors for infection, morbidity and mortality of COVID-19, to measure the impact of COVID-19 on healthcare utilisation and long-term health, and to enable the evaluation of natural experiments of policy interventions. Two privacy-protecting population-level cohorts have been created and derived from multisourced demographic and healthcare data. The C20 cohort consists of 3.2 million people in Wales on the 1 January 2020 with follow-up until 31 May 2020. The complete cohort dataset will be updated monthly with some individual datasets available daily. The C16 cohort consists of 3 million people in Wales on the 1 January 2016 with follow-up to 31 December 2019. C16 is designed as a counterfactual cohort to provide contextual comparative population data on disease, health service utilisation and mortality. Study outcomes will: (a) characterise the epidemiology of COVID-19, (b) assess socioeconomic and demographic influences on infection and outcomes, (c) measure the impact of COVID-19 on short -term and longer-term population outcomes and (d) undertake studies on the transmission and spatial spread of infection. The Secure Anonymised Information Linkage-independent Information Governance Review Panel has approved this study. The study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/10/e043010.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043010; html:https://europepmc.org/articles/PMC7580065; pdf:https://europepmc.org/articles/PMC7580065?pdf=render
 33079204,https://doi.org/10.1093/ehjqcco/qcaa079,Impact of COVID-19 on cardiac procedure activity in England and associated 30-day mortality.,"Mohamed MO, Banerjee A, Clarke S, de Belder M, Patwala A, Goodwin AT, Kwok CS, Rashid M, Gale CP, Curzen N, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2021,2021-05-01,Y,Mortality; Cardiac; England; Procedures; Covid-19,,,"<h4>Aims</h4>Limited data exist on the impact of COVID-19 on national changes in cardiac procedure activity, including patient characteristics and clinical outcomes before and during the COVID-19 pandemic.<h4>Methods and results</h4>All major cardiac procedures (n = 374 899) performed between 1 January and 31 May for the years 2018, 2019, and 2020 were analysed, stratified by procedure type and time-period (pre-COVID: January-May 2018 and 2019 and January-February 2020 and COVID: March-May 2020). Multivariable logistic regression was performed to examine the odds ratio (OR) of 30-day mortality for procedures performed in the COVID period. Overall, there was a deficit of 45 501 procedures during the COVID period compared to the monthly averages (March-May) in 2018-2019. Cardiac catheterization and device implantations were the most affected in terms of numbers (n = 19 637 and n = 10 453), whereas surgical procedures such as mitral valve replacement, other valve replacement/repair, atrioseptal defect/ventriculoseptal defect repair, and coronary artery bypass grafting were the most affected as a relative percentage difference (Δ) to previous years' averages. Transcatheter aortic valve replacement was the least affected (Δ -10.6%). No difference in 30-day mortality was observed between pre-COVID and COVID time-periods for all cardiac procedures except cardiac catheterization [OR 1.25 95% confidence interval (CI) 1.07-1.47, P = 0.006] and cardiac device implantation (OR 1.35 95% CI 1.15-1.58, P < 0.001).<h4>Conclusion</h4>Cardiac procedural activity has significantly declined across England during the COVID-19 pandemic, with a deficit in excess of 45 000 procedures, without an increase in risk of mortality for most cardiac procedures performed during the pandemic. Major restructuring of cardiac services is necessary to deal with this deficit, which would inevitably impact long-term morbidity and mortality.",,pdf:https://academic.oup.com/ehjqcco/article-pdf/7/3/247/37776880/qcaa079.pdf; doi:https://doi.org/10.1093/ehjqcco/qcaa079; html:https://europepmc.org/articles/PMC7665465; pdf:https://europepmc.org/articles/PMC7665465?pdf=render
@@ -354,8 +354,8 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 34461893,https://doi.org/10.1186/s12916-021-02096-0,The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study.,"Wilde H, Mellan T, Hawryluk I, Dennis JM, Denaxas S, Pagel C, Duncan A, Bhatt S, Flaxman S, Mateen BA, Vollmer SJ.",,BMC medicine,2021,2021-08-30,Y,Critical Care; Hospital Mortality; Quality Of Healthcare; Public Health Surveillance; Coronavirus Infection,,,"<h4>Background</h4>The literature paints a complex picture of the association between mortality risk and ICU strain. In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain.<h4>Methods</h4>A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease).<h4>Results</h4>One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (< 45% relative to the baseline) [OR 0.83 (95% PCI 0.75 to 0.94)].<h4>Conclusion</h4>Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Further research is required to establish if this is a causal relationship or whether it reflects strain on other operational factors such as staff. If causal, the result highlights the importance of strategies to keep ICU occupancy low to mitigate the impact of this type of resource saturation.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02096-0; doi:https://doi.org/10.1186/s12916-021-02096-0; html:https://europepmc.org/articles/PMC8404408; pdf:https://europepmc.org/articles/PMC8404408?pdf=render
 34148733,https://doi.org/10.1016/j.bja.2021.05.018,Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study.,"Abbott TEF, Fowler AJ, Dobbs TD, Gibson J, Shahid T, Dias P, Akbari A, Whitaker IS, Pearse RM.",,British journal of anaesthesia,2021,2021-06-11,Y,Surgery; Anaesthesia; epidemiology; Public Policy; Covid-19,,,"<h4>Background</h4>The COVID-19 pandemic has heavily impacted elective and emergency surgery around the world. We aimed to confirm the incidence of perioperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated mortality after surgery.<h4>Methods</h4>Analysis of routine electronic health record data from NHS hospitals in England. We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between January 1, 2020 and February 28, 2021. The exposure was SARS-CoV-2 infection defined by International Classification of Diseases (ICD)-10 codes. The primary outcome measure was 90 day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson Comorbidity Index, Index of Multiple Deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals (CI).<h4>Results</h4>We identified 2 666 978 patients undergoing surgery of whom 28 777 (1.1%) had SARS-CoV-2 infection. In total, 26 364 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 6153/28 777 [21.4%] vs no SARS-CoV-2: 20 211/2 638 201 [0.8%]; OR=5.7 [95% CI, 5.5-5.9]; P<0.001). Amongst patients undergoing elective surgery, 2412/1 857 586 (0.1%) had SARS-CoV-2, of whom 172/2412 (7.1%) died, compared with 1414/1 857 586 (0.1%) patients without SARS-CoV-2 (OR=25.8 [95% CI, 21.7-30.9]; P<0.001). Amongst patients undergoing emergency surgery, 22 918/582 292 (3.9%) patients had SARS-CoV-2, of whom 5752/22 918 (25.1%) died, compared with 18 060/559 374 (3.4%) patients without SARS-CoV-2 (OR=5.5 [95% CI, 5.3-5.7]; P<0.001).<h4>Conclusions</h4>The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.",,pdf:http://www.bjanaesthesia.org/article/S0007091221003123/pdf; doi:https://doi.org/10.1016/j.bja.2021.05.018; html:https://europepmc.org/articles/PMC8192173; pdf:https://europepmc.org/articles/PMC8192173?pdf=render
 35909578,https://doi.org/10.23889/ijpds.v7i1.1717,"Health and household environment factors linked with early alcohol use in adolescence: a record-linked, data-driven, longitudinal cohort study.","Bandyopadhyay A, Brophy S, Akbari A, Demmler J, Kennedy J, Paranjothy S, Lyons RA, Moore S.",,International journal of population data science,2022,2022-07-07,Y,Alcohol; Adolescent; Cohort study; Data Linkage; Electronic Health Records (Ehrs),,,"<h4>Introduction</h4>Early alcohol use has significant association with poor health outcomes. Individual risk factors around early alcohol use have been identified, but a holistic, data-driven investigation into health and household environmental factors on early alcohol use is yet to be undertaken.<h4>Objectives</h4>This study aims to investigate the relationship between preceding health events, household exposures and early alcohol use during adolescence using a two-stage data-driven approach.<h4>Methods</h4>In stage one, a study population (N = 1,072) were derived from the Millennium Cohort Study (MCS) Wales (born between 2000-2002). MCS data were first linked with electronic-health records. Factors associated with early (<=eleven years old) alcohol use were identified using feature selection and stepwise logistic regression. In stage two, analogous risk factors from MCS were recreated for whole population (N = 59,231) of children (born between 1998-2002 in the Welsh Demographic Service Dataset) using routine data to predict the alcohol-related health events in hospital or GP records.<h4>Results</h4>Significant risk factors from stage two included poor maternal mental (adjusted odds ratio [aOR] = 1.31) and physical health (aOR = 1.25), living with someone with alcohol-related problem (aOR = 2.16), single-adult household (aOR = 1.45), ever in deprivation (aOR = 1.66), child's high hyperactivity (aOR = 3.57), and conduct disorder (aOR = 3.26). Children with health events, whose health needs are supported (e.g., are taken to the doctor), are at lower risk of early alcohol use.<h4>Conclusion</h4>Health events of the family members and the child can act as modifiable exposures and may therefore inform the development of prevention initiatives. Families with known alcohol problems, living in deprivation, experiencing child behavioural problems and those who are not taken to the doctor are at higher risk of early drinking behaviour and should be prioritised for early years support and interventions to target problem drinking in young people.",,pdf:https://ijpds.org/article/download/1717/3510; doi:https://doi.org/10.23889/ijpds.v7i1.1717; html:https://europepmc.org/articles/PMC9284510; pdf:https://europepmc.org/articles/PMC9284510?pdf=render
-36863848,https://doi.org/10.1136/archdischild-2022-325152,Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England.,"Atchison CJ, Whitaker M, Donnelly CA, Chadeau-Hyam M, Riley S, Darzi A, Ashby D, Barclay W, Cooke GS, Elliott P, Ward H.",,Archives of disease in childhood,2023,2023-03-02,Y,epidemiology; Paediatrics; Adolescent Health; Infectious Disease Medicine; Covid-19,,,"<h4>Objective</h4>To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.<h4>Design</h4>Serial cross-sectional study.<h4>Setting</h4>Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England).<h4>Study population</h4>Children aged 5-17 years in the community.<h4>Predictors</h4>Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset.<h4>Main outcome measures</h4>Prevalence of persistent symptoms, reported as those lasting ≥3 months post-COVID-19.<h4>Results</h4>Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11 year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17 year-olds with prior symptomatic infection reported at least one symptom lasting ≥3 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms.<h4>Conclusions</h4>One in 23 5-11 year-olds and one in eight 12-17 year-olds post-COVID-19 report persistent symptoms lasting ≥3 months, of which one in nine report a large impact on performing day-to-day activities.",,pdf:https://adc.bmj.com/content/archdischild/early/2023/03/01/archdischild-2022-325152.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render
 35361119,https://doi.org/10.1186/s12859-022-04641-x,classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes.,"Quinn GP, Sessler T, Ahmaderaghi B, Lambe S, VanSteenhouse H, Lawler M, Wappett M, Seligmann B, Longley DB, McDade SS.",,BMC bioinformatics,2022,2022-03-31,Y,Gene Expression; Functional Annotation; Cancer Subtype; Shiny Application; Colorectal Shiny Cms Cris Immune,,,"<h4>Background</h4>Transcriptionally informed predictions are increasingly important for sub-typing cancer patients, understanding underlying biology and to inform novel treatment strategies. For instance, colorectal cancers (CRCs) can be classified into four CRC consensus molecular subgroups (CMS) or five intrinsic (CRIS) sub-types that have prognostic and predictive value. Breast cancer (BRCA) has five PAM50 molecular subgroups with similar value, and the OncotypeDX test provides transcriptomic based clinically actionable treatment-risk stratification. However, assigning samples to these subtypes and other transcriptionally inferred predictions is time consuming and requires significant bioinformatics experience. There is no ""universal"" method of using data from diverse assay/sequencing platforms to provide subgroup classification using the established classifier sets of genes (CMS, CRIS, PAM50, OncotypeDX), nor one which in provides additional useful functional annotations such as cellular composition, single-sample Gene Set Enrichment Analysis, or prediction of transcription factor activity.<h4>Results</h4>To address this bottleneck, we developed classifieR, an easy-to-use R-Shiny based web application that supports flexible rapid single sample annotation of transcriptional profiles derived from cancer patient samples form diverse platforms. We demonstrate the utility of the "" classifieR"" framework to applications focused on the analysis of transcriptional profiles from colorectal (classifieRc) and breast (classifieRb). Samples are annotated with disease relevant transcriptional subgroups (CMS/CRIS sub-types in classifieRc and PAM50/inferred OncotypeDX in classifieRb), estimation of cellular composition using MCP-counter and xCell, single-sample Gene Set Enrichment Analysis (ssGSEA) and transcription factor activity predictions with Discriminant Regulon Expression Analysis (DoRothEA).<h4>Conclusions</h4>classifieR provides a framework which enables labs without access to a dedicated bioinformation can get information on the molecular makeup of their samples, providing an insight into patient prognosis, druggability and also as a tool for analysis and discovery. Applications are hosted online at https://generatr.qub.ac.uk/app/classifieRc and https://generatr.qub.ac.uk/app/classifieRb after signing up for an account on https://generatr.qub.ac.uk .",,pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-022-04641-x; doi:https://doi.org/10.1186/s12859-022-04641-x; html:https://europepmc.org/articles/PMC8974006; pdf:https://europepmc.org/articles/PMC8974006?pdf=render
+36863848,https://doi.org/10.1136/archdischild-2022-325152,Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England.,"Atchison CJ, Whitaker M, Donnelly CA, Chadeau-Hyam M, Riley S, Darzi A, Ashby D, Barclay W, Cooke GS, Elliott P, Ward H.",,Archives of disease in childhood,2023,2023-03-02,Y,epidemiology; Paediatrics; Adolescent Health; Infectious Disease Medicine; Covid-19,,,"<h4>Objective</h4>To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.<h4>Design</h4>Serial cross-sectional study.<h4>Setting</h4>Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England).<h4>Study population</h4>Children aged 5-17 years in the community.<h4>Predictors</h4>Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset.<h4>Main outcome measures</h4>Prevalence of persistent symptoms, reported as those lasting ≥3 months post-COVID-19.<h4>Results</h4>Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11 year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17 year-olds with prior symptomatic infection reported at least one symptom lasting ≥3 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms.<h4>Conclusions</h4>One in 23 5-11 year-olds and one in eight 12-17 year-olds post-COVID-19 report persistent symptoms lasting ≥3 months, of which one in nine report a large impact on performing day-to-day activities.",,pdf:https://adc.bmj.com/content/archdischild/early/2023/03/01/archdischild-2022-325152.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render
 34210356,https://doi.org/10.1186/s13059-021-02395-y,CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.,"Nicholls SM, Poplawski R, Bull MJ, Underwood A, Chapman M, Abu-Dahab K, Taylor B, Colquhoun RM, Rowe WPM, Jackson B, Hill V, O'Toole Á, Rey S, Southgate J, Amato R, Livett R, Gonçalves S, Harrison EM, Peacock SJ, Aanensen DM, Rambaut A, Connor TR, Loman NJ, COVID-19 Genomics UK (COG-UK) Consortium.",,Genome biology,2021,2021-07-01,Y,,,,"In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-021-02395-y; doi:https://doi.org/10.1186/s13059-021-02395-y; html:https://europepmc.org/articles/PMC8247108; pdf:https://europepmc.org/articles/PMC8247108?pdf=render
 32946449,https://doi.org/10.1371/journal.pone.0237676,"Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK.","Cooksey R, Kennedy J, Dennis MS, Escott-Price V, Lyons RA, Seaborne M, Brophy S.",,PloS one,2020,2020-09-18,Y,,,,"<h4>Objectives</h4>Proton pump inhibitors (PPIs) are commonly prescribed for prevention and treatment of gastrointestinal conditions or for gastroprotection from other drugs. Research suggests they are linked to increased dementia risk. We use linked national health data to examine the association between PPI use and the development of incident dementia.<h4>Methods and findings</h4>A population-based study using electronic health-data from the Secure Anonymised Information Linkage (SAIL) Databank, Wales (UK) from 1999 to 2015. Of data available on 3,765,744 individuals, a cohort who had ever been prescribed a PPI was developed (n = 183,968) for people aged 55 years and over and compared to non-PPI exposed individuals (131,110). Those with prior dementia, mild-cognitive-impairment or delirium codes were excluded. Confounding factors included comorbidities and/or drugs associated with them. Comorbidities might include head injury and some examples of medications include antidepressants, antiplatelets and anticoagulants. These commonly prescribed drugs were investigated as it was not feasible to explore all drugs in this study. The main outcome was a diagnosis of incident dementia. Cox proportional hazard regression modelling was used to calculate the Hazard ratio (HR) of developing dementia in PPI-exposed compared to unexposed individuals while controlling for potential confounders. The mean age of the PPI exposed individuals was 69.9 years and 39.8% male while the mean age of the unexposed individuals was 72.1 years and 41.1% male. The rate of PPI usage was 58.4% (183,968) and incident dementia rate was 11.8% (37,148/315,078). PPI use was associated with decreased dementia risk (HR: 0.67, 95% CI: 0.65 to 0.67, p<0.01).<h4>Conclusions</h4>This study, using large-scale, multi-centre health-data was unable to confirm an association between PPI use and increased dementia risk. Previously reported links may be associated with confounders of people using PPI's, such as increased risk of cardiovascular disease and/or depression and their associated medications which may be responsible for any increased risk of developing dementia.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237676&type=printable; doi:https://doi.org/10.1371/journal.pone.0237676; html:https://europepmc.org/articles/PMC7500586; pdf:https://europepmc.org/articles/PMC7500586?pdf=render
 34672950,https://doi.org/10.1016/s2213-2600(21)00435-5,"Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The Lancet. Respiratory medicine,2021,2021-10-18,Y,,,,"<h4>Background</h4>Colchicine has been proposed as a treatment for COVID-19 based on its anti-inflammatory actions. We aimed to evaluate the efficacy and safety of colchicine in patients admitted to hospital with COVID-19.<h4>Methods</h4>In this streamlined, randomised, controlled, open-label trial, underway at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Patients were eligible for inclusion in the study if they were admitted to hospital with clinically suspected or laboratory confirmed SARS-CoV-2 infection and had no medical history that might, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial. Eligible and consenting adults were randomly assigned (1:1) to receive either usual standard of care alone (usual care group) or usual standard of care plus colchicine (colchicine group) using web-based simple (unstratified) randomisation with allocation concealment. Participants received colchicine 1 mg after randomisation followed by 500 μg 12 h later and then 500 μg twice a day by mouth or nasogastric tube for 10 days in total or until discharge. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor (eg, diltiazem), patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m<sup>2</sup>, and those with an estimated bodyweight of less than 70 kg. The primary outcome was 28-day mortality, secondary endpoints included time to discharge, the proportion of patients discharged from hospital within 28 days, and, in patients not on invasive mechanical ventilation at randomisation, a composite endpoint of invasive mechanical ventilation or death. All analyses were by intention-to-treat. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.<h4>Findings</h4>Between Nov 27, 2020, and March 4, 2021, 11 340 (58%) of 19 423 patients enrolled into the RECOVERY trial were eligible to receive colchicine; 5610 (49%) patients were randomly assigned to the colchicine group and 5730 (51%) to the usual care group. Overall, 1173 (21%) patients in the colchicine group and 1190 (21%) patients in the usual care group died within 28 days (rate ratio 1·01 [95% CI 0·93 to 1·10]; p=0·77). Consistent results were seen in all prespecified subgroups of patients. Median time to discharge alive (10 days [IQR 5 to >28]) was the same in both groups, and there was no significant difference in the proportion of patients discharged from hospital alive within 28 days (3901 [70%] patients in the colchicine group and 4032 [70%] usual care group; rate ratio 0·98 [95% CI 0·94 to 1·03]; p=0·44). In those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (1344 [25%] in the colchicine group vs 1343 [25%] patients in the usual care group; risk ratio 1·02 [95% CI 0·96 to 1·09]; p=0·47).<h4>Interpretation</h4>In adults hospitalised with COVID-19, colchicine was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.<h4>Funding</h4>UK Research and Innovation (Medical Research Council), National Institute of Health Research, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2213260021004355/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00435-5; html:https://europepmc.org/articles/PMC8523117
@@ -371,12 +371,12 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 34376451,https://doi.org/10.1136/bmjopen-2021-048852,Ethnic and social inequalities in COVID-19 outcomes in Scotland: protocol for early pandemic evaluation and enhanced surveillance of COVID-19 (EAVE II).,"Henery P, Vasileiou E, Hainey KJ, Buchanan D, Harrison E, Leyland AH, Alexis T, Robertson C, Agrawal U, Ritchie L, Stock SJ, McCowan C, Docherty A, Kerr S, Marple J, Wood R, Moore E, Simpson CR, Sheikh A, Katikireddi SV.",,BMJ open,2021,2021-08-10,Y,epidemiology; Public Health; Protocols & Guidelines; Covid-19,,,"<h4>Introduction</h4>Evidence from previous pandemics, and the current COVID-19 pandemic, has found that risk of infection/severity of disease is disproportionately higher for ethnic minority groups, and those in lower socioeconomic positions. It is imperative that interventions to prevent the spread of COVID-19 are targeted towards high-risk populations. We will investigate the associations between social characteristics (such as ethnicity, occupation and socioeconomic position) and COVID-19 outcomes and the extent to which characteristics/risk factors might explain observed relationships in Scotland.The primary objective of this study is to describe the epidemiology of COVID-19 by social factors. Secondary objectives are to (1) examine receipt of treatment and prevention of COVID-19 by social factors; (2) quantify ethnic/social differences in adverse COVID-19 outcomes; (3) explore potential mediators of relationships between social factors and SARS-CoV-2 infection/COVID-19 prognosis; (4) examine whether occupational COVID-19 differences differ by other social factors and (5) assess quality of ethnicity coding within National Health Service datasets.<h4>Methods and analysis</h4>We will use a national cohort comprising the adult population of Scotland who completed the 2011 Census and were living in Scotland on 31 March 2020 (~4.3 million people). Census data will be linked to the Early Assessment of Vaccine and Anti-Viral Effectiveness II cohort consisting of primary/secondary care, laboratory data and death records. Sensitivity/specificity and positive/negative predictive values will be used to assess coding quality of ethnicity. Descriptive statistics will be used to examine differences in treatment and prevention of COVID-19. Poisson/Cox regression analyses and mediation techniques will examine ethnic and social differences, and drivers of inequalities in COVID-19. Effect modification (on additive and multiplicative scales) between key variables (such as ethnicity and occupation) will be assessed.<h4>Ethics and dissemination</h4>Ethical approval was obtained from the National Research Ethics Committee, South East Scotland 02. We will present findings of this study at international conferences, in peer-reviewed journals and to policy-makers.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/8/e048852.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-048852; html:https://europepmc.org/articles/PMC8359861; pdf:https://europepmc.org/articles/PMC8359861?pdf=render
 33240522,https://doi.org/10.1177/2055207620965046,Electronic-prescribing tools improve N-acetylcysteine prescription accuracy and timeliness for patients who present following a paracetamol overdose: A digital innovation quality-improvement project.,"McCulloch A, Sarwar A, Bate T, Thompson D, McDowell P, Sharif Q, Sapey E, Seccombe A.",,Digital health,2020,2020-01-01,Y,Antidote; Digital; paracetamol; Prescription Errors; Electronic Health Systems,,,"<h4>Objectives</h4>Prescription error rates and delays in treatment provision are high for N-acetylcysteine (NAC) when prescribed for paracetamol overdose (POD). We hypothesised that an electronic tool which proposed the complete NAC regimen would reduce prescription errors and improve the timeliness of NAC provision. Error rates and delays in the provision of NAC were assessed following POD, before and after the implementation of an electronic prescribing tool.<h4>Methods</h4>The NAC electronic prescribing tool proposed the three NAC infusions (dosed for weight) following entry of the patient's weight. All NAC prescriptions were reviewed during a three-month period prior to and after the tool's implementation. Error rates were divided into dose, infusion volume or infusion rate. Delays in NAC provision were identified using national Emergency Medicine guidelines.<h4>Results</h4>108 NAC prescriptions were analysed for all adult patients admitted to the emergency department of a secondary care hospital in the UK between July-September 2017 and August-October 2018, respectively. There were no differences in the demographics of patients or the seniority of the prescribing clinician before or after the introduction of the electronic tool. The electronic prescribing tool was associated with a decrease in prescribing errors (25% to 0%, p < 0.0071) and an increase in the provision of NAC within recommended times (11.1% to 47.4%, p = 0.029).<h4>Conclusions</h4>An electronic prescribing tool improved prescription errors and the timeliness of NAC provision following POD. Further studies will determine the effect of this on length of stay and the benefit of wider implementation in other secondary care hospitals.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/2055207620965046; doi:https://doi.org/10.1177/2055207620965046; html:https://europepmc.org/articles/PMC7675911; pdf:https://europepmc.org/articles/PMC7675911?pdf=render
 33846368,https://doi.org/10.1038/s41598-021-86324-w,Intake of food rich in saturated fat in relation to subclinical atherosclerosis and potential modulating effects from single genetic variants.,"Laguzzi F, Maitusong B, Strawbridge RJ, Baldassarre D, Veglia F, Humphries SE, Rauramaa R, Kurl S, Smit AJ, Giral P, Silveira A, Tremoli E, Hamsten A, de Faire U, Gigante B, Leander K, IMPROVE Study group.",,Scientific reports,2021,2021-04-12,Y,,,,"The relationship between intake of saturated fats and subclinical atherosclerosis, as well as the possible influence of genetic variants, is poorly understood and investigated. We aimed to investigate this relationship, with a hypothesis that it would be positive, and to explore whether genetics may modulate it, using data from a European cohort including 3,407 participants aged 54-79 at high risk of cardiovascular disease. Subclinical atherosclerosis was assessed by carotid intima-media thickness (C-IMT), measured at baseline and after 30 months. Logistic regression (OR; 95% CI) was employed to assess the association between high intake of food rich in saturated fat (vs. low) and: (1) the mean and the maximum values of C-IMT in the whole carotid artery (C-IMT<sub>mean</sub>, C-IMT<sub>max</sub>), in the bifurcation (Bif-), the common (CC-) and internal (ICA-) carotid arteries at baseline (binary, cut-point ≥ 75th), and (2) C-IMT progression (binary, cut-point > zero). For the genetic-diet interaction analyses, we considered 100,350 genetic variants. We defined interaction as departure from additivity of effects. After age- and sex-adjustment, high intake of saturated fat was associated with increased C-IMT<sub>mean</sub> (OR:1.27;1.06-1.47), CC-IMT<sub>mean</sub> (OR:1.22;1.04-1.44) and ICA-IMT<sub>mean</sub> (OR:1.26;1.07-1.48). However, in multivariate analysis results were no longer significant. No clear associations were observed between high intake of saturated fat and risk of atherosclerotic progression. There was no evidence of interactions between high intake of saturated fat and any of the genetic variants considered, after multiple testing corrections. High intake of saturated fats was not independently associated with subclinical atherosclerosis. Moreover, we did not identify any significant genetic-dietary fat interactions in relation to risk of subclinical atherosclerosis.",,pdf:https://www.nature.com/articles/s41598-021-86324-w.pdf; doi:https://doi.org/10.1038/s41598-021-86324-w; html:https://europepmc.org/articles/PMC8042105; pdf:https://europepmc.org/articles/PMC8042105?pdf=render
-37634386,https://doi.org/10.1016/j.schres.2023.08.014,Trends in socioeconomic inequalities in incidence of severe mental illness - A population-based linkage study using primary and secondary care routinely collected data between 2000 and 2017.,"Lee SC, DelPozo-Banos M, Lloyd K, Jones I, Walters JTR, John A.",,Schizophrenia research,2023,2023-08-25,N,Deprivation; Severe Mental Illness; Inequality; Recession; Urbanicity; Austerity,,,"<h4>Objective</h4>In 2008, the UK entered a period of economic recession followed by sustained austerity measures. We investigate changes in inequalities by area deprivation and urbanicity in incidence of severe mental illness (SMI, including schizophrenia-related disorders and bipolar disorder) between 2000 and 2017.<h4>Methods</h4>We analysed 4.4 million individuals from primary and secondary care routinely collected datasets (2000-2017) in Wales and estimated the incidence of SMI by deprivation and urbanicity measured by the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator respectively. Using linear modelling and joinpoint regression approaches, we examined time trends of the incidence and incidence rate ratios (IRR) of SMI by the WIMD and urban/rural indicator adjusted for available confounders.<h4>Results</h4>We observed a turning point of time trends of incidence of SMI at 2008/2009 where slope changes of time trends were significantly increasing. IRRs by deprivation/urbanicity remained stable or significantly decreased over the study period except for those with bipolar disorder sourced from secondary care settings, with increasing trend of IRRs (increase in IRR by deprivation after 2010: 1.6 % per year, 95 % CI: 1.0 %-2.2 %; increase in IRR by urbanicity 1.0 % per year, 95 % CI: 0.6 %-1.3 %).<h4>Conclusions</h4>There was an association between recession/austerity and an increase in the incidence of SMI over time. There were variations in the effects of deprivation/urbanicity on incidence of SMI associated with short- and long-term socioeconomic change. These findings may support targeted interventions and social protection systems to reduce incidence of SMI.",,doi:https://doi.org/10.1016/j.schres.2023.08.014
 31757986,https://doi.org/10.1038/s41598-019-53454-1,Ontology-based prediction of cancer driver genes.,"Althubaiti S, Karwath A, Dallol A, Noor A, Alkhayyat SS, Alwassia R, Mineta K, Gojobori T, Beggs AD, Schofield PN, Gkoutos GV, Hoehndorf R.",,Scientific reports,2019,2019-11-22,Y,,Applied Analytics,,"Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.",This study investigated which genes encourage cancer tumors to grow. The study identifies genes and distinguishes their role in different types of cancers. Their method is validated using whole exome and whole genome sequencing,pdf:https://www.nature.com/articles/s41598-019-53454-1.pdf; doi:https://doi.org/10.1038/s41598-019-53454-1; html:https://europepmc.org/articles/PMC6874647; pdf:https://europepmc.org/articles/PMC6874647?pdf=render
+37634386,https://doi.org/10.1016/j.schres.2023.08.014,Trends in socioeconomic inequalities in incidence of severe mental illness - A population-based linkage study using primary and secondary care routinely collected data between 2000 and 2017.,"Lee SC, DelPozo-Banos M, Lloyd K, Jones I, Walters JTR, John A.",,Schizophrenia research,2023,2023-08-25,N,Deprivation; Severe Mental Illness; Inequality; Recession; Urbanicity; Austerity,,,"<h4>Objective</h4>In 2008, the UK entered a period of economic recession followed by sustained austerity measures. We investigate changes in inequalities by area deprivation and urbanicity in incidence of severe mental illness (SMI, including schizophrenia-related disorders and bipolar disorder) between 2000 and 2017.<h4>Methods</h4>We analysed 4.4 million individuals from primary and secondary care routinely collected datasets (2000-2017) in Wales and estimated the incidence of SMI by deprivation and urbanicity measured by the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator respectively. Using linear modelling and joinpoint regression approaches, we examined time trends of the incidence and incidence rate ratios (IRR) of SMI by the WIMD and urban/rural indicator adjusted for available confounders.<h4>Results</h4>We observed a turning point of time trends of incidence of SMI at 2008/2009 where slope changes of time trends were significantly increasing. IRRs by deprivation/urbanicity remained stable or significantly decreased over the study period except for those with bipolar disorder sourced from secondary care settings, with increasing trend of IRRs (increase in IRR by deprivation after 2010: 1.6 % per year, 95 % CI: 1.0 %-2.2 %; increase in IRR by urbanicity 1.0 % per year, 95 % CI: 0.6 %-1.3 %).<h4>Conclusions</h4>There was an association between recession/austerity and an increase in the incidence of SMI over time. There were variations in the effects of deprivation/urbanicity on incidence of SMI associated with short- and long-term socioeconomic change. These findings may support targeted interventions and social protection systems to reduce incidence of SMI.",,doi:https://doi.org/10.1016/j.schres.2023.08.014
 37159441,https://doi.org/10.1371/journal.pdig.0000218,Hospital-wide natural language processing summarising the health data of 1 million patients.,"Bean DM, Kraljevic Z, Shek A, Teo J, Dobson RJB.",,PLOS digital health,2023,2023-05-09,Y,,,,"Electronic health records (EHRs) represent a major repository of real world clinical trajectories, interventions and outcomes. While modern enterprise EHR's try to capture data in structured standardised formats, a significant bulk of the available information captured in the EHR is still recorded only in unstructured text format and can only be transformed into structured codes by manual processes. Recently, Natural Language Processing (NLP) algorithms have reached a level of performance suitable for large scale and accurate information extraction from clinical text. Here we describe the application of open-source named-entity-recognition and linkage (NER+L) methods (CogStack, MedCAT) to the entire text content of a large UK hospital trust (King's College Hospital, London). The resulting dataset contains 157M SNOMED concepts generated from 9.5M documents for 1.07M patients over a period of 9 years. We present a summary of prevalence and disease onset as well as a patient embedding that captures major comorbidity patterns at scale. NLP has the potential to transform the health data lifecycle, through large-scale automation of a traditionally manual task.",,doi:https://doi.org/10.1371/journal.pdig.0000218; doi:https://doi.org/10.1371/journal.pdig.0000218; html:https://europepmc.org/articles/PMC10168555; pdf:https://europepmc.org/articles/PMC10168555?pdf=render
 32723851,https://doi.org/10.1136/bmjhci-2019-100122,HDR UK supporting mobilising computable biomedical knowledge in the UK. ,"Sebire NJ, Cake C, Morris AD.",,BMJ health & care informatics,2020,2020-07-01,Y,,,,"Computable biomedical knowledge (CBK) represents an evolving area of health informatics, with potential for rapid translational patient benefit. Health Data Research UK (HDR UK) is the national Institute for Health Data Science, whose aim is to unite the UK's health data to enable discoveries that improve people's lives. The three main components include the UK HDR Alliance of data custodians, committed to making health data available for research and innovation purposes for public benefit while ensuring safe use of data and building public trust, the HDR Hubs, as centres of expertise for curating data and providing expert domain-specific services, and the HDR Innovation Gateway ('Gateway'), providing discovery, accessibility, security and interoperability services. To support CBK developments, HDR UK is encouraging use of open data standards for research purposes, with guidance around areas in which standards are emerging, aims to work closely with the international CBK community to support initiatives and aid with evaluation and collaboration, and has established a phenomics workstream to create a national platform for dissemination of machine readable and computable phenotypical algorithms to reduce duplication of effort and improve reproducibility in clinical studies.",,pdf:https://informatics.bmj.com/content/bmjhci/27/2/e100122.full.pdf; doi:https://doi.org/10.1136/bmjhci-2019-100122; html:https://europepmc.org/articles/PMC7388881; pdf:https://europepmc.org/articles/PMC7388881?pdf=render
-37185201,https://doi.org/10.1136/bmjopen-2022-067337,Prevalence of HIV in mental health service users: a retrospective cohort study.,"Heslin M, Jewell A, Croxford S, Chau C, Smith S, Pittrof R, Covshoff E, Sullivan A, Delpech V, Brown A, King HP, Kakaiya M, Campbell L, Hughes E, Stewart R.",,BMJ open,2023,2023-04-25,Y,Mental health; Hiv & Aids; Sexual Medicine,,,"<h4>Objective</h4>To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.<h4>Participants</h4>All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.<h4>Primary outcome</h4>Point prevalence of HIV.<h4>Results</h4>There were 181 177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).<h4>Conclusions</h4>The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e067337.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067337; html:https://europepmc.org/articles/PMC10186409; pdf:https://europepmc.org/articles/PMC10186409?pdf=render
 35902613,https://doi.org/10.1038/s41467-022-32096-4,Dynamics of competing SARS-CoV-2 variants during the Omicron epidemic in England.,"Eales O, de Oliveira Martins L, Page AJ, Wang H, Bodinier B, Tang D, Haw D, Jonnerby J, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Elliott P, Donnelly CA, Chadeau-Hyam M.",,Nature communications,2022,2022-07-28,Y,,,,"The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant (first detected in November 2021) exhibited a high degree of immune evasion, leading to increased infection rates worldwide. However, estimates of the magnitude of this Omicron wave have often relied on routine testing data, which are prone to several biases. Using data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys assessing prevalence of SARS-CoV-2 infection in England, we estimated the dynamics of England's Omicron wave (from 9 September 2021 to 1 March 2022). We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct variants, intermittent epidemics of similar magnitudes may become the 'new normal'.",,pdf:https://www.nature.com/articles/s41467-022-32096-4.pdf; doi:https://doi.org/10.1038/s41467-022-32096-4; html:https://europepmc.org/articles/PMC9330949; pdf:https://europepmc.org/articles/PMC9330949?pdf=render
+37185201,https://doi.org/10.1136/bmjopen-2022-067337,Prevalence of HIV in mental health service users: a retrospective cohort study.,"Heslin M, Jewell A, Croxford S, Chau C, Smith S, Pittrof R, Covshoff E, Sullivan A, Delpech V, Brown A, King HP, Kakaiya M, Campbell L, Hughes E, Stewart R.",,BMJ open,2023,2023-04-25,Y,Mental health; Hiv & Aids; Sexual Medicine,,,"<h4>Objective</h4>To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.<h4>Participants</h4>All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.<h4>Primary outcome</h4>Point prevalence of HIV.<h4>Results</h4>There were 181 177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).<h4>Conclusions</h4>The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e067337.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067337; html:https://europepmc.org/articles/PMC10186409; pdf:https://europepmc.org/articles/PMC10186409?pdf=render
 37068951,https://doi.org/10.1136/thorax-2022-219901,Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019.,"Konstantinoudis G, Minelli C, Lam HCY, Fuertes E, Ballester J, Davies B, Vicedo-Cabrera AM, Gasparrini A, Blangiardo M.",,Thorax,2023,2023-04-17,Y,Asthma Epidemiology,,,"<h4>Background</h4>Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space.<h4>Methods</h4>We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km×1 km resolution was retrieved from the UK Met Office. We focused on lag 0-3 days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays).<h4>Results</h4>After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable.<h4>Conclusion</h4>This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2023/04/17/thorax-2022-219901.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219901; html:https://europepmc.org/articles/PMC10447396; pdf:https://europepmc.org/articles/PMC10447396?pdf=render
 35197134,https://doi.org/10.1192/bjo.2022.24,Birth without intervention in women with severe mental illness: cohort study.,"Taylor C, Stewart R, Gibson R, Pasupathy D, Shetty H, Howard L.",,BJPsych open,2022,2022-02-24,Y,Schizophrenia; epidemiology; Perinatal Psychiatry; Bipolar Affective Disorders; Birth Without Intervention,,,"<h4>Summary</h4>The rate of normal birth outcomes (i.e. full-term births without intervention) for women with severe mental illness (SMI - psychotic and bipolar disorders) is not known. We examined rates of birth without intervention (spontaneous labour onset, spontaneous vaginal delivery without instruments, no episiotomy and no indication of pre- or post-delivery anaesthesia) in women with SMI (584 pregnancies) compared with a control population (70 942 pregnancies). Outcome ratios were calculated standardising for age. Women with SMI were less likely to have a birth without intervention (29.5%) relative to the control population (36.8%) (standardised outcome ratio 0.74, 95% CI 0.63-0.87).",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/4FEB5E5A08973A5347ABA87F440CF09B/S2056472422000242a.pdf/div-class-title-birth-without-intervention-in-women-with-severe-mental-illness-cohort-study-div.pdf; doi:https://doi.org/10.1192/bjo.2022.24; html:https://europepmc.org/articles/PMC8935938; pdf:https://europepmc.org/articles/PMC8935938?pdf=render
 36841835,https://doi.org/10.1038/s41541-023-00614-0,Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.,"Holt H, Jolliffe DA, Talaei M, Faustini S, Vivaldi G, Greenig M, Richter AG, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Davies GA, Shaheen SO, Martineau AR.",,NPJ vaccines,2023,2023-02-25,Y,,,,"Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.",,pdf:https://www.nature.com/articles/s41541-023-00614-0.pdf; doi:https://doi.org/10.1038/s41541-023-00614-0; html:https://europepmc.org/articles/PMC9959934; pdf:https://europepmc.org/articles/PMC9959934?pdf=render
@@ -384,8 +384,8 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 35927670,https://doi.org/10.1186/s12882-022-02902-8,Pre-operative Waterlow score and outcomes after kidney transplantation.,"Brotherton A, Evison F, Gallier S, Sharif A.",,BMC nephrology,2022,2022-08-04,Y,Mortality; Kidney transplantation; Length Of Stay; Readmission; Surrogate; Waterlow,,,"<h4>Background</h4>Waterlow scoring was introduced in the 1980s as a nursing tool to risk stratify for development of decubitus ulcers (pressure sores) and is commonly used in UK hospitals. Recent interest has focussed on its value as a pre-op surrogate marker for adverse surgical outcomes, but utility after kidney transplantation has never been explored.<h4>Methods</h4>In this single-centre observational study, data was extracted from hospital informatics systems for all kidney allograft recipients transplanted between 1<sup>st</sup> January 2007 and 30<sup>th</sup> June 2020. Waterlow scores were categorised as per national standards; 0-9 (low risk), 10-14 (at risk), 15-19 (high risk) and ≥ 20 (very high risk). Multiple imputation was used to replace missing data with substituted values. Primary outcomes of interest were post-operative length of stay, emergency re-admission within 90-days and mortality analysed by linear, logistic or Cox regression models respectively.<h4>Results</h4>Data was available for 2,041 kidney transplant patients, with baseline demographics significantly different across Waterlow categories. As a continuous variable, the median Waterlow score across the study cohort was 10 (interquartile range 8-13). As a categorical variable, Waterlow scores pre-operatively were classified as low risk (n = 557), at risk (n = 543), high risk (n = 120), very high risk (n = 27) and a large proportion of missing data (n = 794). Median length of stay in days varied significantly with pre-op Waterlow category scores, progressively getting longer with increasing severity of Waterlow category. However, no difference was observed in risk for emergency readmission within 90-days of surgery with severity of Waterlow category. Patients with 'very high risk' Waterlow scores had increased risk for mortality at 41.9% versus high risk (23.7%), at risk (17.4%) and low risk (13.4%). In adjusted analyses, 'very high risk' Waterlow group (as a categorical variable) or Waterlow score (as a continuous variable) had an independent association with increase length of stay after transplant surgery only. No association was observed between any Waterlow risk group/score with emergency 90-day readmission rates or post-transplant mortality after adjustment.<h4>Conclusions</h4>Pre-operative Waterlow scoring is a poor surrogate marker to identify kidney transplant patients at risk of emergency readmission or death and should not be utilised outside its intended use.",,pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-022-02902-8; doi:https://doi.org/10.1186/s12882-022-02902-8; html:https://europepmc.org/articles/PMC9351155; pdf:https://europepmc.org/articles/PMC9351155?pdf=render
 32935048,https://doi.org/10.23889/ijpds.v5i1.1121,The Secure Anonymised Information Linkage databank Dementia e-cohort (SAIL-DeC).,"Schnier C, Wilkinson T, Akbari A, Orton C, Sleegers K, Gallacher J, Lyons RA, Sudlow C.",,International journal of population data science,2020,2020-02-25,Y,,,,"<h4>Introduction</h4>The rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during clinical care.<h4>Objectives</h4>We aimed to apply reproducible methods to create the SAIL dementia e-cohort (SAIL-DeC). We created SAIL-DeC with a view to maximising its utility for a broad range of research questions whilst minimising duplication of effort for researchers.<h4>Methods</h4>SAIL contains individual-level, linked primary care, hospital admission, mortality and demographic data. Data are currently available until 2018 and future updates will extend participant follow-up time. We included participants who were born between 1st January 1900 and 1st January 1958 and for whom primary care data were available. We applied algorithms consisting of International Classification of Diseases (versions 9 and 10) and Read (version 2) codes to identify participants with and without all-cause dementia and dementia subtypes. We also created derived variables for comorbidities and risk factors.<h4>Results</h4>From 4.4 million unique participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia, with 77,978 (60%) having dementia subtype codes. Alzheimer's disease was the most common subtype diagnosis (62%). Among the dementia cases, the median duration of observation time was 14 years.<h4>Conclusion</h4>We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research.",,pdf:https://ijpds.org/article/download/1121/2984; doi:https://doi.org/10.23889/ijpds.v5i1.1121; html:https://europepmc.org/articles/PMC7473277; pdf:https://europepmc.org/articles/PMC7473277?pdf=render
 35418418,https://doi.org/10.1136/bmjopen-2021-049441,"Health checks for adults with intellectual disability and association with survival rates: a linked electronic records matched cohort study in Wales, UK.","Kennedy N, Kennedy J, Kerr M, Dredge S, Brophy S.",,BMJ open,2022,2022-04-13,Y,epidemiology; Quality In Health Care; General Medicine (See Internal Medicine),,,"<h4>Objective</h4>To examine if mortality rates are lower in people with intellectual disability who have had a health check compared with those who have not had health checks.<h4>Setting</h4>General practice records of 26 954 people with an intellectual disability in Wales between 2005-2017, of which 7650 (28.4%) with a health check were matched 1:2 with those without a health check.<h4>Primary outcome measure</h4>Office of National Statistics mortality data; a Cox regression was utilised to examine time to death adjusted for comorbidities and gender.<h4>Results</h4>Patients who had a health check were stratified by those who (1) had a confirmed health check, that is, Read Code for a health check (n=7650 (28.4 %)) and (2) had no evidence of receiving a health check in their medical record. Patients with a health check were matched for age at time of health check with two people who did not have a health check. The health check was associated with improved survival for those with autism or Down's Syndrome (HR 0.58 (95% CI 0.37 to 0.91) and HR 0.76 (95% CI 0.64 to 0.91), respectively). There was no evidence of improved survival for those diagnosed with diabetes or cancer. The people who had a health check were more likely to be older, have epilepsy and less likely to have autism or Down's syndrome.<h4>Conclusions</h4>Health checks are likely to influence survival if started before a person is diagnosed with a chronic condition, especially for people with autism or Down's syndrome.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e049441.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049441; html:https://europepmc.org/articles/PMC9013997; pdf:https://europepmc.org/articles/PMC9013997?pdf=render
-37080124,https://doi.org/10.1016/j.seizure.2023.04.006,COVID-19 vaccination uptake in people with epilepsy in wales.,"Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",,Seizure,2023,2023-04-06,Y,"Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",,,"<h4>Purpose</h4>People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.<h4>Methods</h4>We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.<h4>Results</h4>There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.<h4>Conclusions</h4>COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",,doi:https://doi.org/10.1016/j.seizure.2023.04.006; doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render
 34158305,https://doi.org/10.1136/bmjopen-2020-048333,Association between community-based self-reported COVID-19 symptoms and social deprivation explored using symptom tracker apps: a repeated cross-sectional study in Northern Ireland.,"McKinley JM, Cutting D, Anderson N, Graham C, Johnston B, Mueller U, Atkinson PM, Van Woerden H, Bradley DT, Kee F.",,BMJ open,2021,2021-06-22,Y,Public Health; Statistics & Research Methods; Covid-19,,,"<h4>Objectives</h4>The aim of the study was to investigate the spatial and temporal relationships between the prevalence of COVID-19 symptoms in the community-level and area-level social deprivation.<h4>Design</h4>Spatial mapping, generalised linear models, using time as a factor and spatial-lag models were used to explore the relationship between self-reported COVID-19 symptom prevalence as recorded through two smartphone symptom tracker apps and a range of socioeconomic factors using a repeated cross-sectional study design.<h4>Setting</h4>In the community in Northern Ireland, UK. The analysis period included the earliest stages of non-pharmaceutical interventions and societal restrictions or 'lockdown' in 2020.<h4>Participants</h4>Users of two smartphone symptom tracker apps recording self-reported health information who recorded their location as Northern Ireland, UK.<h4>Primary outcome measures</h4>Population standardised self-reported COVID-19 symptoms and correlation between population standardised self-reported COVID-19 symptoms and area-level characteristics from measures of multiple deprivation including employment levels and population housing density, derived as the mean number of residents per household for each census super output area.<h4>Results</h4>Higher self-reported prevalence of COVID-19 symptoms was associated with the most deprived areas (p<0.001) and with those areas with the lowest employment levels (p<0.001). Higher rates of self-reported COVID-19 symptoms within the age groups, 18-24 and 25-34 years were found within the most deprived areas during the earliest stages of non-pharmaceutical interventions and societal restrictions ('lockdown').<h4>Conclusions</h4>Through spatial regression of self-reporting COVID-19 smartphone data in the community, this research shows how a lens of social deprivation can deepen our understanding of COVID-19 transmission and prevention. Our findings indicate that social inequality, as measured by area-level deprivation, is associated with disparities in potential COVID-19 infection, with higher prevalence of self-reported COVID-19 symptoms in urban areas associated with area-level social deprivation, housing density and age.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e048333.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048333; html:https://europepmc.org/articles/PMC8228811; pdf:https://europepmc.org/articles/PMC8228811?pdf=render
+37080124,https://doi.org/10.1016/j.seizure.2023.04.006,COVID-19 vaccination uptake in people with epilepsy in wales.,"Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",,Seizure,2023,2023-04-06,Y,"Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",,,"<h4>Purpose</h4>People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.<h4>Methods</h4>We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.<h4>Results</h4>There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.<h4>Conclusions</h4>COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",,doi:https://doi.org/10.1016/j.seizure.2023.04.006; doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render
 32499256,https://doi.org/10.1136/bmjopen-2019-033424,Point-of-care tests for urinary tract infections: protocol for a systematic review and meta-analysis of diagnostic test accuracy.,"Fraile Navarro D, Sullivan F, Azcoaga-Lorenzo A, Hernandez Santiago V.",,BMJ open,2020,2020-06-03,Y,Urinary tract infections; epidemiology; Molecular Diagnostics; Diagnostic Microbiology,,,"<h4>Introduction</h4>Urinary tract infections (UTIs) are the second most common type of infection worldwide, accounting for a large number of primary care consultations and antibiotic prescribing. Current diagnosis is based on an empirical approach, relying on symptoms and occasional use of urine dipsticks. The diagnostic reference standard is still urine culture, although it is not routinely recommended for uncomplicated UTIs in the community, due to time to diagnosis (48 hours). Faster point-of-care tests have been developed, but their diagnostic accuracy has not been compared. Our objective is to systematically review and meta-analyse the diagnostic accuracy of currently available point-of-care tests for UTIs.<h4>Methods and analysis</h4>Studies evaluating the diagnostic accuracy of point-of-care tests for UTIs will be included. PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews were searched from inception to 1 June 2019. Data extraction and risk-of-bias assessment will be assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Meta-analysis will be performed depending on data availability and heterogeneity.<h4>Ethics and dissemination</h4>This is a systematic review protocol and therefore formal ethical approval is not required, as no primary, identifiable, personal data will be collected. Patients or the public were not involved in the design of our research. However, the findings from this review will be shared with key stakeholders, including patient groups, clinicians and guideline developers, and will also be presented and national and international conferences.<h4>Prospero registration number</h4>CRD42018112019.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/6/e033424.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033424; html:https://europepmc.org/articles/PMC7282288; pdf:https://europepmc.org/articles/PMC7282288?pdf=render
 35332197,https://doi.org/10.1038/s41598-022-08690-3,Identifying multimorbidity clusters in an unselected population of hospitalised patients.,"Robertson L, Vieira R, Butler J, Johnston M, Sawhney S, Black C.",,Scientific reports,2022,2022-03-24,Y,,,,"Multimorbidity (multiple coexisting chronic health conditions) is common and increasing worldwide, and makes care challenging for both patients and healthcare systems. To ensure care is patient-centred rather than specialty-centred, it is important to know which conditions commonly occur together and identify the corresponding patient profile. To date, no studies have described multimorbidity clusters within an unselected hospital population. Our aim was to identify and characterise multimorbidity clusters, in a large, unselected hospitalised patient population. Linked inpatient hospital episode data were used to identify adults admitted to hospital in Grampian, Scotland in 2014 who had ≥ 2 of 30 chronic conditions diagnosed in the 5 years prior. Cluster analysis (Gower distance and Partitioning around Medoids) was used to identify groups of patients with similar conditions. Clusters of conditions were defined based on clinical review and assessment of prevalence within patient groups and labelled according to the most prevalent condition. Patient profiles for each group were described by age, sex, admission type, deprivation and urban-rural area of residence. 11,389 of 41,545 hospitalised patients (27%) had ≥ 2 conditions. Ten clusters of conditions were identified: hypertension; asthma; alcohol misuse; chronic kidney disease and diabetes; chronic kidney disease; chronic pain; cancer; chronic heart failure; diabetes; hypothyroidism. Age ranged from 51 (alcohol misuse) to 79 (chronic heart failure). Women were a higher proportion in the chronic pain and hypothyroidism clusters. The proportion of patients from the most deprived quintile of the population ranged from 6% (hypertension) to 14% (alcohol misuse). Identifying clusters of conditions in hospital patients is a first step towards identifying opportunities to target patient-centred care towards people with unmet needs, leading to improved outcomes and increased efficiency. Here we have demonstrated the face validity of cluster analysis as an exploratory method for identifying clusters of conditions in hospitalised patients with multimorbidity.",,pdf:https://www.nature.com/articles/s41598-022-08690-3.pdf; doi:https://doi.org/10.1038/s41598-022-08690-3; html:https://europepmc.org/articles/PMC8948299; pdf:https://europepmc.org/articles/PMC8948299?pdf=render
 33934335,https://doi.org/10.1111/anae.15466,Long-term trends in critical care admissions in Wales*. ,"Pugh RJ, Bailey R, Szakmany T, Al Sallakh M, Hollinghurst J, Akbari A, Griffiths R, Battle C, Thorpe C, Subbe CP, Lyons RA.",,Anaesthesia,2021,2021-05-02,Y,,,,"As national populations age, demands on critical care services are expected to increase. In many healthcare settings, longitudinal trends indicate rising numbers and proportions of patients admitted to ICU who are older; elsewhere, including some parts of the UK, a decrease has raised concerns with regard to rationing according to age. Our aim was to investigate admission trends in Wales, where critical care capacity has not risen in the last decade. We used the Secure Anonymised Information Linkage Databank to identify and characterise critical care admissions in patients aged ≥ 18 years from 1 January 2008 to 31 December 2017. We categorised 85,629 ICU admissions as youngest (18-64 years), older (65-79 years) and oldest (≥ 80 years). The oldest group accounted for 15% of admissions, the older age group 39% and the youngest group 46%. Relative to the national population, the incidence of admission rates per 10,000 population in the oldest group decreased significantly over the study period from 91.5/10,000 in 2008 to 77.5/10,000 (a relative decrease of 15%), and among the older group from 89.2/10,000 in 2008 to 75.3/10,000 in 2017 (a relative decrease of 16%). We observed significant decreases in admissions with high comorbidity (modified Charlson comorbidity index); increases in the proportion of older patients admitted who were considered 'fit' rather than frail (electronic frailty index); and decreases in admissions with a medical diagnosis. In contrast to other healthcare settings, capacity constraints and surgical imperatives appear to have contributed to a relative exclusion of older patients presenting with acute medical illness.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56830/Download/56830__24941__ed34d96421c74ecca52d5a3aaf9afc85.pdf; doi:https://doi.org/10.1111/anae.15466; html:https://europepmc.org/articles/PMC10138728; pdf:https://europepmc.org/articles/PMC10138728?pdf=render
@@ -402,8 +402,8 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 36745545,https://doi.org/10.1099/mgen.0.000887,The use of representative community samples to assess SARS-CoV-2 lineage competition: Alpha outcompetes Beta and wild-type in England from January to March 2021.,"Eales O, Page AJ, Tang SN, Walters CE, Wang H, Haw D, Trotter AJ, Le Viet T, Foster-Nyarko E, Prosolek S, Atchison C, Ashby D, Cooke G, Barclay W, Donnelly CA, O'Grady J, Volz E, The Covid-Genomics Uk Cog-Uk Consortium, Darzi A, Ward H, Elliott P, Riley S.",,Microbial genomics,2023,2023-02-01,Y,,,,"Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy and will be a high priority for public health for the foreseeable future. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained using a variety of methods all of which are known to contain biases. As a case study, using an approach which is largely free of biases, we here describe lineage dynamics and phylogenetic relationships of the Alpha and Beta variant in England during the first 3 months of 2021 using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the Alpha variant (first identified in Kent) becoming predominant, driven by a reproduction number 0.3 higher than for the prior wild-type. During January, positive samples were more likely to be Alpha in those aged 18 to 54 years old. Although individuals infected with the Alpha variant were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild-type, they were more likely to be antibody-positive 6 weeks after infection. Further, viral load was higher in those infected with the Alpha variant as measured by cycle threshold (Ct) values. The presence of infections with non-imported Beta variant (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing. These results highlight how sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance during periods of lineage diversity.",,doi:https://doi.org/10.1099/mgen.0.000887; html:https://europepmc.org/articles/PMC9997751; pdf:https://europepmc.org/articles/PMC9997751?pdf=render
 34966903,https://doi.org/10.3389/fdgth.2021.778305,Development of a Lexicon for Pain.,"Chaturvedi J, Mascio A, Velupillai SU, Roberts A.",,Frontiers in digital health,2021,2021-12-13,Y,Pain; Mental health; Lexicon; Electronic Health Records; Natural Language Processing,,,"Pain has been an area of growing interest in the past decade and is known to be associated with mental health issues. Due to the ambiguous nature of how pain is described in text, it presents a unique natural language processing (NLP) challenge. Understanding how pain is described in text and utilizing this knowledge to improve NLP tasks would be of substantial clinical importance. Not much work has previously been done in this space. For this reason, and in order to develop an English lexicon for use in NLP applications, an exploration of pain concepts within free text was conducted. The exploratory text sources included two hospital databases, a social media platform (Twitter), and an online community (Reddit). This exploration helped select appropriate sources and inform the construction of a pain lexicon. The terms within the final lexicon were derived from three sources-literature, ontologies, and word embedding models. This lexicon was validated by two clinicians as well as compared to an existing 26-term pain sub-ontology and MeSH (Medical Subject Headings) terms. The final validated lexicon consists of 382 terms and will be used in downstream NLP tasks by helping select appropriate pain-related documents from electronic health record (EHR) databases, as well as pre-annotating these words to help in development of an NLP application for classification of mentions of pain within the documents. The lexicon and the code used to generate the embedding models have been made publicly available.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710455; doi:https://doi.org/10.3389/fdgth.2021.778305; html:https://europepmc.org/articles/PMC8710455; pdf:https://europepmc.org/articles/PMC8710455?pdf=render
 35133177,https://doi.org/10.1126/science.abn8347,Rapid increase in Omicron infections in England during December 2021: REACT-1 study.,"Elliott P, Bodinier B, Eales O, Wang H, Haw D, Elliott J, Whitaker M, Jonnerby J, Tang D, Walters CE, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Chadeau-Hyam M, Donnelly CA.",,"Science (New York, N.Y.)",2022,2022-02-08,Y,,,,"The unprecedented rise in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during December 2021 was concurrent with rapid spread of the Omicron variant in England and globally. We analyzed the prevalence of SARS-CoV-2 and its dynamics in England from the end of November to mid-December 2021 among almost 100,000 participants in the REACT-1 study. Prevalence was high with rapid growth nationally and particularly in London during December 2021, with an increasing proportion of infections due to Omicron. We observed large decreases in swab positivity among mostly vaccinated older children (12 to 17 years) relative to unvaccinated younger children (5 to 11 years), and in adults who received a third (booster) vaccine dose versus two doses. Our results reinforce the importance of vaccination and booster campaigns, although additional measures have been needed to control the rapid growth of the Omicron variant.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/94586/2/science.abn8347.pdf; doi:https://doi.org/10.1126/science.abn8347; html:https://europepmc.org/articles/PMC8939772; pdf:https://europepmc.org/articles/PMC8939772?pdf=render
-36936594,https://doi.org/10.1136/bmjmed-2022-000247,Measuring multimorbidity in research: Delphi consensus study.,"Ho ISS, Azcoaga-Lorenzo A, Akbari A, Davies J, Khunti K, Kadam UT, Lyons RA, McCowan C, Mercer SW, Nirantharakumar K, Staniszewska S, Guthrie B.",,BMJ medicine,2022,2022-07-27,Y,Medicine; epidemiology; Primary Health Care; Public Health; Research Design,,,"<h4>Objective</h4>To develop international consensus on the definition and measurement of multimorbidity in research.<h4>Design</h4>Delphi consensus study.<h4>Setting</h4>International consensus; data collected in three online rounds from participants between 30 November 2020 and 18 May 2021.<h4>Participants</h4>Professionals interested in multimorbidity and people with long term conditions were recruited to professional and public panels.<h4>Results</h4>150 professional and 25 public participants completed the first survey round. Response rates for rounds 2/3 were 83%/92% for professionals and 88%/93% in the public panel, respectively. Across both panels, the consensus was that multimorbidity should be defined as two or more long term conditions. Complex multimorbidity was perceived to be a useful concept, but the panels were unable to agree on how to define it. Both panels agreed that conditions should be included in a multimorbidity measure if they were one or more of the following: currently active; permanent in their effects; requiring current treatment, care, or therapy; requiring surveillance; or relapsing-remitting conditions requiring ongoing care. Consensus was reached for 24 conditions to always include in multimorbidity measures, and 35 conditions to usually include unless a good reason not to existed. Simple counts were preferred for estimating prevalence and examining clustering or trajectories, and weighted measures were preferred for risk adjustment and outcome prediction.<h4>Conclusions</h4>Previous multimorbidity research is limited by inconsistent definitions and approaches to measuring multimorbidity. This Delphi study identifies professional and public panel consensus guidance to facilitate consistency of definition and measurement, and to improve study comparability and reproducibility.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000247.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000247; html:https://europepmc.org/articles/PMC9978673; pdf:https://europepmc.org/articles/PMC9978673?pdf=render
 32877922,https://doi.org/10.1093/gerona/glaa216,Frailty Is Associated With Neutrophil Dysfunction Which Is Correctable With Phosphoinositol-3-Kinase Inhibitors.,"Wilson D, Drew W, Jasper A, Crisford H, Nightingale P, Newby P, Jackson T, Lord JM, Sapey E.",,"The journals of gerontology. Series A, Biological sciences and medical sciences",2020,2020-11-01,Y,Inflammation; Proteinases; innate immunity; Comorbidity,,,"Neutrophil dysfunction has been described with age, appears exaggerated in infection, with altered phosphoinositol signaling a potential mechanism. However, functional aging is heterogeneous. Frailty is a negative health status and is more common in older adults. We hypothesized that neutrophil migration may be compromised in frailty, associated with the degree of frailty experienced by the older person. We compared measures of frailty, neutrophil function, and systemic inflammation in 40 young and 77 older community-dwelling adults in the United Kingdom. Systemic neutrophils exhibited an age-associated reduction in the accuracy of migration (chemotaxis) which was further blunted with frailty. The degree of migratory inaccuracy correlated with physical (adjusted hand grip strength) and cognitive (Stroop test) markers of frailty. Regression analysis demonstrated that age, Charlson comorbidity index, and frailty index were able to predict neutrophil chemotaxis. Reduced chemotaxis of neutrophils from frail adults could be reversed using selective PI3K inhibitors. Exposure of neutrophils from young adults to plasma from chronically inflamed frail older adults could not recapitulate the migratory deficit in vitro, and there were no relationships with systemic inflammation and neutrophil dysfunction. Frailty exaggerated the neutrophil deficits seen with advanced age but aspects of the frailty-associated deficit in neutrophil function are rescuable and thus potentially form a therapeutic target to improve outcomes from infection in older adults.",,pdf:https://academic.oup.com/biomedgerontology/article-pdf/75/12/2320/34289886/glaa216.pdf; doi:https://doi.org/10.1093/gerona/glaa216; html:https://europepmc.org/articles/PMC7662170; pdf:https://europepmc.org/articles/PMC7662170?pdf=render
+36936594,https://doi.org/10.1136/bmjmed-2022-000247,Measuring multimorbidity in research: Delphi consensus study.,"Ho ISS, Azcoaga-Lorenzo A, Akbari A, Davies J, Khunti K, Kadam UT, Lyons RA, McCowan C, Mercer SW, Nirantharakumar K, Staniszewska S, Guthrie B.",,BMJ medicine,2022,2022-07-27,Y,Medicine; epidemiology; Primary Health Care; Public Health; Research Design,,,"<h4>Objective</h4>To develop international consensus on the definition and measurement of multimorbidity in research.<h4>Design</h4>Delphi consensus study.<h4>Setting</h4>International consensus; data collected in three online rounds from participants between 30 November 2020 and 18 May 2021.<h4>Participants</h4>Professionals interested in multimorbidity and people with long term conditions were recruited to professional and public panels.<h4>Results</h4>150 professional and 25 public participants completed the first survey round. Response rates for rounds 2/3 were 83%/92% for professionals and 88%/93% in the public panel, respectively. Across both panels, the consensus was that multimorbidity should be defined as two or more long term conditions. Complex multimorbidity was perceived to be a useful concept, but the panels were unable to agree on how to define it. Both panels agreed that conditions should be included in a multimorbidity measure if they were one or more of the following: currently active; permanent in their effects; requiring current treatment, care, or therapy; requiring surveillance; or relapsing-remitting conditions requiring ongoing care. Consensus was reached for 24 conditions to always include in multimorbidity measures, and 35 conditions to usually include unless a good reason not to existed. Simple counts were preferred for estimating prevalence and examining clustering or trajectories, and weighted measures were preferred for risk adjustment and outcome prediction.<h4>Conclusions</h4>Previous multimorbidity research is limited by inconsistent definitions and approaches to measuring multimorbidity. This Delphi study identifies professional and public panel consensus guidance to facilitate consistency of definition and measurement, and to improve study comparability and reproducibility.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000247.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000247; html:https://europepmc.org/articles/PMC9978673; pdf:https://europepmc.org/articles/PMC9978673?pdf=render
 32704561,https://doi.org/10.1002/edm2.140,"Prevalence of admission plasma glucose in 'diabetes' or 'at risk' ranges in hospital emergencies with no prior diagnosis of diabetes by gender, age and ethnicity.","Ghosh S, Manley SE, Nightingale PG, Williams JA, Susarla R, Alonso-Perez I, Stratton IM, Gkoutos GV, Webber J, Luzio SD, Hanif W, Roberts GA.",,"Endocrinology, diabetes & metabolism",2020,2020-05-15,Y,Hyperglycaemia; Undiagnosed Diabetes; Emergency Admissions,,,"<h4>Aims</h4>To establish the prevalence of admission plasma glucose in 'diabetes' and 'at risk' ranges in emergency hospital admissions with no prior diagnosis of diabetes; characteristics of people with hyperglycaemia; and factors influencing glucose measurement.<h4>Methods</h4>Electronic patient records for 113 097 hospital admissions over 1 year from 2014 to 2015 included 43 201 emergencies with glucose available for 31 927 (74%) admissions, comprising 22 045 people. Data are presented for 18 965 people with no prior diagnosis of diabetes and glucose available on first attendance.<h4>Results</h4>Three quarters (14 214) were White Europeans aged 62 (43-78) years, median (IQ range); 12% (2241) South Asians 46 (32-64) years; 9% (1726) Unknown/Other ethnicities 43 (29-61) years; and 4% (784) Afro-Caribbeans 49 (33-63) years, <i>P</i> < .001. Overall, 5% (1003) had glucose in the 'diabetes' range (≥11.1 mmol/L) higher at 8% (175) for South Asians; 16% (3042) were 'at risk' (7.8-11.0 mmol/L), that is 17% (2379) White Europeans, 15% (338) South Asians, 14% (236) Unknown/Others and 11% (89) Afro-Caribbeans, <i>P</i> < .001. The prevalence for South Asians aged <30 years was 2.1% and 5.2%, respectively, 2.6% and 8.6% for Afro-Caribbeans <30 years, and 2.0% and 8.4% for White Europeans <40 years. Glucose increased with age and was more often in the 'diabetes' range for South Asians than White Europeans with South Asian men particularly affected. One third of all emergency admissions were for <24 hours with 58% of these having glucose measured compared to 82% with duration >24 hours.<h4>Conclusions</h4>Hyperglycaemia was evident in 21% of adults admitted as an emergency; various aspects related to follow-up and initial testing, age and ethnicity need to be considered by professional bodies addressing undiagnosed diabetes in hospital admissions.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.140; doi:https://doi.org/10.1002/edm2.140; html:https://europepmc.org/articles/PMC7375073; pdf:https://europepmc.org/articles/PMC7375073?pdf=render
 35944928,https://doi.org/10.1136/bmjhci-2021-100488,Software development skills for health data researchers.,"Morton C, Devito N, Morley J, Dillingham I, Schultze A, Bacon S, Inglesby P, Maude S, Goldacre B.",,BMJ health & care informatics,2022,2022-08-01,Y,Documentation; data management; Medical Informatics Computing; Data Science; Programming Languages,,,,,pdf:https://informatics.bmj.com/content/bmjhci/29/1/e100488.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100488; html:https://europepmc.org/articles/PMC9367192; pdf:https://europepmc.org/articles/PMC9367192?pdf=render
 37236697,https://doi.org/10.1016/s2589-7500(23)00065-1,"Identifying subtypes of heart failure from three electronic health record sources with machine learning: an external, prognostic, and genetic validation study.","Banerjee A, Dashtban A, Chen S, Pasea L, Thygesen JH, Fatemifar G, Tyl B, Dyszynski T, Asselbergs FW, Lund LH, Lumbers T, Denaxas S, Hemingway H.",,The Lancet. Digital health,2023,2023-06-01,N,,,,"<h4>Background</h4>Machine learning has been used to analyse heart failure subtypes, but not across large, distinct, population-based datasets, across the whole spectrum of causes and presentations, or with clinical and non-clinical validation by different machine learning methods. Using our published framework, we aimed to discover heart failure subtypes and validate them upon population representative data.<h4>Methods</h4>In this external, prognostic, and genetic validation study we analysed individuals aged 30 years or older with incident heart failure from two population-based databases in the UK (Clinical Practice Research Datalink [CPRD] and The Health Improvement Network [THIN]) from 1998 to 2018. Pre-heart failure and post-heart failure factors (n=645) included demographic information, history, examination, blood laboratory values, and medications. We identified subtypes using four unsupervised machine learning methods (K-means, hierarchical, K-Medoids, and mixture model clustering) with 87 of 645 factors in each dataset. We evaluated subtypes for (1) external validity (across datasets); (2) prognostic validity (predictive accuracy for 1-year mortality); and (3) genetic validity (UK Biobank), association with polygenic risk score (PRS) for heart failure-related traits (n=11), and single nucleotide polymorphisms (n=12).<h4>Findings</h4>We included 188 800, 124 262, and 9573 individuals with incident heart failure from CPRD, THIN, and UK Biobank, respectively, between Jan 1, 1998, and Jan 1, 2018. After identifying five clusters, we labelled heart failure subtypes as (1) early onset, (2) late onset, (3) atrial fibrillation related, (4) metabolic, and (5) cardiometabolic. In the external validity analysis, subtypes were similar across datasets (c-statistics: THIN model in CPRD ranged from 0·79 [subtype 3] to 0·94 [subtype 1], and CPRD model in THIN ranged from 0·79 [subtype 1] to 0·92 [subtypes 2 and 5]). In the prognostic validity analysis, 1-year all-cause mortality after heart failure diagnosis (subtype 1 0·20 [95% CI 0·14-0·25], subtype 2 0·46 [0·43-0·49], subtype 3 0·61 [0·57-0·64], subtype 4 0·11 [0·07-0·16], and subtype 5 0·37 [0·32-0·41]) differed across subtypes in CPRD and THIN data, as did risk of non-fatal cardiovascular diseases and all-cause hospitalisation. In the genetic validity analysis the atrial fibrillation-related subtype showed associations with the related PRS. Late onset and cardiometabolic subtypes were the most similar and strongly associated with PRS for hypertension, myocardial infarction, and obesity (p<0·0009). We developed a prototype app for routine clinical use, which could enable evaluation of effectiveness and cost-effectiveness.<h4>Interpretation</h4>Across four methods and three datasets, including genetic data, in the largest study of incident heart failure to date, we identified five machine learning-informed subtypes, which might inform aetiological research, clinical risk prediction, and the design of heart failure trials.<h4>Funding</h4>European Union Innovative Medicines Initiative-2.",,pdf:http://www.thelancet.com/article/S2589750023000651/pdf; doi:https://doi.org/10.1016/S2589-7500(23)00065-1
@@ -419,9 +419,9 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 34356905,https://doi.org/10.3390/biomedicines9070841,Relationship between Circulating PCSK9 and Markers of Subclinical Atherosclerosis-The IMPROVE Study. ,"Coggi D, Frigerio B, Bonomi A, Ruscica M, Ferri N, Sansaro D, Ravani A, Ferrante P, Damigella M, Veglia F, Capra N, Lupo MG, Macchi C, Savonen K, Silveira A, Kurl S, Giral P, Pirro M, Strawbridge RJ, Gigante B, Smit AJ, Tremoli E, Amato M, Baldassarre D, On Behalf Of The Improve Study Group.",,Biomedicines,2021,2021-07-19,Y,,,,"(1) Background and purpose: circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of cholesterol metabolism. Despite this, its role as a player in atherosclerosis development is still matter of debate. Here, we investigated the relationships between this protein and several markers of subclinical atherosclerosis. (2) Methods: the IMPROVE study enrolled 3703 European subjects (54-79 years; 48% men; with ≥3 vascular risk factors), asymptomatic for cardiovascular diseases. PCSK9 levels were measured by ELISA. B-mode ultrasound was used to measure markers of carotid subclinical atherosclerosis. (3) Results: in the crude analysis, PCSK9 levels were associated with several baseline measures of carotid intima-media thickness (cIMT) (all p < 0.0001); with cIMT change over time (Fastest-IMTmax-progr) (p = 0.01); with inter-adventitia common carotid artery diameter (ICCAD) (p < 0.0001); and with the echolucency (Grey Scale Median; GSM) of both carotid plaque and plaque-free common carotid IMT (both p < 0.0001). However, after adjustment for age, sex, latitude, and pharmacological treatment, all the afore-mentioned correlations were no longer statistically significant. The lack of correlation was also observed after stratification for sex, latitude, and pharmacological treatments. (4) Conclusions: in subjects who are asymptomatic for cardiovascular diseases, PCSK9 plasma levels do not correlate with vascular damage and/or subclinical atherosclerosis of extracranial carotid arteries.",,pdf:https://www.mdpi.com/2227-9059/9/7/841/pdf?version=1626837519; doi:https://doi.org/10.3390/biomedicines9070841; html:https://europepmc.org/articles/PMC8301759; pdf:https://europepmc.org/articles/PMC8301759?pdf=render
 35608440,https://doi.org/10.1126/science.abq4411,Twin peaks: The Omicron SARS-CoV-2 BA.1 and BA.2 epidemics in England.,"Elliott P, Eales O, Steyn N, Tang D, Bodinier B, Wang H, Elliott J, Whitaker M, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Donnelly CA, Chadeau-Hyam M.",,"Science (New York, N.Y.)",2022,2022-06-24,Y,,,,"Rapid transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has led to record-breaking incidence rates around the world. The Real-time Assessment of Community Transmission-1 (REACT-1) study has tracked SARS-CoV-2 infection in England using reverse transcription polymerase chain reaction (RT-PCR) results from self-administered throat and nose swabs from randomly selected participants aged 5 years and older approximately monthly from May 2020 to March 2022. Weighted prevalence in March 2022 was the highest recorded in REACT-1 at 6.37% (<i>N</i> = 109,181), with the Omicron BA.2 variant largely replacing the BA.1 variant. Prevalence was increasing overall, with the greatest increase in those aged 65 to 74 years and 75 years and older. This was associated with increased hospitalizations and deaths, but at much lower levels than in previous waves against a backdrop of high levels of vaccination.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161371; doi:https://doi.org/10.1126/science.abq4411; html:https://europepmc.org/articles/PMC9161371; pdf:https://europepmc.org/articles/PMC9161371?pdf=render
 34782484,https://doi.org/10.1136/thoraxjnl-2021-217580,External validation of the QCovid risk prediction algorithm for risk of COVID-19 hospitalisation and mortality in adults: national validation cohort study in Scotland.,"Simpson CR, Robertson C, Kerr S, Shi T, Vasileiou E, Moore E, McCowan C, Agrawal U, Docherty A, Mulholland R, Murray J, Ritchie LD, McMenamin J, Hippisley-Cox J, Sheikh A.",,Thorax,2022,2021-11-15,Y,Clinical Epidemiology; Covid-19,,,"<h4>Background</h4>The QCovid algorithm is a risk prediction tool that can be used to stratify individuals by risk of COVID-19 hospitalisation and mortality. Version 1 of the algorithm was trained using data covering 10.5 million patients in England in the period 24 January 2020 to 30 April 2020. We carried out an external validation of version 1 of the QCovid algorithm in Scotland.<h4>Methods</h4>We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisations and deaths in our dataset for two time periods matching the original study: 1 March 2020 to 30 April 2020, and 1 May 2020 to 30 June 2020.<h4>Results</h4>Our dataset comprised 5 384 819 individuals, representing 99% of the estimated population (5 463 300) resident in Scotland in 2020. The algorithm showed good calibration in the first period, but systematic overestimation of risk in the second period, prior to temporal recalibration. Harrell's C for deaths in females and males in the first period was 0.95 (95% CI 0.94 to 0.95) and 0.93 (95% CI 0.92 to 0.93), respectively. Harrell's C for hospitalisations in females and males in the first period was 0.81 (95% CI 0.80 to 0.82) and 0.82 (95% CI 0.81 to 0.82), respectively.<h4>Conclusions</h4>Version 1 of the QCovid algorithm showed high levels of discrimination in predicting the risk of COVID-19 hospitalisations and deaths in adults resident in Scotland for the original two time periods studied, but is likely to need ongoing recalibration prospectively.",,pdf:https://thorax.bmj.com/content/thoraxjnl/77/5/497.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217580; html:https://europepmc.org/articles/PMC8595052; pdf:https://europepmc.org/articles/PMC8595052?pdf=render
-35213664,https://doi.org/10.1371/journal.pone.0264529,Achievement of European Society of Cardiology/European Atherosclerosis Society lipid targets in very high-risk patients: Influence of depression and sex.,"Ellins EA, Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, John A, Gravenor MB, Halcox JP.",,PloS one,2022,2022-02-25,Y,,,,"<h4>Aims</h4>To explore differences in the use of lipid lowering therapy and/or achievement of lipid guideline targets in patients with and without prior depression and influence of sex in very high-risk coronary patients.<h4>Methods & findings</h4>A retrospective observational cohort study was conducted using individual-level linked electronic health record data in patients who underwent percutaneous coronary intervention (2012-2017) in Wales. The cohort comprised of 13,781 patients (27.4% female), with 26.1% having prior depression. Lipid levels were recorded in 10,050 patients of whom 25% had depression. History of depression was independently associated with not having lipids checked (OR 0.79 95%CI 0.72-0.87 p<0.001). Patients with prior depression were less likely to achieve targets for low density lipoprotein cholesterol (LDL-C <1.8mmol/l), non-high density lipoprotein cholesterol (non-HDL-C <2.6mmol/l) and triglycerides (<2.3mmol/l) than patients without depression (OR 0.86 95%CI 0.78-0.96 p = 0.007, OR 0.80 95%CI 0.69-0.92 p = 0.003 & OR 0.69 95CI% 0.61-0.79 p<0.001 respectively). Females were less likely to achieve targets for LDL-C and non-HDL-C than males (OR 0.55 95%CI 0.50-0.61 p<0.001 & OR 0.63 95%CI 0.55-0.73 p<0.001). There was an additive effect of depression and sex; females with depression were not only least likely to be tested (OR 0.74 95%CI 0.65-0.84 p<0.001) but also (where levels were known) less likely to achieve LDL-C (OR 0.47 95%CI 0.41-0.55 p<0.001) and non-HDL-C targets (OR 0.50 95%CI 0.41-0.60 p<0.001). It was not possible to look at the influence of medication adherence on achievement of lipid targets due to limitations of the use of anonymised routinely-held clinical care data.<h4>Conclusion</h4>Patients with prior depression were less likely to have their lipids monitored and achieve guideline targets within 1-year. Females with depression are the least likely to be tested and achieve lipid targets, suggesting not only a greater risk of future events, but also an opportunity to improve care.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264529&type=printable; doi:https://doi.org/10.1371/journal.pone.0264529; html:https://europepmc.org/articles/PMC8880762; pdf:https://europepmc.org/articles/PMC8880762?pdf=render
 34693751,https://doi.org/10.1177/14799731211053332,The diagnosis of asthma. Can physiological tests of small airways function help?,"Almeshari MA, Stockley J, Sapey E.",,Chronic respiratory disease,2021,2021-01-01,Y,Diagnosis; Asthma; Spirometry; Oscillometry; Small Airways Function,,,"Asthma is a common, chronic, and heterogeneous disease with a global impact and substantial economic costs. It is also associated with significant mortality and morbidity and the burden of undiagnosed asthma is significant. Asthma can be difficult to diagnose as there is no gold standard test and, while spirometry is central in diagnosing asthma, it may not be sufficient to confirm or exclude the diagnosis. The most commonly reported spirometric measures (forced expiratory volume in one second (FEV<sub>1</sub>) and forced vital capacity assess function in the larger airways. However, small airway dysfunction is highly prevalent in asthma and some studies suggest small airway involvement is one of the earliest disease manifestations. Moreover, there are new inhaled therapies with ultrafine particles that are specifically designed to target the small airways. Potentially, tests of small airways may more accurately diagnose early or mild asthma and assess the response to treatment than spirometry. Furthermore, some assessment techniques do not rely on forced ventilatory manoeuvres and may, therefore, be easier for certain groups to perform. This review discusses the current evidence of small airways tests in asthma and future research that may be needed to further assess their utility.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/14799731211053332; doi:https://doi.org/10.1177/14799731211053332; html:https://europepmc.org/articles/PMC8543738; pdf:https://europepmc.org/articles/PMC8543738?pdf=render
 34183342,https://doi.org/10.1136/bmjopen-2020-046392,"United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): a retrospective cohort study using linked routinely collected data, study protocol.","Teece L, Gray LJ, Melbourne C, Orton C, Ford DV, Martin CA, McAllister D, Khunti K, Tobin M, John C, Abrams KR, Pareek M, UK-REACH Study Collaborative Group.",,BMJ open,2021,2021-06-28,Y,epidemiology; Public Health; Adult Intensive & Critical Care; Covid-19,,,"<h4>Introduction</h4>COVID-19 has spread rapidly worldwide, causing significant morbidity and mortality. People from ethnic minorities, particularly those working in healthcare settings, have been disproportionately affected. Current evidence of the association between ethnicity and COVID-19 outcomes in people working in healthcare settings is insufficient to inform plans to address health inequalities.<h4>Methods and analysis</h4>This study combines anonymised human resource databases with professional registration and National Health Service data sets to assess associations between ethnicity and COVID-19 diagnosis, hospitalisation and death in healthcare workers in the UK. Adverse COVID-19 outcomes will be assessed between 1 February 2020 (date following first confirmed COVID-19 case in UK) and study end date (31 January 2021), allowing 1-year of follow-up. Planned analyses include multivariable Poisson, logistic and flexible parametric time-to-event regression within each country, adjusting for core predictors, followed by meta-analysis of country-specific results to produce combined effect estimates for the UK. Mediation analysis methods will be explored to examine the direct, indirect and mediated interactive effects between ethnicity, occupational group and COVID-19 outcomes.<h4>Ethics and dissemination</h4>Ethical approval for the UK-REACH programme has been obtained via the expedited HRA COVID-19 processes (REC ref: 20/HRA/4718, IRAS ID: 288316). Research information will be anonymised via the Secure Anonymised Information Linkage Databank before release to researchers. Study results will be submitted for publication in an open access peer-reviewed journal and made available on our dedicated website (https://uk-reach.org/).<h4>Trial registration number</h4>ISRCTN11811602.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?pdf=render
+35213664,https://doi.org/10.1371/journal.pone.0264529,Achievement of European Society of Cardiology/European Atherosclerosis Society lipid targets in very high-risk patients: Influence of depression and sex.,"Ellins EA, Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, John A, Gravenor MB, Halcox JP.",,PloS one,2022,2022-02-25,Y,,,,"<h4>Aims</h4>To explore differences in the use of lipid lowering therapy and/or achievement of lipid guideline targets in patients with and without prior depression and influence of sex in very high-risk coronary patients.<h4>Methods & findings</h4>A retrospective observational cohort study was conducted using individual-level linked electronic health record data in patients who underwent percutaneous coronary intervention (2012-2017) in Wales. The cohort comprised of 13,781 patients (27.4% female), with 26.1% having prior depression. Lipid levels were recorded in 10,050 patients of whom 25% had depression. History of depression was independently associated with not having lipids checked (OR 0.79 95%CI 0.72-0.87 p<0.001). Patients with prior depression were less likely to achieve targets for low density lipoprotein cholesterol (LDL-C <1.8mmol/l), non-high density lipoprotein cholesterol (non-HDL-C <2.6mmol/l) and triglycerides (<2.3mmol/l) than patients without depression (OR 0.86 95%CI 0.78-0.96 p = 0.007, OR 0.80 95%CI 0.69-0.92 p = 0.003 & OR 0.69 95CI% 0.61-0.79 p<0.001 respectively). Females were less likely to achieve targets for LDL-C and non-HDL-C than males (OR 0.55 95%CI 0.50-0.61 p<0.001 & OR 0.63 95%CI 0.55-0.73 p<0.001). There was an additive effect of depression and sex; females with depression were not only least likely to be tested (OR 0.74 95%CI 0.65-0.84 p<0.001) but also (where levels were known) less likely to achieve LDL-C (OR 0.47 95%CI 0.41-0.55 p<0.001) and non-HDL-C targets (OR 0.50 95%CI 0.41-0.60 p<0.001). It was not possible to look at the influence of medication adherence on achievement of lipid targets due to limitations of the use of anonymised routinely-held clinical care data.<h4>Conclusion</h4>Patients with prior depression were less likely to have their lipids monitored and achieve guideline targets within 1-year. Females with depression are the least likely to be tested and achieve lipid targets, suggesting not only a greater risk of future events, but also an opportunity to improve care.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264529&type=printable; doi:https://doi.org/10.1371/journal.pone.0264529; html:https://europepmc.org/articles/PMC8880762; pdf:https://europepmc.org/articles/PMC8880762?pdf=render
 34957254,https://doi.org/10.3389/fcvm.2021.766287,Radiomics Analysis Derived From LGE-MRI Predict Sudden Cardiac Death in Participants With Hypertrophic Cardiomyopathy.,"Wang J, Bravo L, Zhang J, Liu W, Wan K, Sun J, Zhu Y, Han Y, Gkoutos GV, Chen Y.",,Frontiers in cardiovascular medicine,2021,2021-12-10,Y,hypertrophic cardiomyopathy; Sudden Cardiac Death; Machine Learning; Late Gadolinium Enhancement; Radiomics,,,"<b>Objectives:</b> To identify significant radiomics features derived from late gadolinium enhancement (LGE) images in participants with hypertrophic cardiomyopathy (HCM) and assess their prognostic value in predicting sudden cardiac death (SCD) endpoint. <b>Method:</b> The 157 radiomic features of 379 sequential participants with HCM who underwent cardiovascular magnetic resonance imaging (MRI) were extracted. CoxNet (Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net) and Random Forest models were applied to optimize feature selection for the SCD risk prediction and cross-validation was performed. <b>Results:</b> During a median follow-up of 29 months (interquartile range, 20-42 months), 27 participants with HCM experienced SCD events. Cox analysis revealed that two selected features, local binary patterns (LBP) (19) (hazard ratio (HR), 1.028, 95% CI: 1.032-1.134; <i>P</i> = 0.001) and Moment (1) (HR, 1.212, 95%CI: 1.032-1.423; <i>P</i> = 0.02) provided significant prognostic value to predict the SCD endpoints after adjustment for the clinical risk predictors and late gadolinium enhancement. Furthermore, the univariately significant risk predictor was improved by the addition of the selected radiomics features, LBP (19) and Moment (1), to predict SCD events (<i>P</i> < 0.05). <b>Conclusion:</b> The radiomics features of LBP (19) and Moment (1) extracted from LGE images, reflecting scar heterogeneity, have independent prognostic value in identifying high SCD risk patients with HCM.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.766287/pdf; doi:https://doi.org/10.3389/fcvm.2021.766287; html:https://europepmc.org/articles/PMC8702805; pdf:https://europepmc.org/articles/PMC8702805?pdf=render
 33838587,https://doi.org/10.1016/j.epidem.2021.100460,Competition between RSV and influenza: Limits of modelling inference from surveillance data.,"Waterlow NR, Flasche S, Minter A, Eggo RM.",,Epidemics,2021,2021-03-26,Y,Interaction; Competition; Influenza; Respiratory syncytial virus; Inference,,,"Respiratory Syncytial Virus (RSV) and Influenza cause a large burden of disease. Evidence of their interaction via temporary cross-protection implies that prevention of one could inadvertently lead to an increase in the burden of the other. However, evidence for the public health impact of such interaction is sparse and largely derives from ecological analyses of peak shifts in surveillance data. To test the robustness of estimates of interaction parameters between RSV and Influenza from surveillance data we conducted a simulation and back-inference study. We developed a two-pathogen interaction model, parameterised to simulate RSV and Influenza epidemiology in the UK. Using the infection model in combination with a surveillance-like stochastic observation process we generated a range of possible RSV and Influenza trajectories and then used Markov Chain Monte Carlo (MCMC) methods to back-infer parameters including those describing competition. We find that in most scenarios both the strength and duration of RSV and Influenza interaction could be estimated from the simulated surveillance data reasonably well. However, the robustness of inference declined towards the extremes of the plausible parameter ranges, with misleading results. It was for instance not possible to tell the difference between low/moderate interaction and no interaction. In conclusion, our results illustrate that in a plausible parameter range, the strength of RSV and Influenza interaction can be estimated from a single season of high-quality surveillance data but also highlights the importance to test parameter identifiability a priori in such situations.",,doi:https://doi.org/10.1016/j.epidem.2021.100460; doi:https://doi.org/10.1016/j.epidem.2021.100460; html:https://europepmc.org/articles/PMC8193815
 35310465,https://doi.org/10.23889/ijpds.v5i4.1697,"Validating the QCOVID risk prediction algorithm for risk of mortality from COVID-19 in the adult population in Wales, UK.","Lyons J, Nafilyan V, Akbari A, Davies G, Griffiths R, Harrison EM, Hippisley-Cox J, Hollinghurst J, Khunti K, North L, Sheikh A, Torabi F, Lyons RA.",,International journal of population data science,2020,2020-01-01,Y,Risk Prediction Models; Sail Databank; Covid-19 Outcomes; Population Data-Linkage; Qcovid Algorithm,,,"<h4>Introduction</h4>COVID-19 risk prediction algorithms can be used to identify at-risk individuals from short-term serious adverse COVID-19 outcomes such as hospitalisation and death. It is important to validate these algorithms in different and diverse populations to help guide risk management decisions and target vaccination and treatment programs to the most vulnerable individuals in society.<h4>Objectives</h4>To validate externally the QCOVID risk prediction algorithm that predicts mortality outcomes from COVID-19 in the adult population of Wales, UK.<h4>Methods</h4>We conducted a retrospective cohort study using routinely collected individual-level data held in the Secure Anonymised Information Linkage (SAIL) Databank. The cohort included individuals aged between 19 and 100 years, living in Wales on 24<sup>th</sup> January 2020, registered with a SAIL-providing general practice, and followed-up to death or study end (28<sup>th</sup> July 2020). Demographic, primary and secondary healthcare, and dispensing data were used to derive all the predictor variables used to develop the published QCOVID algorithm. Mortality data were used to define time to confirmed or suspected COVID-19 death. Performance metrics, including R<sup>2</sup> values (explained variation), Brier scores, and measures of discrimination and calibration were calculated for two periods (24<sup>th</sup> January-30<sup>th</sup> April 2020 and 1<sup>st</sup> May-28<sup>th</sup> July 2020) to assess algorithm performance.<h4>Results</h4>1,956,760 individuals were included. 1,192 (0.06%) and 610 (0.03%) COVID-19 deaths occurred in the first and second time periods, respectively. The algorithms fitted the Welsh data and population well, explaining 68.8% (95% CI: 66.9-70.4) of the variation in time to death, Harrell's C statistic: 0.929 (95% CI: 0.921-0.937) and D statistic: 3.036 (95% CI: 2.913-3.159) for males in the first period. Similar results were found for females and in the second time period for both sexes.<h4>Conclusions</h4>The QCOVID algorithm developed in England can be used for public health risk management for the adult Welsh population.",,pdf:https://ijpds.org/article/download/1697/3337; doi:https://doi.org/10.23889/ijpds.v5i4.1697; html:https://europepmc.org/articles/PMC8900650; pdf:https://europepmc.org/articles/PMC8900650?pdf=render
@@ -443,37 +443,37 @@ PMC10624988,https://doi.org/,Comparative effectiveness of nirmatrelvir/ritonavir
 36036238,https://doi.org/10.1002/clt2.12180,Mixed-methods evaluation of a nurse-led allergy clinic model in primary care: Feasibility trial.,"Hammersley V, Kelman M, Morrice L, Kendall M, Mukerjhee M, Harley S, Schwarze J, Sheikh A.",,Clinical and translational allergy,2022,2022-08-01,Y,Allergy; Quality of life; Primary Care,,,"<h4>Introduction</h4>It is now widely acknowledged that there are serious shortcomings in allergy care provision for patients seen in primary care. We sought to assess the feasibility of delivering and evaluating a new nurse-led allergy service in primary care, measured by recruitment, retention and estimates of the potential impact of the intervention on disease-specific quality of life.<h4>Methods</h4>Mixed-methods evaluation of a nurse-led primary care-based allergy clinic in Edinburgh, UK undertaken during the period 2017-2021 with a focus on suspected food allergy and atopic eczema in young children, allergic rhinitis in children and young people, and suspected anaphylaxis in adults. Prior to March 2020, patients were seen face-to-face (Phase 1). Due to COVID-19 pandemic restrictions, recruitment was halted between March-August 2020, and a remote clinic was restarted in September 2020 (Phase 2). Disease-specific quality of life was measured at baseline and 6-12 weeks post intervention using validated instruments. Quantitative data were descriptively analysed. We undertook interviews with 16 carers/patients and nine healthcare professionals, which were thematically analysed.<h4>Results</h4>During Phase 1, 426/506 (84%) referred patients met the eligibility criteria; 40/46 (87%) of Phase 2 referrals were eligible. Males and females were recruited in approximately equal numbers. The majority (83%) of referrals were for possible food allergy or anaphylaxis. Complete data were available for 338/426 (79%) patients seen in Phase 1 and 30/40 (75%) in Phase 2. Compared with baseline assessments, there were improvements in disease-specific quality of life for most categories of patients. Patients/carers and healthcare professionals reported high levels of satisfaction, this being reinforced by the qualitative interviews in which convenience and speed of access to expert opinion, the quality of the consultation, and patient/care empowerment were particularly emphasised.<h4>Conclusion</h4>This large feasibility trial has demonstrated that it is possible to recruit, deliver and retain individuals into a nurse-led allergy clinic with both face-to-face and remote consultations. Our data indicate that the intervention was considered acceptable to patients/carers and healthcare professionals. The before-after data of disease-specific quality of life suggest that the intervention may prove effective, but this now needs to be confirmed through a formal randomised controlled trial.<h4>Trial registration</h4>ClinicalTrials.gov reference NCT03826953.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362986; doi:https://doi.org/10.1002/clt2.12180; html:https://europepmc.org/articles/PMC9362986; pdf:https://europepmc.org/articles/PMC9362986?pdf=render
 30474191,https://doi.org/10.1111/dme.13870,Utility of HbA<sub>1c</sub> assessment in people with diabetes awaiting liver transplantation.,"Bhattacharjee D, Vracar S, Round RA, Nightingale PG, Williams JA, Gkoutos GV, Stratton IM, Parker R, Luzio SD, Webber J, Manley SE, Roberts GA, Ghosh S.",,Diabetic medicine : a journal of the British Diabetic Association,2019,2019-04-30,Y,,The Human Phenome,,"<h4>Aims</h4>To investigate the relationship between HbA<sub>1c</sub> and glucose in people with co-existing liver disease and diabetes awaiting transplant, and in those with diabetes but no liver disease.<h4>Methods</h4>HbA<sub>1c</sub> and random plasma glucose data were collected for 125 people with diabetes without liver disease and for 29 people awaiting liver transplant with diabetes and cirrhosis. Cirrhosis was caused by non-alcoholic fatty liver disease, hepatitis C, alcoholic liver disease, hereditary haemochromatosis, polycystic liver/kidneys, cryptogenic/non-cirrhotic portal hypertension and α-1-antitrypsin-related disease.<h4>Results</h4>The median (interquartile range) age of the diabetes with cirrhosis group was 55 (49-63) years compared to 60 (50-71) years (P=0.13) in the group without cirrhosis. In the diabetes with cirrhosis group there were 21 men (72%) compared with 86 men (69%) in the group with diabetes and no cirrhosis (P=0.82). Of the group with diabetes and cirrhosis, 27 people (93%) were of white European ethnicity, two (7%) were South Asian and none was of Afro-Caribbean/other ethnicity compared with 94 (75%), 16 (13%), 10 (8%)/5 (4%), respectively, in the group with diabetes and no cirrhosis (P=0.20). Median (interquartile range) HbA<sub>1c</sub> was 41 (32-56) mmol/mol [5.9 (5.1-7.3)%] vs 61 (52-70) mmol/mol [7.7 (6.9-8.6)%] (P<0.001), respectively, in the diabetes with cirrhosis group vs the diabetes without cirrhosis group. The glucose concentrations were 8.4 (7.0-11.2) mmol/l vs 7.3 (5.2-11.5) mmol/l (P=0.17). HbA<sub>1c</sub> was depressed by 20 mmol/mol (1.8%; P<0.001) in 28 participants with cirrhosis but elevated by 28 mmol/mol (2.6%) in the participant with α-1-antitrypsin disorder. Those with cirrhosis and depressed HbA<sub>1c</sub> had fewer larger erythrocytes, and higher red cell distribution width and reticulocyte count. This was reflected in the positive association of glucose with mean cell volume (r=0.39) and haemoglobin level (r=0.49) and the negative association for HbA<sub>1c</sub> (r=-0.28 and r=-0.26, respectively) in the diabetes group with cirrhosis.<h4>Conclusion</h4>HbA<sub>1c</sub> is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant as it reflects altered erythrocyte presentation.","The aim of this article was to investigate the relationship between HbA1c and glucose in patients with diabetes awaiting transplant due to a co-existing liver disease, and in those with diabetes but no liver disease. Statistical analyses results indicated that HbA1c is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant, and it might cause misdiagnosis of diabetes and inappropirate clinical care in people with cirrhotic liver disease.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.13870; doi:https://doi.org/10.1111/dme.13870; html:https://europepmc.org/articles/PMC6850030; pdf:https://europepmc.org/articles/PMC6850030?pdf=render
 37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"<h4>Introduction</h4>In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.<h4>Methods and analysis</h4>Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.<h4>Ethics and dissemination</h4>Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render
-35997000,https://doi.org/10.1111/ene.15530,Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia.,"Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",,European journal of neurology,2022,2022-09-11,Y,Psychiatric disorders; Movement Disorders; Dystonia; Neurological Disorders,,,"<h4>Background and purpose</h4>Although psychiatric diagnoses are recognized in idiopathic dystonia, no previous studies have examined the temporal relationship between idiopathic dystonia and psychiatric diagnoses at scale. Here, we determine rates of psychiatric diagnoses and psychiatric medication prescription in those diagnosed with idiopathic dystsuponia compared to matched controls.<h4>Methods</h4>A longitudinal population-based cohort study using anonymized electronic health care data in Wales (UK) was conducted to identify individuals with idiopathic dystonia and comorbid psychiatric diagnoses/prescriptions between 1 January 1994 and 31 December 2017. Psychiatric diagnoses/prescriptions were identified from primary and secondary health care records.<h4>Results</h4>Individuals with idiopathic dystonia (n = 52,589) had higher rates of psychiatric diagnosis and psychiatric medication prescription when compared to controls (n = 216,754, 43% vs. 31%, p &lt; 0.001; 45% vs. 37.9%, p &lt; 0.001, respectively), with depression and anxiety being most common (cases: 31% and 28%). Psychiatric diagnoses predominantly predated dystonia diagnosis, particularly in the 12 months prior to diagnosis (incidence rate ratio [IRR] = 1.98, 95% confidence interval [CI] = 1.9-2.1), with an IRR of 12.4 (95% CI = 11.8-13.1) for anxiety disorders. There was, however, an elevated rate of most psychiatric diagnoses throughout the study period, including the 12 months after dystonia diagnosis (IRR = 1.96, 95% CI = 1.85-2.07).<h4>Conclusions</h4>This study suggests a bidirectional relationship between psychiatric disorders and dystonia, particularly with mood disorders. Psychiatric and motor symptoms in dystonia may have common aetiological mechanisms, with psychiatric disorders potentially forming prodromal symptoms of idiopathic dystonia.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62203/Download/62203__26254__0c88bfc9ff7e4fe2acaea5e2a2d74058.pdf; doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render
-35813279,https://doi.org/10.1016/s2666-7568(22)00147-7,"Duration of vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, and death in residents and staff of long-term care facilities in England (VIVALDI): a prospective cohort study.","Shrotri M, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Giddings R, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,The lancet. Healthy longevity,2022,2022-07-04,Y,,,,"<h4>Background</h4>Residents and staff in long-term care facilities have been prioritised for vaccination against SARS-CoV-2, but data on potential waning of vaccine effectiveness and the effect of booster doses in this vulnerable population are scarce. We aimed to evaluate effectiveness of one, two, and three vaccine doses against infection and severe clinical outcomes in staff and residents of long-term care facilities in England over the first year following vaccine roll-out.<h4>Methods</h4>The VIVALDI study is a prospective cohort study done in 331 long-term care facilities in England. Residents aged 65 years or older and staff aged 18 years or older were eligible for participation. Participants had routine PCR testing throughout the study period between Dec 8, 2020, and Dec 11, 2021. We retrieved all PCR results and cycle threshold values for PCR-positive samples from routine testing in long-term care facilities, and positive PCR results from clinical testing in hospitals through the UK's COVID-19 Datastore. PCR results were linked to participants using pseudo-identifiers based on individuals' unique UK National Health Service (NHS) numbers, which were also used to retrieve vaccination records from the National Immunisation Management Service, hospitalisation records from NHS England, and deaths data from the Office for National Statistics through the COVID-19 Datastore. In a Cox proportional hazards regression, we estimated vaccine effectiveness against SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death after one, two, and three vaccine doses, separately by previous SARS-CoV-2 exposure. This study is registered with the ISRCTN Registry, ISRCTN 14447421.<h4>Findings</h4>80 186 residents and staff of long-term care facilities had records available for the study period, of whom 15 518 eligible residents and 19 515 eligible staff were included in the analysis. For residents without evidence of previous SARS-CoV-2 exposure, vaccine effectiveness decreased from 61·7% (95% CI 35·1 to 77·4) to 22·0% (-14·9 to 47·0) against infection; from 89·0% (70·6 to 95·9) to 56·3% (30·1 to 72·6) against hospitalisation; and from 96·4% (84·3 to 99·2) to 64·4% (36·1 to 80·1) against death, when comparing 14-83 days after dose two and 84 days or more after dose two. For staff without evidence of previous exposure, vaccine effectiveness against infection decreased slightly from 57·9% (43·1 to 68·9) at 14-83 days after dose two to 42·1% (29·9 to 52·2) at 84 days or more after dose two. There were no hospitalisations or deaths among unexposed staff at 14-83 days, but seven hospitalisations (vaccine effectiveness 91·0% [95% CI 74·3 to 96·8]) and one death were observed at 84 days or more after dose two. High vaccine effectiveness was restored following a third vaccine dose, with vaccine effectiveness in unexposed residents of 72·7% (55·8 to 83·1) against infection, 90·1% (80·6 to 95·0) against hospitalisation, and 97·5% (88·1 to 99·5) against death; and vaccine effectiveness in unexposed staff of 78·2% (70·0 to 84·1) against infection and 95·8% (49·9 to 99·6) against hospitalisation. There were no COVID-19-related deaths among unexposed staff after the third vaccine dose.<h4>Interpretation</h4>Our findings showed substantial waning of SARS-CoV-2 vaccine effectiveness against all outcomes in residents of long-term care facilities from 12 weeks after a primary course of ChAdOx1-S or mRNA vaccines. Boosters restored protection, and maximised immunity across all outcomes. These findings show the importance of boosting and the need for ongoing surveillance in this vulnerable cohort.<h4>Funding</h4>UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/s2666-7568(22)00147-7; doi:https://doi.org/10.1016/S2666-7568(22)00147-7; html:https://europepmc.org/articles/PMC9252508; pdf:https://europepmc.org/articles/PMC9252508?pdf=render
 34145260,https://doi.org/10.1038/s41467-021-23935-x,Community factors and excess mortality in first wave of the COVID-19 pandemic in England.,"Davies B, Parkes BL, Bennett J, Fecht D, Blangiardo M, Ezzati M, Elliott P.",,Nature communications,2021,2021-06-18,Y,,,,"Risk factors for increased risk of death from COVID-19 have been identified, but less is known on characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. We applied a two-stage Bayesian spatial model to quantify inequalities in excess mortality in people aged 40 years and older at the community level during the first wave of the pandemic in England, March-May 2020 compared with 2015-2019. Here we show that communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or with a non-white ethnicity. We found no association between population density or air pollution and excess mortality. Effective and timely public health and healthcare measures that target the communities at greatest risk are urgently needed to avoid further widening of inequalities in mortality patterns as the pandemic progresses.",,pdf:https://www.nature.com/articles/s41467-021-23935-x.pdf; doi:https://doi.org/10.1038/s41467-021-23935-x; html:https://europepmc.org/articles/PMC8213785; pdf:https://europepmc.org/articles/PMC8213785?pdf=render
+35813279,https://doi.org/10.1016/s2666-7568(22)00147-7,"Duration of vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, and death in residents and staff of long-term care facilities in England (VIVALDI): a prospective cohort study.","Shrotri M, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Giddings R, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,The lancet. Healthy longevity,2022,2022-07-04,Y,,,,"<h4>Background</h4>Residents and staff in long-term care facilities have been prioritised for vaccination against SARS-CoV-2, but data on potential waning of vaccine effectiveness and the effect of booster doses in this vulnerable population are scarce. We aimed to evaluate effectiveness of one, two, and three vaccine doses against infection and severe clinical outcomes in staff and residents of long-term care facilities in England over the first year following vaccine roll-out.<h4>Methods</h4>The VIVALDI study is a prospective cohort study done in 331 long-term care facilities in England. Residents aged 65 years or older and staff aged 18 years or older were eligible for participation. Participants had routine PCR testing throughout the study period between Dec 8, 2020, and Dec 11, 2021. We retrieved all PCR results and cycle threshold values for PCR-positive samples from routine testing in long-term care facilities, and positive PCR results from clinical testing in hospitals through the UK's COVID-19 Datastore. PCR results were linked to participants using pseudo-identifiers based on individuals' unique UK National Health Service (NHS) numbers, which were also used to retrieve vaccination records from the National Immunisation Management Service, hospitalisation records from NHS England, and deaths data from the Office for National Statistics through the COVID-19 Datastore. In a Cox proportional hazards regression, we estimated vaccine effectiveness against SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death after one, two, and three vaccine doses, separately by previous SARS-CoV-2 exposure. This study is registered with the ISRCTN Registry, ISRCTN 14447421.<h4>Findings</h4>80 186 residents and staff of long-term care facilities had records available for the study period, of whom 15 518 eligible residents and 19 515 eligible staff were included in the analysis. For residents without evidence of previous SARS-CoV-2 exposure, vaccine effectiveness decreased from 61·7% (95% CI 35·1 to 77·4) to 22·0% (-14·9 to 47·0) against infection; from 89·0% (70·6 to 95·9) to 56·3% (30·1 to 72·6) against hospitalisation; and from 96·4% (84·3 to 99·2) to 64·4% (36·1 to 80·1) against death, when comparing 14-83 days after dose two and 84 days or more after dose two. For staff without evidence of previous exposure, vaccine effectiveness against infection decreased slightly from 57·9% (43·1 to 68·9) at 14-83 days after dose two to 42·1% (29·9 to 52·2) at 84 days or more after dose two. There were no hospitalisations or deaths among unexposed staff at 14-83 days, but seven hospitalisations (vaccine effectiveness 91·0% [95% CI 74·3 to 96·8]) and one death were observed at 84 days or more after dose two. High vaccine effectiveness was restored following a third vaccine dose, with vaccine effectiveness in unexposed residents of 72·7% (55·8 to 83·1) against infection, 90·1% (80·6 to 95·0) against hospitalisation, and 97·5% (88·1 to 99·5) against death; and vaccine effectiveness in unexposed staff of 78·2% (70·0 to 84·1) against infection and 95·8% (49·9 to 99·6) against hospitalisation. There were no COVID-19-related deaths among unexposed staff after the third vaccine dose.<h4>Interpretation</h4>Our findings showed substantial waning of SARS-CoV-2 vaccine effectiveness against all outcomes in residents of long-term care facilities from 12 weeks after a primary course of ChAdOx1-S or mRNA vaccines. Boosters restored protection, and maximised immunity across all outcomes. These findings show the importance of boosting and the need for ongoing surveillance in this vulnerable cohort.<h4>Funding</h4>UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/s2666-7568(22)00147-7; doi:https://doi.org/10.1016/S2666-7568(22)00147-7; html:https://europepmc.org/articles/PMC9252508; pdf:https://europepmc.org/articles/PMC9252508?pdf=render
+35997000,https://doi.org/10.1111/ene.15530,Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia.,"Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",,European journal of neurology,2022,2022-09-11,Y,Psychiatric disorders; Movement Disorders; Dystonia; Neurological Disorders,,,"<h4>Background and purpose</h4>Although psychiatric diagnoses are recognized in idiopathic dystonia, no previous studies have examined the temporal relationship between idiopathic dystonia and psychiatric diagnoses at scale. Here, we determine rates of psychiatric diagnoses and psychiatric medication prescription in those diagnosed with idiopathic dystsuponia compared to matched controls.<h4>Methods</h4>A longitudinal population-based cohort study using anonymized electronic health care data in Wales (UK) was conducted to identify individuals with idiopathic dystonia and comorbid psychiatric diagnoses/prescriptions between 1 January 1994 and 31 December 2017. Psychiatric diagnoses/prescriptions were identified from primary and secondary health care records.<h4>Results</h4>Individuals with idiopathic dystonia (n = 52,589) had higher rates of psychiatric diagnosis and psychiatric medication prescription when compared to controls (n = 216,754, 43% vs. 31%, p &lt; 0.001; 45% vs. 37.9%, p &lt; 0.001, respectively), with depression and anxiety being most common (cases: 31% and 28%). Psychiatric diagnoses predominantly predated dystonia diagnosis, particularly in the 12 months prior to diagnosis (incidence rate ratio [IRR] = 1.98, 95% confidence interval [CI] = 1.9-2.1), with an IRR of 12.4 (95% CI = 11.8-13.1) for anxiety disorders. There was, however, an elevated rate of most psychiatric diagnoses throughout the study period, including the 12 months after dystonia diagnosis (IRR = 1.96, 95% CI = 1.85-2.07).<h4>Conclusions</h4>This study suggests a bidirectional relationship between psychiatric disorders and dystonia, particularly with mood disorders. Psychiatric and motor symptoms in dystonia may have common aetiological mechanisms, with psychiatric disorders potentially forming prodromal symptoms of idiopathic dystonia.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62203/Download/62203__26254__0c88bfc9ff7e4fe2acaea5e2a2d74058.pdf; doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render
 PMC9644982,https://doi.org/,Assessing the impacts of COVID-19 on Care Homes in Wales.,"Fry R, Hollinghurst J, North L, Emmerson C, Long S, Akbari A, Gravenor M, Lyons R.",,International journal of population data science,,2022-11-21,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644982/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644982/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9644982; pdf:https://europepmc.org/articles/PMC9644982?pdf=render
 36992264,https://doi.org/10.3390/vaccines11030680,"Determinants of Equity in Coverage of Measles-Containing Vaccines in Wales, UK, during the Elimination Era.","Perry M, Cottrell S, Gravenor MB, Griffiths L.",,Vaccines,2023,2023-03-17,Y,"Vaccination; Measles; Socioeconomic Factors; Immunisation; Mmr; Measles, Mumps And Rubella Vaccine",,,"In the context of the WHO's measles and rubella elimination targets and European Immunization Agenda 2030, this large cross-sectional study aimed to identify inequalities in measles vaccination coverage in Wales, UK. The vaccination status of individuals aged 2 to 25 years of age, alive and resident in Wales as of 31 August 2021, was ascertained through linkage of the National Community Child Health Database and primary care data. A series of predictor variables were derived from five national datasets and all analysis was carried out in the Secure Anonymised Information Linkage Databank at Swansea University. In these 648,895 individuals, coverage of the first dose of measles-containing vaccine (due at 12-13 months of age) was 97.1%, and coverage of the second dose (due at 3 years and 4 months) in 4 to 25-year-olds was 93.8%. In multivariable analysis, excluding 0.7% with known refusal, the strongest association with being unvaccinated was birth order (families with six or more children) and being born outside of the UK. Living in a deprived area, being eligible for free school meals, a lower level of maternal education, and having a recorded language other than English or Welsh were also associated with lower coverage. Some of these factors may also be associated with refusal. This knowledge can be used to target future interventions and prioritise areas for catch up in a time of limited resource.",,pdf:https://www.mdpi.com/2076-393X/11/3/680/pdf?version=1679031223; doi:https://doi.org/10.3390/vaccines11030680; html:https://europepmc.org/articles/PMC10057771; pdf:https://europepmc.org/articles/PMC10057771?pdf=render
-37663407,https://doi.org/10.1093/jamiaopen/ooad072,Identifying factors associated with user retention and outcomes of a digital intervention for substance use disorder: a retrospective analysis of real-world data.,"Günther F, Wong D, Elison-Davies S, Yau C.",,JAMIA open,2023,2023-09-02,Y,Substance Use Disorder; Secondary Use; Digital Health Intervention; Real-World Data Exploration; Real-World Uptake,,,"<h4>Objectives</h4>Successful delivery of digital health interventions is affected by multiple real-world factors. These factors may be identified in routinely collected, ecologically valid data from these interventions. We propose ideas for exploring these data, focusing on interventions targeting complex, comorbid conditions.<h4>Materials and methods</h4>This study retrospectively explores pre-post data collected between 2016 and 2019 from users of digital cognitive behavioral therapy (CBT)-containing psychoeducation and practical exercises-for substance use disorder (SUD) at UK addiction services. To identify factors associated with heterogenous user responses to the technology, we employed multivariable and multivariate regressions and random forest models of user-reported questionnaire data.<h4>Results</h4>The dataset contained information from 14 078 individuals of which 12 529 reported complete data at baseline and 2925 did so again after engagement with the CBT. Ninety-three percent screened positive for dependence on 1 of 43 substances at baseline, and 73% screened positive for anxiety or depression. Despite pre-post improvements independent of user sociodemographics, women reported more frequent and persistent symptoms of SUD, anxiety, and depression. Retention-minimum 2 use events recorded-was associated more with deployment environment than user characteristics. Prediction accuracy of post-engagement outcomes was acceptable (Area Under Curve [AUC]: 0.74-0.79), depending non-trivially on user characteristics.<h4>Discussion</h4>Traditionally, performance of digital health interventions is determined in controlled trials. Our analysis showcases multivariate models with which real-world data from these interventions can be explored and sources of user heterogeneity in retention and symptom reduction uncovered.<h4>Conclusion</h4>Real-world data from digital health interventions contain information on natural user-technology interactions which could enrich results from controlled trials.",,doi:https://doi.org/10.1093/jamiaopen/ooad072; html:https://europepmc.org/articles/PMC10474970; pdf:https://europepmc.org/articles/PMC10474970?pdf=render
 32180562,https://doi.org/10.1016/j.molmet.2020.01.009,Genome-wide association study of adipocyte lipolysis in the GENetics of adipocyte lipolysis (GENiAL) cohort.,"Kulyté A, Lundbäck V, Lindgren CM, Luan J, Lotta LA, Langenberg C, Arner P, Strawbridge RJ, Dahlman I.",,Molecular metabolism,2020,2020-01-25,Y,Adipocytes; Gene Expression; Subcutaneous; Genetic Variants; Lipolysis,The Human Phenome,,"<h4>Objectives</h4>Lipolysis, hydrolysis of triglycerides to fatty acids in adipocytes, is tightly regulated, poorly understood, and, if perturbed, can lead to metabolic diseases including obesity and type 2 diabetes. The goal of this study was to identify the genetic regulators of lipolysis and elucidate their molecular mechanisms.<h4>Methods</h4>Adipocytes from abdominal subcutaneous adipose tissue biopsies were isolated and were incubated without (spontaneous lipolysis) or with a catecholamine (stimulated lipolysis) to analyze lipolysis. DNA was extracted and genome-wide genotyping and imputation conducted. After quality control, 939 samples with genetic and lipolysis data were available. Genome-wide association studies of spontaneous and stimulated lipolysis were conducted. Subsequent in vitro gene expression analyses were used to identify candidate genes and explore their regulation of adipose tissue biology.<h4>Results</h4>One locus on chromosome 19 demonstrated genome-wide significance with spontaneous lipolysis. 60 loci showed suggestive associations with spontaneous or stimulated lipolysis, of which many influenced both traits. In the chromosome 19 locus, only HIF3A was expressed in the adipocytes and displayed genotype-dependent gene expression. HIF3A knockdown in vitro increased lipolysis and the expression of key lipolysis-regulating genes.<h4>Conclusions</h4>In conclusion, we identified a genetic regulator of spontaneous lipolysis and provided evidence of HIF3A as a novel key regulator of lipolysis in subcutaneous adipocytes as the mechanism through which the locus influences adipose tissue biology.","How the body breaks down fat is poorly understood, and, if this mechanism does not happen effiently in the body it can lead to metabolic diseases including obesity and type 2 diabetes. The goal of this study was to identify the genetic regulators of how the body break down fat and explain their molecular mechanisms.",doi:https://doi.org/10.1016/j.molmet.2020.01.009; doi:https://doi.org/10.1016/j.molmet.2020.01.009; html:https://europepmc.org/articles/PMC7021539; pdf:https://europepmc.org/articles/PMC7021539?pdf=render
+37663407,https://doi.org/10.1093/jamiaopen/ooad072,Identifying factors associated with user retention and outcomes of a digital intervention for substance use disorder: a retrospective analysis of real-world data.,"Günther F, Wong D, Elison-Davies S, Yau C.",,JAMIA open,2023,2023-09-02,Y,Substance Use Disorder; Secondary Use; Digital Health Intervention; Real-World Data Exploration; Real-World Uptake,,,"<h4>Objectives</h4>Successful delivery of digital health interventions is affected by multiple real-world factors. These factors may be identified in routinely collected, ecologically valid data from these interventions. We propose ideas for exploring these data, focusing on interventions targeting complex, comorbid conditions.<h4>Materials and methods</h4>This study retrospectively explores pre-post data collected between 2016 and 2019 from users of digital cognitive behavioral therapy (CBT)-containing psychoeducation and practical exercises-for substance use disorder (SUD) at UK addiction services. To identify factors associated with heterogenous user responses to the technology, we employed multivariable and multivariate regressions and random forest models of user-reported questionnaire data.<h4>Results</h4>The dataset contained information from 14 078 individuals of which 12 529 reported complete data at baseline and 2925 did so again after engagement with the CBT. Ninety-three percent screened positive for dependence on 1 of 43 substances at baseline, and 73% screened positive for anxiety or depression. Despite pre-post improvements independent of user sociodemographics, women reported more frequent and persistent symptoms of SUD, anxiety, and depression. Retention-minimum 2 use events recorded-was associated more with deployment environment than user characteristics. Prediction accuracy of post-engagement outcomes was acceptable (Area Under Curve [AUC]: 0.74-0.79), depending non-trivially on user characteristics.<h4>Discussion</h4>Traditionally, performance of digital health interventions is determined in controlled trials. Our analysis showcases multivariate models with which real-world data from these interventions can be explored and sources of user heterogeneity in retention and symptom reduction uncovered.<h4>Conclusion</h4>Real-world data from digital health interventions contain information on natural user-technology interactions which could enrich results from controlled trials.",,doi:https://doi.org/10.1093/jamiaopen/ooad072; html:https://europepmc.org/articles/PMC10474970; pdf:https://europepmc.org/articles/PMC10474970?pdf=render
 33182605,https://doi.org/10.3390/genes11111326,"Exploring the Role of Contactins across Psychological, Psychiatric and Cardiometabolic Traits within UK Biobank.","Morris J, Leung SSY, Bailey MES, Cullen B, Ferguson A, Graham N, Johnston KJA, Lyall DM, Lyall LM, Ward J, Smith DJ, Strawbridge RJ.",,Genes,2020,2020-11-10,Y,Hypertension; Genetic variation; Type 2 diabetes; Psychiatric disorders; Single Nucleotide Polymorphisms; Gene Expression; Uk Biobank; Contactins; Cardiometabolic Diseases,,,"Individuals with severe mental illness have an increased risk of cardiometabolic diseases compared to the general population. Shared risk factors and medication effects explain part of this excess risk; however, there is growing evidence to suggest that shared biology (including genetic variation) is likely to contribute to comorbidity between mental and physical illness. Contactins are a family of genes involved in development of the nervous system and implicated, though genome-wide association studies, in a wide range of psychological, psychiatric and cardiometabolic conditions. Contactins are plausible candidates for shared pathology between mental and physical health. We used data from UK Biobank to systematically assess how genetic variation in contactin genes was associated with a wide range of psychological, psychiatric and cardiometabolic conditions. We also investigated whether associations for cardiometabolic and psychological traits represented the same or distinct signals and how the genetic variation might influence the measured traits. We identified: A novel genetic association between variation in <i>CNTN1</i> and current smoking; two independent signals in <i>CNTN4</i> for BMI; and demonstrated that associations between <i>CNTN5</i> and neuroticism were distinct from those between <i>CNTN5</i> and blood pressure/HbA1c. There was no evidence that the contactin genes contributed to shared aetiology between physical and mental illness.",,pdf:https://www.mdpi.com/2073-4425/11/11/1326/pdf?version=1605520057; doi:https://doi.org/10.3390/genes11111326; html:https://europepmc.org/articles/PMC7697406; pdf:https://europepmc.org/articles/PMC7697406?pdf=render
 35151397,https://doi.org/10.1016/s0140-6736(22)00163-5,"Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-02-01,Y,,,,"<h4>Background</h4>Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19.<h4>Methods</h4>RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).<h4>Findings</h4>Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69-0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86-1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab.<h4>Interpretation</h4>In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline.<h4>Funding</h4>UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/95149/5/1-s2.0-S0140673622001635-main.pdf; doi:https://doi.org/10.1016/S0140-6736(22)00163-5; html:https://europepmc.org/articles/PMC8830904
 34543508,https://doi.org/10.1111/ene.15114,"Adult-onset idiopathic dystonia: A national data-linkage study to determine epidemiological, social deprivation, and mortality characteristics.","Bailey GA, Rawlings A, Torabi F, Pickrell O, Peall KJ.",,European journal of neurology,2022,2021-10-15,Y,Mortality; Prevalence; Socioeconomic Factors; incidence; Dystonia,,,"<h4>Background and purpose</h4>Accurate epidemiological information is essential for the improved understanding of dystonia syndromes, as well as better provisioning of clinical services and providing context for diagnostic decision-making. Here, we determine epidemiological, social deprivation, and mortality characteristics of adult-onset idiopathic dystonia in the Welsh population.<h4>Methods</h4>A retrospective population-based cohort study using anonymized electronic health care data in Wales was conducted to identify individuals with dystonia between 1 January 1994 and 31 December 2017. We developed a case-ascertainment algorithm to determine dystonia incidence and prevalence, as well as characterization of the dystonia cohort, based on social deprivation and mortality.<h4>Results</h4>The case-ascertainment algorithm (79% sensitivity) identified 54,966 cases; of these cases, 41,660 had adult-onset idiopathic dystonia (≥20 years). Amongst the adult-onset form, the median age at diagnosis was 41 years, with males significantly older at time of diagnosis compared to females. Prevalence rates ranged from 0.02% in 1994 to 1.2% in 2017. The average annual incidence was 87.7/100,000/year, increasing from 49.9/100,000/year (1994) to 96.21/100,000/year (2017). In 2017, people with dystonia had a similar life expectancy to the Welsh population.<h4>Conclusions</h4>We have developed a case-ascertainment algorithm, supported by the introduction of a neurologist-reviewed validation cohort, providing a platform for future population-based dystonia studies. We have established robust population-level prevalence and incidence values for adult-onset idiopathic forms of dystonia, with this reflecting increasing clinical recognition and identification of causal genes. Underlying causes of death mirrored those of the general population, including circulatory disorders, respiratory disorders, cancers, and dementia.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ene.15114; doi:https://doi.org/10.1111/ene.15114; html:https://europepmc.org/articles/PMC9377012; pdf:https://europepmc.org/articles/PMC9377012?pdf=render
 33965593,https://doi.org/10.1016/j.jaip.2021.04.055,Intolerance to Angiotensin Converting Enzyme Inhibitors in Asthma and the General Population: A UK Population-Based Cohort Study.,"Morales DR, Lipworth BJ, Donnan PT, Wang H.",,The journal of allergy and clinical immunology. In practice,2021,2021-05-06,Y,Hypertension; Angiotensin converting enzyme; Asthma; epidemiology; Cough,,,"<h4>Background</h4>Angiotensin converting enzyme inhibitor (ACEI) intolerance commonly occurs, requiring switching to an angiotensin-II receptor blocker (ARB). Angiotensin converting enzyme inhibitor intolerance may be mediated by bradykinin, potentially affecting airway hyperresponsiveness.<h4>Objective</h4>To assess the risk for switching to ARBs in asthma.<h4>Methods</h4>We conducted a new-user cohort study of ACEI initiators identified from electronic health records from the UK Clinical Practice Research Datalink. The risk for switching to ARBs in people with asthma or chronic obstructive pulmonary disease and the general population was compared. Adjusted hazard ratios (HRs) were calculated using Cox regression, stratified by British Thoracic Society (BTS) treatment step and ACEI type.<h4>Results</h4>Of 642,336 new users of ACEI, 6.4% had active asthma. The hazard of switching to ARB was greater in people with asthma (HR = 1.16; 95% confidence interval [CI], 1.14-1.18; P ≤ .001) and highest in those at BTS step 3 or greater (HR = 1.35, 95% CI, 1.32-1.39; and HR = 1.18, 95% CI, 1.15-1.22, P ≤ .001 for patients aged ≥60 and <60 years, respectively). Hazard was highest with enalapril (HR = 1.25, 95% CI, 1.18-1.34, P ≤ .001; HR = 1.44, 95% CI, 1.32-1.58, P ≤ .001 for BTS step 3 or greater asthma). No increased hazard was observed in chronic obstructive pulmonary disease or those younger than age 60 years at BTS step 1/2. The number needed to treat varied by age, sex, and body mass index (BMI), ranging between 21 and 4, and was lowest in older women with a BMI of 25 or greater.<h4>Conclusions</h4>People with active asthma are more likely to switch to ARBs after commencing ACEI therapy. The number needed to treat varies by age, sex, BMI, and BTS step. Angiotensin-II receptor blocker could potentially be considered first-line in people with asthma and in those with high-risk characteristics.",,pdf:https://europepmc.org/articles/pmc8443840?pdf=render; doi:https://doi.org/10.1016/j.jaip.2021.04.055; html:https://europepmc.org/articles/PMC8443840; pdf:https://europepmc.org/articles/PMC8443840?pdf=render
 33667930,https://doi.org/10.1016/j.ijmedinf.2021.104400,Real-time spatial health surveillance: Mapping the UK COVID-19 epidemic.,"Fry R, Hollinghurst J, Stagg HR, Thompson DA, Fronterre C, Orton C, Lyons RA, Ford DV, Sheikh A, Diggle PJ.",,International journal of medical informatics,2021,2021-01-28,Y,,,,"Introduction The COVID-19 pandemic has highlighted the need for robust data linkage systems and methods for identifying outbreaks of disease in near real-time. Objectives The primary objective of this study was to develop a real-time geospatial surveillance system to monitor the spread of COVID-19 across the UK. Methods Using self-reported app data and the Secure Anonymised Information Linkage (SAIL) Databank, we demonstrate the use of sophisticated spatial modelling for near-real-time prediction of COVID-19 prevalence at small-area resolution to inform strategic government policy areas. Results We demonstrate that using a combination of crowd-sourced app data and sophisticated geo-statistical techniques it is possible to predict hot spots of COVID-19 at fine geographic scales, nationally. We are also able to produce estimates of their precision, which is an important pre-requisite to an effective control strategy to guard against over-reaction to potentially spurious features of 'best guess' predictions. Conclusion In the UK, important emerging risk-factors such as social deprivation or ethnicity vary over small distances, hence risk needs to be modelled at fine spatial resolution to avoid aggregation bias. We demonstrate that existing geospatial statistical methods originally developed for global health applications are well-suited to this task and can be used in an anonymised databank environment, thus preserving the privacy of the individuals who contribute their data.",,doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; html:https://europepmc.org/articles/PMC7843148
-PMC9644860,https://doi.org/,Maternal mental health and children’s development: a bi-directional relationship?,"Lowthian E, Bedston S, Akbari A, Katz A, Huxley K, Johnson R, Kristensen S, Owen R, Taylor C, Griffiths L.",,International journal of population data science,,2022-11-21,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9644860; pdf:https://europepmc.org/articles/PMC9644860?pdf=render
 33939953,https://doi.org/10.1016/s0140-6736(21)00634-6,"Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.","Mathur R, Rentsch CT, Morton CE, Hulme WJ, Schultze A, MacKenna B, Eggo RM, Bhaskaran K, Wong AYS, Williamson EJ, Forbes H, Wing K, McDonald HI, Bates C, Bacon S, Walker AJ, Evans D, Inglesby P, Mehrkar A, Curtis HJ, DeVito NJ, Croker R, Drysdale H, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Tomlinson L, Evans SJW, Grieve R, Harrison D, Rowan K, Khunti K, Chaturvedi N, Smeeth L, Goldacre B, OpenSAFELY Collaborative.",,"Lancet (London, England)",2021,2021-04-30,Y,,,,"<h4>Background</h4>COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.<h4>Methods</h4>We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region.<h4>Findings</h4>Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories.<h4>Interpretation</h4>Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.<h4>Funding</h4>Medical Research Council.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659476/13/PIIS0140673621006346.pdf; doi:https://doi.org/10.1016/S0140-6736(21)00634-6; html:https://europepmc.org/articles/PMC8087292; pdf:https://europepmc.org/articles/PMC8087292?pdf=render
+PMC9644860,https://doi.org/,Maternal mental health and children’s development: a bi-directional relationship?,"Lowthian E, Bedston S, Akbari A, Katz A, Huxley K, Johnson R, Kristensen S, Owen R, Taylor C, Griffiths L.",,International journal of population data science,,2022-11-21,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9644860; pdf:https://europepmc.org/articles/PMC9644860?pdf=render
 33644411,https://doi.org/10.23889/ijpds.v5i1.1346,Identifying children with Cystic Fibrosis in population-scale routinely collected data in Wales: A Retrospective Review.,"Griffiths R, Schlüter DK, Akbari A, Cosgriff R, Tucker D, Taylor-Robinson D.",,International journal of population data science,2020,2020-08-11,Y,,,,"<h4>Introduction</h4>The challenges in identifying a cohort of people with a rare condition can be addressed by routinely collected, population-scale electronic health record (EHR) data, which provide large volumes of data at a national level. This paper describes the challenges of accurately identifying a cohort of children with Cystic Fibrosis (CF) using EHR and their validation against the UK CF Registry.<h4>Objectives</h4>To establish a proof of principle and provide insight into the merits of linked data in CF research; to identify the benefits of access to multiple data sources, in particular the UK CF Registry data, and to demonstrate the opportunity it represents as a resource for future CF research.<h4>Methods</h4>Three EHR data sources were used to identify children with CF born in Wales between 1<sup>st</sup> January 1998 and 31<sup>st</sup> August 2015 within the Secure Anonymised Information Linkage (SAIL) Databank. The UK CF Registry was later acquired by SAIL and linked to the EHR cohort to validate the cases and explore the reasons for misclassifications.<h4>Results</h4>We identified 352 children with CF in the three EHR data sources. This was greater than expected based on historical incidence rates in Wales. Subsequent validation using the UK CF Registry found that 257 (73%) of these were true cases. Approximately 98.7% (156/158) of individuals identified as CF cases in all three EHR data sources were confirmed as true cases; but this was only the case for 19.8% (20/101) of all those identified in just a single data source.<h4>Conclusion</h4>Identifying health conditions in EHR data can be challenging, so data quality assurance and validation is important or the merit of the research is undermined. This retrospective review identifies some of the challenges in identifying CF cases and demonstrates the benefits of linking cases across multiple data sources to improve quality.",,pdf:https://ijpds.org/article/download/1346/2853; doi:https://doi.org/10.23889/ijpds.v5i1.1346; html:https://europepmc.org/articles/PMC7898022; pdf:https://europepmc.org/articles/PMC7898022?pdf=render
 36936262,https://doi.org/10.1136/bmjmed-2022-000371,Association between coeliac disease and cardiovascular disease: prospective analysis of UK Biobank data.,"Conroy M, Allen N, Lacey B, Soilleux E, Littlejohns T.",,BMJ medicine,2023,2023-01-04,Y,epidemiology; Cardiology; Celiac Disease,,,"<h4>Objectives</h4>To investigate whether people with coeliac disease are at increased risk of cardiovascular disease, including ischaemic heart disease, myocardial infarction, and stroke.<h4>Design</h4>Prospective analysis of a large cohort study.<h4>Setting</h4>UK Biobank database.<h4>Participants</h4>469 095 adults, of which 2083 had coeliac disease, aged 40-69 years from England, Scotland, and Wales between 2006 and 2010 without cardiovascular disease at baseline.<h4>Main outcome measure</h4>A composite primary outcome was relative risk of cardiovascular disease, ischaemic heart disease, myocardial infarction, and stroke in people with coeliac disease compared with people who do not have coeliac disease, assessed using Cox proportional hazard models.<h4>Results</h4>40 687 incident cardiovascular disease events occurred over a median follow-up of 12.4 years (interquartile range 11.5-13.1), with 218 events among people with coeliac disease. Participants with coeliac disease were more likely to have a lower body mass index and systolic blood pressure, less likely to smoke, and more likely to have an ideal cardiovascular risk score than people who do not have coeliac disease. Despite this, participants with coeliac disease had an incidence rate of 9.0 cardiovascular disease cases per 1000 person years (95% confidence interval 7.9 to 10.3) compared with 7.4 per 1000 person years (7.3 to 7.4) in people with no coeliac disease. Coeliac disease was associated with an increased risk of cardiovascular disease (hazard ratio 1.27 (95% confidence interval 1.11 to 1.45)), which was not influenced by adjusting for lifestyle factors (1.27 (1.11 to 1.45)), but was strengthened by further adjusting for other cardiovascular risk factors (1.44 (1.26 to 1.65)). Similar associations were identified for ischaemic heart disease and myocardial infarction but fewer stroke events were reported and no evidence of an association between coeliac disease and risk of stroke.<h4>Conclusions</h4>Individuals with coeliac disease had a lower prevalence of traditional cardiovascular risk factors but had a higher risk of developing cardiovascular disease than did people with no coeliac disease. Cardiovascular risk scores used in clinical practice might therefore not adequately capture the excess risk of cardiovascular disease in people with coeliac disease, and clinicians should be aware of the need to optimise cardiovascular health in this population.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000371.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000371; html:https://europepmc.org/articles/PMC9951384; pdf:https://europepmc.org/articles/PMC9951384?pdf=render
 36921681,https://doi.org/10.1016/j.cca.2023.117271,"Letter to the editor regarding: ""A haemochromatosis-causing HFE mutation is associated with SARS-CoV-2 susceptibility in the Czech population"" clinica chimica acta 538 (2023) 211-215.","Atkins JL, Lucas MR, Pilling LC, Melzer D.",,Clinica chimica acta; international journal of clinical chemistry,2023,2023-03-13,Y,Iron; Haemochromatosis; Hfe; Covd-19,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009995; doi:https://doi.org/10.1016/j.cca.2023.117271; html:https://europepmc.org/articles/PMC10009995; pdf:https://europepmc.org/articles/PMC10009995?pdf=render
 34489241,https://doi.org/10.1136/bjsports-2021-104050,Reallocation of time between device-measured movement behaviours and risk of incident cardiovascular disease.,"Walmsley R, Chan S, Smith-Byrne K, Ramakrishnan R, Woodward M, Rahimi K, Dwyer T, Bennett D, Doherty A.",,British journal of sports medicine,2021,2021-09-06,Y,Cardiovascular diseases; Sleep; Methods; Physical Activity; Sedentary Behavior,,,"<h4>Objective</h4>To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults.<h4>Methods</h4>Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence.<h4>Results</h4>In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen's kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average individual, reallocating 20 min/day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk.<h4>Conclusion</h4>Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines.",,pdf:https://bjsm.bmj.com/content/bjsports/early/2022/02/15/bjsports-2021-104050.full.pdf; doi:https://doi.org/10.1136/bjsports-2021-104050; html:https://europepmc.org/articles/PMC9484395; pdf:https://europepmc.org/articles/PMC9484395?pdf=render
 32613083,https://doi.org/10.12688/wellcomeopenres.15922.2,"Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data.","Aldridge RW, Lewer D, Katikireddi SV, Mathur R, Pathak N, Burns R, Fragaszy EB, Johnson AM, Devakumar D, Abubakar I, Hayward A.",,Wellcome open research,2020,2020-06-24,Y,Mortality; Minority Ethnic Groups; Covid-19; Sars-cov-2,,,"<b>Background</b>: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. <b>Methods</b>: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. <b>Results</b>: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. <b>Conclusion:</b> Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications.",,doi:https://doi.org/10.12688/wellcomeopenres.15922.2; html:https://europepmc.org/articles/PMC7317462; pdf:https://europepmc.org/articles/PMC7317462?pdf=render
 37934728,https://doi.org/10.1093/jamia/ocad212,Multi-faceted analysis and prediction for the outbreak of pediatric respiratory syncytial virus.,"Yang C, Gao J, Glass L, Cross A, Sun J.",,Journal of the American Medical Informatics Association : JAMIA,2023,2023-11-02,N,Respiratory syncytial virus (RSV); Pediatric Diseases; Deep Learning; Tensor Factorization,,,"<h4>Objectives</h4>Respiratory syncytial virus (RSV) is a significant cause of pediatric hospitalizations. This article aims to utilize multisource data and leverage the tensor methods to uncover distinct RSV geographic clusters and develop an accurate RSV prediction model for future seasons.<h4>Materials and methods</h4>This study utilizes 5-year RSV data from sources, including medical claims, CDC surveillance data, and Google search trends. We conduct spatiotemporal tensor analysis and prediction for pediatric RSV in the United States by designing (i) a nonnegative tensor factorization model for pediatric RSV diseases and location clustering; (ii) and a recurrent neural network tensor regression model for county-level trend prediction using the disease and location features.<h4>Results</h4>We identify a clustering hierarchy of pediatric diseases: Three common geographic clusters of RSV outbreaks were identified from independent sources, showing an annual RSV trend shifting across different US regions, from the South and Southeast regions to the Central and Northeast regions and then to the West and Northwest regions, while precipitation and temperature were found as correlative factors with the coefficient of determination R2≈0.5, respectively. Our regression model accurately predicted the 2022-2023 RSV season at the county level, achieving R2≈0.3 mean absolute error MAE < 0.4 and a Pearson correlation greater than 0.75, which significantly outperforms the baselines with P-values <.05.<h4>Conclusion</h4>Our proposed framework provides a thorough analysis of RSV disease in the United States, which enables healthcare providers to better prepare for potential outbreaks, anticipate increased demand for services and supplies, and save more lives with timely interventions.",,doi:https://doi.org/10.1093/jamia/ocad212
-37868035,https://doi.org/10.1016/j.xgen.2023.100385,Gene expression and RNA splicing explain large proportions of the heritability for complex traits in cattle.,"Xiang R, Fang L, Liu S, Macleod IM, Liu Z, Breen EJ, Gao Y, Liu GE, Tenesa A, CattleGTEx Consortium, Mason BA, Chamberlain AJ, Wray NR, Goddard ME.",,Cell genomics,2023,2023-08-23,Y,RNA splicing; Heritability; Gene Expression; Complex Traits; Eqtl; Sqtl; Bayesr; Bayesrc,,,"Many quantitative trait loci (QTLs) are in non-coding regions. Therefore, QTLs are assumed to affect gene regulation. Gene expression and RNA splicing are primary steps of transcription, so DNA variants changing gene expression (eVariants) or RNA splicing (sVariants) are expected to significantly affect phenotypes. We quantify the contribution of eVariants and sVariants detected from 16 tissues (n = 4,725) to 37 traits of ∼120,000 cattle (average magnitude of genetic correlation between traits = 0.13). Analyzed in Bayesian mixture models, averaged across 37 traits, <i>cis</i> and <i>trans</i> eVariants and sVariants detected from 16 tissues jointly explain 69.2% (SE = 0.5%) of heritability, 44% more than expected from the same number of random variants. This 69.2% includes an average of 24% from <i>trans</i> e-/sVariants (14% more than expected). Averaged across 56 lipidomic traits, multi-tissue <i>cis</i> and <i>trans</i> e-/sVariants also explain 71.5% (SE = 0.3%) of heritability, demonstrating the essential role of proximal and distal regulatory variants in shaping mammalian phenotypes.",,doi:https://doi.org/10.1016/j.xgen.2023.100385; html:https://europepmc.org/articles/PMC10589627; pdf:https://europepmc.org/articles/PMC10589627?pdf=render
 32463370,https://doi.org/10.2196/16452,Challenges of Clustering Multimodal Clinical Data: Review of Applications in Asthma Subtyping.,"Horne E, Tibble H, Sheikh A, Tsanas A.",,JMIR medical informatics,2020,2020-05-28,Y,Cluster analysis; Asthma; data mining; Machine Learning; Unsupervised Machine Learning,,,"<h4>Background</h4>In the current era of personalized medicine, there is increasing interest in understanding the heterogeneity in disease populations. Cluster analysis is a method commonly used to identify subtypes in heterogeneous disease populations. The clinical data used in such applications are typically multimodal, which can make the application of traditional cluster analysis methods challenging.<h4>Objective</h4>This study aimed to review the research literature on the application of clustering multimodal clinical data to identify asthma subtypes. We assessed common problems and shortcomings in the application of cluster analysis methods in determining asthma subtypes, such that they can be brought to the attention of the research community and avoided in future studies.<h4>Methods</h4>We searched PubMed and Scopus bibliographic databases with terms related to cluster analysis and asthma to identify studies that applied dissimilarity-based cluster analysis methods. We recorded the analytic methods used in each study at each step of the cluster analysis process.<h4>Results</h4>Our literature search identified 63 studies that applied cluster analysis to multimodal clinical data to identify asthma subtypes. The features fed into the cluster algorithms were of a mixed type in 47 (75%) studies and continuous in 12 (19%), and the feature type was unclear in the remaining 4 (6%) studies. A total of 23 (37%) studies used hierarchical clustering with Ward linkage, and 22 (35%) studies used k-means clustering. Of these 45 studies, 39 had mixed-type features, but only 5 specified dissimilarity measures that could handle mixed-type features. A further 9 (14%) studies used a preclustering step to create small clusters to feed on a hierarchical method. The original sample sizes in these 9 studies ranged from 84 to 349. The remaining studies used hierarchical clustering with other linkages (n=3), medoid-based methods (n=3), spectral clustering (n=1), and multiple kernel k-means clustering (n=1), and in 1 study, the methods were unclear. Of 63 studies, 54 (86%) explained the methods used to determine the number of clusters, 24 (38%) studies tested the quality of their cluster solution, and 11 (17%) studies tested the stability of their solution. Reporting of the cluster analysis was generally poor in terms of the methods employed and their justification.<h4>Conclusions</h4>This review highlights common issues in the application of cluster analysis to multimodal clinical data to identify asthma subtypes. Some of these issues were related to the multimodal nature of the data, but many were more general issues in the application of cluster analysis. Although cluster analysis may be a useful tool for investigating disease subtypes, we recommend that future studies carefully consider the implications of clustering multimodal data, the cluster analysis process itself, and the reporting of methods to facilitate replication and interpretation of findings.",,pdf:https://medinform.jmir.org/2020/5/e16452/PDF; doi:https://doi.org/10.2196/16452; html:https://europepmc.org/articles/PMC7290450
+37868035,https://doi.org/10.1016/j.xgen.2023.100385,Gene expression and RNA splicing explain large proportions of the heritability for complex traits in cattle.,"Xiang R, Fang L, Liu S, Macleod IM, Liu Z, Breen EJ, Gao Y, Liu GE, Tenesa A, CattleGTEx Consortium, Mason BA, Chamberlain AJ, Wray NR, Goddard ME.",,Cell genomics,2023,2023-08-23,Y,RNA splicing; Heritability; Gene Expression; Complex Traits; Eqtl; Sqtl; Bayesr; Bayesrc,,,"Many quantitative trait loci (QTLs) are in non-coding regions. Therefore, QTLs are assumed to affect gene regulation. Gene expression and RNA splicing are primary steps of transcription, so DNA variants changing gene expression (eVariants) or RNA splicing (sVariants) are expected to significantly affect phenotypes. We quantify the contribution of eVariants and sVariants detected from 16 tissues (n = 4,725) to 37 traits of ∼120,000 cattle (average magnitude of genetic correlation between traits = 0.13). Analyzed in Bayesian mixture models, averaged across 37 traits, <i>cis</i> and <i>trans</i> eVariants and sVariants detected from 16 tissues jointly explain 69.2% (SE = 0.5%) of heritability, 44% more than expected from the same number of random variants. This 69.2% includes an average of 24% from <i>trans</i> e-/sVariants (14% more than expected). Averaged across 56 lipidomic traits, multi-tissue <i>cis</i> and <i>trans</i> e-/sVariants also explain 71.5% (SE = 0.3%) of heritability, demonstrating the essential role of proximal and distal regulatory variants in shaping mammalian phenotypes.",,doi:https://doi.org/10.1016/j.xgen.2023.100385; html:https://europepmc.org/articles/PMC10589627; pdf:https://europepmc.org/articles/PMC10589627?pdf=render
 35749561,https://doi.org/10.1371/journal.pcbi.1010234,"Evidence for influenza and RSV interaction from 10 years of enhanced surveillance in Nha Trang, Vietnam, a modelling study.","Waterlow NR, Toizumi M, van Leeuwen E, Thi Nguyen HA, Myint-Yoshida L, Eggo RM, Flasche S.",,PLoS computational biology,2022,2022-06-24,Y,,,,"Influenza and Respiratory Syncytial Virus (RSV) interact within their host posing the concern for impacts on heterologous viruses following vaccination. We aimed to estimate the population level impact of their interaction. We developed a dynamic age-stratified two-pathogen mathematical model that includes pathogen interaction through competition for infection and enhanced severity of dual infections. We used parallel tempering to fit its parameters to 11 years of enhanced hospital-based surveillance for acute respiratory illnesses (ARI) in children under 5 years old in Nha Trang, Vietnam. The data supported either a 41% (95%CrI: 36-54) reduction in susceptibility following infection and for 10.0 days (95%CrI 7.1-12.8) thereafter, or no change in susceptibility following infection. We estimate that co-infection increased the probability for an infection in <2y old children to be reported 7.2 fold (95%CrI 5.0-11.4); or 16.6 fold (95%CrI 14.5-18.4) in the moderate or low interaction scenarios. Absence of either pathogen was not to the detriment of the other. We find stronger evidence for severity enhancing than for acquisition limiting interaction. In this setting vaccination against either pathogen is unlikely to have a major detrimental effect on the burden of disease caused by the other.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010234&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010234; html:https://europepmc.org/articles/PMC9262224; pdf:https://europepmc.org/articles/PMC9262224?pdf=render
 34389694,https://doi.org/10.1158/1535-7163.mct-20-1050,Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer.,"Crawford N, Stott KJ, Sessler T, McCann C, McDaid W, Lees A, Latimer C, Fox JP, Munck JM, Smyth T, Shah A, Martins V, Lawler M, Dunne PD, Kerr EM, McDade SS, Coyle VM, Longley DB.",,Molecular cancer therapeutics,2021,2021-08-13,Y,,,,"Inhibitors of apoptosis proteins (IAPs) are intracellular proteins, with important roles in regulating cell death, inflammation, and immunity. Here, we examined the clinical and therapeutic relevance of IAPs in colorectal cancer. We found that elevated expression of cIAP1 and cIAP2 (but not XIAP) significantly correlated with poor prognosis in patients with microsatellite stable (MSS) stage III colorectal cancer treated with 5-fluorouracil (5FU)-based adjuvant chemotherapy, suggesting their involvement in promoting chemoresistance. A novel IAP antagonist tolinapant (ASTX660) potently and rapidly downregulated cIAP1 in colorectal cancer models, demonstrating its robust on-target efficacy. In cells co-cultured with TNFα to mimic an inflammatory tumor microenvironment, tolinapant induced caspase-8-dependent apoptosis in colorectal cancer cell line models; however, the extent of apoptosis was limited because of inhibition by the caspase-8 paralogs FLIP and, unexpectedly, caspase-10. Importantly, tolinapant-induced apoptosis was augmented by FOLFOX in human colorectal cancer and murine organoid models <i>in vitro</i> and <i>in vivo</i>, due (at least in part) to FOLFOX-induced downregulation of class I histone deacetylases (HDAC), leading to acetylation of the FLIP-binding partner Ku70 and downregulation of FLIP. Moreover, the effects of FOLFOX could be phenocopied using the clinically relevant class I HDAC inhibitor, entinostat, which also induced acetylation of Ku70 and FLIP downregulation. Further analyses revealed that caspase-8 knockout RIPK3-positive colorectal cancer models were sensitive to tolinapant-induced necroptosis, an effect that could be exploited in caspase-8-proficient models using the clinically relevant caspase inhibitor emricasan. Our study provides evidence for immediate clinical exploration of tolinapant in combination with FOLFOX in poor prognosis MSS colorectal cancer with elevated cIAP1/2 expression.",,pdf:https://aacrjournals.org/mct/article-pdf/20/9/1627/3076208/1627.pdf; doi:https://doi.org/10.1158/1535-7163.MCT-20-1050; html:https://europepmc.org/articles/PMC7611622; pdf:https://europepmc.org/articles/PMC7611622?pdf=render
 34837975,https://doi.org/10.1186/s12885-021-09014-w,Temporality of clinical factors associated with pancreatic cancer: a case-control study using linked electronic health records.,"Dayem Ullah AZM, Stasinos K, Chelala C, Kocher HM.",,BMC cancer,2021,2021-11-27,Y,Risk factor; Pancreatic cancer; Lifestyle; Ethnicity; Comorbidity,,,"<h4>Background</h4>Pancreatic cancer risk is poorly quantified in relation to the temporal presentation of medical comorbidities and lifestyle. This study aimed to examine this aspect, with possible influence of demographics.<h4>Methods</h4>We conducted a retrospective case-control study on the ethnically-diverse population of East London, UK, using linked electronic health records. We evaluated the independent and two-way interaction effects of 19 clinico-demographic factors in patients with pancreatic cancer (N = 965), compared with non-malignant pancreatic conditions (N = 3963) or hernia (control; N = 4355), reported between April 1, 2008 and March 6, 2020. Risks were quantified by odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models.<h4>Results</h4>We observed increased odds of pancreatic cancer incidence associated with recent-onset diabetes occurring within 6 months to 3 years before cancer diagnosis (OR 1.95, 95% CI 1.25-3.03), long-standing diabetes for over 3 years (OR 1.74, 95% CI 1.32-2.29), recent smoking (OR 1.81, 95% CI 1.36-2.4) and drinking (OR 1.76, 95% CI 1.31-2.35), as compared to controls but not non-malignant pancreatic conditions. Pancreatic cancer odds was highest for chronic pancreatic disease patients (recent-onset: OR 4.76, 95% CI 2.19-10.3, long-standing: OR 5.1, 95% CI 2.18-11.9), amplified by comorbidities or harmful lifestyle. Concomitant diagnosis of diabetes, upper gastrointestinal or chronic pancreatic conditions followed by a pancreatic cancer diagnosis within 6 months were common, particularly in South Asians. Long-standing cardiovascular, respiratory and hepatobiliary conditions were associated with lower odds of pancreatic cancer.<h4>Conclusions</h4>Several factors are, independently or via effect modifications, associated with higher incidence of pancreatic cancer, but some established risk factors demonstrate similar magnitude of risk measures of developing non-malignant pancreatic conditions. The findings may inform refined risk-stratification strategies and better surveillance for high-risk individuals, and also provide a means for systematic identification of target population for prospective cohort-based early detection research initiatives.",,pdf:https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-021-09014-w; doi:https://doi.org/10.1186/s12885-021-09014-w; html:https://europepmc.org/articles/PMC8626898; pdf:https://europepmc.org/articles/PMC8626898?pdf=render
 36211555,https://doi.org/10.3389/fcvm.2022.983091,Cardiac aging synthesis from cross-sectional data with conditional generative adversarial networks.,"Campello VM, Xia T, Liu X, Sanchez P, Martín-Isla C, Petersen SE, Seguí S, Tsaftaris SA, Lekadir K.",,Frontiers in cardiovascular medicine,2022,2022-09-23,Y,Synthesis; Magnetic Resonance Imaging; Data Augmentation; Aging Heart; Generative Adversarial Network,,,"Age has important implications for health, and understanding how age manifests in the human body is the first step for a potential intervention. This becomes especially important for cardiac health, since age is the main risk factor for development of cardiovascular disease. Data-driven modeling of age progression has been conducted successfully in diverse applications such as face or brain aging. While longitudinal data is the preferred option for training deep learning models, collecting such a dataset is usually very costly, especially in medical imaging. In this work, a conditional generative adversarial network is proposed to synthesize older and younger versions of a heart scan by using only cross-sectional data. We train our model with more than 14,000 different scans from the UK Biobank. The induced modifications focused mainly on the interventricular septum and the aorta, which is consistent with the existing literature in cardiac aging. We evaluate the results by measuring image quality, the mean absolute error for predicted age using a pre-trained regressor, and demonstrate the application of synthetic data for counter-balancing biased datasets. The results suggest that the proposed approach is able to model realistic changes in the heart using only cross-sectional data and that these data can be used to correct age bias in a dataset.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.983091/pdf; doi:https://doi.org/10.3389/fcvm.2022.983091; html:https://europepmc.org/articles/PMC9537599; pdf:https://europepmc.org/articles/PMC9537599?pdf=render
 36227072,https://doi.org/10.1093/jamia/ocac203,Transforming and evaluating the UK Biobank to the OMOP Common Data Model for COVID-19 research and beyond.,"Papez V, Moinat M, Voss EA, Bazakou S, Van Winzum A, Peviani A, Payralbe S, Kallfelz M, Asselbergs FW, Prieto-Alhambra D, Dobson RJB, Denaxas S.",,Journal of the American Medical Informatics Association : JAMIA,2022,2022-12-01,Y,Phenotyping; Electronic Health Records; Omop; Common Data Model; Medical Ontologies,,,"<h4>Objective</h4>The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the value of real-world data for public health research. International federated analyses are crucial for informing policy makers. Common data models (CDMs) are critical for enabling these studies to be performed efficiently. Our objective was to convert the UK Biobank, a study of 500 000 participants with rich genetic and phenotypic data to the Observational Medical Outcomes Partnership (OMOP) CDM.<h4>Materials and methods</h4>We converted UK Biobank data to OMOP CDM v. 5.3. We transformedparticipant research data on diseases collected at recruitment and electronic health records (EHRs) from primary care, hospitalizations, cancer registrations, and mortality from providers in England, Scotland, and Wales. We performed syntactic and semantic validations and compared comorbidities and risk factors between source and transformed data.<h4>Results</h4>We identified 502 505 participants (3086 with COVID-19) and transformed 690 fields (1 373 239 555 rows) to the OMOP CDM using 8 different controlled clinical terminologies and bespoke mappings. Specifically, we transformed self-reported noncancer illnesses 946 053 (83.91% of all source entries), cancers 37 802 (70.81%), medications 1 218 935 (88.25%), and prescriptions 864 788 (86.96%). In EHR, we transformed 13 028 182 (99.95%) hospital diagnoses, 6 465 399 (89.2%) procedures, 337 896 333 primary care diagnoses (CTV3, SNOMED-CT), 139 966 587 (98.74%) prescriptions (dm+d) and 77 127 (99.95%) deaths (ICD-10). We observed good concordance across demographic, risk factor, and comorbidity factors between source and transformed data.<h4>Discussion and conclusion</h4>Our study demonstrated that the OMOP CDM can be successfully leveraged to harmonize complex large-scale biobanked studies combining rich multimodal phenotypic data. Our study uncovered several challenges when transforming data from questionnaires to the OMOP CDM which require further research. The transformed UK Biobank resource is a valuable tool that can enable federated research, like COVID-19 studies.",,pdf:https://academic.oup.com/jamia/article-pdf/30/1/103/47829607/ocac203.pdf; doi:https://doi.org/10.1093/jamia/ocac203; html:https://europepmc.org/articles/PMC9619789; pdf:https://europepmc.org/articles/PMC9619789?pdf=render
-35868811,https://doi.org/10.1016/s2589-7500(22)00122-4,Data provenance and integrity of health-care systems data for clinical trials.,"Murray ML, Love SB, Carpenter JR, Hartley S, Landray MJ, Mafham M, Parmar MKB, Pinches H, Sydes MR, Healthcare Systems Data for Clinical Trials Collaborative Group.",,The Lancet. Digital health,2022,2022-08-01,Y,,,,,,pdf:http://www.thelancet.com/article/S2589750022001224/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00122-4; html:https://europepmc.org/articles/PMC9296098; pdf:https://europepmc.org/articles/PMC9296098?pdf=render
 31591592,https://doi.org/10.1038/s41591-019-0597-x,Avoidable flaws in observational analyses: an application to statins and cancer.,"Dickerman BA, García-Albéniz X, Logan RW, Denaxas S, Hernán MA.",,Nature medicine,2019,2019-10-07,N,,,,"The increasing availability of large healthcare databases is fueling an intense debate on whether real-world data should play a role in the assessment of the benefit-risk of medical treatments. In many observational studies, for example, statin users were found to have a substantially lower risk of cancer than in meta-analyses of randomized trials. Although such discrepancies are often attributed to a lack of randomization in the observational studies, they might be explained by flaws that can be avoided by explicitly emulating a target trial (the randomized trial that would answer the question of interest). Using the electronic health records of 733,804 UK adults, we emulated a target trial of statins and cancer and compared our estimates with those obtained using previously applied analytic approaches. Over the 10-yr follow-up, 28,408 individuals developed cancer. Under the target trial approach, estimated observational analogs of intention-to-treat and per-protocol 10-yr cancer-free survival differences were -0.5% (95% confidence interval (CI) -1.0%, 0.0%) and -0.3% (95% CI -1.5%, 0.5%), respectively. By contrast, previous analytic approaches yielded estimates that appeared to be strongly protective. Our findings highlight the importance of explicitly emulating a target trial to reduce bias in the effect estimates derived from observational analyses.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076561; doi:https://doi.org/10.1038/s41591-019-0597-x; html:https://europepmc.org/articles/PMC7076561; pdf:https://europepmc.org/articles/PMC7076561?pdf=render; doi:https://doi.org/10.1038/s41591-019-0597-x
-36384890,https://doi.org/10.1136/bmj-2022-071932,Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform.,"Zheng B, Green ACA, Tazare J, Curtis HJ, Fisher L, Nab L, Schultze A, Mahalingasivam V, Parker EPK, Hulme WJ, Bacon SCJ, DeVito NJ, Bates C, Evans D, Inglesby P, Drysdale H, Davy S, Cockburn J, Morton CE, Hickman G, Ward T, Smith RM, Parry J, Hester F, Harper S, Mehrkar A, Eggo RM, Walker AJ, Evans SJW, Douglas IJ, MacKenna B, Goldacre B, Tomlinson LA.",,BMJ (Clinical research ed.),2022,2022-11-16,Y,,,,"<h4>Objective</h4>To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19.<h4>Design</h4>Observational cohort study with the OpenSAFELY platform.<h4>Setting</h4>With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings.<h4>Participants</h4>Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.<h4>Interventions</h4>Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units.<h4>Main outcome measures</h4>Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment.<h4>Results</h4>Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England.<h4>Conclusions</h4>In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.",,pdf:https://www.bmj.com/content/bmj/379/bmj-2022-071932.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071932; html:https://europepmc.org/articles/PMC9667468
+35868811,https://doi.org/10.1016/s2589-7500(22)00122-4,Data provenance and integrity of health-care systems data for clinical trials.,"Murray ML, Love SB, Carpenter JR, Hartley S, Landray MJ, Mafham M, Parmar MKB, Pinches H, Sydes MR, Healthcare Systems Data for Clinical Trials Collaborative Group.",,The Lancet. Digital health,2022,2022-08-01,Y,,,,,,pdf:http://www.thelancet.com/article/S2589750022001224/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00122-4; html:https://europepmc.org/articles/PMC9296098; pdf:https://europepmc.org/articles/PMC9296098?pdf=render
 31462651,https://doi.org/10.1038/s41598-019-48927-2,Hierarchical Template Matching for 3D Myocardial Tracking and Cardiac Strain Estimation.,"Bhalodiya JM, Palit A, Ferrante E, Tiwari MK, Bhudia SK, Arvanitis TN, Williams MA.",,Scientific reports,2019,2019-08-28,Y,,Applied Analytics,,"Myocardial tracking and strain estimation can non-invasively assess cardiac functioning using subject-specific MRI. As the left-ventricle does not have a uniform shape and functioning from base to apex, the development of 3D MRI has provided opportunities for simultaneous 3D tracking, and 3D strain estimation. We have extended a Local Weighted Mean (LWM) transformation function for 3D, and incorporated in a Hierarchical Template Matching model to solve 3D myocardial tracking and strain estimation problem. The LWM does not need to solve a large system of equations, provides smooth displacement of myocardial points, and adapt local geometric differences in images. Hence, 3D myocardial tracking can be performed with 1.49 mm median error, and without large error outliers. The maximum error of tracking is up to 24% reduced compared to benchmark methods. Moreover, the estimated strain can be insightful to improve 3D imaging protocols, and the computer code of LWM could also be useful for geo-spatial and manufacturing image analysis researchers.",,pdf:https://www.nature.com/articles/s41598-019-48927-2.pdf; doi:https://doi.org/10.1038/s41598-019-48927-2; html:https://europepmc.org/articles/PMC6713749; pdf:https://europepmc.org/articles/PMC6713749?pdf=render
+36384890,https://doi.org/10.1136/bmj-2022-071932,Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform.,"Zheng B, Green ACA, Tazare J, Curtis HJ, Fisher L, Nab L, Schultze A, Mahalingasivam V, Parker EPK, Hulme WJ, Bacon SCJ, DeVito NJ, Bates C, Evans D, Inglesby P, Drysdale H, Davy S, Cockburn J, Morton CE, Hickman G, Ward T, Smith RM, Parry J, Hester F, Harper S, Mehrkar A, Eggo RM, Walker AJ, Evans SJW, Douglas IJ, MacKenna B, Goldacre B, Tomlinson LA.",,BMJ (Clinical research ed.),2022,2022-11-16,Y,,,,"<h4>Objective</h4>To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19.<h4>Design</h4>Observational cohort study with the OpenSAFELY platform.<h4>Setting</h4>With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings.<h4>Participants</h4>Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.<h4>Interventions</h4>Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units.<h4>Main outcome measures</h4>Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment.<h4>Results</h4>Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England.<h4>Conclusions</h4>In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.",,pdf:https://www.bmj.com/content/bmj/379/bmj-2022-071932.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071932; html:https://europepmc.org/articles/PMC9667468
 36472984,https://doi.org/10.1371/journal.pmed.1004124,Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study.,"Chen S, Price AC, Cardinal RN, Moylett S, Kershenbaum AD, Fitzgerald J, Mueller C, Stewart R, O'Brien JT.",,PLoS medicine,2022,2022-12-06,Y,,,,"<h4>Background</h4>Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality than Alzheimer's disease (AD). The reasons for this are unclear, but antidementia drugs (including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit people with DLB and might improve outcomes. We investigated whether AChEIs and/or memantine were associated with reduced hospital admissions and mortality.<h4>Methods and findings</h4>We performed a retrospective cohort study of those diagnosed with DLB between 1 January 2005 and 31 December 2019, using data from electronic clinical records of secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million), as well as linked records from national Hospital Episode Statistics (HES) data. Eligible patients were those who started AChEIs or memantine within 3 months of their diagnosis (cases) and those who never used AChEIs or memantine (controls). Outcomes included admission, length of stay, and mortality. Cox proportional hazard and linear regression models were used. Of 592 patients with DLB, 219 never took AChEIs or memantine, 100 took AChEIs only, and 273 took both AChEIs and memantine. The cohorts were followed up for an average of 896 days, 981 days, and 1,004 days, respectively. There were no significant differences in the cohorts' baseline characteristics, except for socioeconomic status that was lower in patients who never took AChEIs or memantine (χ2 = 23.34, P = 0.003). After controlling for confounding by sociodemographic factors (age, sex, marital status, ethnicity, socioeconomic status), antipsychotic use, antidepressant use, cognitive status, physical comorbidity, anticholinergic burden, and global health performance, compared with patients who never took AChEIs or memantine, patients taking AChEIs only or taking both had a significantly lower risk of death (adjusted hazard ratio (HR) = 0.67, 95% CI = 0.48 to 0.93, p = 0.02; adjusted HR = 0.64, 95% CI = 0.50 to 0.83, P = 0.001, respectively). Those taking AChEIs or both AChEIs and memantine had significantly shorter periods of unplanned hospital admission for physical disorders (adjusted coefficient -13.48, 95% CI = [-26.87, -0.09], P = 0.049; adjusted coefficient -14.21, 95% CI = [-24.58, -3.85], P = 0.007, respectively), but no difference in length of stay for planned admissions for physical disorders, or for admissions for mental health disorders. No significant additional associations of memantine on admission, length of stay, and mortality were found (all P > 0.05). The main limitation was that this was a naturalistic study and possible confounds cannot be fully controlled, and there may be selection bias resulting from nonrandom prescription behaviour in clinical practice. However, we mimicked the intention-to-treat design of clinical trials, and the majority of baseline characters were balanced between cohorts. In addition, our series of sensitivity analyses confirmed the consistency of our results.<h4>Conclusion</h4>In this study, we observed that use of AChEIs with or without memantine in DLB was associated with shorter duration of hospital admissions and decreased risk of mortality. Although our study was naturalistic, it supports further the use of AChEIs in DLB.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004124&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004124; html:https://europepmc.org/articles/PMC9725132; pdf:https://europepmc.org/articles/PMC9725132?pdf=render
 33801002,https://doi.org/10.3390/s21062190,A Novel Coupled Reaction-Diffusion System for Explainable Gene Expression Profiling. ,"Farouq MW, Boulila W, Hussain Z, Rashid A, Shah M, Hussain S, Ng N, Ng D, Hanif H, Shaikh MG, Sheikh A, Hussain A.",,"Sensors (Basel, Switzerland)",2021,2021-03-21,Y,,,,"Machine learning (ML)-based algorithms are playing an important role in cancer diagnosis and are increasingly being used to aid clinical decision-making. However, these commonly operate as 'black boxes' and it is unclear how decisions are derived. Recently, techniques have been applied to help us understand how specific ML models work and explain the rational for outputs. This study aims to determine why a given type of cancer has a certain phenotypic characteristic. Cancer results in cellular dysregulation and a thorough consideration of cancer regulators is required. This would increase our understanding of the nature of the disease and help discover more effective diagnostic, prognostic, and treatment methods for a variety of cancer types and stages. Our study proposes a novel explainable analysis of potential biomarkers denoting tumorigenesis in non-small cell lung cancer. A number of these biomarkers are known to appear following various treatment pathways. An enhanced analysis is enabled through a novel mathematical formulation for the regulators of mRNA, the regulators of ncRNA, and the coupled mRNA-ncRNA regulators. Temporal gene expression profiles are approximated in a two-dimensional spatial domain for the transition states before converging to the stationary state, using a system comprised of coupled-reaction partial differential equations. Simulation experiments demonstrate that the proposed mathematical gene-expression profile represents a best fit for the population abundance of these oncogenes. In future, our proposed solution can lead to the development of alternative interpretable approaches, through the application of ML models to discover unknown dynamics in gene regulatory systems.",,pdf:https://www.mdpi.com/1424-8220/21/6/2190/pdf?version=1616388230; doi:https://doi.org/10.3390/s21062190; html:https://europepmc.org/articles/PMC8003942; pdf:https://europepmc.org/articles/PMC8003942?pdf=render
 33495722,https://doi.org/10.1109/access.2021.3050524,Remote Assessment of Parkinson's Disease Symptom Severity Using the Simulated Cellular Mobile Telephone Network.,"Tsanas A, Little MA, Ramig LO.",,"IEEE access : practical innovations, open solutions",2021,2021-01-11,Y,Telemedicine; Parkinson’s Disease; Decision Support Tool; Nonlinear Speech Signal Processing,,,"Telemonitoring of Parkinson's Disease (PD) has attracted considerable research interest because of its potential to make a lasting, positive impact on the life of patients and their carers. Purpose-built devices have been developed that record various signals which can be associated with average PD symptom severity, as quantified on standard clinical metrics such as the Unified Parkinson's Disease Rating Scale (UPDRS). Speech signals are particularly promising in this regard, because they can be easily recorded without the use of expensive, dedicated hardware. Previous studies have demonstrated replication of UPDRS to within less than 2 points of a clinical raters' assessment of symptom severity, using high-quality speech signals collected using dedicated telemonitoring hardware. Here, we investigate the potential of using the standard voice-over-GSM (2G) or UMTS (3G) cellular mobile telephone networks for PD telemonitoring, networks that, together, have greater than 5 billion subscribers worldwide. We test the robustness of this approach using a simulated noisy mobile communication network over which speech signals are transmitted, and approximately 6000 recordings from 42 PD subjects. We show that UPDRS can be estimated to within less than 3.5 points difference from the clinical raters' assessment, which is clinically useful given that the inter-rater variability for UPDRS can be as high as 4-5 UPDRS points. This provides compelling evidence that the existing voice telephone network has potential towards facilitating inexpensive, mass-scale PD symptom telemonitoring applications.",,pdf:https://ieeexplore.ieee.org/ielx7/6287639/9312710/09319241.pdf; doi:https://doi.org/10.1109/ACCESS.2021.3050524; html:https://europepmc.org/articles/PMC7821632; pdf:https://europepmc.org/articles/PMC7821632?pdf=render
@@ -485,8 +485,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development:
 35067242,https://doi.org/10.1192/bjp.2021.219,Prediction models in first-episode psychosis: systematic review and critical appraisal.,"Lee R, Leighton SP, Thomas L, Gkoutos GV, Wood SJ, Fenton SH, Deligianni F, Cavanagh J, Mallikarjun PK.",,The British journal of psychiatry : the journal of mental science,2022,2022-01-24,N,Prediction; Schizophrenia; Psychotic Disorders; Outcome Studies; Precision Medicine,,,"<h4>Background</h4>People presenting with first-episode psychosis (FEP) have heterogenous outcomes. More than 40% fail to achieve symptomatic remission. Accurate prediction of individual outcome in FEP could facilitate early intervention to change the clinical trajectory and improve prognosis.<h4>Aims</h4>We aim to systematically review evidence for prediction models developed for predicting poor outcome in FEP.<h4>Method</h4>A protocol for this study was published on the International Prospective Register of Systematic Reviews, registration number CRD42019156897. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, we systematically searched six databases from inception to 28 January 2021. We used the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and the Prediction Model Risk of Bias Assessment Tool to extract and appraise the outcome prediction models. We considered study characteristics, methodology and model performance.<h4>Results</h4>Thirteen studies reporting 31 prediction models across a range of clinical outcomes met criteria for inclusion. Eleven studies used logistic regression with clinical and sociodemographic predictor variables. Just two studies were found to be at low risk of bias. Methodological limitations identified included a lack of appropriate validation, small sample sizes, poor handling of missing data and inadequate reporting of calibration and discrimination measures. To date, no model has been applied to clinical practice.<h4>Conclusions</h4>Future prediction studies in psychosis should prioritise methodological rigour and external validation in larger samples. The potential for prediction modelling in FEP is yet to be realised.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/597A326F6B5258801F61CA211322F96F/S0007125021002191a.pdf/div-class-title-prediction-models-in-first-episode-psychosis-systematic-review-and-critical-appraisal-div.pdf; doi:https://doi.org/10.1192/bjp.2021.219; html:https://europepmc.org/articles/PMC7612705; pdf:https://europepmc.org/articles/PMC7612705?pdf=render; doi:https://doi.org/10.1192/bjp.2021.219
 34518162,https://doi.org/10.1136/bjophthalmol-2021-319383,Predicting the immediate impact of national lockdown on neovascular age-related macular degeneration and associated visual morbidity: an INSIGHT Health Data Research Hub for Eye Health report.,"Mollan SP, Fu DJ, Chuo CY, Gannon JG, Lee WH, Hopkins JJ, Hughes C, Denniston AK, Keane PA, Cantrell R.",,The British journal of ophthalmology,2023,2021-09-13,Y,Clinical Trial; Neovascularisation; Covid-19,,,"<h4>Objective</h4>Predicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2.<h4>Methods and analysis</h4>This retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238).<h4>Results</h4>At our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%-7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%-7.8%) after 12 months without treatment.<h4>Conclusions</h4>Here, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments.<h4>Trial registration number</h4>NCT00056836.",,pdf:https://discovery.ucl.ac.uk/10164981/1/267.full.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319383; html:https://europepmc.org/articles/PMC9887382; pdf:https://europepmc.org/articles/PMC9887382?pdf=render
 34431993,https://doi.org/10.1093/eurheartj/ehab581,Risk factors for type 1 and type 2 myocardial infarction.,"Wereski R, Kimenai DM, Bularga A, Taggart C, Lowe DJ, Mills NL, Chapman AR.",,European heart journal,2022,2022-01-01,Y,Myocardial infarction; acute coronary syndrome; type 2; risk factors; Universal Definition,,,"<h4>Aims</h4>Whilst the risk factors for type 1 myocardial infarction due to atherosclerotic plaque rupture and thrombosis are established, our understanding of the factors that predispose to type 2 myocardial infarction during acute illness is still emerging. Our aim was to evaluate and compare the risk factors for type 1 and type 2 myocardial infarction.<h4>Methods and results</h4>We conducted a secondary analysis of a multi-centre randomized trial population of 48 282 consecutive patients attending hospital with suspected acute coronary syndrome. The diagnosis of myocardial infarction during the index presentation and all subsequent reattendances was adjudicated according to the Universal Definition of Myocardial Infarction. Cox regression was used to identify predictors of future type 1 and type 2 myocardial infarction during a 1-year follow-up period. Within 1 year, 1331 patients had a subsequent myocardial infarction, with 924 and 407 adjudicated as type 1 and type 2 myocardial infarction, respectively. Risk factors for type 1 and type 2 myocardial infarction were similar, with age, hyperlipidaemia, diabetes, abnormal renal function, and known coronary disease predictors for both (P < 0.05 for all). Whilst women accounted for a greater proportion of patients with type 2 as compared to type 1 myocardial infarction, after adjustment for other risk factors, sex was not a predictor of type 2 myocardial events [adjusted hazard ratio (aHR) 0.82, 95% confidence interval (CI) 0.66-1.01]. The strongest predictor of type 2 myocardial infarction was a prior history of type 2 events (aHR 6.18, 95% CI 4.70-8.12).<h4>Conclusions</h4>Risk factors for coronary disease that are associated with type 1 myocardial infarction are also important predictors of type 2 events during acute illness. Treatment of these risk factors may reduce future risk of both type 1 and type 2 myocardial infarction.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/2/127/42182731/ehab581.pdf; doi:https://doi.org/10.1093/eurheartj/ehab581; html:https://europepmc.org/articles/PMC8757580; pdf:https://europepmc.org/articles/PMC8757580?pdf=render
-37550086,https://doi.org/10.1136/bmjment-2023-300762,Associations between air pollution and mental health service use in dementia: a retrospective cohort study.,"Ronaldson A, Stewart R, Mueller C, Das-Munshi J, Newbury JB, Mudway IS, Broadbent M, Fisher HL, Beevers S, Dajnak D, Hotopf M, Hatch SL, Bakolis I.",,BMJ mental health,2023,2023-07-01,Y,Psychiatry; Adult Psychiatry; Delirium & Cognitive Disorders,,,"<h4>Background</h4>Little is known about the role of air pollution in how people with dementia use mental health services.<h4>Objective</h4>We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia.<h4>Methods</h4>In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO<sub>2</sub>) and particulate matter (PM<sub>2.5</sub> and PM<sub>10</sub>) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models.<h4>Findings</h4>In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO<sub>2</sub>: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11 to 1.45, p<0.001). Dose-response patterns between PM<sub>2.5</sub> and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO<sub>2</sub> levels were linked with poor functional status, but not cognitive function.<h4>Conclusions</h4>Residential air pollution exposure is associated with increased CMHT usage among people with dementia.<h4>Clinical implications</h4>Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.",,doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?pdf=render
 34164795,https://doi.org/10.1007/s40801-021-00256-5,Associations Between Anticholinergic Medication Exposure and Adverse Health Outcomes in Older People with Frailty: A Systematic Review and Meta-analysis.,"Mehdizadeh D, Hale M, Todd O, Zaman H, Marques I, Petty D, Alldred DP, Johnson O, Faisal M, Gardner P, Clegg A.",,Drugs - real world outcomes,2021,2021-06-23,Y,,,,"<h4>Introduction</h4>There are robust associations between use of anticholinergic medicines and adverse effects in older people. However, the nature of these associations for older people living with frailty is yet to be established.<h4>Objectives</h4>The aims were to identify and investigate associations between anticholinergics and adverse outcomes in older people living with frailty and to investigate whether exposure is associated with greater risks according to frailty status.<h4>Methods</h4>MEDLINE, CINAHL, EMBASE, Cochrane Database of Systematic Reviews, Web of Science and PsycINFO were searched to 1 August 2019. Observational studies reporting associations between anticholinergics and outcomes in older adults (average age ≥ 65 years) that reported frailty using validated measures were included. Primary outcomes were physical impairment, cognitive dysfunction, and change in frailty status. Risk of bias was evaluated using the Cochrane Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was undertaken where appropriate.<h4>Results</h4>Thirteen studies (21,516 participants) were included (ten community, one residential aged-care facility and two hospital studies). Observed associations included reduced ability for chair standing, slower gait speeds, poorer physical performance, increased risk of falls and mortality. Conflicting results were reported for grip strength, timed up and go test, cognition and activities of daily living. No associations were observed for transitions between frailty states, psychological wellbeing or benzodiazepine-related adverse reactions. There was no clear evidence of differences in risks according to frailty status.<h4>Conclusions</h4>Anticholinergics are associated with adverse outcomes in older people living with frailty; however, the literature has significant methodological limitations. There is insufficient evidence to suggest greater risks based on frailty, and there is an urgent need to evaluate this further in well-designed studies stratifying by frailty.",,pdf:https://link.springer.com/content/pdf/10.1007/s40801-021-00256-5.pdf; doi:https://doi.org/10.1007/s40801-021-00256-5; html:https://europepmc.org/articles/PMC8605959; pdf:https://europepmc.org/articles/PMC8605959?pdf=render
+37550086,https://doi.org/10.1136/bmjment-2023-300762,Associations between air pollution and mental health service use in dementia: a retrospective cohort study.,"Ronaldson A, Stewart R, Mueller C, Das-Munshi J, Newbury JB, Mudway IS, Broadbent M, Fisher HL, Beevers S, Dajnak D, Hotopf M, Hatch SL, Bakolis I.",,BMJ mental health,2023,2023-07-01,Y,Psychiatry; Adult Psychiatry; Delirium & Cognitive Disorders,,,"<h4>Background</h4>Little is known about the role of air pollution in how people with dementia use mental health services.<h4>Objective</h4>We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia.<h4>Methods</h4>In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO<sub>2</sub>) and particulate matter (PM<sub>2.5</sub> and PM<sub>10</sub>) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models.<h4>Findings</h4>In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO<sub>2</sub>: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11 to 1.45, p<0.001). Dose-response patterns between PM<sub>2.5</sub> and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO<sub>2</sub> levels were linked with poor functional status, but not cognitive function.<h4>Conclusions</h4>Residential air pollution exposure is associated with increased CMHT usage among people with dementia.<h4>Clinical implications</h4>Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.",,doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?pdf=render
 36949447,https://doi.org/10.1186/s12889-023-15345-z,Inequalities in colorectal cancer screening uptake in Wales: an examination of the impact of the temporary suspension of the screening programme during the COVID-19 pandemic.,"Bright D, Hillier S, Song J, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,BMC public health,2023,2023-03-22,Y,Colorectal Cancer; Inequalities; Bowel; Ethnicity; Cancer Screening; Covid-19,,,"<h4>Background</h4>Response to the early stages of the COVID-19 pandemic resulted in the temporary disruption of cancer screening in the UK, and strong public messaging to stay safe and to protect NHS capacity. Following reintroduction in services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who may benefit from tailored interventions.<h4>Methods</h4>Records within the BSW were linked to electronic health records (EHR) and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank. Ethnic group was obtained from a linked data method available within SAIL. We examined uptake for the first 3 months of invitations (August to October) following the reintroduction of BSW programme in 2020, compared to the same period in the preceding 3 years. Uptake was measured across a 6 month follow-up period. Logistic models were conducted to analyse variations in uptake by sex, age group, income deprivation quintile, urban/rural location, ethnic group, and clinically extremely vulnerable (CEV) status in each period; and to compare uptake within sociodemographic groups between different periods.<h4>Results</h4>Uptake during August to October 2020 (period 2020/21; 60.4%) declined compared to the same period in 2019/20 (62.7%) but remained above the 60% Welsh standard. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Compared to the pre-pandemic period in 2019/20, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most income deprived group. Uptake continues to be lower in males, younger individuals, people living in the most income deprived areas and those of Asian and unknown ethnic backgrounds.<h4>Conclusion</h4>Our findings are encouraging with overall uptake achieving the 60% Welsh standard during the first three months after the programme restarted in 2020 despite the disruption. Inequalities did not worsen after the programme resumed activities but variations in CRC screening in Wales associated with sex, age, deprivation and ethnic group remain. This needs to be considered in targeting strategies to improve uptake and informed choice in CRC screening to avoid exacerbating disparities in CRC outcomes as screening services recover from the pandemic.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-15345-z; doi:https://doi.org/10.1186/s12889-023-15345-z; html:https://europepmc.org/articles/PMC10031708; pdf:https://europepmc.org/articles/PMC10031708?pdf=render
 35958702,https://doi.org/10.1007/s40653-021-00433-2,The Secondary Harms of Parental Substance Use on Children's Educational Outcomes: A Review.,Lowthian E.,,Journal of child & adolescent trauma,2022,2022-01-14,Y,Drugs; Review; Alcohol; Education; Parental Substance Use,,,"Parental substance use, that is alcohol and illicit drugs, can have a deleterious impact on child health and wellbeing. An area that can be affected by parental substance use is the educational outcomes of children. Current reviews of the literature in the field of parental substance use and children's educational outcomes have only identified a small number of studies, and most focus on children's educational attainment. To grasp the available literature, the method from Arksey and O'Malley (2005) was used to identify literature. Studies were included if they were empirical, after 1950, and focused on children's school or educational outcomes. From this, 51 empirical studies were identified which examined the relationship between parental alcohol and illicit drug use on children's educational outcomes. Five main themes emerged which included attainment, behavior and adjustment, attendance, school enjoyment and satisfaction, academic self-concept, along with other miscellaneous outcomes. This paper highlights the main findings of the studies, the gaps in the current literature, and the challenges presented. Recommendations are made for further research and interventions in the areas of parental substance use and child educational outcomes specifically, but also for broader areas of adversity and child wellbeing.",,pdf:https://link.springer.com/content/pdf/10.1007/s40653-021-00433-2.pdf; doi:https://doi.org/10.1007/s40653-021-00433-2; html:https://europepmc.org/articles/PMC9360289; pdf:https://europepmc.org/articles/PMC9360289?pdf=render
 37004203,https://doi.org/10.1093/qjmed/hcad050,Classifying the unclassifiable-a Delphi study to reach consensus on the fibrotic nature of diseases.,"Massen GM, Allen RJ, Leavy OC, Selby NM, Aithal GP, Oliver N, Parfrey H, Wain LV, Jenkins G, Stewart I, Quint JK.",,QJM : monthly journal of the Association of Physicians,2023,2023-06-01,Y,,,,"<h4>Background</h4>Traditionally, clinical research has focused on individual fibrotic diseases or fibrosis in a particular organ. However, it is possible for people to have multiple fibrotic diseases. While multi-organ fibrosis may suggest shared pathogenic mechanisms, yet there is no consensus on what constitutes a fibrotic disease and therefore fibrotic multimorbidity.<h4>Aim</h4>A Delphi study was performed to reach consensus on which diseases may be described as fibrotic.<h4>Methods</h4>Participants were asked to rate a list of diseases, sub-grouped according to eight body regions, as 'fibrotic manifestation always present', 'can develop fibrotic manifestations', 'associated with fibrotic manifestations' or 'not fibrotic nor associated'. Classifications of 'fibrotic manifestation always present' and 'can develop fibrotic manifestations' were merged and termed 'fibrotic'. Clinical consensus was defined according to the interquartile range, having met a minimum number of responses. Clinical agreement was used for classification where diseases did not meet the minimum number of responses (required for consensus measure), were only classified if there was 100% consensus on disease classification.<h4>Results</h4>After consulting experts, searching the literature and coding dictionaries, a total of 323 non-overlapping diseases which might be considered fibrotic were identified; 92 clinical specialists responded to the first round of the survey. Over three survey rounds, 240 diseases were categorized as fibrotic via clinical consensus and 25 additional diseases through clinical agreement.<h4>Conclusion</h4>Using a robust methodology, an extensive list of diseases was classified. The findings lay the foundations for studies estimating the burden of fibrotic multimorbidity, as well as investigating shared mechanisms and therapies.",,pdf:https://academic.oup.com/qjmed/advance-article-pdf/doi/10.1093/qjmed/hcad050/50051055/hcad050.pdf; doi:https://doi.org/10.1093/qjmed/hcad050; html:https://europepmc.org/articles/PMC10250078; pdf:https://europepmc.org/articles/PMC10250078?pdf=render
@@ -499,8 +499,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development:
 29992526,https://doi.org/10.1007/s11906-018-0877-8,An Overview of Metabolic Phenotyping in Blood Pressure Research.,"Tzoulaki I, Iliou A, Mikros E, Elliott P.",,Current hypertension reports,2018,2018-07-10,Y,Hypertension; Blood pressure; Metabolomics; Microbiome; Epidemiological Studies; Metabolic Phenotyping,,,"<h4>Purpose of the review</h4>This review presents the analytical techniques, processing and analytical steps used in metabolomics phenotyping studies, as well as the main results from epidemiological studies on the associations between metabolites and high blood pressure.<h4>Recent findings</h4>A variety of metabolomic approaches have been applied to a range of epidemiological studies to uncover the pathophysiology of high blood pressure. Several pathways have been suggested in relation to blood pressure including the possible role of the gut microflora, inflammatory, oxidative stress, and lipid pathways. Metabolic changes have also been identified associated with blood pressure lowering effects of diets high in fruits and vegetables and low in meat intake. However, the current body of literature on metabolic profiling and blood pressure is still in its infancy, not fully consistent and requires careful interpretation. Metabolic phenotyping is a promising approach to uncover metabolic pathways associated with high blood pressure and throw light into the complex pathophysiology of hypertension.",,pdf:https://link.springer.com/content/pdf/10.1007%2Fs11906-018-0877-8.pdf; doi:https://doi.org/10.1007/s11906-018-0877-8; html:https://europepmc.org/articles/PMC6061189; pdf:https://europepmc.org/articles/PMC6061189?pdf=render
 37398988,https://doi.org/10.1007/s40258-023-00821-9,Correction to: The False Economy of Seeking to Eliminate Delayed Transfers of Care: Some Lessons from Queueing Theory.,"Wood RM, Harper AL, Onen-Dumlu Z, Forte PG, Pitt M, Vasilakis C.",,Applied health economics and health policy,2023,2023-09-01,Y,,,,,,pdf:https://link.springer.com/content/pdf/10.1007/s40258-023-00821-9.pdf; doi:https://doi.org/10.1007/s40258-023-00821-9; html:https://europepmc.org/articles/PMC10403424; pdf:https://europepmc.org/articles/PMC10403424?pdf=render
 34071236,https://doi.org/10.3390/ijms22115763,"Integration of the Microbiome, Metabolome and Transcriptomics Data Identified Novel Metabolic Pathway Regulation in Colorectal Cancer. ","Bisht V, Nash K, Xu Y, Agarwal P, Bosch S, Gkoutos GV, Acharjee A.",,International journal of molecular sciences,2021,2021-05-28,Y,,,,"Integrative multiomics data analysis provides a unique opportunity for the mechanistic understanding of colorectal cancer (CRC) in addition to the identification of potential novel therapeutic targets. In this study, we used public omics data sets to investigate potential associations between microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing datasets. We identified multiple potential interactions, for example 5-aminovalerate interacting with Adlercreutzia; cholesteryl ester interacting with bacterial genera Staphylococcus, Blautia and Roseburia. Using public single cell and bulk RNA sequencing, we identified 17 overlapping genes involved in epithelial cell pathways, with particular significance of the oxidative phosphorylation pathway and the ACAT1 gene that indirectly regulates the esterification of cholesterol. These findings demonstrate that the integration of multiomics data sets from diverse populations can help us in untangling the colorectal cancer pathogenesis as well as postulate the disease pathology mechanisms and therapeutic targets.",,pdf:https://www.mdpi.com/1422-0067/22/11/5763/pdf?version=1622194941; doi:https://doi.org/10.3390/ijms22115763; html:https://europepmc.org/articles/PMC8198673; pdf:https://europepmc.org/articles/PMC8198673?pdf=render
-37678576,https://doi.org/10.1016/j.jaci.2023.08.025,E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.,"Jasper AE, Faniyi AA, Davis LC, Grudzinska FS, Halston R, Hazeldine J, Parekh D, Sapey E, Thickett DR, Scott A.",,The Journal of allergy and clinical immunology,2023,2023-09-05,N,Neutrophils; Phagocytosis; Oxidative burst; Nicotine; Netosis; E-cigarettes,,,"<h4>Background</h4>Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.<h4>Objective</h4>We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.<h4>Methods</h4>Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed.<h4>Results</h4>Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls.<h4>Conclusions</h4>The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.",,doi:https://doi.org/10.1016/j.jaci.2023.08.025
 35954935,https://doi.org/10.3390/ijerph19159578,Comparing Peak Burn Injury Times and Characteristics in Australia and New Zealand.,"Hong R, Perkins M, Gabbe BJ, Tracy LM.",,International journal of environmental research and public health,2022,2022-08-04,Y,Burns; Cooking; Registry; scald; Flame,,,"Burns are a leading cause of morbidity and mortality worldwide. Understanding when and how burns occur, as well as the differences between countries, would aid prevention efforts. A review of burn injuries occurring between July 2009 and June 2021 was undertaken using data from the Burns Registry of Australia and New Zealand. Peak injury times were identified on a country-by-country basis. Variations in demographic and injury event profiles between countries were compared using descriptive statistics. There were 26,925 admissions recorded across the two countries (23,323 for Australia; 3602 for New Zealand). The greatest number of injuries occurred between 6 PM to 7 PM in Australia (1871, 8.0%) and between 5 PM to 6 PM in New Zealand (280, 7.8%). In both countries, scalds accounted for the greatest proportion of injuries during peak times (988, 45.8%), but a greater proportion of young children (under three years) sustained burns during New Zealand's peak times. The number of burn injuries associated with the preparation and/or consumption of food offers an opportunity for a targeted prevention program that may yield benefits across the two countries. Age- and mechanism-related differences in the profile of burn-injured patients need to be considered when developing and implementing such a program.",,pdf:https://www.mdpi.com/1660-4601/19/15/9578/pdf?version=1659598966; doi:https://doi.org/10.3390/ijerph19159578; html:https://europepmc.org/articles/PMC9368485; pdf:https://europepmc.org/articles/PMC9368485?pdf=render
+37678576,https://doi.org/10.1016/j.jaci.2023.08.025,E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.,"Jasper AE, Faniyi AA, Davis LC, Grudzinska FS, Halston R, Hazeldine J, Parekh D, Sapey E, Thickett DR, Scott A.",,The Journal of allergy and clinical immunology,2023,2023-09-05,N,Neutrophils; Phagocytosis; Oxidative burst; Nicotine; Netosis; E-cigarettes,,,"<h4>Background</h4>Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.<h4>Objective</h4>We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.<h4>Methods</h4>Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed.<h4>Results</h4>Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls.<h4>Conclusions</h4>The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.",,doi:https://doi.org/10.1016/j.jaci.2023.08.025
 35962974,https://doi.org/10.1093/ije/dyac158,Association between household composition and severe COVID-19 outcomes in older people by ethnicity: an observational cohort study using the OpenSAFELY platform.,"Wing K, Grint DJ, Mathur R, Gibbs HP, Hickman G, Nightingale E, Schultze A, Forbes H, Nafilyan V, Bhaskaran K, Williamson E, House T, Pellis L, Herrett E, Gautam N, Curtis HJ, Rentsch CT, Wong AYS, MacKenna B, Mehrkar A, Bacon S, Douglas IJ, Evans SJW, Tomlinson L, Goldacre B, Eggo RM.",,International journal of epidemiology,2022,2022-12-01,Y,Household; Older People; Ethnicity; Deprivation; Comorbidities; Multigenerational; Population-level; Covid-19; Opensafely,,,"<h4>Background</h4>Ethnic differences in the risk of severe COVID-19 may be linked to household composition. We quantified the association between household composition and risk of severe COVID-19 by ethnicity for older individuals.<h4>Methods</h4>With the approval of NHS England, we analysed ethnic differences in the association between household composition and severe COVID-19 in people aged 67 or over in England. We defined households by number of age-based generations living together, and used multivariable Cox regression stratified by location and wave of the pandemic and accounted for age, sex, comorbidities, smoking, obesity, housing density and deprivation. We included 2 692 223 people over 67 years in Wave 1 (1 February 2020-31 August 2020) and 2 731 427 in Wave 2 (1 September 2020-31 January 2021).<h4>Results</h4>Multigenerational living was associated with increased risk of severe COVID-19 for White and South Asian older people in both waves [e.g. Wave 2, 67+ living with three other generations vs 67+-year-olds only: White hazard ratio (HR) 1.61 95% CI 1.38-1.87, South Asian HR 1.76 95% CI 1.48-2.10], with a trend for increased risks of severe COVID-19 with increasing generations in Wave 2. There was also an increased risk of severe COVID-19 in Wave 1 associated with living alone for White (HR 1.35 95% CI 1.30-1.41), South Asian (HR 1.47 95% CI 1.18-1.84) and Other (HR 1.72 95% CI 0.99-2.97) ethnicities, an effect that persisted for White older people in Wave 2.<h4>Conclusions</h4>Both multigenerational living and living alone were associated with severe COVID-19 in older adults. Older South Asian people are over-represented within multigenerational households in England, especially in the most deprived settings, whereas a substantial proportion of White older people live alone. The number of generations in a household, number of occupants, ethnicity and deprivation status are important considerations in the continued roll-out of COVID-19 vaccination and targeting of interventions for future pandemics.",,pdf:https://academic.oup.com/ije/article-pdf/51/6/1745/47882630/dyac158.pdf; doi:https://doi.org/10.1093/ije/dyac158; html:https://europepmc.org/articles/PMC9384728; pdf:https://europepmc.org/articles/PMC9384728?pdf=render
 33739254,https://doi.org/10.2807/1560-7917.es.2021.26.11.2100256,"Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February.","Grint DJ, Wing K, Williamson E, McDonald HI, Bhaskaran K, Evans D, Evans SJ, Walker AJ, Hickman G, Nightingale E, Schultze A, Rentsch CT, Bates C, Cockburn J, Curtis HJ, Morton CE, Bacon S, Davy S, Wong AY, Mehrkar A, Tomlinson L, Douglas IJ, Mathur R, Blomquist P, MacKenna B, Ingelsby P, Croker R, Parry J, Hester F, Harper S, DeVito NJ, Hulme W, Tazare J, Goldacre B, Smeeth L, Eggo RM.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-03-01,Y,Mortality; Coronavirus; Cfr; Case Fatality Risk; Covid-19; Sars-cov-2; Variant Of Concern,,,The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34-2.09; p < 0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date.,,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/11/eurosurv-26-11-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.11.2100256&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.11.2100256; html:https://europepmc.org/articles/PMC7976383; pdf:https://europepmc.org/articles/PMC7976383?pdf=render
 33082154,https://doi.org/10.1136/bmj.m3731,Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study.,"Clift AK, Coupland CAC, Keogh RH, Diaz-Ordaz K, Williamson E, Harrison EM, Hayward A, Hemingway H, Horby P, Mehta N, Benger J, Khunti K, Spiegelhalter D, Sheikh A, Valabhji J, Lyons RA, Robson J, Semple MG, Kee F, Johnson P, Jebb S, Williams T, Hippisley-Cox J.",,BMJ (Clinical research ed.),2020,2020-10-20,Y,,,,"<h4>Objective</h4>To derive and validate a risk prediction algorithm to estimate hospital admission and mortality outcomes from coronavirus disease 2019 (covid-19) in adults.<h4>Design</h4>Population based cohort study.<h4>Setting and participants</h4>QResearch database, comprising 1205 general practices in England with linkage to covid-19 test results, Hospital Episode Statistics, and death registry data. 6.08 million adults aged 19-100 years were included in the derivation dataset and 2.17 million in the validation dataset. The derivation and first validation cohort period was 24 January 2020 to 30 April 2020. The second temporal validation cohort covered the period 1 May 2020 to 30 June 2020.<h4>Main outcome measures</h4>The primary outcome was time to death from covid-19, defined as death due to confirmed or suspected covid-19 as per the death certification or death occurring in a person with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the period 24 January to 30 April 2020. The secondary outcome was time to hospital admission with confirmed SARS-CoV-2 infection. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance, including measures of discrimination and calibration, was evaluated in each validation time period.<h4>Results</h4>4384 deaths from covid-19 occurred in the derivation cohort during follow-up and 1722 in the first validation cohort period and 621 in the second validation cohort period. The final risk algorithms included age, ethnicity, deprivation, body mass index, and a range of comorbidities. The algorithm had good calibration in the first validation cohort. For deaths from covid-19 in men, it explained 73.1% (95% confidence interval 71.9% to 74.3%) of the variation in time to death (R<sup>2</sup>); the D statistic was 3.37 (95% confidence interval 3.27 to 3.47), and Harrell's C was 0.928 (0.919 to 0.938). Similar results were obtained for women, for both outcomes, and in both time periods. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths within 97 days was 75.7%. People in the top 20% of predicted risk of death accounted for 94% of all deaths from covid-19.<h4>Conclusion</h4>The QCOVID population based risk algorithm performed well, showing very high levels of discrimination for deaths and hospital admissions due to covid-19. The absolute risks presented, however, will change over time in line with the prevailing SARS-C0V-2 infection rate and the extent of social distancing measures in place, so they should be interpreted with caution. The model can be recalibrated for different time periods, however, and has the potential to be dynamically updated as the pandemic evolves.",,pdf:https://www.bmj.com/content/bmj/371/bmj.m3731.full.pdf; doi:https://doi.org/10.1136/bmj.m3731; html:https://europepmc.org/articles/PMC7574532; pdf:https://europepmc.org/articles/PMC7574532?pdf=render
@@ -524,11 +524,11 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development:
 31612961,https://doi.org/10.1093/nar/gkz895,GWAS Central: a comprehensive resource for the discovery and comparison of genotype and phenotype data from genome-wide association studies.,"Beck T, Shorter T, Brookes AJ.",,Nucleic acids research,2020,2020-01-01,Y,,,,"The GWAS Central resource provides a toolkit for integrative access and visualization of a uniquely extensive collection of genome-wide association study data, while ensuring safe open access to prevent research participant identification. GWAS Central is the world's most comprehensive openly accessible repository of summary-level GWAS association information, providing over 70 million P-values for over 3800 studies investigating over 1400 unique phenotypes. The database content comprises direct submissions received from GWAS authors and consortia, in addition to actively gathered data sets from various public sources. GWAS data are discoverable from the perspective of genetic markers, genes, genome regions or phenotypes, via graphical visualizations and detailed downloadable data reports. Tested genetic markers and relevant genomic features can be visually interrogated across up to sixteen multiple association data sets in a single view using the integrated genome browser. The semantic standardization of phenotype descriptions with Medical Subject Headings and the Human Phenotype Ontology allows the precise identification of genetic variants associated with diseases, phenotypes and traits of interest. Harmonization of the phenotype descriptions used across several GWAS-related resources has extended the phenotype search capabilities to enable cross-database study discovery using a range of ontologies. GWAS Central is updated regularly and available at https://www.gwascentral.org.",,pdf:https://academic.oup.com/nar/article-pdf/48/D1/D933/31697824/gkz895.pdf; doi:https://doi.org/10.1093/nar/gkz895; html:https://europepmc.org/articles/PMC7145571; pdf:https://europepmc.org/articles/PMC7145571?pdf=render
 36329425,https://doi.org/10.1186/s12890-022-02189-3,Derivation of asthma severity from electronic prescription records using British thoracic society treatment steps.,"Tibble H, Sheikh A, Tsanas A.",,BMC pulmonary medicine,2022,2022-11-03,Y,Asthma; Pharmacotherapy; Severity; Pharmacoepidemiology; Electronic Health Records; Treatment Guidelines,,,"<h4>Background</h4>Asthma severity is typically assessed through a retrospective assessment of the treatment required to control symptoms and to prevent exacerbations. The joint British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) guidelines encourage a stepwise approach to pharmacotherapy, and as such, current treatment step can be considered as a severity categorisation proxy. Briefly, the steps for adults can be summarised as: no controller therapy (Step 0), low-strength Inhaled Corticosteroids (ICS; Step 1), ICS plus Long-Acting Beta-2 Agonist (LABA; Step 2), medium-dose ICS + LABA (Step 3), and finally either an increase in strength or additional therapies (Step 4). This study aimed to investigate how BTS/SIGN Steps can be estimated from across a large cohort using electronic prescription records, and to describe the incidence of each BTS/SIGN Step in a general population.<h4>Methods</h4>There were 41,433,707 prescriptions, for 671,304 individuals, in the Asthma Learning Health System Scottish cohort, between 1/2009 and 3/2017. Days on which an individual had a prescription for at least one asthma controller (preventer) medication were labelled prescription events. A rule-based algorithm was developed for extracting the strength and volume of medication instructed to be taken daily from free-text data fields. Asthma treatment regimens were categorised by the combination of medications prescribed in the 120 days preceding any prescription event and categorised into BTS/SIGN treatment steps.<h4>Results</h4>Almost 4.5 million ALHS prescriptions were for asthma controllers. 26% of prescription events had no inhaled corticosteroid prescriptions in the preceding 120 days (Step 0), 16% were assigned to BTS/SIGN Step 1, 7% to Step 2, 21% to Step 3, and 30% to Step 4. The median days spent on a treatment step before a step-down in treatment was 297 days, whereas a step-up only took a median of 134 days.<h4>Conclusion</h4>We developed a reproducible methodology enabling researchers to estimate BTS/SIGN asthma treatment steps in population health studies, providing valuable insights into population and patient-specific trajectories, towards improving the management of asthma.",,pdf:https://bmcpulmmed.biomedcentral.com/counter/pdf/10.1186/s12890-022-02189-3; doi:https://doi.org/10.1186/s12890-022-02189-3; html:https://europepmc.org/articles/PMC9635147; pdf:https://europepmc.org/articles/PMC9635147?pdf=render
 36073628,https://doi.org/10.1161/jaha.122.026432,Differential Patterns and Outcomes of 20.6 Million Cardiovascular Emergency Department Encounters for Men and Women in the United States.,"Raisi-Estabragh Z, Kobo O, Elbadawi A, Velagapudi P, Sharma G, Bullock-Palmer RP, Petersen SE, Mehta LS, Ullah W, Roguin A, Sun LY, Mamas MA.",,Journal of the American Heart Association,2022,2022-09-08,Y,Men; Essential hypertension; Atrial fibrillation; Stroke; Women; Sex characteristics; United States,,,"Background We describe sex-differential disease patterns and outcomes of >20.6 million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54-78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, atrial fibrillation/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke. Men were more likely to present with acute myocardial infarction or cardiac arrest. In logistic regression models adjusted for baseline covariates, compared with men, women with intracranial hemorrhage had higher risk of hospitalization and death. Women presenting with pulmonary embolism or deep vein thrombosis were less likely to be hospitalized. Women with aortic aneurysm/dissection had higher odds of hospitalization and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, atrial fibrillation/flutter, acute myocardial infarction, or cardiac arrest. Conclusions In this large nationally representative sample of cardiovascular emergency department presentations, we demonstrate significant sex differences in disease distribution, hospitalization, and death.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.026432; doi:https://doi.org/10.1161/JAHA.122.026432; html:https://europepmc.org/articles/PMC9673731; pdf:https://europepmc.org/articles/PMC9673731?pdf=render
-37080566,https://doi.org/10.1183/13993003.01720-2022,Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.,"Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Moisés J, Peché R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.",,The European respiratory journal,2023,2023-05-18,Y,,,,"<h4>Background</h4>Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.<h4>Methods</h4>The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.<h4>Results</h4>In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.<h4>Conclusion</h4>A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.",,pdf:https://erj.ersjournals.com/content/erj/early/2023/03/15/13993003.01720-2022.full.pdf; doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render
 33200120,https://doi.org/10.1016/j.eclinm.2020.100630,Ethnicity and clinical outcomes in COVID-19: A systematic review and meta-analysis.,"Sze S, Pan D, Nevill CR, Gray LJ, Martin CA, Nazareth J, Minhas JS, Divall P, Khunti K, Abrams KR, Nellums LB, Pareek M.",,EClinicalMedicine,2020,2020-11-12,Y,Infection; Transmission; RACE; Death; Ethnicity; Outcome; Asian; Hispanic; Ethnic; Sars-cov-2; Covid-19 Black; Disporportionate; Itu Admission,,,"<h4>Background</h4>Patients from ethnic minority groups are disproportionately affected by Coronavirus disease (COVID-19). We performed a systematic review and meta-analysis to explore the relationship between ethnicity and clinical outcomes in COVID-19.<h4>Methods</h4>Databases (MEDLINE, EMBASE, PROSPERO, Cochrane library and <i>MedRxiv</i>) were searched up to 31st August 2020, for studies reporting COVID-19 data disaggregated by ethnicity. Outcomes were: risk of infection; intensive therapy unit (ITU) admission and death. PROSPERO ID: 180654.<h4>Findings</h4>18,728,893 patients from 50 studies were included; 26 were peer-reviewed; 42 were from the United States of America and 8 from the United Kingdom. Individuals from Black and Asian ethnicities had a higher risk of COVID-19 infection compared to White individuals. This was consistent in both the main analysis (pooled adjusted RR for Black: 2.02, 95% CI 1.67-2.44; pooled adjusted RR for Asian: 1.50, 95% CI 1.24-1.83) and sensitivity analyses examining peer-reviewed studies only (pooled adjusted RR for Black: 1.85, 95%CI: 1.46-2.35; pooled adjusted RR for Asian: 1.51, 95% CI 1.22-1.88). Individuals of Asian ethnicity may also be at higher risk of ITU admission (pooled adjusted RR 1.97 95% CI 1.34-2.89) (but no studies had yet been peer-reviewed) and death (pooled adjusted RR/HR 1.22 [0.99-1.50]).<h4>Interpretation</h4>Individuals of Black and Asian ethnicity are at increased risk of COVID-19 infection compared to White individuals; Asians may be at higher risk of ITU admission and death. These findings are of critical public health importance in informing interventions to reduce morbidity and mortality amongst ethnic minority groups.",,pdf:https://figshare.com/articles/journal_contribution/Ethnicity_and_clinical_outcomes_in_COVID-19_A_Systematic_Review_and_Meta-analysis/13147892/1/files/25502810.pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100630; html:https://europepmc.org/articles/PMC7658622; pdf:https://europepmc.org/articles/PMC7658622?pdf=render
+37080566,https://doi.org/10.1183/13993003.01720-2022,Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.,"Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Moisés J, Peché R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.",,The European respiratory journal,2023,2023-05-18,Y,,,,"<h4>Background</h4>Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.<h4>Methods</h4>The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.<h4>Results</h4>In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.<h4>Conclusion</h4>A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.",,pdf:https://erj.ersjournals.com/content/erj/early/2023/03/15/13993003.01720-2022.full.pdf; doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render
 36753492,https://doi.org/10.1371/journal.pone.0281466,Combinations of medicines in patients with polypharmacy aged 65-100 in primary care: Large variability in risks of adverse drug related and emergency hospital admissions.,"Fahmi A, Wong D, Walker L, Buchan I, Pirmohamed M, Sharma A, Cant H, Ashcroft DM, van Staa TP.",,PloS one,2023,2023-02-08,Y,,,,"<h4>Background</h4>Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.<h4>Methods</h4>We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.<h4>Results</h4>In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.<h4>Conclusions</h4>Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0281466&type=printable; doi:https://doi.org/10.1371/journal.pone.0281466; html:https://europepmc.org/articles/PMC9907844; pdf:https://europepmc.org/articles/PMC9907844?pdf=render
-PMC9645061,https://doi.org/,Using population-scale medication data to evaluate the impact of the COVID-19 pandemic on the usage of analgesics by cancer patients.,"Han J, Akbari A, Torabi F, Griffiths R, Lyons J, Rolles M, Arnold C, Huws D, Lawler M, Lyons R.",,International journal of population data science,,2022-11-25,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9645061; pdf:https://europepmc.org/articles/PMC9645061?pdf=render
 33185672,https://doi.org/10.1093/jamia/ocaa295,Ensemble learning for poor prognosis predictions: A case study on SARS-CoV-2.,"Wu H, Zhang H, Karwath A, Ibrahim Z, Shi T, Zhang X, Wang K, Sun J, Dhaliwal K, Bean D, Cardoso VR, Li K, Teo JT, Banerjee A, Gao-Smith F, Whitehouse T, Veenith T, Gkoutos GV, Wu X, Dobson R, Guthrie B.",,Journal of the American Medical Informatics Association : JAMIA,2021,2021-03-01,Y,Decision Support; Risk Prediction; Ensemble Learning; Covid-19; Model Synergy,,,"<h4>Objective</h4>Risk prediction models are widely used to inform evidence-based clinical decision making. However, few models developed from single cohorts can perform consistently well at population level where diverse prognoses exist (such as the SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] pandemic). This study aims at tackling this challenge by synergizing prediction models from the literature using ensemble learning.<h4>Materials and methods</h4>In this study, we selected and reimplemented 7 prediction models for COVID-19 (coronavirus disease 2019) that were derived from diverse cohorts and used different implementation techniques. A novel ensemble learning framework was proposed to synergize them for realizing personalized predictions for individual patients. Four diverse international cohorts (2 from the United Kingdom and 2 from China; N = 5394) were used to validate all 8 models on discrimination, calibration, and clinical usefulness.<h4>Results</h4>Results showed that individual prediction models could perform well on some cohorts while poorly on others. Conversely, the ensemble model achieved the best performances consistently on all metrics quantifying discrimination, calibration, and clinical usefulness. Performance disparities were observed in cohorts from the 2 countries: all models achieved better performances on the China cohorts.<h4>Discussion</h4>When individual models were learned from complementary cohorts, the synergized model had the potential to achieve better performances than any individual model. Results indicate that blood parameters and physiological measurements might have better predictive powers when collected early, which remains to be confirmed by further studies.<h4>Conclusions</h4>Combining a diverse set of individual prediction models, the ensemble method can synergize a robust and well-performing model by choosing the most competent ones for individual patients.",,pdf:https://academic.oup.com/jamia/article-pdf/28/4/791/41182395/ocaa295.pdf; doi:https://doi.org/10.1093/jamia/ocaa295; html:https://europepmc.org/articles/PMC7717299; pdf:https://europepmc.org/articles/PMC7717299?pdf=render
+PMC9645061,https://doi.org/,Using population-scale medication data to evaluate the impact of the COVID-19 pandemic on the usage of analgesics by cancer patients.,"Han J, Akbari A, Torabi F, Griffiths R, Lyons J, Rolles M, Arnold C, Huws D, Lawler M, Lyons R.",,International journal of population data science,,2022-11-25,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9645061; pdf:https://europepmc.org/articles/PMC9645061?pdf=render
 33152012,https://doi.org/10.1371/journal.pone.0241800,Effect of long-chain polyunsaturated fatty acids in infant formula on long-term cognitive function in childhood: A systematic review and meta-analysis of randomised controlled trials.,"Verfuerden ML, Dib S, Jerrim J, Fewtrell M, Gilbert RE.",,PloS one,2020,2020-11-05,Y,,,,<h4>Study registration</h4>PROSPERO registration numbers CRD42018105196 and CRD42018088868.,,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0241800&type=printable; doi:https://doi.org/10.1371/journal.pone.0241800; html:https://europepmc.org/articles/PMC7644261; pdf:https://europepmc.org/articles/PMC7644261?pdf=render
 37644002,https://doi.org/10.1038/s41467-023-40965-9,Neonatal and maternal outcomes following SARS-CoV-2 infection and COVID-19 vaccination: a population-based matched cohort study.,"Lindsay L, Calvert C, Shi T, Carruthers J, Denny C, Donaghy J, Hopcroft LEM, Hopkins L, Goulding A, McLaughlin T, Moore E, Taylor B, Bhaskaran K, Katikireddi SV, McCabe R, McCowan C, Simpson CR, Robertson C, Sheikh A, Wood R, Stock SJ.",,Nature communications,2023,2023-08-29,Y,,,,"Understanding the impact of SARS-CoV-2 infection and COVID-19 vaccination in pregnancy on neonatal and maternal outcomes informs clinical decision-making. Here we report a national, population-based, matched cohort study to investigate associations between SARS-CoV-2 infection and, separately, COVID-19 vaccination just before or during pregnancy and the risk of adverse neonatal and maternal outcomes among women in Scotland with a singleton pregnancy ending at ≥20 weeks gestation. Neonatal outcomes are stillbirth, neonatal death, extended perinatal mortality, preterm birth (overall, spontaneous, and provider-initiated), small-for-gestational age, and low Apgar score. Maternal outcomes are admission to critical care or death, venous thromboembolism, hypertensive disorders of pregnancy, and pregnancy-related bleeding. We use conditional logistic regression to derive odds ratios adjusted for socio-demographic and clinical characteristics (aORs). We find that infection is associated with an increased risk of preterm (aOR=1.36, 95% Confidence Interval [CI] = 1.16-1.59) and very preterm birth (aOR = 1.90, 95% CI 1.20-3.02), maternal admission to critical care or death (aOR=1.72, 95% CI = 1.39-2.12), and venous thromboembolism (aOR = 2.53, 95% CI = 1.47-4.35). We find no evidence of increased risk for any of our outcomes following vaccination. These data suggest SARS-CoV-2 infection during pregnancy is associated with adverse neonatal and maternal outcomes, and COVID-19 vaccination remains a safe way for pregnant women to protect themselves and their babies against infection.",,doi:https://doi.org/10.1038/s41467-023-40965-9; html:https://europepmc.org/articles/PMC10465539; pdf:https://europepmc.org/articles/PMC10465539?pdf=render
 32614817,https://doi.org/10.1371/journal.pcbi.1008031,Estimation of country-level basic reproductive ratios for novel Coronavirus (SARS-CoV-2/COVID-19) using synthetic contact matrices.,"Hilton J, Keeling MJ.",,PLoS computational biology,2020,2020-07-02,Y,,,,"The 2019-2020 pandemic of atypical pneumonia (COVID-19) caused by the virus SARS-CoV-2 has spread globally and has the potential to infect large numbers of people in every country. Estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of human contacts through which the disease can spread, which is itself dependent on population age structure and household composition. Here we introduce a transmission model combining age-stratified contact frequencies with age-dependent susceptibility, probability of clinical symptoms, and transmission from asymptomatic (or mild) cases, which we use to estimate the country-specific basic reproductive ratio of COVID-19 for 152 countries. Using early outbreak data from China and a synthetic contact matrix, we estimate an age-stratified transmission structure which can then be extrapolated to 151 other countries for which synthetic contact matrices also exist. This defines a set of country-specific transmission structures from which we can calculate the basic reproductive ratio for each country. Our predicted R0 is critically sensitive to the intensity of transmission from asymptomatic cases; with low asymptomatic transmission the highest values are predicted across Eastern Europe and Japan and the lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly. If asymptomatic cases have comparable transmission to detected cases, the pattern is reversed. Our results demonstrate the importance of age-specific heterogeneities going beyond contact structure to the spread of COVID-19. These heterogeneities give COVID-19 the capacity to spread particularly quickly in countries with older populations, and that intensive control measures are likely to be necessary to impede its progress in these countries.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008031&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1008031; html:https://europepmc.org/articles/PMC7363110; pdf:https://europepmc.org/articles/PMC7363110?pdf=render
@@ -540,9 +540,9 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 31789939,https://doi.org/10.1097/ede.0000000000001113,Could Greater Physical Activity Reduce Population Prevalence and Socioeconomic Inequalities in Children's Mental Health Problems? A Policy Simulation.,"Chigogora S, Pearce A, Law C, Viner R, Chittleborough C, Griffiths LJ, Hope S.",,"Epidemiology (Cambridge, Mass.)",2020,2020-01-01,Y,,,,"<h4>Background</h4>One in four children 5-16 years (y) of age shows signs of mental health problems in the United Kingdom; risk is higher in economically disadvantaged groups. Greater physical activity is associated with lower risk of internalizing problems such as depression and anxiety. We simulated the potential impact of population-wide physical activity interventions on overall prevalence of internalizing problems, and by family income. Interventions were based on the World Health Organization (WHO) children's target of 60 minutes (min) of moderate-to-vigorous physical activity per day and trial evidence.<h4>Methods</h4>Data were from the UK Millennium Cohort Study, a population-representative cohort of children born in 2000-2002. Household income (5 y) was the exposure; internalizing problems (outcome) were measured using the Strengths and Difficulties Questionnaire (11 y). Of 18,296 singletons, 6,497 had accelerometer physical activity data (mediator, manipulated to simulate interventions) at 7 y. We predicted probabilities of outcome according to exposure in marginal structural models, weighted for attrition and confounding, and adjusted for observed mediator. We then re-estimated probabilities in different physical activity intervention scenarios, assessing income inequalities in internalizing problems with risk ratios (RRs) and differences (RDs) according to income quintile.<h4>Results</h4>Simulating universal achievement of the WHO target led to little change in prevalence (10% [95% CI = 8%, 12%]) and socioeconomic inequalities in internalizing problems; RR: 2.2 (1.1, 3.4); RD: 8% [5%,13%]). More modest increases in physical activity achieved weaker results.<h4>Conclusions</h4>Our simulations suggest that large increases in moderate-to-vigorous physical activity in the United Kingdom would have little effect on prevalence and inequalities in child mental health problems.","This UK based prospective cohort study looked at the potential impact of physical activity on 'internalizing problems' such as depression in children. They measured physical activity level at 7 years, and looked whether mental health problems existed at 11 years, adjusting approrpiately for confounders (ethnicity, maternal age at birth, neighbourhood safety, childhood illness, etc). They conclude that a small reduction in mental health problems could be observed but not enough to justify the national policy of encouraging 60 min of mod-vigorous exercise a day for all children",html:https://journals.lww.com/epidem/Fulltext/2020/01000/Could_Greater_Physical_Activity_Reduce_Population.13.aspx; doi:https://doi.org/10.1097/EDE.0000000000001113; html:https://europepmc.org/articles/PMC6889907; pdf:https://europepmc.org/articles/PMC6889907?pdf=render
 36609412,https://doi.org/10.1136/archdischild-2022-324713,"Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study.","Goulding A, McQuaid F, Lindsay L, Agrawal U, Auyeung B, Calvert C, Carruthers J, Denny C, Donaghy J, Hillman S, Hopcroft L, Hopkins L, McCowan C, McLaughlin T, Moore E, Ritchie L, Simpson CR, Taylor B, Fenton L, Pollock L, Gale C, Kurinczuk JJ, Robertson C, Sheikh A, Stock S, Wood R.",,Archives of disease in childhood. Fetal and neonatal edition,2023,2023-01-06,Y,epidemiology; Neonatology; Covid-19,,,"<h4>Objectives</h4>To examine neonates in Scotland aged 0-27 days with SARS-CoV-2 infection confirmed by viral testing; the risk of confirmed neonatal infection by maternal and infant characteristics; and hospital admissions associated with confirmed neonatal infections.<h4>Design</h4>Population-based cohort study.<h4>Setting and population</h4>All live births in Scotland, 1 March 2020-31 January 2022.<h4>Results</h4>There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100 000 live births (141/92 009, 0.15%). Among infants born to women with confirmed infection around the time of birth, the confirmed neonatal infection rate was 1812 per 100 000 live births (15/828, 1.8%). Two-thirds (92/141, 65.2%) of neonates with confirmed infection had an associated admission to neonatal or (more commonly) paediatric care. Six of these babies (6/92, 6.5%) were admitted to neonatal and/or paediatric intensive care; however, none of these six had COVID-19 recorded as their main diagnosis. There were no neonatal deaths among babies with confirmed infection.<h4>Implications and relevance</h4>Confirmed neonatal SARS-CoV-2 infection was uncommon over the first 23 months of the pandemic in Scotland. Secular trends in the neonatal confirmed infection rate broadly followed those seen in the general population, although at a lower level. Maternal confirmed infection at birth was associated with an increased risk of neonatal confirmed infection. Two-thirds of neonates with confirmed infection had an associated admission to hospital, with resulting implications for the baby, family and services, although their outcomes were generally good. Ascertainment of confirmed infection depends on the extent of testing, and this is likely to have varied over time and between groups: the extent of unconfirmed infection is inevitably unknown.",,pdf:https://fn.bmj.com/content/fetalneonatal/early/2023/01/05/archdischild-2022-324713.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-324713; html:https://europepmc.org/articles/PMC10313998; pdf:https://europepmc.org/articles/PMC10313998?pdf=render
 36384749,https://doi.org/10.1136/heartjnl-2022-321733,Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults.,"Raisi-Estabragh Z, Cooper J, Bethell MS, McCracken C, Lewandowski AJ, Leeson P, Neubauer S, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2023,2023-03-10,Y,epidemiology; Magnetic Resonance Imaging; risk factors,,,"<h4>Objective</h4>To examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.<h4>Methods</h4>Competing risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7-12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight-MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.<h4>Results</h4>258 787 participants from white ethnicities (61% women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2 kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0×10<sup>-5</sup>) and attenuation to the null above this threshold. The birth weight-MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight-mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19 314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).<h4>Conclusions</h4>Lower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.",,pdf:https://heart.bmj.com/content/heartjnl/early/2022/11/15/heartjnl-2022-321733.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321733; html:https://europepmc.org/articles/PMC10086465; pdf:https://europepmc.org/articles/PMC10086465?pdf=render
-37781298,https://doi.org/10.3389/fcvm.2023.1141026,Radiomics analysis enhances the diagnostic performance of CMR stress perfusion: a proof-of-concept study using the Dan-NICAD dataset.,"Raisi-Estabragh Z, Martin-Isla C, Nissen L, Szabo L, Campello VM, Escalera S, Winther S, Bøttcher M, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2023,2023-09-15,Y,Machine Learning (Ml); Radiomics; Cmr (Cardiovascular Magnetic Resonance); Stress Perfusion Cardiac Mri; Dan-nicad,,,"<h4>Objectives</h4>To assess the feasibility of extracting radiomics signal intensity based features from the myocardium using cardiovascular magnetic resonance (CMR) imaging stress perfusion sequences. Furthermore, to compare the diagnostic performance of radiomics models against standard-of-care qualitative visual assessment of stress perfusion images, with the ground truth stenosis label being defined by invasive Fractional Flow Reserve (FFR) and quantitative coronary angiography.<h4>Methods</h4>We used the Dan-NICAD 1 dataset, a multi-centre study with coronary computed tomography angiography, 1,5 T CMR stress perfusion, and invasive FFR available for a subset of 148 patients with suspected coronary artery disease. Image segmentation was performed by two independent readers. We used the Pyradiomics platform to extract radiomics first-order (<i>n</i> = 14) and texture (<i>n</i> = 75) features from the LV myocardium (basal, mid, apical) in rest and stress perfusion images.<h4>Results</h4>Overall, 92 patients (mean age 62 years, 56 men) were included in the study, 39 with positive FFR. We double-cross validated the model and, in each inner fold, we trained and validated a per territory model. The conventional analysis results reported sensitivity of 41% and specificity of 84%. Our final radiomics model demonstrated an improvement on these results with an average sensitivity of 53% and specificity of 86%.<h4>Conclusion</h4>In this proof-of-concept study from the Dan-NICAD dataset, we demonstrate the feasibility of radiomics analysis applied to CMR perfusion images with a suggestion of superior diagnostic performance of radiomics models over conventional visual analysis of perfusion images in picking up perfusion defects defined by invasive coronary angiography.",,doi:https://doi.org/10.3389/fcvm.2023.1141026; html:https://europepmc.org/articles/PMC10541220; pdf:https://europepmc.org/articles/PMC10541220?pdf=render
 33371011,https://doi.org/10.1136/bmjresp-2020-000770,Physiological tests of small airways function in diagnosing asthma: a systematic review.,"Almeshari MA, Alobaidi NY, Edgar RG, Stockley J, Sapey E.",,BMJ open respiratory research,2020,2020-12-01,Y,Asthma; Lung Physiology,,,"<h4>Background</h4>Asthma is a common, heterogeneous disease that is characterised by chronic airway inflammation and variable expiratory airflow limitation. Current guidelines use spirometric measures for asthma assessment. This systematic review aimed to assess whether the most commonly reported tests of small airways function could contribute to the diagnosis of asthma.<h4>Methods</h4>Standard systematic review methodology was used, and a range of electronic databases was searched (Embase, MEDLINE, CINAHL, CENTRAL, Web of Science, DARE). Studies that included physiological tests of small airways function to diagnose asthma in adults were included, with no restrictions on language or date. The risk of bias and quality assessment tools used were Agency for Healthcare Research and Quality tool for cross-sectional studies and Quality Assessment of Diagnostic Accuracy Studies 2 for diagnostic test accuracy (DTA) studies.<h4>Results</h4>7072 studies were identified and 10 studies met review criteria. 7 included oscillation techniques and 5 included maximal mid-expiratory flow (MMEF). Studies were small and of variable quality. In oscillometry, total resistance (R5) and reactance at 5 Hz (X5) was altered in asthma compared with healthy controls. The percentage predicted of MMEF was lower in patients with asthma compared with controls in all studies and lower than the % predicted forced expiratory volume in 1 s. In DTA of oscillometry, R5 showed a sensitivity between 69% and 72% and specificity between 61% and 86%.<h4>Conclusion</h4>There were differences in the results of physiological tests of small airway function in patients with asthma compared with controls. However, studies are small and heterogeneous. Further studies are needed to assess the effectiveness of these tests on a larger scale, including studies to determine which test methodology is the most useful in asthma.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000770.full.pdf; doi:https://doi.org/10.1136/bmjresp-2020-000770; html:https://europepmc.org/articles/PMC7754643; pdf:https://europepmc.org/articles/PMC7754643?pdf=render
 35443953,https://doi.org/10.1136/bmjopen-2021-056523,Can we accurately forecast non-elective bed occupancy and admissions in the NHS? A time-series MSARIMA analysis of longitudinal data from an NHS Trust.,"Eyles E, Redaniel MT, Jones T, Prat M, Keen T.",,BMJ open,2022,2022-04-20,Y,epidemiology; Statistics & Research Methods; Health Services Administration & Management; Accident & Emergency Medicine,,,"<h4>Objectives</h4>The main objective of the study was to develop more accurate and precise short-term forecasting models for admissions and bed occupancy for an NHS Trust located in Bristol, England. Subforecasts for the medical and surgical specialties, and for different lengths of stay were realised DESIGN: Autoregressive integrated moving average models were specified on a training dataset of daily count data, then tested on a 6-week forecast horizon. Explanatory variables were included in the models: day of the week, holiday days, lagged temperature and precipitation.<h4>Setting</h4>A secondary care hospital in an NHS Trust in South West England.<h4>Participants</h4>Hospital admissions between September 2016 and March 2020, comprising 1291 days.<h4>Primary and secondary outcome measures</h4>The accuracy of the forecasts was assessed through standard measures, as well as compared with the actual data using accuracy thresholds of 10% and 20% of the mean number of admissions or occupied beds.<h4>Results</h4>The overall Autoregressive Integrated Moving Average (ARIMA) admissions forecast was compared with the Trust's forecast, and found to be more accurate, namely, being closer to the actual value 95.6% of the time. Furthermore, it was more precise than the Trust's. The subforecasts, as well as those for bed occupancy, tended to be less accurate compared with the overall forecasts. All of the explanatory variables improved the forecasts.<h4>Conclusions</h4>ARIMA models can forecast non-elective admissions in an NHS Trust accurately on a 6-week horizon, which is an improvement on the current predictive modelling in the Trust. These models can be readily applied to other contexts, improving patient flow.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render
+37781298,https://doi.org/10.3389/fcvm.2023.1141026,Radiomics analysis enhances the diagnostic performance of CMR stress perfusion: a proof-of-concept study using the Dan-NICAD dataset.,"Raisi-Estabragh Z, Martin-Isla C, Nissen L, Szabo L, Campello VM, Escalera S, Winther S, Bøttcher M, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2023,2023-09-15,Y,Machine Learning (Ml); Radiomics; Cmr (Cardiovascular Magnetic Resonance); Stress Perfusion Cardiac Mri; Dan-nicad,,,"<h4>Objectives</h4>To assess the feasibility of extracting radiomics signal intensity based features from the myocardium using cardiovascular magnetic resonance (CMR) imaging stress perfusion sequences. Furthermore, to compare the diagnostic performance of radiomics models against standard-of-care qualitative visual assessment of stress perfusion images, with the ground truth stenosis label being defined by invasive Fractional Flow Reserve (FFR) and quantitative coronary angiography.<h4>Methods</h4>We used the Dan-NICAD 1 dataset, a multi-centre study with coronary computed tomography angiography, 1,5 T CMR stress perfusion, and invasive FFR available for a subset of 148 patients with suspected coronary artery disease. Image segmentation was performed by two independent readers. We used the Pyradiomics platform to extract radiomics first-order (<i>n</i> = 14) and texture (<i>n</i> = 75) features from the LV myocardium (basal, mid, apical) in rest and stress perfusion images.<h4>Results</h4>Overall, 92 patients (mean age 62 years, 56 men) were included in the study, 39 with positive FFR. We double-cross validated the model and, in each inner fold, we trained and validated a per territory model. The conventional analysis results reported sensitivity of 41% and specificity of 84%. Our final radiomics model demonstrated an improvement on these results with an average sensitivity of 53% and specificity of 86%.<h4>Conclusion</h4>In this proof-of-concept study from the Dan-NICAD dataset, we demonstrate the feasibility of radiomics analysis applied to CMR perfusion images with a suggestion of superior diagnostic performance of radiomics models over conventional visual analysis of perfusion images in picking up perfusion defects defined by invasive coronary angiography.",,doi:https://doi.org/10.3389/fcvm.2023.1141026; html:https://europepmc.org/articles/PMC10541220; pdf:https://europepmc.org/articles/PMC10541220?pdf=render
 33632765,https://doi.org/10.1136/thoraxjnl-2020-215986,"Neutrophils in asthma: the good, the bad and the bacteria.","Crisford H, Sapey E, Rogers GB, Taylor S, Nagakumar P, Lokwani R, Simpson JL.",,Thorax,2021,2021-02-25,Y,Asthma; Bacterial Infection; Paediatric Asthma; Asthma Mechanisms; Neutrophil Biology,,,"Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics.Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients.The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic.In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America.",,pdf:https://thorax.bmj.com/content/thoraxjnl/76/8/835.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-215986; html:https://europepmc.org/articles/PMC8311087; pdf:https://europepmc.org/articles/PMC8311087?pdf=render
 31249320,https://doi.org/10.1038/s41598-019-45562-9,"Antenatal exposure to solar radiation and learning disabilities: Population cohort study of 422,512 children.","Hastie CE, Mackay DF, Clemens TL, Cherrie MPC, King A, Dibben C, Pell JP.",,Scientific reports,2019,2019-06-27,Y,,Improving Public Health,,"Learning disability varies by month of conception. The underlying mechanism is unknown but vitamin D, necessary for normal brain development, is commonly deficient over winter in high latitude countries due to insufficient ultraviolet radiation. We linked the 2007-2016 Scottish School Pupil Censuses to Scottish maternity records and to sunshine hours and antenatal ultraviolet A/B radiation exposure derived from weather stations and satellites respectively. Logistic regression analyses were used to explore the associations between solar radiation, then ultraviolet B, and learning disabilities, adjusting for the potential confounding effects of month of conception and sex. Of the 422,512 eligible, singleton schoolchildren born at term in Scotland, 79,616 (18.8%) had a learning disability. Total antenatal sunshine hours (highest quintile; adjusted OR 0.89; 95% CI: 0.86, 0.93; p < 0.001) and ultraviolet B exposure (highest quintile; adjusted OR 0.55; 95% CI: 0.51, 0.60; p < 0.001) were inversely associated with learning disabilities with evidence of a dose-relationship. The latter association was independent of ultraviolet A exposure. Significant associations were demonstrated for exposure in all three trimesters. Low maternal exposure to ultraviolet B radiation may play a role in the seasonal patterning of learning disabilities. Further studies are required to corroborate findings and determine the effectiveness of supplements.",,pdf:https://www.nature.com/articles/s41598-019-45562-9.pdf; doi:https://doi.org/10.1038/s41598-019-45562-9; html:https://europepmc.org/articles/PMC6597711; pdf:https://europepmc.org/articles/PMC6597711?pdf=render
 37053113,https://doi.org/10.1097/bot.0000000000002612,The Translated Proximal Humerus Fracture: A Comparison of Operative and Nonoperative Management.,"Cosic F, Kirzner N, Edwards E, Page R, Kimmel L, Gabbe B.",,Journal of orthopaedic trauma,2023,2023-09-01,N,,,,"<h4>Objectives</h4>To report on the long-term outcomes of the management of translated proximal humerus fractures.<h4>Design</h4>A prospective cohort study was conducted from January 2010 to December 2018.<h4>Setting</h4>Academic Level 1 trauma center.<h4>Participants/patients</h4>A total of 108 patients with a proximal humerus fracture with ≥100% translation, defined as no cortical bony contact between the shaft and humeral head fragments, were included.<h4>Intervention</h4>Patients were managed nonoperatively with sling immobilization or with operative management as determined by the treating surgeon.<h4>Main outcome measures</h4>Outcome measures were the Oxford Shoulder Score, EQ-5D-5L, return to work, and radiological outcomes. Complications recorded included further surgery, loss of position/fixation, nonunion/malunion, and avascular necrosis.<h4>Results</h4>Of the 108 patients, 76 underwent operative intervention and 32 were managed nonoperatively. The mean (SD) age in the operative group was 54.3 (±20.2) years and in the nonoperative group was 73.3 (±15.3) years ( P < 0.001). There was no association between Oxford Shoulder Score and management options (mean 38.5 [±9.5] operative versus mean 41.3 [±8.5] nonoperative, P = 0.48). Operative management was associated with improved health status outcomes; EQ-5D utility score adjusted mean difference was 0.16 (95% CI, 0.04-0.27; P = 0.008); EQ-5D VAS adjusted mean difference was 19.2 (95% CI, 5.2-33.2; P = 0.008). Operative management was associated with a lower odds of nonunion (adjusted OR 0.30; 95% CI, 0.09-0.97; P = 0.04), malunion (adjusted OR 0.14; 95% CI, 0.04-0.51; P = 0.003), and complications (adjusted OR 0.07; 95% CI, 0.02-0.32; P = 0.001).<h4>Conclusion</h4>Translated proximal humerus fractures with ≥100% displacement demonstrate improved health status and radiological outcomes after surgical fixation.<h4>Level of evidence</h4>Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.",,doi:https://doi.org/10.1097/BOT.0000000000002612
@@ -554,8 +554,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 31774502,https://doi.org/10.1093/ehjcvp/pvz071,An observational study of international normalized ratio control according to NICE criteria in patients with non-valvular atrial fibrillation: the SAIL Warfarin Out of Range Descriptors Study (SWORDS).,"Harris DE, Thayer D, Wang T, Brooks C, Murley G, Gravenor M, Hill NR, Lister S, Halcox J.",,European heart journal. Cardiovascular pharmacotherapy,2021,2021-01-01,Y,Atrial fibrillation; Warfarin; Pharmacoepidemiology,Improving Public Health,,"<h4>Aims</h4>In patients with non-valvular atrial fibrillation prescribed warfarin, the UK National Institute of Health and Care Excellence (NICE) defines poor anticoagulation as a time in therapeutic range (TTR) of <65%, any two international normalized ratios (INRs) within a 6-month period of ≤1.5 ('low'), two INRs ≥5 within 6 months, or any INR ≥8 ('high'). Our objectives were to (i) quantify the number of patients with poor INR control and (ii) describe the demographic and clinical characteristics associated with poor INR control.<h4>Method and results</h4>Linked anonymized health record data for Wales, UK (2006-2017) was used to evaluate patients prescribed warfarin who had at least 6 months of INR data. 32 380 patients were included. In total, 13 913 (43.0%) patients had at least one of the NICE markers of poor INR control. Importantly, in the 24 123 (74.6%) of the cohort with an acceptable TTR (≥65%), 5676 (23.5%) had either low or high INR readings at some point in their history. In a multivariable regression female gender, age (≥75 years), excess alcohol, diabetes heart failure, ischaemic heart disease, and respiratory disease were independently associated with all markers of poor INR control.<h4>Conclusion</h4>Acceptable INR control according to NICE standards is poor. Of those with an acceptable TTR (>65%), one-quarter still had unacceptably low or high INR levels according to NICE criteria. Thus, only using TTR to assess effectiveness with warfarin has the potential to miss a large number of patients with non-therapeutic INRs who are likely to be at increased risk.","This retrospective observational cohort study aimed to quanitfy the number of patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin who exhibit NICE-defined poor international normalised ratio (INR) control. Another objective was to describe the relationship between demographic and clinical characteristics of these patients and poor INR control. The results from statistical analyses in this study suggest a considerable opportunity to improve both embloc and bleeding risk, eben though the relationship between poor INR control and these clinical outcomes remains to be determined.",pdf:https://academic.oup.com/ehjcvp/advance-article-pdf/doi/10.1093/ehjcvp/pvz071/31700014/pvz071.pdf; doi:https://doi.org/10.1093/ehjcvp/pvz071; html:https://europepmc.org/articles/PMC7811400; pdf:https://europepmc.org/articles/PMC7811400?pdf=render
 36374585,https://doi.org/10.1177/01410768221131897,Using national electronic health records for pandemic preparedness: validation of a parsimonious model for predicting excess deaths among those with COVID-19-a data-driven retrospective cohort study.,"Mizani MA, Dashtban A, Pasea L, Lai AG, Thygesen J, Tomlinson C, Handy A, Mamza JB, Morris T, Khalid S, Zaccardi F, Macleod MJ, Torabi F, Canoy D, Akbari A, Berry C, Bolton T, Nolan J, Khunti K, Denaxas S, Hemingway H, Sudlow C, Banerjee A, CVD-COVID-UK Consortium.",,Journal of the Royal Society of Medicine,2023,2022-11-14,N,Infectious diseases; Clinical; epidemiology; Public Health; Health Informatics,,,"<h4>Objectives</h4>To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths.<h4>Design</h4>An EHR-based, retrospective cohort study.<h4>Setting</h4>Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE).<h4>Participants</h4>In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.<h4>Main outcome measures</h4>One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.<h4>Results</h4>From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31-4.38) and IR was 6.27% (95% CI, 6.26-6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79.<h4>Conclusions</h4>We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; doi:https://doi.org/10.1177/01410768221131897; html:https://europepmc.org/articles/PMC9909113; pdf:https://europepmc.org/articles/PMC9909113?pdf=render; doi:https://doi.org/10.1177/01410768221131897
 37745706,https://doi.org/10.3389/fendo.2023.1266557,"Editorial: Integrative multi-modal, multi-omics analytics for the better understanding of metabolic diseases.","Acharjee A, Agarwal P, Gkoutos GV.",,Frontiers in endocrinology,2023,2023-09-08,Y,Biomarker; Therapeutic; Diagnostic; Metabolic Disease; Omics,,,,,doi:https://doi.org/10.3389/fendo.2023.1266557; html:https://europepmc.org/articles/PMC10516571; pdf:https://europepmc.org/articles/PMC10516571?pdf=render
-36921925,https://doi.org/10.1136/bmj-2022-072808,Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.,"Hulme WJ, Horne EMF, Parker EPK, Keogh RH, Williamson EJ, Walker V, Palmer TM, Curtis HJ, Walker AJ, Andrews CD, Mehrkar A, Morley J, MacKenna B, Bacon SCJ, Goldacre B, Hernán MA, Sterne JAC.",,BMJ (Clinical research ed.),2023,2023-03-15,Y,,,,"<h4>Objective</h4>To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England.<h4>Design</h4>Matched cohort study, emulating a comparative effectiveness trial.<h4>Setting</h4>Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant.<h4>Participants</h4>3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1.<h4>Intervention</h4>Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose.<h4>Main outcome measures</h4>Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose.<h4>Results</h4>1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras.<h4>Conclusions</h4>This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance.",,pdf:https://www.bmj.com/content/bmj/380/bmj-2022-072808.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072808; html:https://europepmc.org/articles/PMC10014664; pdf:https://europepmc.org/articles/PMC10014664?pdf=render
 35497059,https://doi.org/10.1016/j.eclinm.2022.101392,Health conditions in adults with HIV compared with the general population: A population-based cross-sectional analysis.,"Morales DR, Moreno-Martos D, Matin N, McGettigan P.",,EClinicalMedicine,2022,2022-04-21,Y,HIV; Comorbidity; Multimorbidity,,,"<h4>Background</h4>Life expectancy in adults with human immunodeficiency virus (HIV) has increased and managing other health conditions is increasingly important for patients and healthcare planning. The aim of this study was to examine the prevalence and association between different health conditions and HIV status.<h4>Methods</h4>We performed a cross-sectional analysis of adult UK Clinical Practice Research Datalink primary care electronic medical records linked to hospital admissions as of Nov 30, 2015. We examined 47 health condition groups and 304 physical and mental health conditions by HIV status, after adjustment for age, sex, social deprivation status using logistic regression.<h4>Findings</h4>There were 964 patients with HIV (61.7% male; 92.8% aged <65 years) and 941,113 non-HIV patients (49.4% male; 75.2% aged <65 years). Condition groups with the greatest prevalence in HIV that were also highly prevalent in adults without HIV included: lipid disorder (41.4% vs 40.2%), and hypertension (19.1% vs 24.6%). Following adjustment, 18 (37.5%) condition groups were more likely in adults with HIV and ten (20.8%) were less likely. Individual conditions that were less likely in adults with HIV included: atrial fibrillation (odds ratio [OR] 0.37 [95% CI 0.20-0.64]) and hypertension (OR_0.78 [0.65-0.94]); rheumatoid arthritis (OR 0.27 [0.05-0.84]); asthma (OR_0.65 (0.53-0.80]); and certain eye diseases such as macular degeneration (OR_0.30 [0.09-0.70]). Meanwhile individual conditions that were more likely included: liver fibrosis, sclerosis, and cirrhosis (OR_3.23 [1.85-5.20]); pulmonary embolism (OR_2.06 [1.15-3.36]); male infertility (OR_2.23 [1.50-3.16]) and female infertility (OR_2.01 [1.34-2.88]); bipolar disorder (OR_2.93 [1.52-5.05]) and depression (OR_1.49 [1.28-1.71]); cervical malignancy (OR_4.64 [1.15-12.15]); and infections.<h4>Interpretation</h4>Comorbidity is common in adults with HIV, with physical and mental health conditions spanning a wide spectrum. HIV management should consider multidisciplinary care models to provide optimal patient care.<h4>Funding</h4>The project was funded by the Bart's Charity; DRM was funded by a Wellcome Trust Clinical Research Career Development Fellowship; DRM and DMM received funding from the HDR-UK Precision therapeutics programme.",,pdf:http://www.thelancet.com/article/S2589537022001225/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101392; html:https://europepmc.org/articles/PMC9046106; pdf:https://europepmc.org/articles/PMC9046106?pdf=render
+36921925,https://doi.org/10.1136/bmj-2022-072808,Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.,"Hulme WJ, Horne EMF, Parker EPK, Keogh RH, Williamson EJ, Walker V, Palmer TM, Curtis HJ, Walker AJ, Andrews CD, Mehrkar A, Morley J, MacKenna B, Bacon SCJ, Goldacre B, Hernán MA, Sterne JAC.",,BMJ (Clinical research ed.),2023,2023-03-15,Y,,,,"<h4>Objective</h4>To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England.<h4>Design</h4>Matched cohort study, emulating a comparative effectiveness trial.<h4>Setting</h4>Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant.<h4>Participants</h4>3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1.<h4>Intervention</h4>Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose.<h4>Main outcome measures</h4>Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose.<h4>Results</h4>1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras.<h4>Conclusions</h4>This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance.",,pdf:https://www.bmj.com/content/bmj/380/bmj-2022-072808.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072808; html:https://europepmc.org/articles/PMC10014664; pdf:https://europepmc.org/articles/PMC10014664?pdf=render
 36541282,https://doi.org/10.14814/phy2.15546,Reduced oxygen saturation entropy is associated with poor prognosis in critically ill patients with sepsis.,"Gheorghita M, Wikner M, Cawthorn A, Oyelade T, Nemeth K, Rockenschaub P, Gonzalez Hernandez F, Swanepoel N, Lilaonitkul W, Mani AR.",,Physiological reports,2022,2022-12-01,Y,Variability; Survival; Sepsis; Entropy; Oxygen saturation; Spo2,,,"Recent studies have found that oxygen saturation (SpO<sub>2</sub> ) variability analysis has potential for noninvasive assessment of the functional connectivity of cardiorespiratory control systems during hypoxia. Patients with sepsis have suboptimal tissue oxygenation and impaired organ system connectivity. Our objective with this report was to highlight the potential use for SpO<sub>2</sub> variability analysis in predicting intensive care survival in patients with sepsis. MIMIC-III clinical data of 164 adults meeting Sepsis-3 criteria and with 30 min of SpO<sub>2</sub> and respiratory rate data were analyzed. The complexity of SpO<sub>2</sub> signals was measured through various entropy calculations such as sample entropy and multiscale entropy analysis. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multiorgan failure. While the standard deviation of SpO<sub>2</sub> signals was comparable in the non-survivor and survivor groups, non-survivors had significantly lower SpO<sub>2</sub> entropy than those who survived their ICU stay (0.107 ± 0.084 vs. 0.070 ± 0.083, p < 0.05). According to Cox regression analysis, higher SpO<sub>2</sub> entropy was a predictor of survival in patients with sepsis. Multivariate analysis also showed that the prognostic value of SpO<sub>2</sub> entropy was independent of other covariates such as age, SOFA score, mean SpO<sub>2</sub> , and ventilation status. When SpO<sub>2</sub> entropy was combined with mean SpO<sub>2</sub> , the composite had a significantly higher performance in prediction of survival. Analysis of SpO<sub>2</sub> entropy can predict patient outcome, and when combined with SpO<sub>2</sub> mean, can provide improved prognostic information. The prognostic power is on par with the SOFA score. This analysis can easily be incorporated into current ICU practice and has potential for noninvasive assessment of critically ill patients.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.14814/phy2.15546; doi:https://doi.org/10.14814/phy2.15546; html:https://europepmc.org/articles/PMC9768724; pdf:https://europepmc.org/articles/PMC9768724?pdf=render
 34240125,https://doi.org/10.1093/clinchem/hvab109,Sex Differences in Cardiac Troponin I and T and the Prediction of Cardiovascular Events in the General Population.,"Kimenai DM, Shah ASV, McAllister DA, Lee KK, Tsanas A, Meex SJR, Porteous DJ, Hayward C, Campbell A, Sattar N, Mills NL, Welsh P.",,Clinical chemistry,2021,2021-10-01,Y,Sex; cardiac troponin; Cardiovascular events; risk factors,,,"<h4>Background</h4>Cardiac troponin concentrations differ in women and men, but how this influences risk prediction and whether a sex-specific approach is required is unclear. We evaluated whether sex influences the predictive ability of cardiac troponin I and T for cardiovascular events in the general population.<h4>Methods</h4>High-sensitivity cardiac troponin (hs-cTn) I and T were measured in the Generation Scotland Scottish Family Health Study of randomly selected volunteers drawn from the general population between 2006 and 2011. Cox-regression models evaluated associations between hs-cTnI and hs-cTnT and the primary outcome of cardiovascular death, myocardial infarction, or stroke.<h4>Results</h4>In 19 501 (58% women, mean age 47 years) participants, the primary outcome occurred in 2.7% (306/11 375) of women and 5.1% (411/8126) of men during the median follow-up period of 7.9 (IQR, 7.1-9.2) years. Cardiac troponin I and T concentrations were lower in women than men (P < 0.001 for both), and both were more strongly associated with cardiovascular events in women than men. For example, at a hs-cTnI concentration of 10 ng/L, the hazard ratio relative to the limit of blank was 9.7 (95% CI 7.6-12.4) and 5.6 (95% CI 4.7-6.6) for women and men, respectively. The hazard ratio for hs-cTnT at a concentration of 10 ng/L relative to the limit of blank was 3.7 (95% CI 3.1-4.3) and 2.2 (95% CI 2.0-2.5) for women and men, respectively.<h4>Conclusions</h4>Cardiac troponin concentrations differ in women and men and are stronger predictors of cardiovascular events in women. Sex-specific approaches are required to provide equivalent risk prediction.",,pdf:https://academic.oup.com/clinchem/article-pdf/67/10/1351/40494927/hvab109.pdf; doi:https://doi.org/10.1093/clinchem/hvab109; html:https://europepmc.org/articles/PMC8486023; pdf:https://europepmc.org/articles/PMC8486023?pdf=render
 36350656,https://doi.org/10.1093/nar/gkac1010,The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.,"Sollis E, Mosaku A, Abid A, Buniello A, Cerezo M, Gil L, Groza T, Güneş O, Hall P, Hayhurst J, Ibrahim A, Ji Y, John S, Lewis E, MacArthur JAL, McMahon A, Osumi-Sutherland D, Panoutsopoulou K, Pendlington Z, Ramachandran S, Stefancsik R, Stewart J, Whetzel P, Wilson R, Hindorff L, Cunningham F, Lambert SA, Inouye M, Parkinson H, Harris LW.",,Nucleic acids research,2023,2023-01-01,Y,,,,"The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to >200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for >45 000 published GWAS across >5000 human traits, and >40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.",,pdf:https://academic.oup.com/nar/article-pdf/51/D1/D977/48440802/gkac1010.pdf; doi:https://doi.org/10.1093/nar/gkac1010; html:https://europepmc.org/articles/PMC9825413; pdf:https://europepmc.org/articles/PMC9825413?pdf=render
@@ -574,8 +574,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 35256633,https://doi.org/10.1038/s41598-022-07291-4,Shared genetic loci for body fat storage and adipocyte lipolysis in humans.,"Kulyté A, Lundbäck V, Arner P, Strawbridge RJ, Dahlman I.",,Scientific reports,2022,2022-03-07,Y,,,,"Total body fat and central fat distribution are heritable traits and well-established predictors of adverse metabolic outcomes. Lipolysis is the process responsible for the hydrolysis of triacylglycerols stored in adipocytes. To increase our understanding of the genetic regulation of body fat distribution and total body fat, we set out to determine if genetic variants associated with body mass index (BMI) or waist-hip-ratio adjusted for BMI (WHRadjBMI) in genome-wide association studies (GWAS) mediate their effect by influencing adipocyte lipolysis. We utilized data from the recent GWAS of spontaneous and isoprenaline-stimulated lipolysis in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort. GENiAL consists of 939 participants who have undergone abdominal subcutaneous adipose biopsy for the determination of spontaneous and isoprenaline-stimulated lipolysis in adipocytes. We report 11 BMI and 15 WHRadjBMI loci with SNPs displaying nominal association with lipolysis and allele-dependent gene expression in adipose tissue according to in silico analysis. Functional evaluation of candidate genes in these loci by small interfering RNAs (siRNA)-mediated knock-down in adipose-derived stem cells identified ZNF436 and NUP85 as intrinsic regulators of lipolysis consistent with the associations observed in the clinical cohorts. Furthermore, candidate genes in another BMI-locus (STX17) and two more WHRadjBMI loci (NID2, GGA3, GRB2) control lipolysis alone, or in conjunction with lipid storage, and may hereby be involved in genetic control of body fat. The findings expand our understanding of how genetic variants mediate their impact on the complex traits of fat storage and distribution.",,pdf:https://www.nature.com/articles/s41598-022-07291-4.pdf; doi:https://doi.org/10.1038/s41598-022-07291-4; html:https://europepmc.org/articles/PMC8901764; pdf:https://europepmc.org/articles/PMC8901764?pdf=render
 31398891,https://doi.org/10.3390/nu11081839,Intakes and Food Sources of Dietary Fibre and Their Associations with Measures of Body Composition and Inflammation in UK Adults: Cross-Sectional Analysis of the Airwave Health Monitoring Study. ,"Gibson R, Eriksen R, Chambers E, Gao H, Aresu M, Heard A, Chan Q, Elliott P, Frost G.",,Nutrients,2019,2019-08-08,Y,,Improving Public Health,,"The purpose of this study was to investigate the associations between intakes of fibre from the main food sources of fibre in the UK diet with body mass index (BMI), percentage body fat (%BF), waist circumference (WC) and C-reactive protein (CRP). Participants enrolled in the Airwave Health Monitoring Study (2007-2012) with 7-day food records (n = 6898; 61% men) were included for cross-sectional analyses. General linear models evaluated associations across fifths of fibre intakes (total, vegetable, fruit, potato, whole grain and non-whole grain cereal) with BMI, %BF, WC and CRP. Fully adjusted analyses showed inverse linear trends across fifths of total fibre and fibre from fruit with all outcome measures (ptrend < 0.0001). Vegetable fibre intake showed an inverse association with WC (ptrend 0.0156) and CRP (ptrend 0.0005). Fibre from whole grain sources showed an inverse association with BMI (ptrend 0.0002), %BF (ptrend 0.0007) and WC (ptrend 0.0004). Non-whole grain cereal fibre showed an inverse association with BMI (Ptrend 0.0095). Direct associations observed between potato fibre intake and measures of body composition and inflammation were attenuated in fully adjusted analyses controlling for fried potato intake. Higher fibre intake has a beneficial association on body composition, however, there are differential associations based on the food source.",,pdf:https://www.mdpi.com/2072-6643/11/8/1839/pdf?version=1565745447; doi:https://doi.org/10.3390/nu11081839; html:https://europepmc.org/articles/PMC6722677; pdf:https://europepmc.org/articles/PMC6722677?pdf=render
 34308306,https://doi.org/10.1016/j.eclinm.2021.100888,The BCD Triage Sieve outperforms all existing major incident triage tools: Comparative analysis using the UK national trauma registry population.,"Malik NS, Chernbumroong S, Xu Y, Vassallo J, Lee J, Bowley DM, Hodgetts T, Moran CG, Lord JM, Belli A, Keene D, Foster M, Gkoutos GV.",,EClinicalMedicine,2021,2021-05-15,Y,ramp; Disaster; Start; Military Medicine; Major Incident; Triage; Injury Severity Score; Mass Casualty; Major Trauma; Prehospital Medicine; Life-saving Intervention; Careflight; Jumpstart; Bcd Triage Sieve; Mimms; Mptt-24; Mstart,,,"<h4>Background</h4>Natural disasters, conflict, and terrorism are major global causes of death and disability. Central to the healthcare response is triage, vital to ensure the right care is provided to the right patient at the right time. The ideal triage tool has high sensitivity for the highest priority (P1) patients with acceptably low over-triage. This study compared the performance of major incident triage tools in predicting P1 casualty status in adults in the prospective UK Trauma Audit and Research Network (TARN) registry.<h4>Methods</h4>TARN patients aged 16+ years (January 2008-December 2017) were included. Ten existing triage tools were applied using patients' first recorded pre-hospital physiology. Patients were subsequently assigned triage categories (P1, P2, P3, Expectant or Dead) based on pre-defined, intervention-based criteria. Tool performance was assessed by comparing tool-predicted and intervention-based priority status.<h4>Findings</h4>195,709 patients were included; mortality was 7·0% (n=13,601); median Injury Severity Score (ISS) was 9 (IQR 9-17); 97·1% sustained blunt injuries. 22,144 (11·3%) patients fulfilled intervention-based criteria for P1 status, exhibiting higher mortality (12·8% <i>vs.</i> 5·0%, p<0.001), increased intensive care requirement (52·4% <i>vs</i> 5·0%, p<0.001), and more severe injuries (median ISS 21 <i>vs</i> 9, p<0.001) compared with P2 patients.In 16-64 year olds, the highest performing tool was the Battlefield Casualty Drills (BCD) Triage Sieve (Prediction of P1 status: 70·4% sensitivity, over-triage 70·9%, area under the receiver operating curve (AUC) 0·068 [95%CI 0·676-0·684]). The UK National Ambulance Resilience Unit (NARU) Triage Sieve had sensitivity of 44·9%; over-triage 56·4%; AUC 0·666 (95%CI 0·662-0·670). All tools performed poorly amongst the elderly (65+ years).<h4>Interpretation</h4>The BCD Triage Sieve performed best in this nationally representative population; we recommend it supersede the NARU Triage Sieve as the UK primary major incident triage tool. Validated triage category definitions are recommended for appraising future major incidents.<h4>Funding</h4>This study is funded by the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre. GVG also acknowledges support from the MRC Heath Data Research UK (HDRUK/CFC/01). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the Ministry of Defence.",,pdf:http://www.thelancet.com/article/S2589537021001681/pdf; doi:https://doi.org/10.1016/j.eclinm.2021.100888; html:https://europepmc.org/articles/PMC8257989; pdf:https://europepmc.org/articles/PMC8257989?pdf=render
-37543047,https://doi.org/10.1016/s2666-7568(23)00105-8,"Antipsychotic drug prescribing and mortality in people with dementia before and during the COVID-19 pandemic: a retrospective cohort study in Wales, UK.","Schnier C, McCarthy A, Morales DR, Akbari A, Sofat R, Dale C, Takhar R, Mamas MA, Khunti K, Zaccardi F, Sudlow CL, Wilkinson T, CVD-COVID-UK/COVID-IMPACT Consortium.",,The lancet. Healthy longevity,2023,2023-08-01,N,,,,"<h4>Background</h4>Concerns have been raised that antipsychotic drug prescribing, which has been associated with increased mortality in people with dementia, might have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of SARS-CoV-2. We used multisource, routinely collected health-care data from Wales, UK to investigate prescribing and mortality variations in people with dementia before and during the COVID-19 pandemic.<h4>Methods</h4>In this retrospective cohort study, we used individual-level, anonymised, population-scale linked health data to identify adults aged 60 years and older with a diagnosis of dementia in Wales, UK. We used the CVD-COVID-UK initiative to access Welsh routinely collected electronic health record data from the Secure Anonymised Information Linkage (SAIL) Databank. Patients who were alive and registered with a SAIL general practice on Jan 1, 2016, and who received a dementia diagnosis before the age of 60 years and before or during the study period were included. We explored antipsychotic drug prescribing rate changes over 67 months, between Jan 1, 2016, and Aug 1, 2021, overall and stratified by age and dementia subtype. We used time-series analyses to examine all-cause and myocardial infarction and stroke mortality over the study period and identified the leading causes of death in people with dementia between Jan 1, 2020, and Aug 1, 2021.<h4>Findings</h4>Of 3 106 690 participants in SAIL between Jan 1, 2016 and Aug 1, 2021, 57 396 people (35 148 [61·2%] women and 22 248 [38·8%] men) met inclusion criteria for this study and contributed 101 428 person-years of follow-up. Of the 57 396 people with dementia, 11 929 (20·8%) were prescribed an antipsychotic drug at any point during follow-up. Accounting for seasonality, antipsychotic drug prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 prescriptions per 10 000 person-months in March, 2019, to 1305 per 10 000 person-months in September, 2020. All-cause mortality and stroke mortality increased throughout 2020, while myocardial infarction mortality declined. From Jan 1, 2020, to Aug 1, 2021, 1286 (17·1%) of 7508 participants who died had COVID-19 recorded as the underlying cause of death.<h4>Interpretation</h4>During the COVID-19 pandemic, antipsychotic drug prescribing in people with dementia in the UK increased slightly; however, it is unlikely that this was solely related to the pandemic and this increase was unlikely to be a major factor in the substantial increase in mortality during 2020. The long-term increase in antipsychotic drug prescribing in younger people and in those with Alzheimer's disease warrants further investigation using resources with access to more granular clinical data. Although deprescribing antipsychotic medications remains an essential aspect of dementia care, the results of this study suggest that changes in prescribing and deprescribing practices as a result of the COVID-19 pandemic are not required.<h4>Funding</h4>British Heart Foundation (via the British Heart Foundation Data Science Centre led by Health Data Research UK), and the Scottish Neurological Research Fund.",,doi:https://doi.org/10.1016/S2666-7568(23)00105-8
 33952557,https://doi.org/10.1136/bmjopen-2021-049964,Study protocol of the Edinburgh and Lothian Virus Intervention Study in Kids: a randomised controlled trial of hypertonic saline nose drops in children with upper respiratory tract infections (ELVIS Kids).,"Ramalingam S, Graham C, Oatey K, Rayson P, Stoddart A, Sheikh A, Cunningham S, ELVIS Kids Trial Investigators.",,BMJ open,2021,2021-05-05,Y,Virology; Community Child Health; Neonatology; Primary Care; Paediatric Infectious Disease & Immunisation,,,"<h4>Introduction</h4>Edinburgh and Lothians' Viral Intervention Study Kids is a parallel, open-label, randomised controlled trial of hypertonic saline (HS) nose drops (~2.6% sodium chloride) vs standard care in children <7 years of age with symptoms of an upper respiratory tract infection (URTI).<h4>Methods and analysis</h4>Children are recruited prior to URTI or within 48 hours of developing URTI symptoms by advertising in areas such as local schools/nurseries, health centres/hospitals, recreational facilities, public events, workplaces, local/social media. Willing parents/guardians, of children <7 years of age will be asked to contact the research team at their local site. Children will be randomised to either a control arm (standard symptomatic care), or intervention arm (three drops/nostril of HS, at least four times a day, until 24 hours after asymptomatic or a maximum of 28 days). All participants are requested to provide a nasal swab at the start of the study (intervention arm: before HS drops) and then daily for four more days. Parent/guardian complete a validated daily diary, an end of illness diary, a satisfaction questionnaire and a wheeze questionnaire (day 28). The parent/guardian of a child in the intervention arm is taught to prepare HS nose drops. Parent/guardian of children asymptomatic at recruitment are requested to inform the research team within 48 hours of their child developing an URTI and follow the instructions already provided. The day 28 questionnaire determines if the child experienced a wheeze following illness. Participation in the study ends on day 28.<h4>Ethics and dissemination</h4>The study has been approved by the West of Scotland Research Ethics Service (18/WS/0080). It is cosponsored by Academic and Clinical Central Office for Research and Development-a partnership between the University of Edinburgh and National Health Service Lothian Health Board. The findings will be disseminated through peer-reviewed publications, conference presentations and via the study website.<h4>Trial registration number</h4>NCT03463694.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049964.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049964; html:https://europepmc.org/articles/PMC8103393; pdf:https://europepmc.org/articles/PMC8103393?pdf=render
+37543047,https://doi.org/10.1016/s2666-7568(23)00105-8,"Antipsychotic drug prescribing and mortality in people with dementia before and during the COVID-19 pandemic: a retrospective cohort study in Wales, UK.","Schnier C, McCarthy A, Morales DR, Akbari A, Sofat R, Dale C, Takhar R, Mamas MA, Khunti K, Zaccardi F, Sudlow CL, Wilkinson T, CVD-COVID-UK/COVID-IMPACT Consortium.",,The lancet. Healthy longevity,2023,2023-08-01,N,,,,"<h4>Background</h4>Concerns have been raised that antipsychotic drug prescribing, which has been associated with increased mortality in people with dementia, might have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of SARS-CoV-2. We used multisource, routinely collected health-care data from Wales, UK to investigate prescribing and mortality variations in people with dementia before and during the COVID-19 pandemic.<h4>Methods</h4>In this retrospective cohort study, we used individual-level, anonymised, population-scale linked health data to identify adults aged 60 years and older with a diagnosis of dementia in Wales, UK. We used the CVD-COVID-UK initiative to access Welsh routinely collected electronic health record data from the Secure Anonymised Information Linkage (SAIL) Databank. Patients who were alive and registered with a SAIL general practice on Jan 1, 2016, and who received a dementia diagnosis before the age of 60 years and before or during the study period were included. We explored antipsychotic drug prescribing rate changes over 67 months, between Jan 1, 2016, and Aug 1, 2021, overall and stratified by age and dementia subtype. We used time-series analyses to examine all-cause and myocardial infarction and stroke mortality over the study period and identified the leading causes of death in people with dementia between Jan 1, 2020, and Aug 1, 2021.<h4>Findings</h4>Of 3 106 690 participants in SAIL between Jan 1, 2016 and Aug 1, 2021, 57 396 people (35 148 [61·2%] women and 22 248 [38·8%] men) met inclusion criteria for this study and contributed 101 428 person-years of follow-up. Of the 57 396 people with dementia, 11 929 (20·8%) were prescribed an antipsychotic drug at any point during follow-up. Accounting for seasonality, antipsychotic drug prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 prescriptions per 10 000 person-months in March, 2019, to 1305 per 10 000 person-months in September, 2020. All-cause mortality and stroke mortality increased throughout 2020, while myocardial infarction mortality declined. From Jan 1, 2020, to Aug 1, 2021, 1286 (17·1%) of 7508 participants who died had COVID-19 recorded as the underlying cause of death.<h4>Interpretation</h4>During the COVID-19 pandemic, antipsychotic drug prescribing in people with dementia in the UK increased slightly; however, it is unlikely that this was solely related to the pandemic and this increase was unlikely to be a major factor in the substantial increase in mortality during 2020. The long-term increase in antipsychotic drug prescribing in younger people and in those with Alzheimer's disease warrants further investigation using resources with access to more granular clinical data. Although deprescribing antipsychotic medications remains an essential aspect of dementia care, the results of this study suggest that changes in prescribing and deprescribing practices as a result of the COVID-19 pandemic are not required.<h4>Funding</h4>British Heart Foundation (via the British Heart Foundation Data Science Centre led by Health Data Research UK), and the Scottish Neurological Research Fund.",,doi:https://doi.org/10.1016/S2666-7568(23)00105-8
 34141852,https://doi.org/10.1016/j.ssmph.2021.100828,Media representations of opposition to the 'junk food advertising ban' on the Transport for London (TfL) network: A thematic content analysis of UK news and trade press.,"Thompson C, Clary C, Er V, Adams J, Boyland E, Burgoine T, Cornelsen L, de Vocht F, Egan M, Lake AA, Lock K, Mytton O, Petticrew M, White M, Yau A, Cummins S.",,SSM - population health,2021,2021-05-27,Y,Regulation; Media; Advertising; Childhood Obesity,,,"<h4>Background</h4>Advertising of less healthy foods and drinks is hypothesised to be associated with obesity in adults and children. In February 2019, Transport for London implemented restrictions on advertisements for foods and beverages high in fat, salt or sugar across its network as part of a city-wide strategy to tackle childhood obesity. The policy was extensively debated in the press. This paper identifies arguments for and against the restrictions. Focusing on arguments against the restrictions, it then goes on to deconstruct the discursive strategies underpinning them.<h4>Methods</h4>A qualitative thematic content analysis of media coverage of the restrictions (the 'ban') in UK newspapers and trade press was followed by a document analysis of arguments against the ban. A search period of March 1, 2018 to May 31, 2019 covered: (i) the launch of the public consultation on the ban in May 2018; (ii) the announcement of the ban in November 2018; and (iii) its implementation in February 2019. A systematic search of printed and online publications in English distributed in the UK or published on UK-specific websites identified 152 articles.<h4>Results</h4>Arguments in favour of the ban focused on inequalities and childhood obesity. Arguments against the ban centred on two claims: that childhood obesity was not the 'right' priority; and that an advertising ban was not an effective way to address childhood obesity. These claims were justified via three discursive approaches: (i) claiming more 'important' priorities for action; (ii) disputing the science behind the ban; (iii) emphasising potential financial costs of the ban.<h4>Conclusion</h4>The discursive tactics used in media sources to argue against the ban draw on frames widely used by unhealthy commodities industries in response to structural public health interventions. Our analyses highlight the need for interventions to be framed in ways that can pre-emptively counter common criticisms.",,doi:https://doi.org/10.1016/j.ssmph.2021.100828; doi:https://doi.org/10.1016/j.ssmph.2021.100828; html:https://europepmc.org/articles/PMC8184652; pdf:https://europepmc.org/articles/PMC8184652?pdf=render
 33199838,https://doi.org/10.1038/s41598-020-76860-2,Path-based extensions of local link prediction methods for complex networks.,"Aziz F, Gul H, Uddin I, Gkoutos GV.",,Scientific reports,2020,2020-11-16,Y,,,,"Link prediction in a complex network is a problem of fundamental interest in network science and has attracted increasing attention in recent years. It aims to predict missing (or future) links between two entities in a complex system that are not already connected. Among existing methods, local similarity indices are most popular that take into account the information of common neighbours to estimate the likelihood of existence of a connection between two nodes. In this paper, we propose global and quasi-local extensions of some commonly used local similarity indices. We have performed extensive numerical simulations on publicly available datasets from diverse domains demonstrating that the proposed extensions not only give superior performance, when compared to their respective local indices, but also outperform some of the current, state-of-the-art, local and global link-prediction methods.",,pdf:https://www.nature.com/articles/s41598-020-76860-2.pdf; doi:https://doi.org/10.1038/s41598-020-76860-2; html:https://europepmc.org/articles/PMC7670409; pdf:https://europepmc.org/articles/PMC7670409?pdf=render
 36874571,https://doi.org/10.12688/wellcomeopenres.17981.1,Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales - analysis of the Virus Watch household community cohort study.,"Hoskins S, Beale S, Nguyen V, Fragaszy E, Navaratnam AMD, Smith C, French C, Kovar J, Byrne T, Fong WLE, Geismar C, Patel P, Yavlinksy A, Johnson AM, Aldridge RW, Hayward A, Virus Watch Collaborative.",,Wellcome open research,2022,2022-08-03,Y,Transmission; Activities; Pandemic; Work; Public Transport; Shopping; Lockdown; Covid-19; Sars-cov-2,,,"<b>Background</b>: ""Lockdowns"" to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic.  However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics.  <b>Methods</b>: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household.  Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk.  We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic's second wave. <b>Results</b>: Among 10,858 adults, 18% of cases were likely due to household transmission.  Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 - 1.42), APAF 6.9%); public transport (more than once per week AOR 1.82 (1.49 - 2.23), public transport APAF 12.42%); and shopping (more than once per week AOR 1.69 (1.29 - 2.21), shopping APAF 34.56%).  Other non-household activities were rare and not significantly associated with infection. <b>Conclusions:</b> During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities.  Most participants visited shops, accounting for one-third of non-household transmission.  Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective.   If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.",,doi:https://doi.org/10.12688/wellcomeopenres.17981.1; html:https://europepmc.org/articles/PMC9975411; pdf:https://europepmc.org/articles/PMC9975411?pdf=render
@@ -590,8 +590,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 33875444,https://doi.org/10.1136/bmjopen-2020-045077,COVID-19 in patients with hepatobiliary and pancreatic diseases: a single-centre cross-sectional study in East London.,"Dayem Ullah AZM, Sivapalan L, Kocher HM, Chelala C.",,BMJ open,2021,2021-04-19,Y,Pancreatic Disease; Hepatobiliary Disease; Covid-19,,,"<h4>Objective</h4>To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.<h4>Participants</h4>EL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.<h4>Main outcome measure</h4>COVID-19 incidence and mortality.<h4>Results</h4>Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).<h4>Conclusions</h4>In this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/4/e045077.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-045077; html:https://europepmc.org/articles/PMC8057071; pdf:https://europepmc.org/articles/PMC8057071?pdf=render
 37022975,https://doi.org/10.1210/clinem/dgad201,Stable Incidence and Increasing Prevalence of Primary Hyperparathyroidism in a Population-based Study in Scotland.,"Soto-Pedre E, Newey PJ, Leese GP.",,The Journal of clinical endocrinology and metabolism,2023,2023-09-01,Y,Parathyroid gland; Prevalence; epidemiology; incidence; Primary Hyperparathyroidism,,,"<h4>Context</h4>Previous studies, including our own, have demonstrated a highly variable incidence of primary hyperparathyroidism (PHPT) from year to year.<h4>Objective</h4>We planned to provide a current estimate of the incidence and prevalence of PHPT in a community-based study.<h4>Methods</h4>A population-based retrospective follow-up study was conducted in Tayside (Scotland) from 2007 to 2018. Record-linkage technology (demography, biochemistry, prescribing, hospital admissions, radiology, and mortality data) was used to identify all patients. Cases of PHPT were defined as those with at least 2 raised serum corrected calcium concentration CCA (> 2.55 mmol/L) and/or hospital admissions with PHPT diagnoses and/or surgery records with parathyroidectomy during the follow-up period. The number of prevalent and incident cases of PHPT per calendar year by age and sex were estimated.<h4>Results</h4>A total of 2118 people (72.3% female, mean age 65 years) were identified with an incident case of PHPT. The overall prevalence of PHPT over the 12 years of the study was 0.84% (95% CI, 0.68%-1.02%), steadily increasing from 0.71% in 2007 to 1.02% in 2018. From 2008, the incidence of PHPT was relatively stable from 4 to 6 cases per 10 000 person-years, declining from 11.5 per 10 000 person-years in 2007. The incidence varied from 0.59 per 10 000 person-years (95% CI, 0.40%-0.77%) for those aged 20 to 29 years, to 12.4 per 10 000 person-years (95% CI, 11.2%-13.3%) in those aged 70 to 79 years. Incidence of PHPT was 2.5 times higher in women than in men.<h4>Conclusion</h4>This study is the first showing a relatively steady annual incidence of PHPT at 4 to 6 per 10 000 person-years. This population-based study reports a PHPT prevalence of 0.84%.",,pdf:https://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgad201/50034331/dgad201.pdf; doi:https://doi.org/10.1210/clinem/dgad201; html:https://europepmc.org/articles/PMC10505547
 37139857,https://doi.org/10.1111/dom.15102,Impact of severe hypoglycaemia requiring hospitalization on mortality in people with type 1 diabetes: A national retrospective observational cohort study.,"Moser O, Rafferty J, Eckstein ML, Aziz F, Bain SC, Bergenstal R, Sourij H, Thomas RL.",,"Diabetes, obesity & metabolism",2023,2023-05-04,N,Mortality; type 1 diabetes; Risk Prediction; Severe Hypoglycaemia,,,"<h4>Aims</h4>To assess if the risk of all-cause mortality increases in people with type 1 diabetes (T1D) with increasing number of severe hypoglycaemia episodes requiring hospitalization.<h4>Materials and methods</h4>We conducted a national retrospective observational cohort study in people with T1D (diagnosed between 2000 and 2018). Clinical, comorbidity and demographic variables were assessed for impact on mortality for people with no, one, two and three or more episodes of severe hypoglycaemia requiring hospitalization. The time to death (all-cause mortality) from the timepoint of the last episode of severe hypoglycaemia was modelled using a parametric survival model.<h4>Results</h4>A total of 8224 people had a T1D diagnosis in Wales during the study period. The mortality rate (95% confidence interval [CI]) was 6.9 (6.1-7.8) deaths/ 1000 person-years (crude) and 15.31 (13.3-17.63) deaths/ 1000 person-years (age-adjusted) for those with no occurrence of severe hypoglycaemia requiring hospitalization. For those with one episode of severe hypoglycaemia requiring hospitalization the mortality rate (95% CI) was 24.9 (21.0-29.6; crude) and 53.8 (44.6-64.7) deaths/ 1000 person-years (age-adjusted), for those with two episodes of severe hypoglycaemia requiring hospitalization it was 28.0 (23.1-34.0; crude) and 72.8 (59.2-89.5) deaths/ 1000 person-years (age-adjusted), and for those with three or more episodes of severe hypoglycaemia requiring hospitalization it was 33.5 (30.0-37.3; crude) and 86.3 (71.7-103.9) deaths/ 1000 person years (age-adjusted; P < 0.001). A parametric survival model showed that having two episodes of severe hypoglycaemia requiring hospitalization was the strongest predictor for time to death (accelerated failure time coefficient 0.073 [95% CI 0.009-0.565]), followed by having one episode of severe hypoglycaemia requiring hospitalization (0.126 [0.036-0.438]) and age at most recent episode of severe hypoglycaemia requiring hospitalization (0.917 [0.885-0.951]).<h4>Conclusions</h4>The strongest predictor for time to death was having two or more episodes of severe hypoglycaemia requiring hospitalization.",,doi:https://doi.org/10.1111/dom.15102
-36658423,https://doi.org/10.1038/s41591-022-02158-7,The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.,"Dale CE, Takhar R, Carragher R, Katsoulis M, Torabi F, Duffield S, Kent S, Mueller T, Kurdi A, Le Anh TN, McTaggart S, Abbasizanjani H, Hollings S, Scourfield A, Lyons RA, Griffiths R, Lyons J, Davies G, Harris D, Handy A, Mizani MA, Tomlinson C, Thygesen JH, Ashworth M, Denaxas S, Banerjee A, Sterne JAC, Brown P, Bullard I, Priedon R, Mamas MA, Slee A, Lorgelly P, Pirmohamed M, Khunti K, Morris AD, Sudlow C, Akbari A, Bennie M, Sattar N, Sofat R, CVD-COVID-UK Consortium.",,Nature medicine,2023,2023-01-19,N,,,,"How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.",,pdf:https://www.nature.com/articles/s41591-022-02158-7.pdf; doi:https://doi.org/10.1038/s41591-022-02158-7
 34007896,https://doi.org/10.23889/ijpds.v6i1.1387,"A retrospective epidemiological study of type 1 diabetes mellitus in wales, UK between 2008 and 2018.","Rafferty J, Stephens JW, Atkinson MD, Luzio SD, Akbari A, Gregory JW, Bain S, Owens DR, Thomas RL.",,International journal of population data science,2021,2021-04-15,Y,Diabetes mellitus; epidemiology; Electronic Health Records,,,"<h4>Introduction</h4>Studies of prevalence and the demographic profile of type 1 diabetes are challenging because of the relative rarity of the condition, however, these outcomes can be determined using routine healthcare data repositories. Understanding the epidemiology of type 1 diabetes allows for targeted interventions and care of this life-affecting condition.<h4>Objectives</h4>To describe the prevalence, incidence and demographics of persons with type 1 diabetes diagnosed in Wales, UK, using the Secure Anonymised Information Linkage (SAIL) Databank.<h4>Methods</h4>Data derived from primary and secondary care throughout Wales available in the SAIL Databank were used to identify people with type 1 diabetes to determine the prevalence and incidence of type 1 diabetes over a 10 year period (2008-18) and describe the demographic and clinical characteristics of this population by age, socioeconomic deprivation and settlement type. The seasonal variation in incidence rates was also examined.<h4>Results</h4>The prevalence of type 1 diabetes in 2018 was 0.32% in the whole population, being greater in men compared to women (0.35% vs 0.28% respectively); highest in those aged 15-29 years (0.52%) and living in the most socioeconomically deprived areas (0.38%). The incidence of type 1 diabetes over 10 years was 14.0 cases/100,000 people/year for the whole population of Wales. It was highest in children aged 0-14 years (33.6 cases/100,000 people/year) and areas of high socioeconomic deprivation (16.8 cases/100,000 people/year) and least in those aged 45-60 years (6.5 cases/100,000 people/year) and in areas of low socioeconomic deprivation (11.63 cases/100,000 people/year). A seasonal trend in the diagnoses of type 1 diabetes was observed with higher incidence in winter months.<h4>Conclusion</h4>This nation-wide retrospective epidemiological study using routine data revealed that the incidence of type 1 diabetes in Wales was greatest in those aged 0-14 years with a higher incidence and prevalence in the most deprived areas. These findings illustrate the need for health-related policies targeted at high deprivation areas to include type 1 diabetes in their remit.",,pdf:https://ijpds.org/article/download/1387/3155; doi:https://doi.org/10.23889/ijpds.v6i1.1387; html:https://europepmc.org/articles/PMC8103995; pdf:https://europepmc.org/articles/PMC8103995?pdf=render
+36658423,https://doi.org/10.1038/s41591-022-02158-7,The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.,"Dale CE, Takhar R, Carragher R, Katsoulis M, Torabi F, Duffield S, Kent S, Mueller T, Kurdi A, Le Anh TN, McTaggart S, Abbasizanjani H, Hollings S, Scourfield A, Lyons RA, Griffiths R, Lyons J, Davies G, Harris D, Handy A, Mizani MA, Tomlinson C, Thygesen JH, Ashworth M, Denaxas S, Banerjee A, Sterne JAC, Brown P, Bullard I, Priedon R, Mamas MA, Slee A, Lorgelly P, Pirmohamed M, Khunti K, Morris AD, Sudlow C, Akbari A, Bennie M, Sattar N, Sofat R, CVD-COVID-UK Consortium.",,Nature medicine,2023,2023-01-19,N,,,,"How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.",,pdf:https://www.nature.com/articles/s41591-022-02158-7.pdf; doi:https://doi.org/10.1038/s41591-022-02158-7
 35485805,https://doi.org/10.1017/s003329172200109x,Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study.,"Ma R, Romano E, Ashworth M, Yadegarfar ME, Dregan A, Ronaldson A, de Oliveira C, Jacobs R, Stewart R, Stubbs B.",,Psychological medicine,2023,2022-04-29,Y,Mortality; Schizophrenia; Psychosis; Physical Health; Multimorbidity,,,"<h4>Background</h4>People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population.<h4>Methods</h4>People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012-2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership.<h4>Results</h4>The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: 'substance related' (24.9%), 'atopic' (24.2%), 'pure affective' (30.4%), 'cardiovascular' (14.1%), and 'complex multimorbidity' (6.4%). Patients had on average 7-9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the 'pure affective'. Compared to the largest cluster ('pure affective'), the 'substance related' and the 'atopic' clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98-1.00) and 0.96 (0.95-0.97) respectively], and the 'cardiovascular' and 'complex multimorbidity' clusters were older (ORs 1.09 (1.07-1.10) and 1.16 (1.14-1.18) respectively). The 'substance related' cluster was more likely to be White, the 'cardiovascular' cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10-2.79), and both more likely to have schizophrenia, compared to other clusters.<h4>Conclusion</h4>The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/BDE3DC6059EB59B00B2E0CD892963804/S003329172200109Xa.pdf/div-class-title-multimorbidity-clusters-among-people-with-serious-mental-illness-a-representative-primary-and-secondary-data-linkage-cohort-study-div.pdf; doi:https://doi.org/10.1017/S003329172200109X; html:https://europepmc.org/articles/PMC10388332; pdf:https://europepmc.org/articles/PMC10388332?pdf=render
 37000839,https://doi.org/10.1371/journal.pone.0279076,Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.,"Kennedy J, Kennedy N, Cooksey R, Choy E, Siebert S, Rahman M, Brophy S.",,PloS one,2023,2023-03-31,Y,,,,"Ankylosing spondylitis is the second most common cause of inflammatory arthritis. However, a successful diagnosis can take a decade to confirm from symptom onset (via x-rays). The aim of this study was to use machine learning methods to develop a profile of the characteristics of people who are likely to be given a diagnosis of AS in future. The Secure Anonymised Information Linkage databank was used. Patients with ankylosing spondylitis were identified using their routine data and matched with controls who had no record of a diagnosis of ankylosing spondylitis or axial spondyloarthritis. Data was analysed separately for men and women. The model was developed using feature/variable selection and principal component analysis to develop decision trees. The decision tree with the highest average F value was selected and validated with a test dataset. The model for men indicated that lower back pain, uveitis, and NSAID use under age 20 is associated with AS development. The model for women showed an older age of symptom presentation compared to men with back pain and multiple pain relief medications. The models showed good prediction (positive predictive value 70%-80%) in test data but in the general population where prevalence is very low (0.09% of the population in this dataset) the positive predictive value would be very low (0.33%-0.25%). Machine learning can be used to help profile and understand the characteristics of people who will develop AS, and in test datasets with artificially high prevalence, will perform well. However, when applied to a general population with low prevalence rates, such as that in primary care, the positive predictive value for even the best model would be 1.4%. Multiple models may be needed to narrow down the population over time to improve the predictive value and therefore reduce the time to diagnosis of ankylosing spondylitis.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render
 36994768,https://doi.org/10.1002/cphy.c210037,Autonomic Cardiovascular Control in Health and Disease.,"Karim S, Chahal A, Khanji MY, Petersen SE, Somers VK.",,Comprehensive Physiology,2023,2023-03-30,N,,,,"Autonomic neural control of the cardiovascular system is formed of complex and dynamic processes able to adjust rapidly to mitigate perturbations in hemodynamics and maintain homeostasis. Alterations in autonomic control feature in the development or progression of a multitude of diseases with wide-ranging physiological implications given the neural system's responsibility for controlling inotropy, chronotropy, lusitropy, and dromotropy. Imbalances in sympathetic and parasympathetic neural control are also implicated in the development of arrhythmia in several cardiovascular conditions sparking interest in autonomic modulation as a form of treatment. A number of measures of autonomic function have shown prognostic significance in health and in pathological states and have undergone varying degrees of refinement, yet adoption into clinical practice remains extremely limited. The focus of this contemporary narrative review is to summarize the anatomy, physiology, and pathophysiology of the cardiovascular autonomic nervous system and describe the merits and shortfalls of testing modalities available. © 2023 American Physiological Society. Compr Physiol 13:4493-4511, 2023.",,doi:https://doi.org/10.1002/cphy.c210037
@@ -607,21 +607,21 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 33716109,https://doi.org/10.1016/j.jinf.2021.03.002,Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate.,"Chaudhry Z, Shawe-Taylor M, Rampling T, Cutfield T, Bidwell G, Chan XHS, Last A, Williams B, Logan S, Marks M, Esmail H.",,The Journal of infection,2021,2021-03-11,Y,Dexamethasone; Corticosteroids; Hospital; Readmissions; Covid-19,,,"<h4>Objective</h4>Our objective was to describe the characteristics of patients admitted, discharged and readmitted, due to COVID-19, to a central London acute-care hospital during the second peak, in particular in relation to corticosteroids use.<h4>Methods</h4>We reviewed patients admitted from the community to University College Hospital (UCH) with COVID-19 as their primary diagnosis between 1st-31st December 2020. Re-attendance and readmission data were collected for patients who re-presented within 10 days following discharge. Data were retrospectively collected.<h4>Results</h4>196 patients were admitted from the community with a diagnosis of COVID-19 and discharged alive in December 2020. Corticosteroids were prescribed in hospital for a median of 5 days (IQR 3-8). 20 patients (10.2%) were readmitted within 10 days. 11/20 received corticosteroids in the first admission of which 10 had received 1-3 days of corticosteroids. Readmission rate in those receiving 1-3 days of corticosteroids was 25%.<h4>Conclusions</h4>Most international guidelines have recommended providing up to 10 days of corticosteroids for severe COVID-19 but stopping on discharge. Our findings show shorter courses of corticosteroids during admission are associated with an increased risk of being readmitted and support continuing the course of corticosteroids after hospital discharge monitored in the virtual ward setting.",,pdf:http://www.journalofinfection.com/article/S0163445321001158/pdf; doi:https://doi.org/10.1016/j.jinf.2021.03.002; html:https://europepmc.org/articles/PMC7948670; pdf:https://europepmc.org/articles/PMC7948670?pdf=render
 37699069,https://doi.org/10.1093/ehjci/jead218,Phenotyping left ventricular systolic dysfunction in asymptomatic individuals for improved risk stratification.,"Rauseo E, Abdulkareem M, Khan A, Cooper J, Lee AM, Aung N, Slabaugh GG, Petersen SE.",,European heart journal. Cardiovascular Imaging,2023,2023-09-01,Y,Prognosis; Cardiovascular events; Risk stratification; Heart Failure; Cardiovascular Magnetic Resonance; Left Ventricular Systolic Dysfunction,,,"<h4>Aims</h4>Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering.<h4>Methods and results</h4>Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance.<h4>Conclusions</h4>Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.",,doi:https://doi.org/10.1093/ehjci/jead218; html:https://europepmc.org/articles/PMC10531121; pdf:https://europepmc.org/articles/PMC10531121?pdf=render
 36377225,https://doi.org/10.1177/18333583221135710,Concordance between coding sources of burn size and depth across Australian and New Zealand specialist burn services.,"Perkins M, Cleland H, Gabbe BJ, Tracy LM.",,Health information management : journal of the Health Information Management Association of Australia,2022,2022-11-14,N,Burns; Australia; New Zealand; Registries; Health Information Management; International Classification Of Diseases; Clinical Coding,,,"<h4>Background</h4>The percentage of total body surface area (%TBSA) burned and burn depth provide valuable information on burn injury severity.<h4>Objective</h4>This study investigated the concordance between The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes and expert burn clinicians in assessing burn injury severity.<h4>Method</h4>We conducted a retrospective population-based review of all patients who sustained a burn injury between July 1, 2009, and June 30, 2019, requiring admission into a specialist burn service across Australia and New Zealand. The %TBSA burned (including the percentage of full thickness burns) recorded by expert burn clinicians within the Burns Registry of Australia and New Zealand (BRANZ) were compared to ICD-10-AM coding.<h4>Results</h4>20,642 cases (71.5%) with ICD-10-AM code data were recorded. Overall, kappa scores (95% confidence interval [CI]) for burn size ranged from 0.64 (95% CI 0.63-0.66) to 0.86 (95% CI 0.78-0.94) indicating substantial to almost perfect agreement across all %TBSA groups. When stratified by depth, the lowest agreement was observed for < 10% TBSA and < 10% full thickness (kappa 0.03; 95% CI 0.02-0.04) and the highest agreement was observed for burns of ≥ 90% TBSA and ≥ 90% full thickness (kappa 0.72; 95% CI 0.58-0.85).<h4>Conclusion</h4>Overall, there was substantial agreement between the BRANZ and ICD-10-AM coded data for %TBSA classification. When %TBSA classification was stratified by burn depth, greater agreement was observed for larger and deeper burns compared with smaller and superficial burns.<h4>Implications</h4>Greater consistency in the classification of burns is needed.",,doi:https://doi.org/10.1177/18333583221135710
-36794597,https://doi.org/10.1111/trf.17277,Impact of a post-donation hemoglobin testing strategy on efficiency and safety of whole blood donation in England: A modeling study.,"Kim LG, Bolton T, Sweeting MJ, Bell S, Fahle S, McMahon A, Walker M, Ferguson E, Miflin G, Roberts DJ, Di Angelantonio E, Wood AM.",,Transfusion,2023,2023-02-16,N,Blood Donation; Simulation Modeling; Low Hemoglobin Deferral; Post-donation Testing,,,"<h4>Background</h4>Deferrals due to low hemoglobin are time-consuming and costly for blood donors and donation services. Furthermore, accepting donations from those with low hemoglobin could represent a significant safety issue. One approach to reduce them is to use hemoglobin concentration alongside donor characteristics to inform personalized inter-donation intervals.<h4>Study design and methods</h4>We used data from 17,308 donors to inform a discrete event simulation model comparing personalized inter-donation intervals using ""post-donation"" testing (i.e., estimating current hemoglobin from that measured by a hematology analyzer at last donation) versus the current approach in England (i.e., pre-donation testing with fixed intervals of 12-weeks for men and 16-weeks for women). We reported the impact on total donations, low hemoglobin deferrals, inappropriate bleeds, and blood service costs. Personalized inter-donation intervals were defined using mixed-effects modeling to estimate hemoglobin trajectories and probability of crossing hemoglobin donation thresholds.<h4>Results</h4>The model had generally good internal validation, with predicted events similar to those observed. Over 1 year, a personalized strategy requiring ≥90% probability of being over the hemoglobin threshold, minimized adverse events (low hemoglobin deferrals and inappropriate bleeds) in both sexes and costs in women. Donations per adverse event improved from 3.4 (95% uncertainty interval 2.8, 3.7) under the current strategy to 14.8 (11.6, 19.2) in women, and from 7.1 (6.1, 8.5) to 26.9 (20.8, 42.6) in men. In comparison, a strategy incorporating early returns for those with high certainty of being over the threshold maximized total donations in both men and women, but was less favorable in terms of adverse events, with 8.4 donations per adverse event in women (7.0, 10,1) and 14.8 (12.1, 21.0) in men.<h4>Discussion</h4>Personalized inter-donation intervals using post-donation testing combined with modeling of hemoglobin trajectories can help reduce deferrals, inappropriate bleeds, and costs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/trf.17277; doi:https://doi.org/10.1111/trf.17277
 32424068,https://doi.org/10.1101/gr.250704.119,Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.,"Fang L, Cai W, Liu S, Canela-Xandri O, Gao Y, Jiang J, Rawlik K, Li B, Schroeder SG, Rosen BD, Li CJ, Sonstegard TS, Alexander LJ, Van Tassell CP, VanRaden PM, Cole JB, Yu Y, Zhang S, Tenesa A, Ma L, Liu GE.",,Genome research,2020,2020-05-18,Y,,,,"By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide association studies, we detected relevant tissues/cell types and candidate genes for 45 economically important traits in cattle, including blood/immune system (e.g., <i>CCDC88C</i>) for male fertility, brain (e.g., <i>TRIM46</i> and <i>RAB6A</i>) for milk production, and multiple growth-related tissues (e.g., <i>FGF6</i> and <i>CCND2</i>) for body conformation. We validated these findings by using epigenomic data across major somatic tissues and sperm. Collectively, our findings provided novel insights into the genetic and biological mechanisms underlying complex traits in cattle, and our transcriptome atlas can serve as a primary source for biological interpretation, functional validation, studies of adaptive evolution, and genomic improvement in livestock.",,pdf:https://genome.cshlp.org/content/30/5/790.full.pdf; doi:https://doi.org/10.1101/gr.250704.119; html:https://europepmc.org/articles/PMC7263193; pdf:https://europepmc.org/articles/PMC7263193?pdf=render
 33212507,https://doi.org/10.1093/molbev/msaa279,Genomic Analysis Revealed a Convergent Evolution of LINE-1 in Coat Color: A Case Study in Water Buffaloes (Bubalus bubalis).,"Liang D, Zhao P, Si J, Fang L, Pairo-Castineira E, Hu X, Xu Q, Hou Y, Gong Y, Liang Z, Tian B, Mao H, Yindee M, Faruque MO, Kongvongxay S, Khamphoumee S, Liu GE, Wu DD, Barker JSF, Han J, Zhang Y.",,Molecular biology and evolution,2021,2021-03-01,Y,Transposon; Water buffalo; Convergent Evolution; Line-1; Asip Gene; White Coat Color,,,"Visible pigmentation phenotypes can be used to explore the regulation of gene expression and the evolution of coat color patterns in animals. Here, we performed whole-genome and RNA sequencing and applied genome-wide association study, comparative population genomics and biological experiments to show that the 2,809-bp-long LINE-1 insertion in the ASIP (agouti signaling protein) gene is the causative mutation for the white coat phenotype in swamp buffalo (Bubalus bubalis). This LINE-1 insertion (3' truncated and containing only 5' UTR) functions as a strong proximal promoter that leads to a 10-fold increase in the transcription of ASIP in white buffalo skin. The 165 bp of 5' UTR transcribed from the LINE-1 is spliced into the first coding exon of ASIP, resulting in a chimeric transcript. The increased expression of ASIP prevents melanocyte maturation, leading to the absence of pigment in white buffalo skin and hairs. Phylogenetic analyses indicate that the white buffalo-specific ASIP allele originated from a recent genetic transposition event in swamp buffalo. Interestingly, as a similar LINE-1 insertion has been identified in the cattle ASIP gene, we discuss the convergent mechanism of coat color evolution in the Bovini tribe.",,pdf:https://academic.oup.com/mbe/article-pdf/38/3/1122/36533820/msaa279.pdf; doi:https://doi.org/10.1093/molbev/msaa279; html:https://europepmc.org/articles/PMC7947781; pdf:https://europepmc.org/articles/PMC7947781?pdf=render
+36794597,https://doi.org/10.1111/trf.17277,Impact of a post-donation hemoglobin testing strategy on efficiency and safety of whole blood donation in England: A modeling study.,"Kim LG, Bolton T, Sweeting MJ, Bell S, Fahle S, McMahon A, Walker M, Ferguson E, Miflin G, Roberts DJ, Di Angelantonio E, Wood AM.",,Transfusion,2023,2023-02-16,N,Blood Donation; Simulation Modeling; Low Hemoglobin Deferral; Post-donation Testing,,,"<h4>Background</h4>Deferrals due to low hemoglobin are time-consuming and costly for blood donors and donation services. Furthermore, accepting donations from those with low hemoglobin could represent a significant safety issue. One approach to reduce them is to use hemoglobin concentration alongside donor characteristics to inform personalized inter-donation intervals.<h4>Study design and methods</h4>We used data from 17,308 donors to inform a discrete event simulation model comparing personalized inter-donation intervals using ""post-donation"" testing (i.e., estimating current hemoglobin from that measured by a hematology analyzer at last donation) versus the current approach in England (i.e., pre-donation testing with fixed intervals of 12-weeks for men and 16-weeks for women). We reported the impact on total donations, low hemoglobin deferrals, inappropriate bleeds, and blood service costs. Personalized inter-donation intervals were defined using mixed-effects modeling to estimate hemoglobin trajectories and probability of crossing hemoglobin donation thresholds.<h4>Results</h4>The model had generally good internal validation, with predicted events similar to those observed. Over 1 year, a personalized strategy requiring ≥90% probability of being over the hemoglobin threshold, minimized adverse events (low hemoglobin deferrals and inappropriate bleeds) in both sexes and costs in women. Donations per adverse event improved from 3.4 (95% uncertainty interval 2.8, 3.7) under the current strategy to 14.8 (11.6, 19.2) in women, and from 7.1 (6.1, 8.5) to 26.9 (20.8, 42.6) in men. In comparison, a strategy incorporating early returns for those with high certainty of being over the threshold maximized total donations in both men and women, but was less favorable in terms of adverse events, with 8.4 donations per adverse event in women (7.0, 10,1) and 14.8 (12.1, 21.0) in men.<h4>Discussion</h4>Personalized inter-donation intervals using post-donation testing combined with modeling of hemoglobin trajectories can help reduce deferrals, inappropriate bleeds, and costs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/trf.17277; doi:https://doi.org/10.1111/trf.17277
 37468148,https://doi.org/10.1136/bmj-2023-075133,Associations between self-reported healthcare disruption due to covid-19 and avoidable hospital admission: evidence from seven linked longitudinal studies for England.,"Green MA, McKee M, Hamilton OK, Shaw RJ, Macleod J, Boyd A, Katikireddi SV, LH&W NCS Collaborative.",,BMJ (Clinical research ed.),2023,2023-07-19,Y,,,,"<h4>Objectives</h4>To examine whether there is an association between people who experienced disrupted access to healthcare during the covid-19 pandemic and risk of an avoidable hospital admission.<h4>Design</h4>Observational analysis using evidence from seven linked longitudinal cohort studies for England.<h4>Setting</h4>Studies linked to electronic health records from NHS Digital from 1 March 2020 to 25 August 2022. Data were accessed using the UK Longitudinal Linkage Collaboration trusted research environment.<h4>Participants</h4>Individual level records for 29 276 people.<h4>Main outcome measures</h4>Avoidable hospital admissions defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions.<h4>Results</h4>9742 participants (weighted percentage 35%, adjusted for sample structure of longitudinal cohorts) self-reported some form of disrupted access to healthcare during the covid-19 pandemic. People with disrupted access were at increased risk of any (odds ratio 1.80, 95% confidence interval 1.39 to 2.34), acute (2.01, 1.39 to 2.92), and chronic (1.80, 1.31 to 2.48) ambulatory care sensitive hospital admissions. For people who experienced disrupted access to appointments (eg, visiting their doctor or an outpatient department) and procedures (eg, surgery, cancer treatment), positive associations were found with measures of avoidable hospital admissions.<h4>Conclusions</h4>Evidence from linked individual level data shows that people whose access to healthcare was disrupted were more likely to have a potentially preventable hospital admission. The findings highlight the need to increase healthcare investment to tackle the short and long term implications of the pandemic, and to protect treatments and procedures during future pandemics.",,doi:https://doi.org/10.1136/bmj-2023-075133; html:https://europepmc.org/articles/PMC10354595; pdf:https://europepmc.org/articles/PMC10354595?pdf=render
 36808078,https://doi.org/10.1136/pn-2021-003286,Outpatient neurology diagnostic coding: a proposed scheme for standardised implementation.,"Biggin F, Knight J, Dayanandan R, Marson A, Wilson M, Nitkunan A, Rog D, Kipps C, Mummery C, Williams A, Emsley HCA.",,Practical neurology,2023,2023-02-20,Y,Clinical Neurology,,,"Clinical coding uses a classification system to assign standard codes to clinical terms and so facilitates good clinical practice through audit, service design and research. However, despite clinical coding being mandatory for inpatient activity, this is often not so for outpatient services, where most neurological care is delivered. Recent reports by the UK National Neurosciences Advisory Group and NHS England's 'Getting It Right First Time' initiative recommend implementing outpatient coding. The UK currently has no standardised system for outpatient neurology diagnostic coding. However, most new attendances at general neurology clinics appear to be classifiable with a limited number of diagnostic terms. We present the rationale for diagnostic coding and its benefits, and the need for clinical engagement to develop a system that is pragmatic, quick and easy to use. We outline a scheme developed in the UK that could be used elsewhere.",,pdf:https://pn.bmj.com/content/practneurol/early/2023/02/19/pn-2021-003286.full.pdf; doi:https://doi.org/10.1136/pn-2021-003286; html:https://europepmc.org/articles/PMC10423506; pdf:https://europepmc.org/articles/PMC10423506?pdf=render
 35813280,https://doi.org/10.1016/s2666-7568(22)00118-0,Antibody and cellular immune responses following dual COVID-19 vaccination within infection-naive residents of long-term care facilities: an observational cohort study.,"Tut G, Lancaster T, Sylla P, Butler MS, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Ayodele M, Bone D, Tut E, Bruton R, Krutikov M, Giddings R, Shrotri M, Azmi B, Fuller C, Baynton V, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,The lancet. Healthy longevity,2022,2022-07-04,Y,,,,"<h4>Background</h4>Older age and frailty are risk factors for poor clinical outcomes following SARS-CoV-2 infection. As such, COVID-19 vaccination has been prioritised for individuals with these factors, but there is concern that immune responses might be impaired due to age-related immune dysregulation and comorbidity. We aimed to study humoral and cellular responses to COVID-19 vaccines in residents of long-term care facilities (LTCFs).<h4>Methods</h4>In this observational cohort study, we assessed antibody and cellular immune responses following COVID-19 vaccination in members of staff and residents at 74 LTCFs across the UK. Staff and residents were eligible for inclusion if it was possible to link them to a pseudo-identifier in the COVID-19 datastore, if they had received two vaccine doses, and if they had given a blood sample 6 days after vaccination at the earliest. There were no comorbidity exclusion criteria. Participants were stratified by age (<65 years or ≥65 years) and infection status (previous SARS-CoV-2 infection [infection-primed group] or SARS-CoV-2 naive [infection-naive group]). Anticoagulated edetic acid (EDTA) blood samples were assessed and humoral and cellular responses were quantified.<h4>Findings</h4>Between Dec 11, 2020, and June 27, 2021, blood samples were taken from 220 people younger than 65 years (median age 51 years [IQR 39-61]; 103 [47%] had previously had a SARS-CoV-2 infection) and 268 people aged 65 years or older of LTCFs (median age 87 years [80-92]; 144 [43%] had a previous SARS-CoV-2 infection). Samples were taken a median of 82 days (IQR 72-100) after the second vaccination. Antibody responses following dual vaccination were strong and equivalent between participants younger then 65 years and those aged 65 years and older in the infection-primed group (median 125 285 Au/mL [1128 BAU/mL] for <65 year olds <i>vs</i> 157 979 Au/mL [1423 BAU/mL] for ≥65 year olds; p=0·47). The antibody response was reduced by 2·4-times (467 BAU/mL; p≤0·0001) in infection-naive people younger than 65 years and 8·1-times (174 BAU/mL; p≤0·0001) in infection-naive residents compared with their infection-primed counterparts. Antibody response was 2·6-times lower in infection-naive residents than in infection-naive people younger than 65 years (p=0·0006). Impaired neutralisation of delta (1.617.2) variant spike binding was also apparent in infection-naive people younger than 65 years and in those aged 65 years and older. Spike-specific T-cell responses were also significantly enhanced in the infection-primed group. Infection-naive people aged 65 years and older (203 SFU per million [IQR 89-374]) had a 52% lower T-cell response compared with infection-naive people younger than 65 years (85 SFU per million [30-206]; p≤0·0001). Post-vaccine spike-specific CD4 T-cell responses displayed single or dual production of IFN-γ and IL-2 were similar across infection status groups, whereas the infection-primed group had an extended functional profile with TNFα and CXCL10 production.<h4>Interpretation</h4>These data reveal suboptimal post-vaccine immune responses within infection-naive residents of LTCFs, and they suggest the need for optimisation of immune protection through the use of booster vaccination.<h4>Funding</h4>UK Government Department of Health and Social Care.",,pdf:http://pure-oai.bham.ac.uk/ws/files/173553190/1_s2.0_S2666756822001180_main.pdf; doi:https://doi.org/10.1016/S2666-7568(22)00118-0; html:https://europepmc.org/articles/PMC9252532; pdf:https://europepmc.org/articles/PMC9252532?pdf=render
 33634312,https://doi.org/10.1093/bib/bbab006,Benchmarking network-based gene prioritization methods for cerebral small vessel disease.,"Zhang H, Ferguson A, Robertson G, Jiang M, Zhang T, Sudlow C, Smith K, Rannikmae K, Wu H.",,Briefings in bioinformatics,2021,2021-09-01,Y,Cerebral Small Vessel Disease; Protein–protein Interaction; Benchmarking; Disease Gene Association; Network-based Gene Prioritization,,,"Network-based gene prioritization algorithms are designed to prioritize disease-associated genes based on known ones using biological networks of protein interactions, gene-disease associations (GDAs) and other relationships between biological entities. Various algorithms have been developed based on different mechanisms, but it is not obvious which algorithm is optimal for a specific disease. To address this issue, we benchmarked multiple algorithms for their application in cerebral small vessel disease (cSVD). We curated protein-gene interactions (PGIs) and GDAs from databases and assembled PGI networks and disease-gene heterogeneous networks. A screening of algorithms resulted in seven representative algorithms to be benchmarked. Performance of algorithms was assessed using both leave-one-out cross-validation (LOOCV) and external validation with MEGASTROKE genome-wide association study (GWAS). We found that random walk with restart on the heterogeneous network (RWRH) showed best LOOCV performance, with median LOOCV rediscovery rank of 185.5 (out of 19 463 genes). The GenePanda algorithm had most GWAS-confirmable genes in top 200 predictions, while RWRH had best ranks for small vessel stroke-associated genes confirmed in GWAS. In conclusion, RWRH has overall better performance for application in cSVD despite its susceptibility to bias caused by degree centrality. Choice of algorithms should be determined before applying to specific disease. Current pure network-based gene prioritization algorithms are unlikely to find novel disease-associated genes that are not associated with known ones. The tools for implementing and benchmarking algorithms have been made available and can be generalized for other diseases.",,pdf:https://www.pure.ed.ac.uk/ws/files/198917679/bbab006.pdf; doi:https://doi.org/10.1093/bib/bbab006; html:https://europepmc.org/articles/PMC8425308; pdf:https://europepmc.org/articles/PMC8425308?pdf=render
 36567336,https://doi.org/10.1186/s12872-022-03005-w,Diagnostic signature for heart failure with preserved ejection fraction (HFpEF): a machine learning approach using multi-modality electronic health record data.,"Farajidavar N, O'Gallagher K, Bean D, Nabeebaccus A, Zakeri R, Bromage D, Kraljevic Z, Teo JTH, Dobson RJ, Shah AM.",,BMC cardiovascular disorders,2022,2022-12-26,Y,Dyspnea; Machine Learning; Hfpef,,,"<h4>Background</h4>Heart failure with preserved ejection fraction (HFpEF) is thought to be highly prevalent yet remains underdiagnosed. Evidence-based treatments are available that increase quality of life and decrease hospitalization. We sought to develop a data-driven diagnostic model to predict from electronic health records (EHR) the likelihood of HFpEF among patients with unexplained dyspnea and preserved left ventricular EF.<h4>Methods and results</h4>The derivation cohort comprised patients with dyspnea and echocardiography results. Structured and unstructured data were extracted using an automated informatics pipeline. Patients were retrospectively diagnosed as HFpEF (cases), non-HF (control cohort I), or HF with reduced EF (HFrEF; control cohort II). The ability of clinical parameters and investigations to discriminate cases from controls was evaluated by extreme gradient boosting. A likelihood scoring system was developed and validated in a separate test cohort. The derivation cohort included 1585 consecutive patients: 133 cases of HFpEF (9%), 194 non-HF cases (Control cohort I) and 1258 HFrEF cases (Control cohort II). Two HFpEF diagnostic signatures were derived, comprising symptoms, diagnoses and investigation results. A final prediction model was generated based on the averaged likelihood scores from these two models. In a validation cohort consisting of 269 consecutive patients [with 66 HFpEF cases (24.5%)], the diagnostic power of detecting HFpEF had an AUROC of 90% (P < 0.001) and average precision of 74%.<h4>Conclusion</h4>This diagnostic signature enables discrimination of HFpEF from non-cardiac dyspnea or HFrEF from EHR and can assist in the diagnostic evaluation in patients with unexplained dyspnea. This approach will enable identification of HFpEF patients who may then benefit from new evidence-based therapies.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-022-03005-w; doi:https://doi.org/10.1186/s12872-022-03005-w; html:https://europepmc.org/articles/PMC9791783; pdf:https://europepmc.org/articles/PMC9791783?pdf=render
-36447757,https://doi.org/10.1136/gpsych-2022-100819,Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area.,"Chen J, Perera G, Shetty H, Broadbent M, Xu Y, Stewart R.",,General psychiatry,2022,2022-11-04,Y,Schizophrenia; Life style; Mental Health Services,,,"<h4>Background</h4>People with schizophrenia have a high premature mortality risk. Obesity is a key potential underlying risk factor that is relatively unevaluated to date.<h4>Aims</h4>In this study, we investigated the associations of routinely recorded body size with all-cause mortality and deaths from common causes in a large cohort of people with schizophrenia spectrum disorders.<h4>Methods</h4>We assembled a retrospective observational cohort using data from a large mental health service in South London. We followed all patients over the age of 18 years with a clinical diagnosis of schizophrenia spectrum disorders from the date of their first recorded body mass index (BMI) between 1 January 2007 and 31 March 2018.<h4>Results</h4>Of 11 900 patients with a BMI recording, 1566 died. The Cox proportional hazards regression models, after adjusting for sociodemographic, socioeconomic variables and comorbidities, indicated that all-cause mortality was only associated with underweight status compared with healthy weight status (hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.01 to 1.76). Obesity (HR: 1.24, 95% CI: 1.01 to 1.52) and morbid obesity (HR: 1.54, 95% CI: 1.03 to 2.42) were associated with all-cause mortality in the 18-45 years age range, and obesity was associated with lower risk (HR: 0.66, 95% CI: 0.50 to 0.87) in those aged 65+ years. Cancer mortality was raised in underweight individuals (HR: 1.93, 95% CI: 1.03 to 4.10) and respiratory disease mortality raised in those with morbid obesity (HR: 2.17, 95% CI: 1.02 to 5.22).<h4>Conclusions</h4>Overall, being underweight was associated with higher mortality in this disorder group; however, this was potentially accounted for by frailty in older age groups, and obesity was a risk factor for premature mortality in younger ages. The impact of obesity on life expectancy for people with schizophrenia spectrum disorders is clear from our findings. A deeper biological understanding of the relationship between these diseases and schizophrenia will help improve clinical practice.",,pdf:https://gpsych.bmj.com/content/gpsych/35/5/e100819.full.pdf; doi:https://doi.org/10.1136/gpsych-2022-100819; html:https://europepmc.org/articles/PMC9639123; pdf:https://europepmc.org/articles/PMC9639123?pdf=render
 33587202,https://doi.org/10.1007/s10654-021-00722-y,COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors.,"Elliott J, Bodinier B, Whitaker M, Delpierre C, Vermeulen R, Tzoulaki I, Elliott P, Chadeau-Hyam M.",,European journal of epidemiology,2021,2021-02-15,Y,Risk factor; Prospective Cohort; Uk Biobank; Sars-cov-2; Covid-19 Mortality,,,"Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18-3.49] per S.D. [8.1 years], p = 2.6 × 10<sup>-17</sup>), male sex (OR = 1.47 [1.26-1.73], p = 1.3 × 10<sup>-6</sup>) and Black versus White ethnicity (OR = 1.21 [1.12-1.29], p = 3.0 × 10<sup>-7</sup>) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin-angiotensin-aldosterone system inhibitors may be explained by the aforementioned factors.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00722-y.pdf; doi:https://doi.org/10.1007/s10654-021-00722-y; html:https://europepmc.org/articles/PMC7882869; pdf:https://europepmc.org/articles/PMC7882869?pdf=render
+36447757,https://doi.org/10.1136/gpsych-2022-100819,Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area.,"Chen J, Perera G, Shetty H, Broadbent M, Xu Y, Stewart R.",,General psychiatry,2022,2022-11-04,Y,Schizophrenia; Life style; Mental Health Services,,,"<h4>Background</h4>People with schizophrenia have a high premature mortality risk. Obesity is a key potential underlying risk factor that is relatively unevaluated to date.<h4>Aims</h4>In this study, we investigated the associations of routinely recorded body size with all-cause mortality and deaths from common causes in a large cohort of people with schizophrenia spectrum disorders.<h4>Methods</h4>We assembled a retrospective observational cohort using data from a large mental health service in South London. We followed all patients over the age of 18 years with a clinical diagnosis of schizophrenia spectrum disorders from the date of their first recorded body mass index (BMI) between 1 January 2007 and 31 March 2018.<h4>Results</h4>Of 11 900 patients with a BMI recording, 1566 died. The Cox proportional hazards regression models, after adjusting for sociodemographic, socioeconomic variables and comorbidities, indicated that all-cause mortality was only associated with underweight status compared with healthy weight status (hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.01 to 1.76). Obesity (HR: 1.24, 95% CI: 1.01 to 1.52) and morbid obesity (HR: 1.54, 95% CI: 1.03 to 2.42) were associated with all-cause mortality in the 18-45 years age range, and obesity was associated with lower risk (HR: 0.66, 95% CI: 0.50 to 0.87) in those aged 65+ years. Cancer mortality was raised in underweight individuals (HR: 1.93, 95% CI: 1.03 to 4.10) and respiratory disease mortality raised in those with morbid obesity (HR: 2.17, 95% CI: 1.02 to 5.22).<h4>Conclusions</h4>Overall, being underweight was associated with higher mortality in this disorder group; however, this was potentially accounted for by frailty in older age groups, and obesity was a risk factor for premature mortality in younger ages. The impact of obesity on life expectancy for people with schizophrenia spectrum disorders is clear from our findings. A deeper biological understanding of the relationship between these diseases and schizophrenia will help improve clinical practice.",,pdf:https://gpsych.bmj.com/content/gpsych/35/5/e100819.full.pdf; doi:https://doi.org/10.1136/gpsych-2022-100819; html:https://europepmc.org/articles/PMC9639123; pdf:https://europepmc.org/articles/PMC9639123?pdf=render
 37526977,https://doi.org/10.5830/cvja-2023-037,Yield of family screening in dilated cardiomyopathy within low-income setting: Tanzanian experience.,"Fundikira LS, Julius J, Chillo P, Mayala H, Kifai E, van Laake LW, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,Cardiovascular journal of Africa,2023,2023-07-25,N,Screening; Dilated cardiomyopathy; First‐degree Relatives,,,"<h4>Background</h4>Dilated cardiomyopathy (DCM) is often familial and screening of relatives is recommended. However, studies on the yield of screening are scarce in developing countries.<h4>Aim</h4>The aim of the study was to identify and characterise First-degree relatives of patients with DCM in Tanzania.<h4>Methods</h4>We recruited first-degree relatives of 57 DCM patients. DCM in the relatives was diagnosed using the 2016 revised definition by the European Society of Cardiology working group on myocardial and pericardial diseases.<h4>Results</h4>We screened 120 first-degree relatives. All were asymptomatic (100%) with a median age of 39.0 years (29.5-49.0), slightly over a half (53.3%) were females and 17 (14.1%) were found to have previously unknown DCM. The mean (± SD) indexed left ventricular end-diastolic volume was significantly higher in relatives with DCM (71 ± 11.5 ml) compared to relatives without DCM (50 ± 11.5) (<i>p</i> = 0.001).<h4>Conclusion</h4>First-degree relatives of patients with DCM are at risk of developing asymptomatic DCM at a young age.",,doi:https://doi.org/10.5830/CVJA-2023-037
 37381004,https://doi.org/10.1186/s12913-023-09545-x,A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.,"Ferrah N, Parker C, Ibrahim J, Gabbe B, Cameron P.",,BMC health services research,2023,2023-06-28,Y,Trauma; Rural; Interview; Older Adults,,,"<h4>Background</h4>For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.<h4>Method</h4>We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.<h4>Results</h4>Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.<h4>Conclusions</h4>Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09545-x; doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render
 36280346,https://doi.org/10.1136/heartjnl-2022-321492,Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank.,"Raisi-Estabragh Z, Cooper J, Salih A, Raman B, Lee AM, Neubauer S, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2022,2022-12-22,Y,epidemiology; Covid-19,,,"<h4>Objective</h4>To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021.<h4>Methods</h4>COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.<h4>Results</h4>Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.<h4>Conclusions</h4>Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.",,pdf:https://heart.bmj.com/content/heartjnl/109/2/119.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321492; html:https://europepmc.org/articles/PMC9811071; pdf:https://europepmc.org/articles/PMC9811071?pdf=render
-37907891,https://doi.org/10.1186/s12888-023-05217-6,"Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.","Bala JJ, Bala JD, Pell JP, Fleming M.",,BMC psychiatry,2023,2023-10-31,Y,attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score,,,"<h4>Background</h4>Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.<h4>Methods</h4>Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.<h4>Results</h4>Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.<h4>Conclusions</h4>In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.",,doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render
 33635829,https://doi.org/10.1530/eje-20-1163,Increased COVID-19 infections in women with polycystic ovary syndrome: a population-based study.,"Subramanian A, Anand A, Adderley NJ, Okoth K, Toulis KA, Gokhale K, Sainsbury C, O'Reilly MW, Arlt W, Nirantharakumar K.",,European journal of endocrinology,2021,2021-05-01,Y,,,,"<h4>Objective</h4>Several recent observational studies have linked metabolic comorbidities to an increased risk from COVID-19. Here we investigated whether women with PCOS are at an increased risk of COVID-19 infection.<h4>Design</h4>Population-based closed cohort study between 31 January 2020 and 22 July 2020 in the setting of a UK primary care database (The Health Improvement Network, THIN).<h4>Methods</h4>The main outcome was the incidence of COVID-19 coded as suspected or confirmed by the primary care provider. We used Cox proportional hazards regression model with stepwise inclusion of explanatory variables (age, BMI, impaired glucose regulation, androgen excess, anovulation, vitamin D deficiency, hypertension, and cardiovascular disease) to provide unadjusted and adjusted hazard risks (HR) of COVID-19 infection among women with PCOS compared to women without PCOS.<h4>Results</h4>We identified 21 292 women with a coded diagnosis of PCO/PCOS and randomly selected 78 310 aged and general practice matched control women. The crude COVID-19 incidence was 18.1 and 11.9 per 1000 person-years among women with and without PCOS, respectively. Age-adjusted Cox regression analysis suggested a 51% higher risk of COVID-19 among women with PCOS compared to women without PCOS (HR: 1.51 (95% CI: 1.27-1.80), P < 0.001). After adjusting for age and BMI, HR reduced to 1.36 (1.14-1.63)], P = 0.001. In the fully adjusted model, women with PCOS had a 28% increased risk of COVID-19 (aHR: 1.28 (1.05-1.56), P = 0.015).<h4>Conclusion</h4>Women with PCOS are at an increased risk of COVID-19 infection and should be specifically encouraged to adhere to infection control measures during the COVID-19 pandemic.<h4>Significance statement</h4>Women with polycystic ovary syndrome (PCOS) have an increased risk of cardio-metabolic disease, which have been identified as a risk factor for COVID-19. To investigate whether the increased metabolic risk in PCOS translates into an increased risk of COVID-19 infection, we carried out a population-based closed cohort study in the UK during its first wave of the SARS-CoV-2 pandemic (January to July 2020), including 21 292 women with PCOS and 78 310 controls matched for sex, age and general practice location. Results revealed a 52% increased risk of COVID-19 infection in women with PCOS, which remained increased at 28% above controls after adjustment for age, BMI, impaired glucose regulation and other explanatory variables.",,pdf:https://academic.oup.com/ejendo/article-pdf/184/5/637/45221794/eje-20-1163.pdf; doi:https://doi.org/10.1530/EJE-20-1163; html:https://europepmc.org/articles/PMC8052516; pdf:https://europepmc.org/articles/PMC8052516?pdf=render
+37907891,https://doi.org/10.1186/s12888-023-05217-6,"Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.","Bala JJ, Bala JD, Pell JP, Fleming M.",,BMC psychiatry,2023,2023-10-31,Y,attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score,,,"<h4>Background</h4>Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.<h4>Methods</h4>Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.<h4>Results</h4>Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.<h4>Conclusions</h4>In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.",,doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render
 35105585,https://doi.org/10.1136/bmjopen-2021-054376,Development of an algorithm to classify primary care electronic health records of alcohol consumption: experience using data linkage from UK Biobank and primary care electronic health data sources.,"Fraile-Navarro D, Azcoaga-Lorenzo A, Agrawal U, Jani B, Fagbamigbe A, Currie D, Baldacchino A, Sullivan F.",,BMJ open,2022,2022-02-01,Y,Public Health; Primary Care; Health Informatics,,,"<h4>Objectives</h4>Develop a novel algorithm to categorise alcohol consumption using primary care electronic health records (EHRs) and asses its reliability by comparing this classification with self-reported alcohol consumption data obtained from the UK Biobank (UKB) cohort.<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>The UKB, a population-based cohort with participants aged between 40 and 69 years recruited across the UK between 2006 and 2010.<h4>Participants</h4>UKB participants from Scotland with linked primary care data.<h4>Primary and secondary outcome measures</h4>Create a rule-based multiclass algorithm to classify alcohol consumption reported by Scottish UKB participants and compare it with their classification using data present in primary care EHRs based on Read Codes. We evaluated agreement metrics (simple agreement and kappa statistic).<h4>Results</h4>Among the Scottish UKB participants, 18 838 (69%) had at least one Read Code related to alcohol consumption and were used in the classification. The agreement of alcohol consumption categories between UKB and primary care data, including assessments within 5 years was 59.6%, and kappa was 0.23 (95% CI 0.21 to 0.24). Differences in classification between the two sources were statistically significant (p<0.001); More individuals were classified as 'sensible drinkers' and in lower alcohol consumption levels in primary care records compared with the UKB. Agreement improved slightly when using only numerical values (k=0.29; 95% CI 0.27 to 0.31) and decreased when using qualitative descriptors only (k=0.18;95% CI 0.16 to 0.20).<h4>Conclusion</h4>Our algorithm classifies alcohol consumption recorded in Primary Care EHRs into discrete meaningful categories. These results suggest that alcohol consumption may be underestimated in primary care EHRs. Using numerical values (alcohol units) may improve classification when compared with qualitative descriptors.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e054376.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054376; html:https://europepmc.org/articles/PMC8808438; pdf:https://europepmc.org/articles/PMC8808438?pdf=render
 31315158,https://doi.org/10.1002/cnm.3235,Non-invasive coronary CT angiography-derived fractional flow reserve: A benchmark study comparing the diagnostic performance of four different computational methodologies.,"Carson JM, Pant S, Roobottom C, Alcock R, Javier Blanco P, Alberto Bulant C, Vassilevski Y, Simakov S, Gamilov T, Pryamonosov R, Liang F, Ge X, Liu Y, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-08-16,Y,Fractional Flow Reserve; Benchmark; Haemodynamic Models,,,"Non-invasive coronary computed tomography (CT) angiography-derived fractional flow reserve (cFFR) is an emergent approach to determine the functional relevance of obstructive coronary lesions. Its feasibility and diagnostic performance has been reported in several studies. It is unclear if differences in sensitivity and specificity between these studies are due to study design, population, or ""computational methodology."" We evaluate the diagnostic performance of four different computational workflows for the prediction of cFFR using a limited data set of 10 patients, three based on reduced-order modelling and one based on a 3D rigid-wall model. The results for three of these methodologies yield similar accuracy of 6.5% to 10.5% mean absolute difference between computed and measured FFR. The main aspects of modelling which affected cFFR estimation were choice of inlet and outlet boundary conditions and estimation of flow distribution in the coronary network. One of the reduced-order models showed the lowest overall deviation from the clinical FFR measurements, indicating that reduced-order models are capable of a similar level of accuracy to a 3D model. In addition, this reduced-order model did not include a lumped pressure-drop model for a stenosis, which implies that the additional effort of isolating a stenosis and inserting a pressure-drop element in the spatial mesh may not be required for FFR estimation. The present benchmark study is the first of this kind, in which we attempt to homogenize the data required to compute FFR using mathematical models. The clinical data utilised in the cFFR workflows are made publicly available online.","Retrospective case series of 10 patients having coronary angiogram and invasive fractional flow reserve measurement. The authors used 4 different techniques to estimate coronary vessel flow rate and compared their measurement agreement with clinical FFA measurements and with each other. They found that all 4 methods gave different results, but one approach was more similar with the clinical gold standard. They propose this method with most worthy of further investigaiton.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3235; doi:https://doi.org/10.1002/cnm.3235; html:https://europepmc.org/articles/PMC6851543; pdf:https://europepmc.org/articles/PMC6851543?pdf=render
 36805366,https://doi.org/10.2196/43419,Prediction of Suicidal Behaviors in the Middle-aged Population: Machine Learning Analyses of UK Biobank.,"Wang J, Qiu J, Zhu T, Zeng Y, Yang H, Shang Y, Yin J, Sun Y, Qu Y, Valdimarsdóttir UA, Song H.",,JMIR public health and surveillance,2023,2023-02-20,Y,Sex; Model; Behavior; Genetic susceptibility; Data; Suicide; risk; Machine Learning; Risk Prediction; Cost-effective; Machine Learning Approach; Suicidal Behaviors,,,"<h4>Background</h4>Suicidal behaviors, including suicide deaths and attempts, are major public health concerns. However, previous suicide models required a huge amount of input features, resulting in limited applicability in clinical practice.<h4>Objective</h4>We aimed to construct applicable models (ie, with limited features) for short- and long-term suicidal behavior prediction. We further validated these models among individuals with different genetic risks of suicide.<h4>Methods</h4>Based on the prospective cohort of UK Biobank, we included 223 (0.06%) eligible cases of suicide attempts or deaths, according to hospital inpatient or death register data within 1 year from baseline and randomly selected 4460 (1.18%) controls (1:20) without such records. We similarly identified 833 (0.22%) cases of suicidal behaviors 1 to 6 years from baseline and 16,660 (4.42%) corresponding controls. Based on 143 input features, mainly including sociodemographic, environmental, and psychosocial factors; medical history; and polygenic risk scores (PRS) for suicidality, we applied a bagged balanced light gradient-boosting machine (LightGBM) with stratified 10-fold cross-validation and grid-search to construct the full prediction models for suicide attempts or deaths within 1 year or between 1 and 6 years. The Shapley Additive Explanations (SHAP) approach was used to quantify the importance of input features, and the top 20 features with the highest SHAP values were selected to train the applicable models. The external validity of the established models was assessed among 50,310 individuals who participated in UK Biobank repeated assessments both overall and by the level of PRS for suicidality.<h4>Results</h4>Individuals with suicidal behaviors were on average 56 years old, with equal sex distribution. The application of these full models in the external validation data set demonstrated good model performance, with the area under the receiver operating characteristic (AUROC) curves of 0.919 and 0.892 within 1 year and between 1 and 6 years, respectively. Importantly, the applicable models with the top 20 most important features showed comparable external-validated performance (AUROC curves of 0.901 and 0.885) as the full models, based on which we found that individuals in the top quintile of predicted risk accounted for 91.7% (n=11) and 80.7% (n=25) of all suicidality cases within 1 year and during 1 to 6 years, respectively. We further obtained comparable prediction accuracy when applying these models to subpopulations with different genetic susceptibilities to suicidality. For example, for the 1-year risk prediction, the AUROC curves were 0.907 and 0.885 for the high (>2nd tertile of PRS) and low (<1st) genetic susceptibilities groups, respectively.<h4>Conclusions</h4>We established applicable machine learning-based models for predicting both the short- and long-term risk of suicidality with high accuracy across populations of varying genetic risk for suicide, highlighting a cost-effective method of identifying individuals with a high risk of suicidality.",,pdf:https://publichealth.jmir.org/2023/1/e43419/PDF; doi:https://doi.org/10.2196/43419; html:https://europepmc.org/articles/PMC9989910
@@ -629,32 +629,32 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 36001371,https://doi.org/10.2196/38122,Deployment of a Free-Text Analytics Platform at a UK National Health Service Research Hospital: CogStack at University College London Hospitals.,"Noor K, Roguski L, Bai X, Handy A, Klapaukh R, Folarin A, Romao L, Matteson J, Lea N, Zhu L, Asselbergs FW, Wong WK, Shah A, Dobson RJ.",,JMIR medical informatics,2022,2022-08-24,Y,Information Retrieval; Natural Language Processing; Text Mining; Electronic Health Record System; Clinical Support,,,"<h4>Background</h4>As more health care organizations transition to using electronic health record (EHR) systems, it is important for these organizations to maximize the secondary use of their data to support service improvement and clinical research. These organizations will find it challenging to have systems capable of harnessing the unstructured data fields in the record (clinical notes, letters, etc) and more practically have such systems interact with all of the hospital data systems (legacy and current).<h4>Objective</h4>We describe the deployment of the EHR interfacing information extraction and retrieval platform CogStack at University College London Hospitals (UCLH).<h4>Methods</h4>At UCLH, we have deployed the CogStack platform, an information retrieval platform with natural language processing capabilities. The platform addresses the problem of data ingestion and harmonization from multiple data sources using the Apache NiFi module for managing complex data flows. The platform also facilitates the extraction of structured data from free-text records through use of the MedCAT natural language processing library. Finally, data science tools are made available to support data scientists and the development of downstream applications dependent upon data ingested and analyzed by CogStack.<h4>Results</h4>The platform has been deployed at the hospital, and in particular, it has facilitated a number of research and service evaluation projects. To date, we have processed over 30 million records, and the insights produced from CogStack have informed a number of clinical research use cases at the hospital.<h4>Conclusions</h4>The CogStack platform can be configured to handle the data ingestion and harmonization challenges faced by a hospital. More importantly, the platform enables the hospital to unlock important clinical information from the unstructured portion of the record using natural language processing technology.",,pdf:https://medinform.jmir.org/2022/8/e38122/PDF; doi:https://doi.org/10.2196/38122; html:https://europepmc.org/articles/PMC9453582
 34249083,https://doi.org/10.3389/fgene.2021.652878,Polymorphism in <i>INSR</i> Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy.,"Soto-Pedre E, Siddiqui MK, Maroteau C, Dawed AY, Doney AS, Palmer CNA, Pearson ER, Leese GP.",,Frontiers in genetics,2021,2021-06-23,Y,Genetics; Insulin receptor; Hypothyroidism; Atrial fibrillation; Thyroid Hormone Replacement Therapy,,,"<h4>Aims</h4>Atrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.<h4>Methods and results</h4>A retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-<i>INSR</i> locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, <i>P</i> = 1.6e-02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, <i>P</i> = 8.5e-04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (<i>n</i> = 3,190).<h4>Conclusion</h4>Homozygous G/G genotype at the <i>INSR</i> locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2021.652878/pdf; doi:https://doi.org/10.3389/fgene.2021.652878; html:https://europepmc.org/articles/PMC8260687; pdf:https://europepmc.org/articles/PMC8260687?pdf=render
 37859783,https://doi.org/10.1136/bmjmed-2023-000554,"Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog.","Hingorani AD, Gratton J, Finan C, Schmidt AF, Patel R, Sofat R, Kuan V, Langenberg C, Hemingway H, Morris JK, Wald NJ.",,BMJ medicine,2023,2023-10-17,Y,Public Health; Preventive Medicine,,,"<h4>Objective</h4>To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification.<h4>Design</h4>Secondary analysis of data in the Polygenic Score Catalog.<h4>Setting</h4>Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance metric estimates for 926 polygenic risk scores for 310 diseases to generate estimates of performance in population screening, individual risk, and population risk stratification.<h4>Participants</h4>Individuals contributing to the published studies in the Polygenic Score Catalog.<h4>Main outcome measures</h4>Detection rate for a 5% false positive rate (DR<sub>5</sub>) and the population odds of becoming affected given a positive result; individual odds of becoming affected for a person with a particular polygenic score; and odds of becoming affected for groups of individuals in different portions of a polygenic risk score distribution. Coronary artery disease and breast cancer were used as illustrative examples.<h4>Results</h4>For performance in population screening, median DR<sub>5</sub> for all polygenic risk scores and all diseases studied was 11% (interquartile range 8-18%). Median DR<sub>5</sub> was 12% (9-19%) for polygenic risk scores for coronary artery disease and 10% (9-12%) for breast cancer. The population odds of becoming affected given a positive results were 1:8 for coronary artery disease and 1:21 for breast cancer, with background 10 year odds of 1:19 and 1:41, respectively, which are typical for these diseases at age 50. For individual risk prediction, the corresponding 10 year odds of becoming affected for individuals aged 50 with a polygenic risk score at the 2.5th, 25th, 75th, and 97.5th centiles were 1:54, 1:29, 1:15, and 1:8 for coronary artery disease and 1:91, 1:56, 1:34, and 1:21 for breast cancer. In terms of population risk stratification, at age 50, the risk of coronary artery disease was divided into five groups, with 10 year odds of 1:41 and 1:11 for the lowest and highest quintile groups, respectively. The 10 year odds was 1:7 for the upper 2.5% of the polygenic risk score distribution for coronary artery disease, a group that contributed 7% of cases. The corresponding estimates for breast cancer were 1:72 and 1:26 for the lowest and highest quintile groups, and 1:19 for the upper 2.5% of the distribution, which contributed 6% of cases.<h4>Conclusion</h4>Polygenic risk scores performed poorly in population screening, individual risk prediction, and population risk stratification. Strong claims about the effect of polygenic risk scores on healthcare seem to be disproportionate to their performance.",,doi:https://doi.org/10.1136/bmjmed-2023-000554; html:https://europepmc.org/articles/PMC10582890; pdf:https://europepmc.org/articles/PMC10582890?pdf=render
-35580876,https://doi.org/10.1136/bmj-2021-069704,Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records.,"Šumilo D, Nirantharakumar K, Willis BH, Rudge GM, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Harris IM, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",,BMJ (Clinical research ed.),2022,2022-05-17,Y,,,,"<h4>Objective</h4>To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping.<h4>Design</h4>Observational controlled interrupted time series study.<h4>Setting</h4>UK primary and secondary care.<h4>Participants</h4>515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7 147 884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3 945 351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping.<h4>Intervention</h4>Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure.<h4>Main outcome measures</h4>The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally.<h4>Results</h4>Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years.<h4>Conclusions</h4>This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.",,pdf:https://www.bmj.com/content/bmj/377/bmj-2021-069704.full.pdf; doi:https://doi.org/10.1136/bmj-2021-069704; html:https://europepmc.org/articles/PMC9112858
 35216844,https://doi.org/10.1016/j.vaccine.2022.02.056,Localising vaccination services: Qualitative insights on public health and minority group collaborations to co-deliver coronavirus vaccines.,"Kasstan B, Mounier-Jack S, Letley L, Gaskell KM, Roberts CH, Stone NRH, Lal S, Eggo RM, Marks M, Chantler T.",,Vaccine,2022,2022-02-17,Y,Qualitative Research; Ethnic Minorities; Coronavirus Vaccine; Localising Services; Public Health Collaboration,,,"Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation. Methods included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders' response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.",,doi:https://doi.org/10.1016/j.vaccine.2022.02.056; doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863
+35580876,https://doi.org/10.1136/bmj-2021-069704,Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records.,"Šumilo D, Nirantharakumar K, Willis BH, Rudge GM, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Harris IM, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",,BMJ (Clinical research ed.),2022,2022-05-17,Y,,,,"<h4>Objective</h4>To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping.<h4>Design</h4>Observational controlled interrupted time series study.<h4>Setting</h4>UK primary and secondary care.<h4>Participants</h4>515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7 147 884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3 945 351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping.<h4>Intervention</h4>Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure.<h4>Main outcome measures</h4>The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally.<h4>Results</h4>Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years.<h4>Conclusions</h4>This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.",,pdf:https://www.bmj.com/content/bmj/377/bmj-2021-069704.full.pdf; doi:https://doi.org/10.1136/bmj-2021-069704; html:https://europepmc.org/articles/PMC9112858
 35079022,https://doi.org/10.1038/s41467-022-28157-3,Regional excess mortality during the 2020 COVID-19 pandemic in five European countries.,"Konstantinoudis G, Cameletti M, Gómez-Rubio V, Gómez IL, Pirani M, Baio G, Larrauri A, Riou J, Egger M, Vineis P, Blangiardo M.",,Nature communications,2022,2022-01-25,Y,,,,"The impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015-2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15-20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Here, we show that acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.",,pdf:https://www.nature.com/articles/s41467-022-28157-3.pdf; doi:https://doi.org/10.1038/s41467-022-28157-3; html:https://europepmc.org/articles/PMC8789777; pdf:https://europepmc.org/articles/PMC8789777?pdf=render
 37717234,https://doi.org/10.1111/1742-6723.14312,Prevalence of alcohol and other drug detections in non-transport injury events.,"Lau G, Mitra B, Gabbe BJ, Dietze PM, Reeder S, Cameron PA, Smit V, Schneider HG, Symons E, Koolstra C, Stewart C, Beck B.",,Emergency medicine Australasia : EMA,2023,2023-09-17,N,Alcoholic Intoxication; Illicit Drug; Blood Alcohol Content; Wounds And Injury; Substance-related Disorder; Substance Use Detection,,,"<h4>Objective</h4>To measure the prevalence of alcohol and/or other drug (AOD) detections in suspected major trauma patients with non-transport injuries who presented to an adult major trauma centre.<h4>Methods</h4>This registry-based cohort study examined the prevalence of AOD detections in patients aged ≥18 years who: (i) sustained non-transport injuries; and (ii) met predefined trauma call-out criteria and were therefore managed by an interdisciplinary trauma team between 1 July 2021 and 31 December 2022. Prevalence was measured using routine in-hospital blood alcohol and urine drug screens.<h4>Results</h4>A total of 1469 cases met the inclusion criteria. Of cases with a valid blood test (n = 1248, 85.0%), alcohol was detected in 313 (25.1%) patients. Of the 733 (49.9%) cases with urine drug screen results, cannabinoids were most commonly detected (n = 103, 14.1%), followed by benzodiazepines (n = 98, 13.4%), amphetamine-type substances (n = 80, 10.9%), opioids (n = 28, 3.8%) and cocaine (n = 17, 2.3%). Alcohol and/or at least one other drug was detected in 37.4% (n = 472) of cases with either a blood alcohol or urine drug test completed (n = 1263, 86.0%). Multiple substances were detected in 16.6% (n = 119) of cases with both blood alcohol and urine drug screens (n = 718, 48.9%). Detections were prevalent in cases of interpersonal violence (n = 123/179, 68.7%) and intentional self-harm (n = 50/106, 47.2%), and in those occurring on Friday and Saturday nights (n = 118/191, 61.8%).<h4>Conclusion</h4>AOD detections were common in trauma patients with non-transport injury causes. Population-level surveillance is needed to inform prevention strategies that address AOD use as a significant risk factor for serious injury.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.14312; doi:https://doi.org/10.1111/1742-6723.14312
 37657941,https://doi.org/10.1212/wnl.0000000000207777,Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.,"Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.",,Neurology,2023,2023-09-01,Y,,,,"<h4>Background and objectives</h4>There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.<h4>Method</h4>We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) levels and MS risk and severity, and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium, and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci, and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n = 7,069).<h4>Results</h4>The results of MR using the inverse-variance weighted method show that genetically predicted <i>RAC2</i>, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], <i>p</i>-value 3.80E-03), is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], <i>p</i>-value 7.94E-03) increases MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.<h4>Discussion</h4>Evidence from this study suggests that <i>RAC2</i> is a genetic modifier of MS risk. Because <i>RAC2</i> has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.",,pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?pdf=render
 35685390,https://doi.org/10.1016/s2666-7568(22)00072-1,"Modifiable traits, healthy behaviours, and leukocyte telomere length: a population-based study in UK Biobank.","Bountziouka V, Musicha C, Allara E, Kaptoge S, Wang Q, Angelantonio ED, Butterworth AS, Thompson JR, Danesh JN, Wood AM, Nelson CP, Codd V, Samani NJ.",,The lancet. Healthy longevity,2022,2022-05-01,Y,,,,"<h4>Background</h4>Telomere length is associated with risk of several age-related diseases and cancers. We aimed to investigate the extent to which telomere length might be modifiable through lifestyle and behaviour, and whether such modification has any clinical consequences.<h4>Methods</h4>In this population-based study, we included participants from UK Biobank who had leukocyte telomere length (LTL) measurement, ethnicity, and white blood cell count data. We investigated associations of LTL with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating between them smoking, physical activity, diet, maintenance of a healthy bodyweight, and alcohol intake, using both available and imputed data. To help interpretation, associations were summarised as the number of equivalent years of age-related change in LTL by dividing the trait β coefficients with the age β coefficient. We used mendelian randomisation to test causality of selected associations. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease might be mediated through LTL.<h4>Findings</h4>422 797 participants were available for the analysis (227 620 [53·8%] were women and 400 036 [94·6%] were White). 71 traits showed significant (p<4·27 × 10<sup>-4</sup>) associations with LTL but most were modest, equivalent to less than 1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to ≥2 years of age-related change in LTL), oily fish intake, educational attainment, and general health status retained a significant association of this magnitude, with walking pace and current smoking being additionally significant at this level of association in the imputed models. Mendelian randomisation analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the most healthy behaviours having longer LTL equivalent to about 3·5 years of age-related change in LTL than those with the least heathy behaviours (p<0·001). However, healthy behaviours explained less than 0·2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of coronary artery disease were substantially mediated through LTL.<h4>Interpretation</h4>Although several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy. Attempts to change telomere length through lifestyle or behavioural changes might not confer substantial clinical benefit.<h4>Funding</h4>UK Medical Research Council, UK Biotechnology and Biological Sciences Research Council, and British Heart Foundation.",,pdf:http://www.thelancet.com/article/S2666756822000721/pdf; doi:https://doi.org/10.1016/S2666-7568(22)00072-1; html:https://europepmc.org/articles/PMC9068584
-36879385,https://doi.org/10.1097/ta.0000000000003950,Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma.,"Gabbe BJ, Reeder S, Ekegren CL, Mather A, Kimmel L, Cameron PA, Higgins AM.",,The journal of trauma and acute care surgery,2023,2023-03-07,N,,,,"<h4>Background</h4>Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.<h4>Methods</h4>The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.<h4>Results</h4>Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5-17) at baseline, 10 (5-19) in the new ward phase, and 17 (9-23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.<h4>Conclusion</h4>The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.<h4>Level of evidence</h4>Economic and Value-based Evaluations; Level III.",,doi:https://doi.org/10.1097/TA.0000000000003950
 33203640,https://doi.org/10.1136/bmjopen-2020-043828,"Estimated impact of the COVID-19 pandemic on cancer services and excess 1-year mortality in people with cancer and multimorbidity: near real-time data on cancer care, cancer deaths and a population-based cohort study.","Lai AG, Pasea L, Banerjee A, Hall G, Denaxas S, Chang WH, Katsoulis M, Williams B, Pillay D, Noursadeghi M, Linch D, Hughes D, Forster MD, Turnbull C, Fitzpatrick NK, Boyd K, Foster GR, Enver T, Nafilyan V, Humberstone B, Neal RD, Cooper M, Jones M, Pritchard-Jones K, Sullivan R, Davie C, Lawler M, Hemingway H.",,BMJ open,2020,2020-11-17,Y,Oncology; Health Informatics; Covid-19,,,"<h4>Objectives</h4>To estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer.<h4>Methods</h4>We employed near real-time weekly data on cancer care to determine the adverse effect of the pandemic on cancer services. We also used these data, together with national death registrations until June 2020 to model deaths, in excess of background (pre-COVID-19) mortality, in people with cancer. Background mortality risks for 24 cancers with and without COVID-19-relevant comorbidities were obtained from population-based primary care cohort (Clinical Practice Research Datalink) on 3 862 012 adults in England.<h4>Results</h4>Declines in urgent referrals (median=-70.4%) and chemotherapy attendances (median=-41.5%) to a nadir (lowest point) in the pandemic were observed. By 31 May, these declines have only partially recovered; urgent referrals (median=-44.5%) and chemotherapy attendances (median=-31.2%). There were short-term excess death registrations for cancer (without COVID-19), with peak relative risk (RR) of 1.17 at week ending on 3 April. The peak RR for all-cause deaths was 2.1 from week ending on 17 April. Based on these findings and recent literature, we modelled 40% and 80% of cancer patients being affected by the pandemic in the long-term. At 40% affected, we estimated 1-year total (direct and indirect) excess deaths in people with cancer as between 7165 and 17 910, using RRs of 1.2 and 1.5, respectively, where 78% of excess deaths occured in patients with ≥1 comorbidity.<h4>Conclusions</h4>Dramatic reductions were detected in the demand for, and supply of, cancer services which have not fully recovered with lockdown easing. These may contribute, over a 1-year time horizon, to substantial excess mortality among people with cancer and multimorbidity. It is urgent to understand how the recovery of general practitioner, oncology and other hospital services might best mitigate these long-term excess mortality risks.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e043828.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043828; html:https://europepmc.org/articles/PMC7674020; pdf:https://europepmc.org/articles/PMC7674020?pdf=render
+36879385,https://doi.org/10.1097/ta.0000000000003950,Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma.,"Gabbe BJ, Reeder S, Ekegren CL, Mather A, Kimmel L, Cameron PA, Higgins AM.",,The journal of trauma and acute care surgery,2023,2023-03-07,N,,,,"<h4>Background</h4>Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.<h4>Methods</h4>The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.<h4>Results</h4>Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5-17) at baseline, 10 (5-19) in the new ward phase, and 17 (9-23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.<h4>Conclusion</h4>The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.<h4>Level of evidence</h4>Economic and Value-based Evaluations; Level III.",,doi:https://doi.org/10.1097/TA.0000000000003950
 36150783,https://doi.org/10.1016/s2589-7500(22)00147-9,Data capture and sharing in the COVID-19 pandemic: a cause for concern.,"Dron L, Kalatharan V, Gupta A, Haggstrom J, Zariffa N, Morris AD, Arora P, Park J.",,The Lancet. Digital health,2022,2022-10-01,Y,,,,"Routine health care and research have been profoundly influenced by digital-health technologies. These technologies range from primary data collection in electronic health records (EHRs) and administrative claims to web-based artificial-intelligence-driven analyses. There has been increased use of such health technologies during the COVID-19 pandemic, driven in part by the availability of these data. In some cases, this has resulted in profound and potentially long-lasting positive effects on medical research and routine health-care delivery. In other cases, high profile shortcomings have been evident, potentially attenuating the effect of-or representing a decreased appetite for-digital-health transformation. In this Series paper, we provide an overview of how facets of health technologies in routinely collected medical data (including EHRs and digital data sharing) have been used for COVID-19 research and tracking, and how these technologies might influence future pandemics and health-care research. We explore the strengths and weaknesses of digital-health research during the COVID-19 pandemic and discuss how learnings from COVID-19 might translate into new approaches in a post-pandemic era.",,doi:https://doi.org/10.1016/s2589-7500(22)00147-9; doi:https://doi.org/10.1016/S2589-7500(22)00147-9; html:https://europepmc.org/articles/PMC9489064; pdf:https://europepmc.org/articles/PMC9489064?pdf=render
 35074819,https://doi.org/10.1136/bmjopen-2021-054414,Mapping multimorbidity in individuals with schizophrenia and bipolar disorders: evidence from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLAM BRC) case register.,"Bendayan R, Kraljevic Z, Shaari S, Das-Munshi J, Leipold L, Chaturvedi J, Mirza L, Aldelemi S, Searle T, Chance N, Mascio A, Skiada N, Wang T, Roberts A, Stewart R, Bean D, Dobson R.",,BMJ open,2022,2022-01-24,Y,Psychiatry; Mental health; epidemiology; Public Health; Health Informatics,,,"<h4>Objectives</h4>The first aim of this study was to design and develop a valid and replicable strategy to extract physical health conditions from clinical notes which are common in mental health services. Then, we examined the prevalence of these conditions in individuals with severe mental illness (SMI) and compared their individual and combined prevalence in individuals with bipolar (BD) and schizophrenia spectrum disorders (SSD).<h4>Design</h4>Observational study.<h4>Setting</h4>Secondary mental healthcare services from South London PARTICIPANTS: Our maximal sample comprised 17 500 individuals aged 15 years or older who had received a primary or secondary SMI diagnosis (International Classification of Diseases, 10th edition, F20-31) between 2007 and 2018.<h4>Measures</h4>We designed and implemented a data extraction strategy for 21 common physical comorbidities using a natural language processing pipeline, MedCAT. Associations were investigated with sex, age at SMI diagnosis, ethnicity and social deprivation for the whole cohort and the BD and SSD subgroups. Linear regression models were used to examine associations with disability measured by the Health of Nations Outcome Scale.<h4>Results</h4>Physical health data were extracted, achieving precision rates (F1) above 0.90 for all conditions. The 10 most prevalent conditions were diabetes, hypertension, asthma, arthritis, epilepsy, cerebrovascular accident, eczema, migraine, ischaemic heart disease and chronic obstructive pulmonary disease. The most prevalent combination in this population included diabetes, hypertension and asthma, regardless of their SMI diagnoses.<h4>Conclusions</h4>Our data extraction strategy was found to be adequate to extract physical health data from clinical notes, which is essential for future multimorbidity research using text records. We found that around 40% of our cohort had multimorbidity from which 20% had complex multimorbidity (two or more physical conditions besides SMI). Sex, age, ethnicity and social deprivation were found to be key to understand their heterogeneity and their differential contribution to disability levels in this population. These outputs have direct implications for researchers and clinicians.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e054414.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054414; html:https://europepmc.org/articles/PMC8788233; pdf:https://europepmc.org/articles/PMC8788233?pdf=render
 36773891,https://doi.org/10.1016/j.jinf.2023.02.012,"Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study.","Evans A, Qi C, Adebayo JO, Underwood J, Coulson J, Bailey R, Lyons R, Edwards A, Cooper A, John G, Akbari A.",,The Journal of infection,2023,2023-02-10,Y,Health protection; Public Health; Covid-19,,,"<h4>Objective</h4>To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community.<h4>Design</h4>Retrospective cohort study of non-hospitalized adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank.<h4>Setting</h4>A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK.<h4>Participants</h4>Adult patients with COVID-19 in the community, at higher risk of hospitalization and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022.<h4>Interventions</h4>Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales.<h4>Main outcome measures</h4>All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2.<h4>Statistical analysis</h4>Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales.<h4>Results</h4>Between 16th December 2021 and 22nd April 2022, 7013 higher-risk patients were eligible for inclusion in the study. Of these, 2040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalization or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalization or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods.<h4>Conclusions</h4>In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.",,pdf:http://www.journalofinfection.com/article/S0163445323000828/pdf; doi:https://doi.org/10.1016/j.jinf.2023.02.012; html:https://europepmc.org/articles/PMC9911979; pdf:https://europepmc.org/articles/PMC9911979?pdf=render
 34353320,https://doi.org/10.1186/s12916-021-02045-x,Adverse childhood experiences and child mental health: an electronic birth cohort study.,"Lowthian E, Anthony R, Evans A, Daniel R, Long S, Bandyopadhyay A, John A, Bellis MA, Paranjothy S.",,BMC medicine,2021,2021-08-06,Y,Survival analysis; Cohort; Mental health; Wales; Administrative Data; Adverse Childhood Experiences,,,"<h4>Background</h4>Adverse childhood experiences (ACEs) are negatively associated with a range of child health outcomes. In this study, we explored associations between five individual ACEs and child mental health diagnoses or symptoms. ACEs included living with someone who had an alcohol-related problem, common mental health disorder or serious mental illness, or experienced victimisation or death of a household member.<h4>Methods</h4>We analysed data from a population-level electronic cohort of children in Wales, UK, (N = 191,035) between the years of 1998 and 2012. We used Cox regression with discrete time-varying exposure variables to model time to child mental health diagnosis during the first 15 years of life. Child mental health diagnoses include five categories: (i) externalising symptoms (anti-social behaviour), (ii) internalising symptoms (stress, anxiety, depression), (iii) developmental delay (e.g. learning disability), (iv) other (e.g. eating disorder, personality disorders), and (v) any mental health diagnosis, which was created by combining externalising symptoms, internalising symptoms and other. Our analyses were adjusted for social deprivation and perinatal risk factors.<h4>Results</h4>There were strong univariable associations between the five individual ACEs, sociodemographic and perinatal factors (e.g. gestational weight at birth) and an increased risk of child mental health diagnoses. After adjusting for sociodemographic and perinatal aspects, there was a remaining conditional increased risk of any child mental health diagnosis, associated with victimisation (conditional hazard ratio (cHR) 1.90, CI 95% 1.34-2.69), and living with an adult with a common mental health diagnosis (cHR 1.63, CI 95% 1.52-1.75). Coefficients of product terms between ACEs and deprivation were not statistically significant.<h4>Conclusion</h4>The increased risk of child mental health diagnosis associated with victimisation, or exposure to common mental health diagnoses, and alcohol problems in the household supports the need for policy measures and intervention strategies for children and their families.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-02045-x; doi:https://doi.org/10.1186/s12916-021-02045-x; html:https://europepmc.org/articles/PMC8344166; pdf:https://europepmc.org/articles/PMC8344166?pdf=render
-32516805,https://doi.org/10.1093/eurheartj/ehaa375,Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction.,"Hung J, Roos A, Kadesjö E, McAllister DA, Kimenai DM, Shah ASV, Anand A, Strachan FE, Fox KAA, Mills NL, Chapman AR, Holzmann MJ.",,European heart journal,2021,2021-07-01,Y,Troponin; Grace; Type 2 Myocardial Infarction; High-sensitivity; Universal Definition; Type 1 Myocardial Infarction,,,"<h4>Aims</h4>The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain.<h4>Methods and results</h4>In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n = 48 282) and a tertiary care hospital in Sweden (n = 22 589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong's test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82-0.85] and 0.85 (95% CI 0.81-0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70-0.77) and 0.73 (95% CI 0.66-0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts (P < 0.001 and P = 0.008, respectively).<h4>Conclusion</h4>The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction.<h4>Trial registration</h4>ClinicalTrials.gov number, NCT01852123.",,doi:https://doi.org/10.1093/eurheartj/ehaa375; doi:https://doi.org/10.1093/eurheartj/ehaa375; html:https://europepmc.org/articles/PMC8266602; pdf:https://europepmc.org/articles/PMC8266602?pdf=render
 32620158,https://doi.org/10.1186/s12915-020-00792-6,Epigenomics and genotype-phenotype association analyses reveal conserved genetic architecture of complex traits in cattle and human.,"Liu S, Yu Y, Zhang S, Cole JB, Tenesa A, Wang T, McDaneld TG, Ma L, Liu GE, Fang L.",,BMC biology,2020,2020-07-03,Y,Comparative Epigenomics; Gwas Enrichment; Human-cattle Comparison; Trait-relevant Tissues,,,"<h4>Background</h4>Lack of comprehensive functional annotations across a wide range of tissues and cell types severely hinders the biological interpretations of phenotypic variation, adaptive evolution, and domestication in livestock. Here we used a combination of comparative epigenomics, genome-wide association study (GWAS), and selection signature analysis, to shed light on potential adaptive evolution in cattle.<h4>Results</h4>We cross-mapped 8 histone marks of 1300 samples from human to cattle, covering 178 unique tissues/cell types. By uniformly analyzing 723 RNA-seq and 40 whole genome bisulfite sequencing (WGBS) datasets in cattle, we validated that cross-mapped histone marks captured tissue-specific expression and methylation, reflecting tissue-relevant biology. Through integrating cross-mapped tissue-specific histone marks with large-scale GWAS and selection signature results, we for the first time detected relevant tissues and cell types for 45 economically important traits and artificial selection in cattle. For instance, immune tissues are significantly associated with health and reproduction traits, multiple tissues for milk production and body conformation traits (reflecting their highly polygenic architecture), and thyroid for the different selection between beef and dairy cattle. Similarly, we detected relevant tissues for 58 complex traits and diseases in humans and observed that immune and fertility traits in humans significantly correlated with those in cattle in terms of relevant tissues, which facilitated the identification of causal genes for such traits. For instance, PIK3CG, a gene highly specifically expressed in mononuclear cells, was significantly associated with both age-at-menopause in human and daughter-still-birth in cattle. ICAM, a T cell-specific gene, was significantly associated with both allergic diseases in human and metritis in cattle.<h4>Conclusion</h4>Collectively, our results highlighted that comparative epigenomics in conjunction with GWAS and selection signature analyses could provide biological insights into the phenotypic variation and adaptive evolution. Cattle may serve as a model for human complex traits, by providing additional information beyond laboratory model organisms, particularly when more novel phenotypes become available in the near future.",,pdf:https://bmcbiol.biomedcentral.com/counter/pdf/10.1186/s12915-020-00792-6; doi:https://doi.org/10.1186/s12915-020-00792-6; html:https://europepmc.org/articles/PMC7334855; pdf:https://europepmc.org/articles/PMC7334855?pdf=render
+32516805,https://doi.org/10.1093/eurheartj/ehaa375,Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction.,"Hung J, Roos A, Kadesjö E, McAllister DA, Kimenai DM, Shah ASV, Anand A, Strachan FE, Fox KAA, Mills NL, Chapman AR, Holzmann MJ.",,European heart journal,2021,2021-07-01,Y,Troponin; Grace; Type 2 Myocardial Infarction; High-sensitivity; Universal Definition; Type 1 Myocardial Infarction,,,"<h4>Aims</h4>The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain.<h4>Methods and results</h4>In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n = 48 282) and a tertiary care hospital in Sweden (n = 22 589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong's test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82-0.85] and 0.85 (95% CI 0.81-0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70-0.77) and 0.73 (95% CI 0.66-0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts (P < 0.001 and P = 0.008, respectively).<h4>Conclusion</h4>The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction.<h4>Trial registration</h4>ClinicalTrials.gov number, NCT01852123.",,doi:https://doi.org/10.1093/eurheartj/ehaa375; doi:https://doi.org/10.1093/eurheartj/ehaa375; html:https://europepmc.org/articles/PMC8266602; pdf:https://europepmc.org/articles/PMC8266602?pdf=render
 36102151,https://doi.org/10.1210/clinem/dgac527,Identification of 4 New Loci Associated With Primary Hyperparathyroidism (PHPT) and a Polygenic Risk Score for PHPT.,"Soto-Pedre E, Newey PJ, Srinivasan S, Siddiqui MK, Palmer CNA, Leese GP.",,The Journal of clinical endocrinology and metabolism,2022,2022-11-01,Y,Genetics; Genome-wide Association Study; Primary Hyperparathyroidism; Polygenic Risk Score,,,"<h4>Context</h4>A hypothesis-free genetic association analysis has not been reported for patients with primary hyperparathyroidism (PHPT).<h4>Objective</h4>We aimed to investigate genetic associations with PHPT using both genome-wide association study (GWAS) and candidate gene approaches.<h4>Methods</h4>A cross-sectional study was conducted among patients of European White ethnicity recruited in Tayside (Scotland, UK). Electronic medical records were used to identify PHPT cases and controls, and linked to genetic biobank data. Genetic associations were performed by logistic regression models and odds ratios (ORs). The combined effect of the genotypes was researched by genetic risk score (GRS) analysis.<h4>Results</h4>We identified 15 622 individuals for the GWAS that yielded 34 top single-nucleotide variations (formerly single-nucleotide polymorphisms), and LPAR3-rs147672681 reached genome-wide statistical significance (P = 1.2e-08). Using a more restricted PHPT definition, 8722 individuals with data on the GWAS-identified loci were found. Age- and sex-adjusted ORs for the effect alleles of SOX9-rs11656269, SLITRK5-rs185436526, and BCDIN3D-AS1-rs2045094 showed statistically significant increased risks (P < 1.5e-03). GRS analysis of 5482 individuals showed an OR of 2.51 (P = 1.6e-04), 3.78 (P = 4.0e-08), and 7.71 (P = 5.3e-17) for the second, third, and fourth quartiles, respectively, compared to the first, and there was a statistically significant linear trend across quartiles (P < 1.0e-04). Results were similar when stratifying by sex.<h4>Conclusion</h4>Using genetic loci discovered in a GWAS of PHPT carried out in a Scottish population, this study suggests new evidence for the involvement of genetic variants at SOX9, SLITRK5, LPAR3, and BCDIN3D-AS1. It also suggests that male and female carriers of greater numbers of PHPT-risk alleles both have a statistically significant increased risk of PHPT.",,pdf:https://academic.oup.com/jcem/article-pdf/107/12/3302/47260242/dgac527.pdf; doi:https://doi.org/10.1210/clinem/dgac527; html:https://europepmc.org/articles/PMC9693767
 37474315,https://doi.org/10.1093/ehjci/jead174,The added value of abnormal regional myocardial function for risk prediction in arrhythmogenic right ventricular cardiomyopathy.,"Kirkels FP, Rootwelt-Norberg C, Bosman LP, Aabel EW, Muller S, Castrini AI, Taha K, van Osta N, Lie ØH, Asselbergs FW, Lumens J, Te Riele ASJM, Hasselberg NE, Cramer MJ, Haugaa K, Teske AJ.",,European heart journal. Cardiovascular Imaging,2023,2023-07-20,N,Echocardiography; Risk stratification; ventricular arrhythmia; Sudden Cardiac Death; Strain Imaging; Arrhythmogenic Cardiomyopathy,,,"<h4>Background & aims</h4>A risk calculator for individualized prediction of first-time sustained ventricular arrhythmia (VA) in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients has recently been developed and validated (www.ARVCrisk.com). This study aimed to investigate whether regional functional abnormalities, measured by echocardiographic deformation imaging, can provide additional prognostic value.<h4>Methods & results</h4>From two referral centres, 150 consecutive patients with a definite ARVC diagnosis, no prior sustained VA and an echocardiogram suitable for deformation analysis were included (aged 41±17 years, 50% female). During a median follow-up of 6.3 (IQR 3.1-9.8) years, 37 (25%) experienced a first-time sustained VA. All tested left and right ventricular (LV, RV) deformation parameters were univariate predictors for first-time VA. While LV function did not add predictive value in multivariate analysis, two RV deformation parameters did; RV free wall longitudinal strain and regional RV deformation patterns remained independent predictors after adjusting for the calculator-predicted risk (HR 1.07 [1.02-1.11]; p = 0.004 and 4.45 [1.07-18.57]; p = 0.040, respectively) and improved its discriminative value (from C-statistic 0.78 to 0.82 in both. Akaike information criterion change >2). Importantly, all patients who experienced VA within 5 years from the echocardiographic assessment had abnormal regional RV deformation patterns at baseline.<h4>Conclusions</h4>This study showed that regional functional abnormalities measured by echocardiographic deformation imaging can further refine personalized arrhythmic risk prediction when added to the ARVC risk calculator. The excellent negative predictive value of normal RV deformation could support clinicians considering timing of ICD implantation in patients with intermediate arrhythmic risk.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead174/50920074/jead174.pdf; doi:https://doi.org/10.1093/ehjci/jead174
 34649997,https://doi.org/10.2337/dc21-0437,"Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study.","Kumarendran B, O'Reilly MW, Subramanian A, Šumilo D, Toulis K, Gokhale KM, Wijeratne CN, Coomarasamy A, Tahrani AA, Azoulay L, Arlt W, Nirantharakumar K.",,Diabetes care,2021,2021-10-14,Y,,,,"<h4>Objective</h4>Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS.<h4>Research design and methods</h4>Using a large U.K. primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS and 123,545 matched control subjects), as well as a nested pharmacoepidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio, and conditional logistic regression was used to obtain adjusted odds ratios (aORs).<h4>Results</h4>The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, <i>P</i> < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59-0.87).<h4>Conclusions</h4>In this study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered for further understanding of these observations and potential causality.",,pdf:https://diabetesjournals.org/care/article-pdf/44/12/2758/631597/dc210437.pdf; doi:https://doi.org/10.2337/dc21-0437; html:https://europepmc.org/articles/PMC8669537; pdf:https://europepmc.org/articles/PMC8669537?pdf=render
 35301875,https://doi.org/10.1161/jaha.121.023146,Long-Term Cardiovascular Risk and Management of Patients Recorded in Primary Care With Unattributed Chest Pain: An Electronic Health Record Study.,"Jordan KP, Rathod-Mistry T, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, van der Windt DA, Mamas MA.",,Journal of the American Heart Association,2022,2022-03-18,Y,Cardiovascular disease; Chest pain; Primary Care; Electronic Health Records,,,"Background Most adults presenting with chest pain will not receive a diagnosis and be recorded with unattributed chest pain. The objective was to assess if they have increased risk of cardiovascular disease compared with those with noncoronary chest pain and determine whether investigations and interventions are targeted at those at highest risk. Methods and Results We used records from general practices in England linked to hospitalization and mortality information. The study population included patients aged 18 years or over with a new record of chest pain with a noncoronary cause or unattributed between 2002 and 2018, and no cardiovascular disease recorded up to 6 months (diagnostic window) afterward. We compared risk of a future cardiovascular event by type of chest pain, adjusting for cardiovascular risk factors and alternative explanations for chest pain. We determined prevalence of cardiac diagnostic investigations and preventative medication during the diagnostic window in patients with estimated cardiovascular risk ≥10%. There were 375 240 patients with unattributed chest pain (245 329 noncoronary chest pain). There was an increased risk of cardiovascular events for patients with unattributed chest pain, highest in the first year (hazard ratio, 1.25 [95% CI, 1.21-1.29]), persistent up to 10 years. Patients with unattributed chest pain had consistently increased risk of myocardial infarction over time but no increased risk of stroke. Thirty percent of patients at higher risk were prescribed lipid-lowering medication. Conclusions Patients presenting to primary care with unattributed chest pain are at increased risk of cardiovascular events. Primary prevention to reduce cardiovascular events appears suboptimal in those at higher risk.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.023146; doi:https://doi.org/10.1161/JAHA.121.023146; html:https://europepmc.org/articles/PMC9075433; pdf:https://europepmc.org/articles/PMC9075433?pdf=render
 31857590,https://doi.org/10.1038/s41597-019-0337-6,Machine learning for the detection of early immunological markers as predictors of multi-organ dysfunction.,"Bravo-Merodio L, Acharjee A, Hazeldine J, Bentley C, Foster M, Gkoutos GV, Lord JM.",,Scientific data,2019,2019-12-19,Y,,,,"The immune response to major trauma has been analysed mainly within post-hospital admission settings where the inflammatory response is already underway and the early drivers of clinical outcome cannot be readily determined. Thus, there is a need to better understand the immediate immune response to injury and how this might influence important patient outcomes such as multi-organ dysfunction syndrome (MODS). In this study, we have assessed the immune response to trauma in 61 patients at three different post-injury time points (ultra-early (<=1 h), 4-12 h, 48-72 h) and analysed relationships with the development of MODS. We developed a pipeline using Absolute Shrinkage and Selection Operator and Elastic Net feature selection methods that were able to identify 3 physiological features (decrease in neutrophil CD62L and CD63 expression and monocyte CD63 expression and frequency) as possible biomarkers for MODS development. After univariate and multivariate analysis for each feature alongside a stability analysis, the addition of these 3 markers to standard clinical trauma injury severity scores yields a Generalized Liner Model (GLM) with an average Area Under the Curve value of 0.92 ± 0.06. This performance provides an 8% improvement over the Probability of Survival (PS14) outcome measure and a 13% improvement over the New Injury Severity Score (NISS) for identifying patients at risk of MODS.",,pdf:https://www.nature.com/articles/s41597-019-0337-6.pdf; doi:https://doi.org/10.1038/s41597-019-0337-6; html:https://europepmc.org/articles/PMC6923383; pdf:https://europepmc.org/articles/PMC6923383?pdf=render
-36806317,https://doi.org/10.1038/s41746-023-00749-3,Long-term participant retention and engagement patterns in an app and wearable-based multinational remote digital depression study.,"Zhang Y, Pratap A, Folarin AA, Sun S, Cummins N, Matcham F, Vairavan S, Dineley J, Ranjan Y, Rashid Z, Conde P, Stewart C, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Rambla CH, Simblett S, Nica R, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Annas P, Narayan VA, Hotopf M, Dobson RJB, RADAR-CNS consortium.",,NPJ digital medicine,2023,2023-02-17,Y,,,,"Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants' study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8 h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants' age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.",,pdf:https://www.nature.com/articles/s41746-023-00749-3.pdf; doi:https://doi.org/10.1038/s41746-023-00749-3; html:https://europepmc.org/articles/PMC9938183; pdf:https://europepmc.org/articles/PMC9938183?pdf=render
 32206896,https://doi.org/10.1007/s00394-020-02220-5,Alcohol consumption in relation to carotid subclinical atherosclerosis and its progression: results from a European longitudinal multicentre study.,"Laguzzi F, Baldassarre D, Veglia F, Strawbridge RJ, Humphries SE, Rauramaa R, Smit AJ, Giral P, Silveira A, Tremoli E, Hamsten A, de Faire U, Frumento P, Leander K, IMPROVE Study group.",,European journal of nutrition,2021,2020-03-24,Y,Atherosclerosis; epidemiology; Carotid intima-media thickness; Alcohol drinking; Progression,,,"<h4>Background/aim</h4>The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption.<h4>Methods</h4>Between 2002-2004, 1772 men and 1931 women aged 54-79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 - 5 g/d), low (> 5 to  ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women,  > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude.<h4>Results</h4>Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMT<sub>max</sub>[- 0.17(95%CI - 0.32; - 0.02)], and Bif-IMT<sub>mean</sub>[- 0.07(95%CI - 0.13; - 0.01)] at baseline and decreasing C-IMT<sub>mean</sub>[- 0.006 (95%CI - 0.011; - 0.000)], Bif-IMT<sub>mean</sub>[- 0.016(95%CI - 0.027; - 0.005)], ICA-IMT<sub>mean</sub>[- 0.009(95% - 0.016; - 0.002)] and ICA-IMT<sub>max</sub>[- 0.016(95%: - 0.032; - 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT.<h4>Conclusion</h4>In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.",,pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02220-5.pdf; doi:https://doi.org/10.1007/s00394-020-02220-5; html:https://europepmc.org/articles/PMC7867553; pdf:https://europepmc.org/articles/PMC7867553?pdf=render
+36806317,https://doi.org/10.1038/s41746-023-00749-3,Long-term participant retention and engagement patterns in an app and wearable-based multinational remote digital depression study.,"Zhang Y, Pratap A, Folarin AA, Sun S, Cummins N, Matcham F, Vairavan S, Dineley J, Ranjan Y, Rashid Z, Conde P, Stewart C, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Rambla CH, Simblett S, Nica R, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Annas P, Narayan VA, Hotopf M, Dobson RJB, RADAR-CNS consortium.",,NPJ digital medicine,2023,2023-02-17,Y,,,,"Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants' study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8 h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants' age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.",,pdf:https://www.nature.com/articles/s41746-023-00749-3.pdf; doi:https://doi.org/10.1038/s41746-023-00749-3; html:https://europepmc.org/articles/PMC9938183; pdf:https://europepmc.org/articles/PMC9938183?pdf=render
 37777816,https://doi.org/10.1186/s13643-023-02337-8,Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.,"Taylor S, Law K, Coomber-Moore J, Davies M, Thistlewaite F, Calvert M, Aiyegbusi O, Yorke J.",,Systematic reviews,2023,2023-09-30,Y,Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act),,,"<h4>Introduction</h4>Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.<h4>Methods</h4>A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: ""adoptive cell therapy"", ""patient-reported outcomes"" and ""cancer"". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.<h4>Results</h4>One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2 weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3 months.<h4>Discussion</h4>None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render
 37840686,https://doi.org/10.3389/fdgth.2023.1184919,Understanding the performance and reliability of NLP tools: a comparison of four NLP tools predicting stroke phenotypes in radiology reports.,"Casey A, Davidson E, Grover C, Tobin R, Grivas A, Zhang H, Schrempf P, O'Neil AQ, Lee L, Walsh M, Pellie F, Ferguson K, Cvoro V, Wu H, Whalley H, Mair G, Whiteley W, Alex B.",,Frontiers in digital health,2023,2023-09-28,Y,Electronic Health Records; Natural Language Processing; Stroke Phenotype; Brain Radiology,,,"<h4>Background</h4>Natural language processing (NLP) has the potential to automate the reading of radiology reports, but there is a need to demonstrate that NLP methods are adaptable and reliable for use in real-world clinical applications.<h4>Methods</h4>We tested the F1 score, precision, and recall to compare NLP tools on a cohort from a study on delirium using images and radiology reports from NHS Fife and a population-based cohort (Generation Scotland) that spans multiple National Health Service health boards. We compared four off-the-shelf rule-based and neural NLP tools (namely, EdIE-R, ALARM+, ESPRESSO, and Sem-EHR) and reported on their performance for three cerebrovascular phenotypes, namely, ischaemic stroke, small vessel disease (SVD), and atrophy. Clinical experts from the EdIE-R team defined phenotypes using labelling techniques developed in the development of EdIE-R, in conjunction with an expert researcher who read underlying images.<h4>Results</h4>EdIE-R obtained the highest F1 score in both cohorts for ischaemic stroke, ≥93%, followed by ALARM+, ≥87%. The F1 score of ESPRESSO was ≥74%, whilst that of Sem-EHR is ≥66%, although ESPRESSO had the highest precision in both cohorts, 90% and 98%. For F1 scores for SVD, EdIE-R scored ≥98% and ALARM+ ≥90%. ESPRESSO scored lowest with ≥77% and Sem-EHR ≥81%. In NHS Fife, F1 scores for atrophy by EdIE-R and ALARM+ were 99%, dropping in Generation Scotland to 96% for EdIE-R and 91% for ALARM+. Sem-EHR performed lowest for atrophy at 89% in NHS Fife and 73% in Generation Scotland. When comparing NLP tool output with brain image reads using F1 scores, ALARM+ scored 80%, outperforming EdIE-R at 66% in ischaemic stroke. For SVD, EdIE-R performed best, scoring 84%, with Sem-EHR 82%. For atrophy, EdIE-R and both ALARM+ versions were comparable at 80%.<h4>Conclusions</h4>The four NLP tools show varying F1 (and precision/recall) scores across all three phenotypes, although more apparent for ischaemic stroke. If NLP tools are to be used in clinical settings, this cannot be performed ""out of the box."" It is essential to understand the context of their development to assess whether they are suitable for the task at hand or whether further training, re-training, or modification is required to adapt tools to the target task.",,doi:https://doi.org/10.3389/fdgth.2023.1184919; html:https://europepmc.org/articles/PMC10569314; pdf:https://europepmc.org/articles/PMC10569314?pdf=render
-37635632,https://doi.org/10.1111/aor.14628,Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support.,"Numan L, Wösten M, Moazeni M, Aarts E, Van der Kaaij NP, Fresiello L, Asselbergs FW, Van Laake LW.",,Artificial organs,2023,2023-08-28,N,Circadian rhythm; Mechanical Circulatory Support; Left Ventricular Assist Device; Lvad Parameters,,,"<h4>Background</h4>Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR).<h4>Methods</h4>18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation.<h4>Results</h4>A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19).<h4>Conclusions</h4>A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14628; doi:https://doi.org/10.1111/aor.14628
 33446033,https://doi.org/10.1177/1460458220977579,Identifying strategies to overcome roadblocks to utilising near real-time healthcare and administrative data to create a Scotland-wide learning health system.,"Mukherjee M, Cresswell K, Sheikh A.",,Health informatics journal,2021,2021-01-01,N,Qualitative Research; Governance; Electronic Health Records; Health Data; Learning Health System,,,"Creating a learning health system could help reduce variations in quality of care. Success is dependent on timely access to health data. To explore the barriers and facilitators to timely access to patients' data, we conducted in-depth semi-structured interviews with 37 purposively sampled participants from government, the NHS and academia across Scotland. Interviews were analysed using the framework approach. Participants were of the view that Scotland could play a leading role in the exploitation of routine data to drive forward service improvements, but highlighted major impediments: (i) persistence of paper-based records and a variety of information systems; (ii) the need for a proportionate approach to managing information governance; and (iii) the need for support structures to facilitate accrual, processing, linking, analysis and timely use and reuse of data for patient benefit. There is a pressing need to digitise and integrate existing health information infrastructures, guided by a nationwide proportionate information governance approach and the need to enhance technological and human capabilities to support these efforts.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/1460458220977579; doi:https://doi.org/10.1177/1460458220977579
 33469151,https://doi.org/10.1038/s42003-020-01613-w,LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes.,"Herdenberg C, Mutie PM, Billing O, Abdullah A, Strawbridge RJ, Dahlman I, Tuck S, Holmlund C, Arner P, Henriksson R, Franks PW, Hedman H.",,Communications biology,2021,2021-01-19,Y,,,,"Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-β) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease.",,pdf:https://www.nature.com/articles/s42003-020-01613-w.pdf; doi:https://doi.org/10.1038/s42003-020-01613-w; html:https://europepmc.org/articles/PMC7815736; pdf:https://europepmc.org/articles/PMC7815736?pdf=render
+37635632,https://doi.org/10.1111/aor.14628,Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support.,"Numan L, Wösten M, Moazeni M, Aarts E, Van der Kaaij NP, Fresiello L, Asselbergs FW, Van Laake LW.",,Artificial organs,2023,2023-08-28,N,Circadian rhythm; Mechanical Circulatory Support; Left Ventricular Assist Device; Lvad Parameters,,,"<h4>Background</h4>Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR).<h4>Methods</h4>18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation.<h4>Results</h4>A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19).<h4>Conclusions</h4>A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14628; doi:https://doi.org/10.1111/aor.14628
 37105743,https://doi.org/10.3399/bjgp.2022.0353,Impact of COVID-19 pandemic on incidence of long-term conditions in Wales: a population data linkage study using primary and secondary care health records.,"Qi C, Osborne T, Bailey R, Cooper A, Hollinghurst JP, Akbari A, Crowder R, Peters H, Law RJ, Lewis R, Smith D, Edwards A, Lyons RA.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-04-27,Y,Diagnosis; Chronic disease; Anxiety; Primary Health Care; Covid-19,,,"<h4>Background</h4>The COVID-19 pandemic has directly and indirectly had an impact on health service provision owing to surges and sustained pressures on the system. The effects of these pressures on the management of long-term or chronic conditions are not fully understood.<h4>Aim</h4>To explore the effects of COVID-19 on the recorded incidence of 17 long-term conditions.<h4>Design and setting</h4>This was an observational retrospective population data linkage study on the population of Wales using primary and secondary care data within the Secure Anonymised Information Linkage (SAIL) Databank.<h4>Method</h4>Monthly rates of new diagnosis between 2000 and 2021 are presented for each long-term condition. Incidence rates post-2020 were compared with expected rates predicted using time series modelling of pre-2020 trends. The proportion of annual incidence is presented by sociodemographic factors: age, sex, social deprivation, ethnicity, frailty, and learning disability.<h4>Results</h4>A total of 5 476 012 diagnoses from 2 257 992 individuals are included. Incidence rates from 2020 to 2021 were lower than mean expected rates across all conditions. The largest relative deficit in incidence was in chronic obstructive pulmonary disease corresponding to 343 (95% confidence interval = 230 to 456) undiagnosed patients per 100 000 population, followed by depression, type 2 diabetes, hypertension, anxiety disorders, and asthma. A GP practice of 10 000 patients might have over 400 undiagnosed long-term conditions. No notable differences between sociodemographic profiles of post- and pre-2020 incidences were observed.<h4>Conclusion</h4>There is a potential backlog of undiagnosed patients with multiple long-term conditions. Resources are required to tackle anticipated workload as part of COVID-19 recovery, particularly in primary care.",,pdf:https://bjgp.org/content/bjgp/early/2023/03/06/BJGP.2022.0353.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0353; html:https://europepmc.org/articles/PMC9997656; pdf:https://europepmc.org/articles/PMC9997656?pdf=render
 35365351,https://doi.org/10.1016/j.injury.2022.03.039,Injury severity and increased socioeconomic differences: A population-based cohort study.,"Madsen C, Gabbe BJ, Holvik K, Alver K, Grøholt EK, Lund J, Lyons J, Lyons RA, Ohm E.",,Injury,2022,2022-03-24,N,Injury; Socioeconomic status; Hospitalization; Iciss; Injury-vibes; Risk-adjusted Severity,,,"<h4>Background</h4>Several studies have documented an inverse gradient between socioeconomic status (SES) and injury mortality, but the evidence is less consistent for injury morbidity. The aim of this study was to investigate the association between SES and injury severity for acute hospitalizations in a nationwide population-based cohort.<h4>Methods</h4>We conducted a registry-based cohort study of all individuals aged 25-64 years residing in Norway by 1st of January 2008. This cohort was followed from 2008 through 2014 using inpatient registrations for acute hospitalizations due to all-cause injuries. We derived two measures of severity: threat-to-life using the International Classification of Disease-based Injury Severity Score (ICISS), and threat of disability using long-term disability weights from the Injury-VIBES project. Robust Poisson regression models, with adjustment for age, sex, marital status, immigrant status, municipality population size and healthcare region of residence, were used to calculate incidence rate ratios (IRRs) by SES measured as an index of education, income, and occupation.<h4>Results</h4>We identified 177,663 individuals (7% of the population) hospitalized with at least one acute injury in the observation period. Two percent (n = 4,186) had injuries categorized with high threat-to-life, while one quarter (n = 43,530) had injuries with high threat of disability. The overall adjusted IRR of hospitalization among people with low compared to high SES was 1.57 (95% CI 1.55, 1.60). Comparing low to high SES, injuries with low threat-to-life were associated with an IRR of 1.56 (95% CI 1.54, 1.59), while injuries with high threat-to-life had an IRR of 2.25 (95% CI 2.03, 2.51). Comparing low to high SES, injuries with low, medium, and high threat of disability were associated with IRRs of respectively, 1.15 (95% CI 1.11, 1.19), 1.70 (95% CI 1.66, 1.73) and 1.99 (95% CI 1.92, 2.07).<h4>Discussion</h4>We observed an inverse gradient between SES and injury morbidity, with the steepest gradient for the most severe injuries. This suggests a need for targeted preventive measures to reduce the magnitude and burden of severe injuries for patients with low socioeconomic status.",,pdf:http://www.injuryjournal.com/article/S0020138322002327/pdf; doi:https://doi.org/10.1016/j.injury.2022.03.039
 36935397,https://doi.org/10.1093/bjs/znad055,Validating a novel natural language processing pathway for automated quality assurance in surgical oncology: incomplete excision rates of 34 955 basal cell carcinomas.,"Ali SR, Dobbs TD, Jovic M, Strafford H, Fonferko-Shadrach B, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.",,The British journal of surgery,2023,2023-08-01,Y,,,,,,pdf:https://academic.oup.com/bjs/advance-article-pdf/doi/10.1093/bjs/znad055/49561408/znad055.pdf; doi:https://doi.org/10.1093/bjs/znad055; html:https://europepmc.org/articles/PMC10416688; pdf:https://europepmc.org/articles/PMC10416688?pdf=render
@@ -663,8 +663,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 33711543,https://doi.org/10.1016/j.jbi.2021.103728,Explainable automated coding of clinical notes using hierarchical label-wise attention networks and label embedding initialisation.,"Dong H, Suárez-Paniagua V, Whiteley W, Wu H.",,Journal of biomedical informatics,2021,2021-03-09,N,Natural Language Processing; Multi-label Classification; Deep Learning; Attention Mechanisms; Automated Medical Coding; Explainability; Label Correlation,,,"<h4>Background</h4>Diagnostic or procedural coding of clinical notes aims to derive a coded summary of disease-related information about patients. Such coding is usually done manually in hospitals but could potentially be automated to improve the efficiency and accuracy of medical coding. Recent studies on deep learning for automated medical coding achieved promising performances. However, the explainability of these models is usually poor, preventing them to be used confidently in supporting clinical practice. Another limitation is that these models mostly assume independence among labels, ignoring the complex correlations among medical codes which can potentially be exploited to improve the performance.<h4>Methods</h4>To address the issues of model explainability and label correlations, we propose a Hierarchical Label-wise Attention Network (HLAN), which aimed to interpret the model by quantifying importance (as attention weights) of words and sentences related to each of the labels. Secondly, we propose to enhance the major deep learning models with a label embedding (LE) initialisation approach, which learns a dense, continuous vector representation and then injects the representation into the final layers and the label-wise attention layers in the models. We evaluated the methods using three settings on the MIMIC-III discharge summaries: full codes, top-50 codes, and the UK NHS (National Health Service) COVID-19 (Coronavirus disease 2019) shielding codes. Experiments were conducted to compare the HLAN model and label embedding initialisation to the state-of-the-art neural network based methods, including variants of Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs).<h4>Results</h4>HLAN achieved the best Micro-level AUC and F<sub>1</sub> on the top-50 code prediction, 91.9% and 64.1%, respectively; and comparable results on the NHS COVID-19 shielding code prediction to other models: around 97% Micro-level AUC. More importantly, in the analysis of model explanations, by highlighting the most salient words and sentences for each label, HLAN showed more meaningful and comprehensive model interpretation compared to the CNN-based models and its downgraded baselines, HAN and HA-GRU. Label embedding (LE) initialisation significantly boosted the previous state-of-the-art model, CNN with attention mechanisms, on the full code prediction to 52.5% Micro-level F<sub>1</sub>. The analysis of the layers initialised with label embeddings further explains the effect of this initialisation approach. The source code of the implementation and the results are openly available at https://github.com/acadTags/Explainable-Automated-Medical-Coding.<h4>Conclusion</h4>We draw the conclusion from the evaluation results and analyses. First, with hierarchical label-wise attention mechanisms, HLAN can provide better or comparable results for automated coding to the state-of-the-art, CNN-based models. Second, HLAN can provide more comprehensive explanations for each label by highlighting key words and sentences in the discharge summaries, compared to the n-grams in the CNN-based models and the downgraded baselines, HAN and HA-GRU. Third, the performance of deep learning based multi-label classification for automated coding can be consistently boosted by initialising label embeddings that captures the correlations among labels. We further discuss the advantages and drawbacks of the overall method regarding its potential to be deployed to a hospital and suggest areas for future studies.",,doi:https://doi.org/10.1016/j.jbi.2021.103728; doi:https://doi.org/10.1016/j.jbi.2021.103728
 37042240,https://doi.org/10.1161/circimaging.122.014519,Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.,"Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.",,Circulation. Cardiovascular imaging,2023,2023-04-12,N,Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques,,,"Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.",,doi:https://doi.org/10.1161/CIRCIMAGING.122.014519
 36748660,https://doi.org/10.1111/head.14465,Depression and anxiety in women with idiopathic intracranial hypertension compared to migraine: A matched controlled cohort study.,"Mollan SP, Subramanian A, Perrins M, Nirantharakumar K, Adderley NJ, Sinclair AJ.",,Headache,2023,2023-02-07,N,Depression; Migraine; Anxiety; epidemiology; Primary Care; Idiopathic Intracranial Hypertension,,,"<h4>Objective</h4>To evaluate mental health burden in women with idiopathic intracranial hypertension (IIH) compared to matched women with migraine and population controls.<h4>Background</h4>Depression and anxiety are recognized comorbid conditions in those with IIH and lead to worse predicted medical outcomes. The mental health burden in IIH has not been previously evaluated in a large, matched cohort study.<h4>Methods</h4>We performed a population-based matched, retrospective cohort study to explore mental health outcomes (depression and anxiety). We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical records database in the United Kingdom, from January 1, 1995, to September 25, 2019. Women aged ≥16 years were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls).<h4>Results</h4>A total of 3411 women with IIH, 30,879 migraine controls and 33,495 population controls were included. Of these, 237, 2372 and 1695 women with IIH, migraine controls and population controls, respectively, developed depression during follow-up, and 179, 1826 and 1197, respectively, developed anxiety. There was a greater hazard of depression and anxiety in IIH compared to population controls (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.20-1.58; and aHR 1.40, 95% CI 1.19-1.64, respectively), while hazards were similar to migraine controls (aHR 0.98, 95% CI 0.86-1.13; and aHR 0.98, 95% CI 0.83-1.14, respectively).<h4>Conclusion</h4>Depression and anxiety burden in women with IIH is higher than in the general population, and comparable to that in matched women with migraine. This may indicate that presence of headache is a potential driver for comorbid depression and anxiety in IIH.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/head.14465; doi:https://doi.org/10.1111/head.14465
-36112916,https://doi.org/10.1177/09622802211055853,Inferring risks of coronavirus transmission from community household data.,"House T, Riley H, Pellis L, Pouwels KB, Bacon S, Eidukas A, Jahanshahi K, Eggo RM, Sarah Walker A.",,Statistical methods in medical research,2022,2022-09-01,Y,Infection; Model; epidemic; risk factors; Covid-19,,,"The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics COVID-19 Infection Survey data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) susceptible-Infectious transmission probabilities of within-household transmission in the 15-35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range of 25-300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.",,doi:https://doi.org/10.1177/09622802211055853; doi:https://doi.org/10.1177/09622802211055853; html:https://europepmc.org/articles/PMC9465559; pdf:https://europepmc.org/articles/PMC9465559?pdf=render
 35290719,https://doi.org/10.1002/alz.12635,"Incidence, morbidity, mortality and disparities in dementia: A population linked electronic health records study of 4.3 million individuals.","Chung SC, Providencia R, Sofat R, Pujades-Rodriguez M, Torralbo A, Fatemifar G, Fitzpatrick NK, Taylor J, Li K, Dale C, Rossor M, Acosta-Mena D, Whittaker J, Denaxas S.",,Alzheimer's & dementia : the journal of the Alzheimer's Association,2023,2022-03-15,Y,Mortality; Alzheimer's disease; Vascular dementia; Cause of death; Dementia; epidemiology; incidence; United Kingdom; Health Inequality; Comorbidity; Electronic Health Records; Hospitalizations; Health-care Use,,,"<h4>Introduction</h4>We report dementia incidence, comorbidities, reasons for health-care visits, mortality, causes of death, and examined dementia patterns by relative deprivation in the UK.<h4>Method</h4>A longitudinal cohort analysis of linked electronic health records from 4.3 million people in the UK was conducted to investigate dementia incidence and mortality. Reasons for hospitalization and causes of death were compared in individuals with and without dementia.<h4>Results</h4>From 1998 to 2016 we observed 145,319 (3.1%) individuals with incident dementia. Repeated hospitalizations among senior adults for infection, unknown morbidity, and multiple primary care visits for chronic pain were observed prior to dementia diagnosis. Multiple long-term conditions are present in half of the individuals at the time of diagnosis. Individuals living in high deprivation areas had higher dementia incidence and high fatality.<h4>Discussion</h4>There is a considerable disparity of dementia that informs priorities of prevention and provision of patient care.",,pdf:https://discovery.ucl.ac.uk/10145566/1/ChungIncidence%2C%20morbidity%2C%20mortality%20and%20disparities%20in%20dementia_AOP.pdf; doi:https://doi.org/10.1002/alz.12635; html:https://europepmc.org/articles/PMC10078672; pdf:https://europepmc.org/articles/PMC10078672?pdf=render
+36112916,https://doi.org/10.1177/09622802211055853,Inferring risks of coronavirus transmission from community household data.,"House T, Riley H, Pellis L, Pouwels KB, Bacon S, Eidukas A, Jahanshahi K, Eggo RM, Sarah Walker A.",,Statistical methods in medical research,2022,2022-09-01,Y,Infection; Model; epidemic; risk factors; Covid-19,,,"The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics COVID-19 Infection Survey data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) susceptible-Infectious transmission probabilities of within-household transmission in the 15-35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range of 25-300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.",,doi:https://doi.org/10.1177/09622802211055853; doi:https://doi.org/10.1177/09622802211055853; html:https://europepmc.org/articles/PMC9465559; pdf:https://europepmc.org/articles/PMC9465559?pdf=render
 37294923,https://doi.org/10.1093/eurjpc/zwad192,Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.,"Prugger C, Perier MC, Gonzalez-Izquierdo A, Hemingway H, Denaxas S, Empana JP.",,European journal of preventive cardiology,2023,2023-10-01,N,Prevention; Survival analysis; Stroke; epidemiology; Coronary Heart Disease; incidence,,,"<h4>Background</h4>Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.<h4>Aims</h4>This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.<h4>Methods and results</h4>Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people ≥30 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.<h4>Conclusion</h4>Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.",,doi:https://doi.org/10.1093/eurjpc/zwad192
 31845899,https://doi.org/10.2196/14782,Efficient Reuse of Natural Language Processing Models for Phenotype-Mention Identification in Free-text Electronic Medical Records: A Phenotype Embedding Approach.,"Wu H, Hodgson K, Dyson S, Morley KI, Ibrahim ZM, Iqbal E, Stewart R, Dobson RJ, Sudlow C.",,JMIR medical informatics,2019,2019-12-17,Y,Phenotype; Clustering; Machine Learning; Electronic Health Records; Natural Language Processing; Text Mining; Word Embedding; Model Adaptation; Phenotype Embedding,Applied Analytics,,"<h4>Background</h4>Much effort has been put into the use of automated approaches, such as natural language processing (NLP), to mine or extract data from free-text medical records in order to construct comprehensive patient profiles for delivering better health care. Reusing NLP models in new settings, however, remains cumbersome, as it requires validation and retraining on new data iteratively to achieve convergent results.<h4>Objective</h4>The aim of this work is to minimize the effort involved in reusing NLP models on free-text medical records.<h4>Methods</h4>We formally define and analyze the model adaptation problem in phenotype-mention identification tasks. We identify ""duplicate waste"" and ""imbalance waste,"" which collectively impede efficient model reuse. We propose a phenotype embedding-based approach to minimize these sources of waste without the need for labelled data from new settings.<h4>Results</h4>We conduct experiments on data from a large mental health registry to reuse NLP models in four phenotype-mention identification tasks. The proposed approach can choose the best model for a new task, identifying up to 76% waste (duplicate waste), that is, phenotype mentions without the need for validation and model retraining and with very good performance (93%-97% accuracy). It can also provide guidance for validating and retraining the selected model for novel language patterns in new tasks, saving around 80% waste (imbalance waste), that is, the effort required in ""blind"" model-adaptation approaches.<h4>Conclusions</h4>Adapting pretrained NLP models for new tasks can be more efficient and effective if the language pattern landscapes of old settings and new settings can be made explicit and comparable. Our experiments show that the phenotype-mention embedding approach is an effective way to model language patterns for phenotype-mention identification tasks and that its use can guide efficient NLP model reuse.",Wu et el. developed a computer algorithm which can transform clinical letters into databases for research. Their approach in processing information in clinical letters is more flexible compared to those before allowing users to define concepts which they want to find in the letters. ,doi:https://doi.org/10.2196/14782; doi:https://doi.org/10.2196/14782; html:https://europepmc.org/articles/PMC6938594
 35945198,https://doi.org/10.1038/s41467-022-32095-5,Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals.,"Huang QQ, Sallah N, Dunca D, Trivedi B, Hunt KA, Hodgson S, Lambert SA, Arciero E, Wright J, Griffiths C, Trembath RC, Hemingway H, Inouye M, Finer S, van Heel DA, Lumbers RT, Martin HC, Kuchenbaecker K.",,Nature communications,2022,2022-08-09,Y,,,,"Individuals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate. The performance of polygenic scores was high for lipids and blood pressure, but lower for BMI and coronary artery disease. Adding a polygenic score for coronary artery disease to clinical risk factors showed significant improvement in reclassification. In Mendelian randomisation using transferable loci as instruments, our findings were consistent with results in European-ancestry individuals. Taken together, trait-specific transferability of trait loci between populations is an important consideration with implications for risk prediction and causal inference.",,pdf:https://www.nature.com/articles/s41467-022-32095-5.pdf; doi:https://doi.org/10.1038/s41467-022-32095-5; html:https://europepmc.org/articles/PMC9363492; pdf:https://europepmc.org/articles/PMC9363492?pdf=render
@@ -683,22 +683,22 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 34824100,https://doi.org/10.1136/openhrt-2021-001769,Implementation of an early rule-out pathway for myocardial infarction using a high-sensitivity cardiac troponin T assay.,"Sandeman D, Syed MBJ, Kimenai DM, Lee KK, Anand A, Joshi SS, Dinnel L, Wenham PR, Campbell K, Jarvie M, Galloway D, Anderson M, Roy B, Andrews JPM, Strachan FE, Ferry AV, Chapman AR, Elsby S, Francis M, Cargill R, Shah ASV, Mills NL.",,Open heart,2021,2021-11-01,Y,Biomarkers; Chest pain; acute coronary syndrome,,,"<h4>Objectives</h4>Patients with suspected acute coronary syndrome and high-sensitivity cardiac troponin (hs-cTn) concentrations below the limit of detection at presentation are low risk. We aim to determine whether implementing this approach facilitates the safe early discharge of patients.<h4>Methods</h4>In a prospective single-centre cohort study, consecutive patients with suspected acute coronary syndrome were included before (standard care) and after (intervention) implementation of an early rule-out pathway. During standard care, myocardial infarction was ruled out if hs-cTnT concentrations were <99th centile (14 ng/L) at presentation and at 6-12 hours after symptom onset. In the intervention, patients were ruled out if hs-cTnT concentrations were <5 ng/L at presentation and symptoms present for ≥3 hours or were ≥5 ng/L and unchanged within the reference range at 3 hours. We compared duration of stay (efficacy) and all-cause death at 1 year (safety) before and after implementation.<h4>Results</h4>We included 10 315 consecutive patients (64±16 years, 46% women) with 6642 (64%) and 3673 (36%) in the standard care and intervention groups, respectively. Duration of stay was reduced from 534 (IQR, 220-2279) to 390 (IQR, 218-1910) min (p<0.001) after implementation. At 1 year, all-cause death occurred in 10.9% (721 of 6642) and 10.4% (381 of 3673) of patients in the standard care group (referent) and intervention group, respectively (adjusted OR 1.02, 95% CI 0.88 to 1.18).<h4>Conclusion</h4>In patients with suspected acute coronary syndrome, implementing an early rule-out pathway using hs-cTnT concentrations <5 ng/L at presentation reduced the duration of stay in hospital without compromising safety.",,pdf:https://openheart.bmj.com/content/openhrt/8/2/e001769.full.pdf; doi:https://doi.org/10.1136/openhrt-2021-001769; html:https://europepmc.org/articles/PMC8627412; pdf:https://europepmc.org/articles/PMC8627412?pdf=render
 36620207,https://doi.org/10.3389/fphys.2022.1089343,Incorporating structural abnormalities in equivalent dipole layer based ECG simulations.,"Boonstra MJ, Oostendorp TF, Roudijk RW, Kloosterman M, Asselbergs FW, Loh P, Van Dam PM.",,Frontiers in physiology,2022,2022-12-22,Y,Simulation; Myocardial Disease; Electrocardiogram (Ecg); Cardiac Activation; Equivalent Dipole Layer; Ecgsim,,,"<b>Introduction:</b> Electrical activity of the myocardium is recorded with the 12-lead ECG. ECG simulations can improve our understanding of the relation between abnormal ventricular activation in diseased myocardium and body surface potentials (BSP). However, in equivalent dipole layer (EDL)-based ECG simulations, the presence of diseased myocardium breaks the equivalence of the dipole layer. To simulate diseased myocardium, patches with altered electrophysiological characteristics were incorporated within the model. The relation between diseased myocardium and corresponding BSP was investigated in a simulation study. <b>Methods:</b> Activation sequences in normal and diseased myocardium were simulated and corresponding 64-lead BSP were computed in four models with distinct patch locations. QRS-complexes were compared using correlation coefficient (CC). The effect of different types of patch activation was assessed. Of one patient, simulated electrograms were compared to electrograms recorded during invasive electro-anatomical mapping. <b>Results:</b> Hundred-fifty-three abnormal activation sequences were simulated. Median QRS-CC of delayed versus dyssynchronous were significantly different (1.00 vs. 0.97, <i>p</i> < 0.001). Depending on the location of the patch, BSP leads were affected differently. Within diseased regions, fragmentation, low bipolar voltages and late potentials were observed in both recorded and simulated electrograms. <b>Discussion:</b> A novel method to simulate cardiomyopathy in EDL-based ECG simulations was established and evaluated. The new patch-based approach created a realistic relation between ECG waveforms and underlying activation sequences. Findings in the simulated cases were in agreement with clinical observations. With this method, our understanding of disease progression in cardiomyopathies may be further improved and used in advanced inverse ECG procedures.",,pdf:https://www.frontiersin.org/articles/10.3389/fphys.2022.1089343/pdf; doi:https://doi.org/10.3389/fphys.2022.1089343; html:https://europepmc.org/articles/PMC9814485; pdf:https://europepmc.org/articles/PMC9814485?pdf=render
 36475361,https://doi.org/10.1302/2633-1462.312.bjo-2022-0130.r1,Variation in timely surgery for severe open tibial fractures by time and place of presentation in England from 2012 to 2019 : a cohort study using data collected nationally by the Trauma Audit and Research Network.,"Shah A, Judge A, Griffin XL.",,Bone & joint open,2022,2022-12-01,Y,Trauma; Sensitivity analysis; Debridement; Logistic regression; Cohort study; Orthopaedics; Injury Severity Score; Health Care Quality; Soft-tissue; Open Fracture; Tarn; Regression Analyses; Open Fractures Of The Tibia,,,"<h4>Aims</h4>Several studies have reported that patients presenting during the evening or weekend have poorer quality healthcare. Our objective was to examine how timely surgery for patients with severe open tibial fracture varies by day and time of presentation and by type of hospital. This cohort study included patients with severe open tibial fractures from the Trauma Audit and Research Network (TARN).<h4>Methods</h4>Provision of prompt surgery (debridement within 12 hours and soft-tissue coverage in 72 hours) was examined, using multivariate logistic regression to derive adjusted risk ratios (RRs). Time was categorized into three eight-hour intervals for each day of the week. The models were adjusted for treatment in a major trauma centre (MTC), sex, age, year of presentation, injury severity score, injury mechanism, and number of operations each patient received.<h4>Results</h4>We studied 8,258 patients from 175 hospitals. Patients presenting during the day (08:00 to 15:59; risk ratio (RR) 1.11, 95% confidence interval (CI) 1.02 to 1.20) were more likely to receive debridement within 12 hours, and patients presenting at night (16:00 to 23:59; RR 0.56, 95% CI 0.51 to 0.62) were less likely to achieve the target; triage to a MTC had no effect. Day of presentation was associated with soft-tissue coverage within 72 hours; patients presenting on a Thursday or Friday being less likely to receive this surgery within 72 hours (Thursday RR 0.88, 95% CI 0.81 to 0.97; Friday RR 0.89, 95% CI 0.81 to 0.98), and the standard less likely to be achieved for those treated in 'non-MTC' hospitals (RR 0.76, 95% CI 0.70 to 0.82).<h4>Conclusion</h4>Variations in care were observed for timely surgery for severe open tibial fractures with debridement surgery affected by time of presentation and soft-tissue coverage affected by day of presentation and type of hospital. The variation is unwarranted and highlights that there are opportunities to substantially improve the delivery and quality of care for patients with severe open tibial fracture.Cite this article: <i>Bone Jt Open</i> 2022;3(12):941-952.",,pdf:https://boneandjoint.org.uk/article/10.1302/2633-1462.312.BJO-2022-0130.R1/pdf; doi:https://doi.org/10.1302/2633-1462.312.BJO-2022-0130.R1; html:https://europepmc.org/articles/PMC9783273; pdf:https://europepmc.org/articles/PMC9783273?pdf=render
+30727941,https://doi.org/10.1186/s12859-019-2633-8,DeepPVP: phenotype-based prioritization of causative variants using deep learning.,"Boudellioua I, Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,BMC bioinformatics,2019,2019-02-06,Y,Phenotype; Ontology; Machine Learning; Variant Prioritization,Applied Analytics,,"<h4>Background</h4>Prioritization of variants in personal genomic data is a major challenge. Recently, computational methods that rely on comparing phenotype similarity have shown to be useful to identify causative variants. In these methods, pathogenicity prediction is combined with a semantic similarity measure to prioritize not only variants that are likely to be dysfunctional but those that are likely involved in the pathogenesis of a patient's phenotype.<h4>Results</h4>We have developed DeepPVP, a variant prioritization method that combined automated inference with deep neural networks to identify the likely causative variants in whole exome or whole genome sequence data. We demonstrate that DeepPVP performs significantly better than existing methods, including phenotype-based methods that use similar features. DeepPVP is freely available at https://github.com/bio-ontology-research-group/phenomenet-vp .<h4>Conclusions</h4>DeepPVP further improves on existing variant prioritization methods both in terms of speed as well as accuracy.",,pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-019-2633-8; doi:https://doi.org/10.1186/s12859-019-2633-8; html:https://europepmc.org/articles/PMC6364462; pdf:https://europepmc.org/articles/PMC6364462?pdf=render
 34784292,https://doi.org/10.2196/32587,Investigating the Use of Digital Health Technology to Monitor COVID-19 and Its Effects: Protocol for an Observational Study (Covid Collab Study).,"Stewart C, Ranjan Y, Conde P, Rashid Z, Sankesara H, Bai X, Dobson RJB, Folarin AA.",,JMIR research protocols,2021,2021-12-08,Y,Monitoring; Infectious disease; Recovery; Mobile phone; Feasibility; Surveillance; Data; Mental health; Observational; Smartphone; Wearable; Mobile Health; Wearable Devices; Digital Health; Crowdsourced; Covid-19,,,"<h4>Background</h4>The ubiquity of mobile phones and increasing use of wearable fitness trackers offer a wide-ranging window into people's health and well-being. There are clear advantages in using remote monitoring technologies to gain an insight into health, particularly under the shadow of the COVID-19 pandemic.<h4>Objective</h4>Covid Collab is a crowdsourced study that was set up to investigate the feasibility of identifying, monitoring, and understanding the stratification of SARS-CoV-2 infection and recovery through remote monitoring technologies. Additionally, we will assess the impacts of the COVID-19 pandemic and associated social measures on people's behavior, physical health, and mental well-being.<h4>Methods</h4>Participants will remotely enroll in the study through the Mass Science app to donate historic and prospective mobile phone data, fitness tracking wearable data, and regular COVID-19-related and mental health-related survey data. The data collection period will cover a continuous period (ie, both before and after any reported infections), so that comparisons to a participant's own baseline can be made. We plan to carry out analyses in several areas, which will cover symptomatology; risk factors; the machine learning-based classification of illness; and trajectories of recovery, mental well-being, and activity.<h4>Results</h4>As of June 2021, there are over 17,000 participants-largely from the United Kingdom-and enrollment is ongoing.<h4>Conclusions</h4>This paper introduces a crowdsourced study that will include remotely enrolled participants to record mobile health data throughout the COVID-19 pandemic. The data collected may help researchers investigate a variety of areas, including COVID-19 progression; mental well-being during the pandemic; and the adherence of remote, digitally enrolled participants.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/32587.",,pdf:https://www.researchprotocols.org/2021/12/e32587/PDF; doi:https://doi.org/10.2196/32587; html:https://europepmc.org/articles/PMC8658240
 37679419,https://doi.org/10.1038/s41588-023-01462-3,"GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.","Lagou V, Jiang L, Ulrich A, Zudina L, González KSG, Balkhiyarova Z, Faggian A, Maina JG, Chen S, Todorov PV, Sharapov S, David A, Marullo L, Mägi R, Rujan RM, Ahlqvist E, Thorleifsson G, Gao Η, Εvangelou Ε, Benyamin B, Scott RA, Isaacs A, Zhao JH, Willems SM, Johnson T, Gieger C, Grallert H, Meisinger C, Müller-Nurasyid M, Strawbridge RJ, Goel A, Rybin D, Albrecht E, Jackson AU, Stringham HM, Corrêa IR, Farber-Eger E, Steinthorsdottir V, Uitterlinden AG, Munroe PB, Brown MJ, Schmidberger J, Holmen O, Thorand B, Hveem K, Wilsgaard T, Mohlke KL, Wang Z, GWA-PA Consortium, Shmeliov A, den Hoed M, Loos RJF, Kratzer W, Haenle M, Koenig W, Boehm BO, Tan TM, Tomas A, Salem V, Barroso I, Tuomilehto J, Boehnke M, Florez JC, Hamsten A, Watkins H, Njølstad I, Wichmann HE, Caulfield MJ, Khaw KT, van Duijn CM, Hofman A, Wareham NJ, Langenberg C, Whitfield JB, Martin NG, Montgomery G, Scapoli C, Tzoulaki I, Elliott P, Thorsteinsdottir U, Stefansson K, Brittain EL, McCarthy MI, Froguel P, Sexton PM, Wootten D, Groop L, Dupuis J, Meigs JB, Deganutti G, Demirkan A, Pers TH, Reynolds CA, Aulchenko YS, Kaakinen MA, Jones B, Prokopenko I, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC).",,Nature genetics,2023,2023-09-07,Y,,,,"Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.",,doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render
-30727941,https://doi.org/10.1186/s12859-019-2633-8,DeepPVP: phenotype-based prioritization of causative variants using deep learning.,"Boudellioua I, Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,BMC bioinformatics,2019,2019-02-06,Y,Phenotype; Ontology; Machine Learning; Variant Prioritization,Applied Analytics,,"<h4>Background</h4>Prioritization of variants in personal genomic data is a major challenge. Recently, computational methods that rely on comparing phenotype similarity have shown to be useful to identify causative variants. In these methods, pathogenicity prediction is combined with a semantic similarity measure to prioritize not only variants that are likely to be dysfunctional but those that are likely involved in the pathogenesis of a patient's phenotype.<h4>Results</h4>We have developed DeepPVP, a variant prioritization method that combined automated inference with deep neural networks to identify the likely causative variants in whole exome or whole genome sequence data. We demonstrate that DeepPVP performs significantly better than existing methods, including phenotype-based methods that use similar features. DeepPVP is freely available at https://github.com/bio-ontology-research-group/phenomenet-vp .<h4>Conclusions</h4>DeepPVP further improves on existing variant prioritization methods both in terms of speed as well as accuracy.",,pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-019-2633-8; doi:https://doi.org/10.1186/s12859-019-2633-8; html:https://europepmc.org/articles/PMC6364462; pdf:https://europepmc.org/articles/PMC6364462?pdf=render
 36763324,https://doi.org/10.1007/s12687-023-00635-1,What makes a good life: using theatrical performance to enhance communication about polygenic risk scores research in patient and public involvement.,"Mason AM, Obi I, Ayodele O, Lambert SA, Fahle S.",,Journal of community genetics,2023,2023-02-10,Y,,,,"The aim of this patient and public involvement and engagement (PPIE) work was to explore improvised theatre as a tool for facilitating bi-directional dialogue between researchers and patients/members of the public on the topic of polygenic risk scores (PRS) use within primary or secondary care. PRS are a tool to quantify genetic risk for a heritable disease or trait and may be used to predict future health outcomes. In the United Kingdom (UK), they are often cited as a next-in-line public health tool to be implemented, and their use in consumer genetic testing as well as patient-facing settings is increasing. Despite their potential clinical utility, broader themes about how they might influence an individual's perception of disease risk and decision-making are an active area of research; however, this has mostly been in the setting of return of results to patients. We worked with a youth theatre group and patients involved in a PPIE group to develop two short plays about public perceptions of genetic risk information that could be captured by PRS. These plays were shared in a workshop with patients/members of the public to facilitate discussions about PRS and their perceived benefits, concerns and emotional reactions. Discussions with both performers and patients/public raised three key questions: (1) can the data be trusted?; (2) does knowing genetic risk actually help the patient?; and (3) what makes a life worthwhile? Creating and watching fictional narratives helped all participants explore the potential use of PRS in a clinical setting, informing future research considerations and improving communication between the researchers and lay members of the PPIE group.",,pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf; doi:https://doi.org/10.1007/s12687-023-00635-1; html:https://europepmc.org/articles/PMC10576689; pdf:https://europepmc.org/articles/PMC10576689?pdf=render
 34785588,https://doi.org/10.1136/openhrt-2021-001784,OpenSAFELY: impact of national guidance on switching anticoagulant therapy during COVID-19 pandemic.,"OpenSAFELY Collaborative, Curtis HJ, MacKenna B, Walker AJ, Croker R, Mehrkar A, Morton C, Bacon S, Hickman G, Inglesby P, Bates C, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson E, Hulme W, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wong AY, Forbes H, Parry J, Hester F, Harper S, Douglas I, Smeeth L, Goldacre B.",,Open heart,2021,2021-11-01,Y,Stroke; Medication Adherence; Healthcare Economics And Organisations; Covid-19,,,"<h4>Background</h4>Early in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately coprescribed two anticoagulants following a medication change and associated monitoring.<h4>Objective</h4>To describe which people were switched from warfarin to DOACs; identify potentially unsafe coprescribing of anticoagulants; and assess whether abnormal clotting results have become more frequent during the pandemic.<h4>Methods</h4>With the approval of NHS England, we conducted a cohort study using routine clinical data from 24 million NHS patients in England.<h4>Results</h4>20 000 of 164 000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in coprescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. International normalised ratio (INR) testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420).<h4>Conclusions</h4>Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people coprescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.",,pdf:https://openheart.bmj.com/content/openhrt/8/2/e001784.full.pdf; doi:https://doi.org/10.1136/openhrt-2021-001784; html:https://europepmc.org/articles/PMC8595296; pdf:https://europepmc.org/articles/PMC8595296?pdf=render
 37156273,https://doi.org/10.1016/j.jad.2023.04.138,Subjective and objective sleep and circadian parameters as predictors of depression-related outcomes: A machine learning approach in UK Biobank.,"Lyall LM, Sangha N, Zhu X, Lyall DM, Ward J, Strawbridge RJ, Cullen B, Smith DJ.",,Journal of affective disorders,2023,2023-05-06,N,Sleep; Depression; Circadian rhythms; Postnatal Depression; Inactivity; Rest-activity,,,"<h4>Background</h4>Sleep and circadian disruption are associated with depression onset and severity, but it is unclear which features (e.g., sleep duration, chronotype) are important and whether they can identify individuals showing poorer outcomes.<h4>Methods</h4>Within a subset of the UK Biobank with actigraphy and mental health data (n = 64,353), penalised regression identified the most useful of 51 sleep/rest-activity predictors of depression-related outcomes; including case-control (Major Depression (MD) vs. controls; postnatal depression vs. controls) and within-case comparisons (severe vs. moderate MD; early vs. later onset, atypical vs. typical symptoms; comorbid anxiety; suicidality). Best models (of lasso, ridge, and elastic net) were selected based on Area Under the Curve (AUC).<h4>Results</h4>For MD vs. controls (n<sub>(MD)</sub> = 24,229; n<sub>(control)</sub> = 40,124), lasso AUC was 0.68, 95 % confidence interval (CI) 0.67-0.69. Discrimination was reasonable for atypical vs. typical symptoms (n<sub>(atypical)</sub> = 958; n<sub>(typical)</sub> = 18,722; ridge: AUC 0.74, 95 % CI 0.71-0.77) but poor for remaining models (AUCs 0.59-0.67). Key predictors across most models included: difficulty getting up, insomnia symptoms, snoring, actigraphy-measured daytime inactivity and lower morning activity (~8 am). In a distinct subset (n = 310,718), the number of these factors shown was associated with all depression outcomes.<h4>Limitations</h4>Analyses were cross-sectional and in middle-/older aged adults: comparison with longitudinal investigations and younger cohorts is necessary.<h4>Discussion</h4>Sleep and circadian measures alone provided poor to moderate discrimination of depression outcomes, but several characteristics were identified that may be clinically useful. Future work should assess these features alongside broader sociodemographic, lifestyle and genetic features.",,doi:https://doi.org/10.1016/j.jad.2023.04.138; doi:https://doi.org/10.1016/j.jad.2023.04.138
 36715329,https://doi.org/10.1093/bjd/ljac090,"The epidemiology, healthcare and societal burden of basal cell carcinoma in Wales 2000-2018: a retrospective nationwide analysis.","Ibrahim N, Jovic M, Ali S, Williams N, Gibson JAG, Griffiths R, Dobbs TD, Akbari A, Lyons RA, Hutchings HA, Whitaker IS.",,The British journal of dermatology,2023,2023-02-01,N,,,,"<h4>Background</h4>Basal cell carcinoma (BCC) represents the most commonly occurring cancer worldwide within the white population. Reports predict 298 308 cases of BCC in the UK by 2025, at a cost of £265-366 million to the National Health Service (NHS). Despite the morbidity, societal and healthcare pressures brought about by BCC, routinely collected healthcare data and global registration remain limited.<h4>Objectives</h4>To calculate the incidence of BCC in Wales between 2000 and 2018 and to establish the related healthcare utilization and estimated cost of care.<h4>Methods</h4>The Secure Anonymised Information Linkage (SAIL) databank is one of the largest and most robust health and social care data repositories in the UK. Cancer registry data were linked to routinely collected healthcare databases between 2000 and 2018. Pathological data from Swansea Bay University Health Board (SBUHB) were used for internal validation.<h4>Results</h4>A total of 61 404 histologically proven BCCs were identified within the SAIL Databank during the study period. The European age-standardized incidence for BCC in 2018 was 224.6 per 100 000 person-years. Based on validated regional data, a 45% greater incidence was noted within SBUHB pathology vs. matched regions within SAIL between 2016 and 2018. A negative association between deprivation and incidence was noted with a higher incidence in the least socially deprived and rural dwellers. Approximately 2% travelled 25-50 miles for dermatological services compared with 37% for plastic surgery. Estimated NHS costs of surgically managed lesions for 2002-2019 equated to £119.2-164.4 million.<h4>Conclusions</h4>Robust epidemiological data that are internationally comparable and representative are scarce for nonmelanoma skin cancer. The rising global incidence coupled with struggling healthcare systems in the post-COVID-19 recovery period serve to intensify the societal and healthcare impact. This study is the first to demonstrate the incidence of BCC in Wales and is one of a small number in the UK using internally validated large cohort datasets. Furthermore, our findings demonstrate one of the highest published incidences within the UK and Europe.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62055/Download/62055__26915__ae11794993454389b6ceddbb7f50caaa.pdf; doi:https://doi.org/10.1093/bjd/ljac090
 35429382,https://doi.org/10.1093/infdis/jiac146,Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Antibody Levels Following Second Dose of ChAdOx1 nCov-19 or BNT162b2 Vaccine in Residents of Long-term Care Facilities in England (VIVALDI).,"Stirrup O, Krutikov M, Tut G, Palmer T, Bone D, Bruton R, Fuller C, Azmi B, Lancaster T, Sylla P, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Giddings R, Nacer-Laidi H, Baynton V, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,The Journal of infectious diseases,2022,2022-11-01,Y,Antibodies; Vaccination; Waning; Long-term Care Facilities; Covid-19,,,"General population studies have shown strong humoral response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations, but published data are scarce. We measured SARS-CoV-2 anti-spike antibody levels in long-term care facility residents and staff following a second vaccination dose with Oxford-AstraZeneca or Pfizer-BioNTech. Vaccination elicited robust antibody responses in older residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047242; doi:https://doi.org/10.1093/infdis/jiac146; html:https://europepmc.org/articles/PMC9047242; pdf:https://europepmc.org/articles/PMC9047242?pdf=render
-37828025,https://doi.org/10.1038/s41467-023-41876-5,ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon.,"Hartmann S, Yasmeen S, Jacobs BM, Denaxas S, Pirmohamed M, Gamazon ER, Caulfield MJ, Genes & Health Research Team, Hemingway H, Pietzner M, Langenberg C.",,Nature communications,2023,2023-10-12,Y,,,,"Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10<sup>-8</sup>). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p < 9.6 × 10<sup>-27</sup>) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p < 4.8 × 10<sup>-13</sup>) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (r<sub>G</sub> = -0.21; p-value = 2.3 × 10<sup>-3</sup>), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of α<sub>2A</sub>-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.",,pdf:https://www.nature.com/articles/s41467-023-41876-5.pdf; doi:https://doi.org/10.1038/s41467-023-41876-5; html:https://europepmc.org/articles/PMC10570309; pdf:https://europepmc.org/articles/PMC10570309?pdf=render
 36881701,https://doi.org/10.1097/jtn.0000000000000708,Perceptions of an Interactive Trauma Recovery Information Booklet.,"Reeder SC, Ekegren CL, Mather AM, Kimmel LA, Webb MJ, Pellegrini M, Cameron PA, Gabbe BJ.",,Journal of trauma nursing : the official journal of the Society of Trauma Nurses,2023,2023-03-01,N,,,,"<h4>Background</h4>Previous research has shown that people with traumatic injuries have unmet information needs with respect to their injuries, management, and recovery. An interactive trauma recovery information booklet was developed and implemented to address these information needs at a major trauma center in Victoria, Australia.<h4>Objective</h4>The aim of this quality improvement project was to explore patient and clinician perceptions of a recovery information booklet introduced into a trauma ward.<h4>Methods</h4>Semistructured interviews with trauma patients, family members, and health professionals were undertaken and thematically analyzed using a framework approach. In total, 34 patients, 10 family members, and 26 health professionals were interviewed.<h4>Results</h4>Overall, the booklet was well accepted by most participants and was perceived to contain useful information. The design, content, pictures, and readability were all positively appraised. Many participants used the booklet to record personalized information and to ask health professionals questions about their injuries and management.<h4>Conclusion</h4>Our findings highlight the usefulness and acceptability of a low-cost interactive booklet intervention to facilitate the provision of quality of information and patient-health professional interactions on a trauma ward.",,doi:https://doi.org/10.1097/JTN.0000000000000708
+37828025,https://doi.org/10.1038/s41467-023-41876-5,ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon.,"Hartmann S, Yasmeen S, Jacobs BM, Denaxas S, Pirmohamed M, Gamazon ER, Caulfield MJ, Genes & Health Research Team, Hemingway H, Pietzner M, Langenberg C.",,Nature communications,2023,2023-10-12,Y,,,,"Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10<sup>-8</sup>). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p < 9.6 × 10<sup>-27</sup>) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p < 4.8 × 10<sup>-13</sup>) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (r<sub>G</sub> = -0.21; p-value = 2.3 × 10<sup>-3</sup>), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of α<sub>2A</sub>-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.",,pdf:https://www.nature.com/articles/s41467-023-41876-5.pdf; doi:https://doi.org/10.1038/s41467-023-41876-5; html:https://europepmc.org/articles/PMC10570309; pdf:https://europepmc.org/articles/PMC10570309?pdf=render
 36382153,https://doi.org/10.5334/gh.1166,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: A Systematic Review.,"Fundikira LS, Chillo P, Mutagaywa R, Kamuhabwa A, Kwesigabo G, Asselbergs FW, van Laake LW.",,Global heart,2022,2022-10-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiovascular risk factors,,,<b>Highlights</b>  Prevalence of DCM varies widely in SSA.Cardiovascular risk factors are important in patients with DCM.The role of genetics in idiopathic DCM is not studied in major part of SSA.,,pdf:http://globalheartjournal.com/articles/10.5334/gh.1166/galley/1329/download/; doi:https://doi.org/10.5334/gh.1166; html:https://europepmc.org/articles/PMC9585983; pdf:https://europepmc.org/articles/PMC9585983?pdf=render
 37578823,https://doi.org/10.2196/45233,Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.,"Sun S, Folarin AA, Zhang Y, Cummins N, Garcia-Dias R, Stewart C, Ranjan Y, Rashid Z, Conde P, Laiou P, Sankesara H, Matcham F, Leightley D, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Nica R, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Vairavan S, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,Journal of medical Internet research,2023,2023-08-14,Y,Depression; Mobile phone; Missing Data; Smartphones; Mobile Health; Wearable Devices; Behavioral Patterns; Digital Phenotypes,,,"<h4>Background</h4>Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features.<h4>Objective</h4>We aimed to address these 3 challenges to inform future work in stratified analyses.<h4>Methods</h4>Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model.<h4>Results</h4>We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression.<h4>Conclusions</h4>This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.",,pdf:https://www.jmir.org/2023/1/e45233/PDF; doi:https://doi.org/10.2196/45233; html:https://europepmc.org/articles/PMC10463088
 36606535,https://doi.org/10.1111/jdv.18841,The association between atopic eczema and lymphopenia: Results from a UK cohort study with replication in US survey data.,"Hollestein LM, Ye MYF, Ang KL, Forbes H, Mansfield KE, Abuabara K, Smeeth L, Langan SM.",,Journal of the European Academy of Dermatology and Venereology : JEADV,2023,2023-01-25,N,,,,"<h4>Background</h4>Lymphocyte skin homing in atopic eczema (AE) may induce lymphopenia.<h4>Objective</h4>To determine if AE is associated with lymphopenia.<h4>Methods</h4>We used UK primary care electronic health records (Clinical Practice Research Datalink GOLD) for a matched cohort study in adults (18 years+) (1997-2015) with at least one recorded lymphocyte count. We matched people with AE to up to five people without. We used multivariable logistic regression to estimate the association between AE and lymphopenia (two low lymphocyte counts within 3 months) and linear mixed effects regression to estimate the association with absolute lymphocyte counts using all available counts. Cox proportional hazard models were used to investigate the effect of lymphopenia on common infections. We replicated the study using US survey data (National Health and Nutrition Examination Survey [NHANES]).<h4>Results</h4>Among 71,731 adults with AE and 126,349 adults without AE, we found an adjusted odds ratio (OR) for lymphopenia of 1.16 (95% CI: 1.09-1.23); the strength of association increased with increasing eczema severity. When comparing all recorded lymphocyte counts from adults with AE (n = 1,497,306) to those of people without AE (n = 4,035,870) we saw a lower mean lymphocyte (adjusted mean difference -0.047 × 10<sup>9</sup> /L [95% CI: -0.051 to -0.043]) in those with AE. The difference was larger for men, with increasing age, and with increasing AE severity and was present among people with AE not treated with immunosuppressive drugs. In NHANES (n = 22,624), the adjusted OR for lymphopenia in adults with AE was 1.30 (95% CI: 0.80-2.11), and the adjusted mean lymphocyte count difference was -0.03 × 10<sup>9</sup> /L (95% CI: -0.07 to 0.02). Despite having a lower lymphocyte count, adjusting for time with lymphopenia, did not alter risk estimates of infections.<h4>Conclusion</h4>Atopic eczema, including increasing AE severity, is associated with a decreased lymphocyte count, regardless of immunosuppressive drug use. Whether the lower lymphocyte count has wider health implications for people with severe eczema warrants further investigation.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4668507/1/Hollestein_etal_2023_The-association-between-atopic-eczema.pdf; doi:https://doi.org/10.1111/jdv.18841
+35776101,https://doi.org/10.1093/ije/dyac140,Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records.,"Xu Z, Arnold M, Sun L, Stevens D, Chung R, Ip S, Barrett J, Kaptoge S, Pennells L, Di Angelantonio E, Wood AM.",,International journal of epidemiology,2022,2022-12-01,Y,Variability; Cardiovascular disease; Type 2 diabetes; Risk Prediction; Repeated Measurements; Electronic Health Records,,,"<h4>Background</h4>Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.<h4>Methods</h4>We used electronic health records (EHRs) data from 83 910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.<h4>Results</h4>The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P < 0.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index = 0.659, 95% CI: 0.654-0.663) as compared with using last observed values (C-index = 0.651, 95% CI: 0.646-0.656) or means (C-index = 0.650, 95% CI: 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase = 0.005, 95% CI: 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index increase = 0.002, 95% CI: 0.000-0.003), HbA1c (C-index increase = 0.002, 95% CI: 0.000-0.003) or HDL cholesterol (C-index increase= 0.003, 95% CI: 0.002-0.005).<h4>Conclusion</h4>Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render
 37773956,https://doi.org/10.1371/journal.pone.0292240,Prioritising cardiovascular disease risk assessment to high risk individuals based on primary care records.,"Chung R, Xu Z, Arnold M, Stevens D, Keogh R, Barrett J, Harrison H, Pennells L, Kim LG, DiAngelantonio E, Paige E, Usher-Smith JA, Wood AM.",,PloS one,2023,2023-09-29,Y,,,,"<h4>Objective</h4>To provide quantitative evidence for systematically prioritising individuals for full formal cardiovascular disease (CVD) risk assessment using primary care records with a novel tool (eHEART) with age- and sex- specific risk thresholds.<h4>Methods and analysis</h4>eHEART was derived using landmark Cox models for incident CVD with repeated measures of conventional CVD risk predictors in 1,642,498 individuals from the Clinical Practice Research Datalink. Using 119,137 individuals from UK Biobank, we modelled the implications of initiating guideline-recommended statin therapy using eHEART with age- and sex-specific prioritisation thresholds corresponding to 5% false negative rates to prioritise adults aged 40-69 years in a population in England for invitation to a formal CVD risk assessment.<h4>Results</h4>Formal CVD risk assessment on all adults would identify 76% and 49% of future CVD events amongst men and women respectively, and 93 (95% CI: 90, 95) men and 279 (95% CI: 259, 297) women would need to be screened (NNS) to prevent one CVD event. In contrast, if eHEART was first used to prioritise individuals for formal CVD risk assessment, we would identify 73% and 47% of future events amongst men and women respectively, and a NNS of 75 (95% CI: 72, 77) men and 162 (95% CI: 150, 172) women. Replacing the age- and sex-specific prioritisation thresholds with a 10% threshold identify around 10% less events.<h4>Conclusions</h4>The use of prioritisation tools with age- and sex-specific thresholds could lead to more efficient CVD assessment programmes with only small reductions in effectiveness at preventing new CVD events.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0292240&type=printable; doi:https://doi.org/10.1371/journal.pone.0292240; html:https://europepmc.org/articles/PMC10540947; pdf:https://europepmc.org/articles/PMC10540947?pdf=render
 37800588,https://doi.org/10.1097/js9.0000000000000781,Safety outcomes of bariatric surgery iN patients with advanced oRgan disease: the ONWARD study - a prospective cohort study.,"Singhal R, Cardoso VR, Wiggins T, Yashasvi Rajeev M, Ludwig C, Gkoutos GV, Hanif W, Mahawar K, ONWARD & GENEVA collaborators.",,"International journal of surgery (London, England)",2023,2023-10-05,N,,,,"<h4>Introduction</h4>Increasing numbers of patients with advanced organ disease are being considered for Bariatric and Metabolic Surgery (BMS). There is no prospective study on the safety of BMS in these patients. This study aimed to capture outcomes for patients with advanced cardiac, renal, or liver disease undergoing BMS.<h4>Materials and methods</h4>This was a multinational, prospective cohort study on the safety of elective BMS in adults (≥18 y) with advanced disease of the heart, liver, or kidney.<h4>Results</h4>Data on 177 patients with advanced diseases of heart, liver, or kidney were submitted by 75 centres in 33 countries. Mean age and Body Mass Index was 48.56±11.23 years and 45.55±7.35 kg/m 2 respectively. Laparoscopic sleeve gastrectomy was performed in 124 patients (70%). The 30-day morbidity and mortality were 15.9% (n=28) and 1.1% (n=2) respectively. 30-day morbidity was 16.4%, 11.7%, 20.5%, and 50.0% in patients with advanced heart (n=11/61), liver (n=8/68), kidney (n=9/44), and multi-organ disease (n=2/4) respectively. Cardiac patients with left ventricular ejection fraction ≤35% and New York Heart Association classification 3 or 4, liver patients with Model for End-Stage Liver Disease score ≥12, and patients with advanced renal disease not on dialysis were at increased risk of complications. Comparison with a propensity score matched cohort found advanced disease of the heart, liver, or kidney to be significantly associated with higher 30-day morbidity.<h4>Conclusion</h4>Patients with advanced organ disease are at increased risk of 30-day morbidity following BMS. This prospective study quantifies that risk and identifies patients at the highest risk.",,doi:https://doi.org/10.1097/JS9.0000000000000781
-35776101,https://doi.org/10.1093/ije/dyac140,Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records.,"Xu Z, Arnold M, Sun L, Stevens D, Chung R, Ip S, Barrett J, Kaptoge S, Pennells L, Di Angelantonio E, Wood AM.",,International journal of epidemiology,2022,2022-12-01,Y,Variability; Cardiovascular disease; Type 2 diabetes; Risk Prediction; Repeated Measurements; Electronic Health Records,,,"<h4>Background</h4>Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.<h4>Methods</h4>We used electronic health records (EHRs) data from 83 910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.<h4>Results</h4>The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P < 0.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index = 0.659, 95% CI: 0.654-0.663) as compared with using last observed values (C-index = 0.651, 95% CI: 0.646-0.656) or means (C-index = 0.650, 95% CI: 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase = 0.005, 95% CI: 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index increase = 0.002, 95% CI: 0.000-0.003), HbA1c (C-index increase = 0.002, 95% CI: 0.000-0.003) or HDL cholesterol (C-index increase= 0.003, 95% CI: 0.002-0.005).<h4>Conclusion</h4>Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render
 37794179,https://doi.org/10.1038/s41416-023-02450-4,A taxonomy of early diagnosis research to guide study design and funding prioritisation.,"Whitfield E, White B, Denaxas S, Barclay ME, Renzi C, Lyratzopoulos G.",,British journal of cancer,2023,2023-10-04,N,,,,"Researchers and research funders aiming to improve diagnosis seek to identify if, when, where, and how earlier diagnosis is possible. This has led to the propagation of research studies using a wide range of methodologies and data sources to explore diagnostic processes. Many such studies use electronic health record data and focus on cancer diagnosis. Based on this literature, we propose a taxonomy to guide the design and support the synthesis of early diagnosis research, focusing on five key questions: Do healthcare use patterns suggest earlier diagnosis could be possible? How does the diagnostic process begin? How do patients progress from presentation to diagnosis? How long does the diagnostic process take? Could anything have been done differently to reach the correct diagnosis sooner? We define families of diagnostic research study designs addressing each of these questions and appraise their unique or complementary contributions and limitations. We identify three further questions on relationships between the families and their relevance for examining patient group inequalities, supported with examples from the cancer literature. Although exemplified through cancer as a disease model, we recognise the framework is also applicable to non-neoplastic disease. The proposed framework can guide future study design and research funding prioritisation.",,pdf:https://www.nature.com/articles/s41416-023-02450-4.pdf; doi:https://doi.org/10.1038/s41416-023-02450-4
 36038914,https://doi.org/10.1186/s12916-022-02473-3,Polycystic ovary syndrome and risk of adverse obstetric outcomes: a retrospective population-based matched cohort study in England.,"Subramanian A, Lee SI, Phillips K, Toulis KA, Kempegowda P, O'Reilly MW, Adderley NJ, Thangaratinam S, Arlt W, Nirantharakumar K.",,BMC medicine,2022,2022-08-30,Y,Delivery; Preterm; PCOS; Polycystic ovary syndrome; Stillbirth; Birthweight,,,"<h4>Background</h4>Polycystic ovary syndrome (PCOS) affects up to one in five women of childbearing age. Observational studies assessing the association between maternal PCOS and adverse obstetric outcomes have reported varying results, depending on patient population, diagnostic criteria for PCOS and covariates accounted for in their analyses. We aimed to assess the risk of obstetric outcomes among a population-based representative cohort of women with PCOS compared to an age-matched cohort of women without PCOS.<h4>Methods</h4>A retrospective cohort study was conducted of pregnancies of women in England aged 15-49 years identified from the Clinical Practice Research Datalink (CPRD) GOLD pregnancy register and linked Hospital Episodes Statistic (HES) data between March 1997 and March 2020. Pregnancies from the register that had a linked HES delivery record were included. Linked CPRD primary care data was used to ascertain maternal PCOS exposure prior to pregnancy. To improve detection of PCOS, in addition to PCOS diagnostic codes, codes for (1) polycystic ovaries or (2) hyperandrogenism and anovulation together were also considered. Sensitivity analysis was limited to only pregnant women with a diagnostic code for PCOS. Primary outcomes ascertained from linked HES data were (1) preterm delivery (gestation < 37 weeks), (2) mode of delivery, (3) high (> 4000 g) or low birthweight (< 2500 g) and (4) stillbirth. Secondary outcomes were (1) very preterm delivery (< 32 weeks), (2) extremely preterm delivery (< 28 weeks), (3) small and (4) large for gestational age. Conditional logistic regression models were performed adjusting for age, ethnicity, deprivation, dysglycaemia, hypertension, thyroid disorders, number of babies born at index pregnancy, and pre-gravid BMI. Multiple imputation was performed for missing outcome data.<h4>Results</h4>27,586 deliveries with maternal PCOS were matched for age (± 1 year) to 110,344 deliveries without PCOS. In the fully adjusted models, maternal PCOS was associated with an increased risk of (1) preterm birth [aOR: 1.11 (95% CI 1.06-1.17)], and (2) emergency caesarean, elective caesarean and instrumental vaginal compared to spontaneous delivery [aOR: 1.10 (1.05-1.15), 1.07 (1.03-1.12) and 1.04 (1.00-1.09), respectively]. There was absence of association with low birthweight, high birthweight and stillbirth. In the sensitivity analysis, the association with preterm birth [aOR: 1.31 (95% CI 1.13-1.52)], emergency caesarean [aOR: 1.15 (95% CI 1.02-1.30)], and elective caesarean [aOR: 1.03 (95% CI 1.02-1.03)] remained. While there was no significant association with any of the secondary outcomes in the primary analysis, in the sensitivity analysis maternal PCOS was associated with increased risk of extremely preterm delivery [aOR: 1.86 (95% CI 1.31-2.65)], and lower risk of small for gestational age babies [aOR: 0.74 (95% CI 0.59-0.94)].<h4>Conclusions</h4>Maternal PCOS was associated with increased risk of preterm and caesarean delivery. Association with low birthweight may be largely mediated by lower gestational age at birth.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02473-3; doi:https://doi.org/10.1186/s12916-022-02473-3; html:https://europepmc.org/articles/PMC9425992; pdf:https://europepmc.org/articles/PMC9425992?pdf=render
 34189274,https://doi.org/10.23889/ijpds.v5i1.1362,Concept libraries for automatic electronic health record based phenotyping: A review.,"Almowil ZA, Zhou SM, Brophy S.",,International journal of population data science,2021,2021-06-16,Y,Review; Phenotype Algorithms; Concept Libraries; Linked Electronic Health Records,,,"<h4>Introduction</h4>Electronic health records (EHR) are linked together to examine disease history and to undertake research into the causes and outcomes of disease. However, the process of constructing algorithms for phenotyping (e.g., identifying disease characteristics) or health characteristics (e.g., smoker) is very time consuming and resource costly. In addition, results can vary greatly between researchers. Reusing or building on algorithms that others have created is a compelling solution to these problems. However, sharing algorithms is not a common practice and many published studies do not detail the clinical code lists used by the researchers in the disease/characteristic definition. To address these challenges, a number of centres across the world have developed health data portals which contain concept libraries (e.g., algorithms for defining concepts such as disease and characteristics) in order to facilitate disease phenotyping and health studies.<h4>Objectives</h4>This study aims to review the literature of existing concept libraries, examine their utilities, identify the current gaps, and suggest future developments.<h4>Methods</h4>The five-stage framework of Arksey and O'Malley was used for the literature search. This approach included defining the research questions, identifying relevant studies through literature review, selecting eligible studies, charting and extracting data, and summarising and reporting the findings.<h4>Results</h4>This review identified seven publicly accessible Electronic Health data concept libraries which were developed in different countries including UK, USA, and Canada. The concept libraries (n = 7) investigated were either general libraries that hold phenotypes of multiple specialties (n = 4) or specialized libraries that manage only certain specialities such as rare diseases (n = 3). There were some clear differences between the general libraries such as archiving data from different electronic sources, and using a range of different types of coding systems. However, they share some clear similarities such as enabling users to upload their own code lists, and allowing users to use/download the publicly accessible code. In addition, there were some differences between the specialized libraries such as difference in ability to search, and if it was possible to use different searching queries such as simple or complex searches. Conversely, there were some similarities between the specialized libraries such as enabling users to upload their own concepts into the libraries and to show where they were published, which facilitates assessing the validity of the concepts. All the specialized libraries aimed to encourage the reuse of research methods such as lists of clinical code and/or metadata.<h4>Conclusion</h4>The seven libraries identified have been developed independently and appear to replicate similar concepts but in different ways. Collaboration between similar libraries would greatly facilitate the use of these libraries for the user. The process of building code lists takes time and effort. Access to existing code lists increases consistency and accuracy of definitions across studies. Concept library developers should collaborate with each other to raise awareness of their existence and of their various functions, which could increase users' contributions to those libraries and promote their wide-ranging adoption.",,doi:https://doi.org/10.23889/ijpds.v5i1.1362; html:https://europepmc.org/articles/PMC8210840; pdf:https://europepmc.org/articles/PMC8210840?pdf=render
@@ -715,15 +715,15 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 35032176,https://doi.org/10.1007/s00125-021-05640-y,Cardiovascular risk prediction in type 2 diabetes: a comparison of 22 risk scores in primary care settings.,"Dziopa K, Asselbergs FW, Gratton J, Chaturvedi N, Schmidt AF.",,Diabetologia,2022,2022-01-15,Y,Prediction; Diabetes; Cardiovascular disease; Risk Score,,,"<h4>Aims/hypothesis</h4>We aimed to compare the performance of risk prediction scores for CVD (i.e., coronary heart disease and stroke), and a broader definition of CVD including atrial fibrillation and heart failure (CVD+), in individuals with type 2 diabetes.<h4>Methods</h4>Scores were identified through a literature review and were included irrespective of the type of predicted cardiovascular outcome or the inclusion of individuals with type 2 diabetes. Performance was assessed in a contemporary, representative sample of 168,871 UK-based individuals with type 2 diabetes (age ≥18 years without pre-existing CVD+). Missing observations were addressed using multiple imputation.<h4>Results</h4>We evaluated 22 scores: 13 derived in the general population and nine in individuals with type 2 diabetes. The Systemic Coronary Risk Evaluation (SCORE) CVD rule derived in the general population performed best for both CVD (C statistic 0.67 [95% CI 0.67, 0.67]) and CVD+ (C statistic 0.69 [95% CI 0.69, 0.70]). The C statistic of the remaining scores ranged from 0.62 to 0.67 for CVD, and from 0.64 to 0.69 for CVD+. Calibration slopes (1 indicates perfect calibration) ranged from 0.38 (95% CI 0.37, 0.39) to 0.74 (95% CI 0.72, 0.76) for CVD, and from 0.41 (95% CI 0.40, 0.42) to 0.88 (95% CI 0.86, 0.90) for CVD+. A simple recalibration process considerably improved the performance of the scores, with calibration slopes now ranging between 0.96 and 1.04 for CVD. Scores with more predictors did not outperform scores with fewer predictors: for CVD+, QRISK3 (19 variables) had a C statistic of 0.68 (95% CI 0.68, 0.69), compared with SCORE CVD (six variables) which had a C statistic of 0.69 (95% CI 0.69, 0.70). Scores specific to individuals with diabetes did not discriminate better than scores derived in the general population: the UK Prospective Diabetes Study (UKPDS) scores performed significantly worse than SCORE CVD (p value <0.001).<h4>Conclusions/interpretation</h4>CVD risk prediction scores could not accurately identify individuals with type 2 diabetes who experienced a CVD event in the 10 years of follow-up. All 22 evaluated models had a comparable and modest discriminative ability.",,pdf:https://link.springer.com/content/pdf/10.1007/s00125-021-05640-y.pdf; doi:https://doi.org/10.1007/s00125-021-05640-y; html:https://europepmc.org/articles/PMC8894164; pdf:https://europepmc.org/articles/PMC8894164?pdf=render
 37562944,https://doi.org/10.1136/emermed-2023-213186,"Biases in the collection of blood alcohol data for adult major trauma patients in Victoria, Australia.","Lau G, Gabbe B, Mitra B, Dietze P, Reeder S, Cameron P, Read DJ, Symons E, Beck B.",,Emergency medicine journal : EMJ,2023,2023-08-10,N,epidemiology; wounds and injuries; toxicology; Alcohol Abuse,,,"<h4>Background</h4>In-hospital alcohol testing provides an opportunity to implement prevention strategies for patients with high risk of experiencing repeated alcohol-related injuries. However, barriers to alcohol testing in emergency settings can prevent patients from being tested. In this study, we aimed to understand potential biases in current data on the completion of blood alcohol tests for major trauma patients at hospitals in Victoria, Australia.<h4>Methods</h4>Victorian State Trauma Registry data on all adult major trauma patients from 1 January 2018 to 31 December 2021 were used. Characteristics associated with having a blood alcohol test recorded in the registry were assessed using logistic regression models.<h4>Results</h4>This study included 14 221 major trauma patients, of which 4563 (32.1%) had a blood alcohol test recorded. Having a blood alcohol test completed was significantly associated with age, socioeconomic disadvantage level, preferred language, having pre-existing mental health or substance use conditions, smoking status, presenting during times associated with heavy community alcohol consumption, injury cause and intent, and Glasgow Coma Scale scores (p<0.05). Restricting analyses to patients from a trauma centre where blood alcohol testing was part of routine clinical care mitigated most biases. However, relative to patients injured while driving a motor vehicle/motorcycle, lower odds of testing were still observed for patients with injuries from flames/scalds/contact burns (adjusted OR (aOR)=0.33, 95% CI 0.18 to 0.61) and low falls (aOR=0.17, 95% CI 0.12 to 0.25). Higher odds of testing were associated with pre-existing mental health (aOR=1.39, 95% CI 1.02 to 1.89) or substance use conditions (aOR=2.33, 95% CI to 1.47-3.70), and living in a more disadvantaged area (most disadvantaged quintile relative to least disadvantaged quintile: aOR=2.30, 95% CI 1.52 to 3.48).<h4>Conclusion</h4>Biases in the collection of blood alcohol data likely impact the surveillance of alcohol-related injuries. Routine alcohol testing after major trauma is needed to accurately inform epidemiology and the subsequent implementation of strategies for reducing alcohol-related injuries.",,doi:https://doi.org/10.1136/emermed-2023-213186
 35637502,https://doi.org/10.1186/s12889-022-13453-w,Age within schoolyear and attention-deficit hyperactivity disorder in Scotland and Wales.,"Fleming M, Bandyopadhyay A, McLay JS, Clark D, King A, Mackay DF, Lyons RA, Sayal K, Brophy S, Pell JP.",,BMC public health,2022,2022-05-30,Y,Children; Education; Data Linkage; School; Attention-deficit Hyperactivity Disorder; Relative Age,,,"<h4>Background</h4>Previous studies suggest an association between age within schoolyear and attention-deficit hyperactivity disorder (ADHD). Scotland and Wales have different school entry cut-off dates (six months apart) and policies on holding back children. We aim to investigate the association between relative age and treated attention deficit hyperactivity disorder (ADHD) in two countries, accounting for held-back children.<h4>Methods</h4>Routine education and health records of 1,063,256 primary and secondary schoolchildren in Scotland (2009-2013) and Wales (2009-2016) were linked. Logistic regression was used to examine the relationships between age within schoolyear and treated ADHD, adjusting for child, maternity and obstetric confounders.<h4>Results</h4>Amongst children in their expected school year, 8,721 (0.87%) had treated ADHD (Scotland 0.84%; Wales 0.96%). In Wales, ADHD increased with decreasing age (youngest quartile, adjusted OR 1.32, 95% CI 1.19-1.46) but, in Scotland, it did not differ between the youngest and oldest quartiles. Including held-back children in analysis of their expected year, the overall prevalence of treated ADHD was 0.93%, and increased across age quartiles in both countries. More children were held back in Scotland (57,979; 7.66%) than Wales (2,401; 0.78%). Held-back children were more likely to have treated ADHD (Scotland OR 2.18, 95% CI 2.01-2.36; Wales OR 1.70, 95% CI 1.21-2.31) and 81.18% of held-back children would have been in the youngest quartile of their expected year.<h4>Conclusions</h4>Children younger within schoolyear are more likely to be treated for ADHD, suggesting immaturity may influence diagnosis. However, these children are more likely to be held back in countries that permit flexibility, attenuating the relative age effect.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-022-13453-w; doi:https://doi.org/10.1186/s12889-022-13453-w; html:https://europepmc.org/articles/PMC9150337; pdf:https://europepmc.org/articles/PMC9150337?pdf=render
-37794871,https://doi.org/10.1093/ehjdh/ztad044,An artificial intelligence tool for automated analysis of large-scale unstructured clinical cine cardiac magnetic resonance databases.,"Mariscal-Harana J, Asher C, Vergani V, Rizvi M, Keehn L, Kim RJ, Judd RM, Petersen SE, Razavi R, King AP, Ruijsink B, Puyol-Antón E.",,European heart journal. Digital health,2023,2023-07-13,Y,Artificial intelligence; Quality control; Cardiac function; Cardiac Segmentation; Cardiac Magnetic Resonance,,,"<h4>Aims</h4>Artificial intelligence (AI) techniques have been proposed for automating analysis of short-axis (SAX) cine cardiac magnetic resonance (CMR), but no CMR analysis tool exists to automatically analyse large (unstructured) clinical CMR datasets. We develop and validate a robust AI tool for start-to-end automatic quantification of cardiac function from SAX cine CMR in large clinical databases.<h4>Methods and results</h4>Our pipeline for processing and analysing CMR databases includes automated steps to identify the correct data, robust image pre-processing, an AI algorithm for biventricular segmentation of SAX CMR and estimation of functional biomarkers, and automated post-analysis quality control to detect and correct errors. The segmentation algorithm was trained on 2793 CMR scans from two NHS hospitals and validated on additional cases from this dataset (<i>n</i> = 414) and five external datasets (<i>n</i> = 6888), including scans of patients with a range of diseases acquired at 12 different centres using CMR scanners from all major vendors. Median absolute errors in cardiac biomarkers were within the range of inter-observer variability: <8.4 mL (left ventricle volume), <9.2 mL (right ventricle volume), <13.3 g (left ventricular mass), and <5.9% (ejection fraction) across all datasets. Stratification of cases according to phenotypes of cardiac disease and scanner vendors showed good performance across all groups.<h4>Conclusion</h4>We show that our proposed tool, which combines image pre-processing steps, a domain-generalizable AI algorithm trained on a large-scale multi-domain CMR dataset and quality control steps, allows robust analysis of (clinical or research) databases from multiple centres, vendors, and cardiac diseases. This enables translation of our tool for use in fully automated processing of large multi-centre databases.",,doi:https://doi.org/10.1093/ehjdh/ztad044; html:https://europepmc.org/articles/PMC10545512; pdf:https://europepmc.org/articles/PMC10545512?pdf=render
 34514354,https://doi.org/10.1093/jamiaopen/ooab001,Transforming and evaluating electronic health record disease phenotyping algorithms using the OMOP common data model: a case study in heart failure.,"Papez V, Moinat M, Payralbe S, Asselbergs FW, Lumbers RT, Hemingway H, Dobson R, Denaxas S.",,JAMIA open,2021,2021-02-04,Y,Phenotyping; Heart Failure; Algorithms; Ehr; Omop,,,"<h4>Objective</h4>The aim of the study was to transform a resource of linked electronic health records (EHR) to the OMOP common data model (CDM) and evaluate the process in terms of syntactic and semantic consistency and quality when implementing disease and risk factor phenotyping algorithms.<h4>Materials and methods</h4>Using heart failure (HF) as an exemplar, we represented three national EHR sources (Clinical Practice Research Datalink, Hospital Episode Statistics Admitted Patient Care, Office for National Statistics) into the OMOP CDM 5.2. We compared the original and CDM HF patient population by calculating and presenting descriptive statistics of demographics, related comorbidities, and relevant clinical biomarkers.<h4>Results</h4>We identified a cohort of 502 536 patients with the incident and prevalent HF and converted 1 099 195 384 rows of data from 216 581 914 encounters across three EHR sources to the OMOP CDM. The largest percentage (65%) of unmapped events was related to medication prescriptions in primary care. The average coverage of source vocabularies was >98% with the exception of laboratory tests recorded in primary care. The raw and transformed data were similar in terms of demographics and comorbidities with the largest difference observed being 3.78% in the prevalence of chronic obstructive pulmonary disease (COPD).<h4>Conclusion</h4>Our study demonstrated that the OMOP CDM can successfully be applied to convert EHR linked across multiple healthcare settings and represent phenotyping algorithms spanning multiple sources. Similar to previous research, challenges mapping primary care prescriptions and laboratory measurements still persist and require further work. The use of OMOP CDM in national UK EHR is a valuable research tool that can enable large-scale reproducible observational research.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/4/3/ooab001/40325375/ooab001.pdf; doi:https://doi.org/10.1093/jamiaopen/ooab001; html:https://europepmc.org/articles/PMC8423424; pdf:https://europepmc.org/articles/PMC8423424?pdf=render
+37794871,https://doi.org/10.1093/ehjdh/ztad044,An artificial intelligence tool for automated analysis of large-scale unstructured clinical cine cardiac magnetic resonance databases.,"Mariscal-Harana J, Asher C, Vergani V, Rizvi M, Keehn L, Kim RJ, Judd RM, Petersen SE, Razavi R, King AP, Ruijsink B, Puyol-Antón E.",,European heart journal. Digital health,2023,2023-07-13,Y,Artificial intelligence; Quality control; Cardiac function; Cardiac Segmentation; Cardiac Magnetic Resonance,,,"<h4>Aims</h4>Artificial intelligence (AI) techniques have been proposed for automating analysis of short-axis (SAX) cine cardiac magnetic resonance (CMR), but no CMR analysis tool exists to automatically analyse large (unstructured) clinical CMR datasets. We develop and validate a robust AI tool for start-to-end automatic quantification of cardiac function from SAX cine CMR in large clinical databases.<h4>Methods and results</h4>Our pipeline for processing and analysing CMR databases includes automated steps to identify the correct data, robust image pre-processing, an AI algorithm for biventricular segmentation of SAX CMR and estimation of functional biomarkers, and automated post-analysis quality control to detect and correct errors. The segmentation algorithm was trained on 2793 CMR scans from two NHS hospitals and validated on additional cases from this dataset (<i>n</i> = 414) and five external datasets (<i>n</i> = 6888), including scans of patients with a range of diseases acquired at 12 different centres using CMR scanners from all major vendors. Median absolute errors in cardiac biomarkers were within the range of inter-observer variability: <8.4 mL (left ventricle volume), <9.2 mL (right ventricle volume), <13.3 g (left ventricular mass), and <5.9% (ejection fraction) across all datasets. Stratification of cases according to phenotypes of cardiac disease and scanner vendors showed good performance across all groups.<h4>Conclusion</h4>We show that our proposed tool, which combines image pre-processing steps, a domain-generalizable AI algorithm trained on a large-scale multi-domain CMR dataset and quality control steps, allows robust analysis of (clinical or research) databases from multiple centres, vendors, and cardiac diseases. This enables translation of our tool for use in fully automated processing of large multi-centre databases.",,doi:https://doi.org/10.1093/ehjdh/ztad044; html:https://europepmc.org/articles/PMC10545512; pdf:https://europepmc.org/articles/PMC10545512?pdf=render
 33521768,https://doi.org/10.1016/s2666-7568(20)30011-8,Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults.,"Cox LS, Bellantuono I, Lord JM, Sapey E, Mannick JB, Partridge L, Gordon AL, Steves CJ, Witham MD.",,The lancet. Healthy longevity,2020,2020-11-09,Y,,,,,,doi:https://doi.org/10.1016/s2666-7568(20)30011-8; doi:https://doi.org/10.1016/S2666-7568(20)30011-8; html:https://europepmc.org/articles/PMC7834195; pdf:https://europepmc.org/articles/PMC7834195?pdf=render
 36720568,https://doi.org/10.1136/bmjopen-2022-066164,Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study.,"OpenSAFELY Collaborative, Parker EP, Tazare J, Hulme WJ, Bates C, Carr EJ, Cockburn J, Curtis HJ, Fisher L, Green AC, Harper S, Hester F, Horne EM, Loud F, Lyon S, Mahalingasivam V, Mehrkar A, Nab L, Parry J, Santhakumaran S, Steenkamp R, Sterne JA, Walker AJ, Williamson EJ, Willicombe M, Zheng B, Goldacre B, Nitsch D, Tomlinson LA.",,BMJ open,2023,2023-01-31,Y,Public Health; Kidney & Urinary Tract Disorders; Covid-19,,,"<h4>Objective</h4>To characterise factors associated with COVID-19 vaccine uptake among people with kidney disease in England.<h4>Design</h4>Retrospective cohort study using the OpenSAFELY-TPP platform, performed with the approval of NHS England.<h4>Setting</h4>Individual-level routine clinical data from 24 million people across GPs in England using TPP software. Primary care data were linked directly with COVID-19 vaccine records up to 31 August 2022 and with renal replacement therapy (RRT) status via the UK Renal Registry (UKRR).<h4>Participants</h4>A cohort of adults with stage 3-5 chronic kidney disease (CKD) or receiving RRT at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate (eGFR) or inclusion in the UKRR.<h4>Main outcome measures</h4>Dose-specific vaccine coverage over time was determined from 1 December 2020 to 31 August 2022. Individual-level factors associated with receipt of a 3-dose or 4-dose vaccine series were explored via Cox proportional hazards models.<h4>Results</h4>992 205 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 31 August 2022 was 97.5%, 97.0% and 93.9% for doses 1, 2 and 3, respectively, and 81.9% for dose 4 among individuals with one or more indications for eligibility. Delayed 3-dose vaccine uptake was associated with younger age, minority ethnicity, social deprivation and severe mental illness-associations that were consistent across CKD severity subgroups, dialysis patients and kidney transplant recipients. Similar associations were observed for 4-dose uptake.<h4>Conclusion</h4>Although high primary vaccine and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across clinical and demographic groups and 4-dose coverage is suboptimal. Targeted interventions are needed to identify barriers to vaccine uptake among under-vaccinated subgroups identified in the present study.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/1/e066164.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066164; html:https://europepmc.org/articles/PMC9890277; pdf:https://europepmc.org/articles/PMC9890277?pdf=render
 33472631,https://doi.org/10.1186/s12916-020-01893-3,Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.,"Carr E, Bendayan R, Bean D, Stammers M, Wang W, Zhang H, Searle T, Kraljevic Z, Shek A, Phan HTT, Muruet W, Gupta RK, Shinton AJ, Wyatt M, Shi T, Zhang X, Pickles A, Stahl D, Zakeri R, Noursadeghi M, O'Gallagher K, Rogers M, Folarin A, Karwath A, Wickstrøm KE, Köhn-Luque A, Slater L, Cardoso VR, Bourdeaux C, Holten AR, Ball S, McWilliams C, Roguski L, Borca F, Batchelor J, Amundsen EK, Wu X, Gkoutos GV, Sun J, Pinto A, Guthrie B, Breen C, Douiri A, Wu H, Curcin V, Teo JT, Shah AM, Dobson RJB.",,BMC medicine,2021,2021-01-21,Y,Prediction model; Blood parameters; Covid-19; News2 Score,,,"<h4>Background</h4>The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification.<h4>Methods</h4>Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models.<h4>Results</h4>A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites.<h4>Conclusions</h4>NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01893-3; doi:https://doi.org/10.1186/s12916-020-01893-3; html:https://europepmc.org/articles/PMC7817348; pdf:https://europepmc.org/articles/PMC7817348?pdf=render
 34135032,https://doi.org/10.1136/bmjopen-2020-043906,Realising the full potential of data-enabled trials in the UK: a call for action.,"Sydes MR, Barbachano Y, Bowman L, Denwood T, Farmer A, Garfield-Birkbeck S, Gibson M, Gulliford MC, Harrison DA, Hewitt C, Logue J, Navaie W, Norrie J, O'Kane M, Quint JK, Rycroft-Malone J, Sheffield J, Smeeth L, Sullivan F, Tizzard J, Walker P, Wilding J, Williamson PR, Landray M, Morris A, Walker RR, Williams HC, Valentine J, Data Enabled Trials Group Workshop Group members.",,BMJ open,2021,2021-06-16,Y,Clinical Trials; Health Informatics; Statistics & Research Methods,,,"<h4>Rationale</h4>Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up.<h4>Approach</h4>The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation.<h4>Reflection</h4>Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution.<h4>Discussion</h4>EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e043906.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043906; html:https://europepmc.org/articles/PMC8211043; pdf:https://europepmc.org/articles/PMC8211043?pdf=render
 36654802,https://doi.org/10.1002/lrh2.10315,"A framework for understanding, designing, developing and evaluating learning health systems.","Foley T, Vale L.",,Learning health systems,2023,2022-05-20,Y,Quality improvement; Informatics; Implementation Science; Learning Health Systems; Learning Healthcare Systems,,,"<h4>Introduction</h4>A Learning Health System is not a technical project. It is the evolution of an existing health system into one capable of learning from every patient. This paper outlines a recently published framework intended to aid the understanding, design, development and evaluation of Learning Health Systems.<h4>Methods</h4>This work extended an existing repository of Learning Health System evidence, adding five more workshops. The total was subjected to thematic analysis, yielding a framework of elements important to understanding, designing, developing and evaluating Learning Health Systems. Purposeful literature reviews were conducted on each element. The findings were revised following a review by a group of international experts.<h4>Results</h4>The resulting framework was arranged around four questions:What is our rationale for developing a Learning Health System?There can be many reasons for developing a Learning Health System. Understanding these will guide its development.What sources of complexity exist at the system and the intervention level?An understanding of complexity is central to making Learning Health Systems work. The non-adoption, abandonment, scale-up, spread and sustainability framework was utilised to help understand and manage it.What strategic approaches to change do we need to consider?A range of strategic issues must be addressed to enable successful change in a Learning Health System. These include, strategy, organisational structure, culture, workforce, implementation science, behaviour change, co-design and evaluation.What technical building blocks will we need?A Learning Health System must capture data from practice, turn it into knowledge and apply it back into practice. There are many methods to achieve this and a range of platforms to help.<h4>Discussion</h4>The results form a framework for understanding, designing, developing and evaluating Learning Health Systems at any scale.<h4>Conclusion</h4>It is hoped that this framework will evolve with use and feedback.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835047; doi:https://doi.org/10.1002/lrh2.10315; html:https://europepmc.org/articles/PMC9835047; pdf:https://europepmc.org/articles/PMC9835047?pdf=render
-36448824,https://doi.org/10.1002/cpt.2807,Clinical Relevance of Drug-Drug Interactions With Antibiotics as Listed in a National Medication Formulary: Results From Two Large Population-Based Case-Control Studies in Patients Aged 65-100 Years Using Linked English Primary Care and Hospital Data.,"van Staa TP, Pirmohamed M, Sharma A, Buchan I, Ashcroft DM.",,Clinical pharmacology and therapeutics,2023,2022-12-16,Y,,,,"This study evaluated drug-drug interactions (DDIs) between antibiotic and nonantibiotic drugs listed with warnings of severe outcomes in the British National Formulary based on adverse drug reaction (ADR) detectable with routine International Classification of Diseases, Tenth Revision coding. Data sources were Clinical Practice Research Databank GOLD and Aurum anonymized electronic health records from English general practices linked to hospital admission records. In propensity-matched case-control study, outcomes were ADR or emergency admissions. Analyzed were 121,546 ADR-related admission cases matched to 638,238 controls. For most antibiotics, adjusted odds ratios (aORs) for ADR-related hospital admission were large (aOR for trimethoprim 4.13; 95% confidence interval (CI), 3.97-4.30). Of the 51 DDIs evaluated for ADR-related admissions, 38 DDIs (74.5%) had statistically increased aORs of concomitant exposure compared with nonexposure (mean aOR 3.96; range 1.59-11.42); for the 89 DDIs for emergency hospital admission, the results were 75 (84.3%) and mean aOR 2.40; range 1.43-4.17. Changing reference group to single antibiotic exposure reduced aORs for concomitant exposure by 76.5% and 83.0%, respectively. Medicines listed to cause nephrotoxicity substantially increased risks that were related to number of medicines (aOR was 2.55 (95% CI, 2.46-2.64) for current use of 1 and 10.44 (95% CI, 7.36-14.81) for 3 or more medicines). In conclusion, no evidence of substantial risk was found for multiple DDIs with antibiotics despite warnings of severe outcomes in a national formulary and flagging in electronic health record software. It is proposed that the evidence base for inclusion of DDIs in national formularies be strengthened and made publicly accessible and indiscriminate flagging, which compounds alert fatigue, be reduced.",,doi:https://doi.org/10.1002/cpt.2807; doi:https://doi.org/10.1002/cpt.2807; html:https://europepmc.org/articles/PMC10107602; pdf:https://europepmc.org/articles/PMC10107602?pdf=render
 32855306,https://doi.org/10.1136/gutjnl-2020-321650,Prioritisation by FIT to mitigate the impact of delays in the 2-week wait colorectal cancer referral pathway during the COVID-19 pandemic: a UK modelling study.,"Loveday C, Sud A, Jones ME, Broggio J, Scott S, Gronthound F, Torr B, Garrett A, Nicol DL, Jhanji S, Boyce SA, Williams M, Barry C, Riboli E, Kipps E, McFerran E, Muller DC, Lyratzopoulos G, Lawler M, Abulafi M, Houlston RS, Turnbull C.",,Gut,2021,2020-08-27,Y,Colonoscopy; Colorectal Cancer; Colorectal Cancer Screening,,,"<h4>Objective</h4>To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the COVID-19 pandemic.<h4>Design</h4>We modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2-6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19-related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008-2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval.<h4>Results</h4>Delay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk-benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%.<h4>Conclusions</h4>Delays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required.",,pdf:https://gut.bmj.com/content/gutjnl/70/6/1053.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-321650; html:https://europepmc.org/articles/PMC7447105; pdf:https://europepmc.org/articles/PMC7447105?pdf=render
+36448824,https://doi.org/10.1002/cpt.2807,Clinical Relevance of Drug-Drug Interactions With Antibiotics as Listed in a National Medication Formulary: Results From Two Large Population-Based Case-Control Studies in Patients Aged 65-100 Years Using Linked English Primary Care and Hospital Data.,"van Staa TP, Pirmohamed M, Sharma A, Buchan I, Ashcroft DM.",,Clinical pharmacology and therapeutics,2023,2022-12-16,Y,,,,"This study evaluated drug-drug interactions (DDIs) between antibiotic and nonantibiotic drugs listed with warnings of severe outcomes in the British National Formulary based on adverse drug reaction (ADR) detectable with routine International Classification of Diseases, Tenth Revision coding. Data sources were Clinical Practice Research Databank GOLD and Aurum anonymized electronic health records from English general practices linked to hospital admission records. In propensity-matched case-control study, outcomes were ADR or emergency admissions. Analyzed were 121,546 ADR-related admission cases matched to 638,238 controls. For most antibiotics, adjusted odds ratios (aORs) for ADR-related hospital admission were large (aOR for trimethoprim 4.13; 95% confidence interval (CI), 3.97-4.30). Of the 51 DDIs evaluated for ADR-related admissions, 38 DDIs (74.5%) had statistically increased aORs of concomitant exposure compared with nonexposure (mean aOR 3.96; range 1.59-11.42); for the 89 DDIs for emergency hospital admission, the results were 75 (84.3%) and mean aOR 2.40; range 1.43-4.17. Changing reference group to single antibiotic exposure reduced aORs for concomitant exposure by 76.5% and 83.0%, respectively. Medicines listed to cause nephrotoxicity substantially increased risks that were related to number of medicines (aOR was 2.55 (95% CI, 2.46-2.64) for current use of 1 and 10.44 (95% CI, 7.36-14.81) for 3 or more medicines). In conclusion, no evidence of substantial risk was found for multiple DDIs with antibiotics despite warnings of severe outcomes in a national formulary and flagging in electronic health record software. It is proposed that the evidence base for inclusion of DDIs in national formularies be strengthened and made publicly accessible and indiscriminate flagging, which compounds alert fatigue, be reduced.",,doi:https://doi.org/10.1002/cpt.2807; doi:https://doi.org/10.1002/cpt.2807; html:https://europepmc.org/articles/PMC10107602; pdf:https://europepmc.org/articles/PMC10107602?pdf=render
 34641870,https://doi.org/10.1186/s12911-021-01638-z,An informatics consult approach for generating clinical evidence for treatment decisions.,"Lai AG, Chang WH, Parisinos CA, Katsoulis M, Blackburn RM, Shah AD, Nguyen V, Denaxas S, Davey Smith G, Gaunt TR, Nirantharakumar K, Cox MP, Forde D, Asselbergs FW, Harris S, Richardson S, Sofat R, Dobson RJB, Hingorani A, Patel R, Sterne J, Banerjee A, Denniston AK, Ball S, Sebire NJ, Shah NH, Foster GR, Williams B, Hemingway H.",,BMC medical informatics and decision making,2021,2021-10-12,Y,,,,"<h4>Background</h4>An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis.<h4>Methods</h4>We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems.<h4>Results</h4>We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results.<h4>Conclusion</h4>We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service.",,doi:https://doi.org/10.1186/s12911-021-01638-z; doi:https://doi.org/10.1186/s12911-021-01638-z; html:https://europepmc.org/articles/PMC8506488; pdf:https://europepmc.org/articles/PMC8506488?pdf=render
 34716166,https://doi.org/10.1136/bmjopen-2021-053268,Electronic reminders and rewards to improve adherence to inhaled asthma treatment in adolescents: a non-randomised feasibility study in tertiary care.,"De Simoni A, Fleming L, Holliday L, Horne R, Priebe S, Bush A, Sheikh A, Griffiths C.",,BMJ open,2021,2021-10-29,Y,Asthma; Respiratory Medicine (See Thoracic Medicine); Paediatric Thoracic Medicine,,,"<h4>Objective</h4>To test the feasibility and acceptability of a short-term reminder and incentives intervention in adolescents with low adherence to asthma medications.<h4>Methods</h4>Mixed-methods feasibility study in a tertiary care clinic. Adolescents recruited to a 24-week programme with three 8-weekly visits, receiving electronic reminders to prompt inhaled corticosteroid (ICS) inhalation through a mobile app coupled with electronic monitoring devices (EMD). From the second visit, monetary incentives based on adherence of ICS inhalation: £1 per dose, maximum £2 /day, up to £112/study, collected as gift cards at the third visit. End of study interviews and questionnaires assessing perceptions of asthma and ICS, analysed using the Perceptions and Practicalities Framework.<h4>Participants</h4>Adolescents (11-18 years) with documented low ICS adherence (<80% by EMD), and poor asthma control at the first clinic visit.<h4>Results</h4>10 out of 12 adolescents approached were recruited (7 males, 3 females, 12-16 years). Eight participants provided adherence measures up to the fourth visits and received rewards. Mean study duration was 281 days, with 7/10 participants unable to attend their fourth visit due to COVID-19 lockdown. Only 3/10 participants managed to pair the app/EMD up to the fourth visit, which was associated with improved ICS adherence (from 0.51, SD 0.07 to 0.86, SD 0.05). Adherence did not change in adolescents unable to pair the app/EMD. The intervention was acceptable to participants and parents/guardians. Exit interviews showed that participants welcomed reminders and incentives, though expressed frustration with app/EMD technological difficulties. Participants stated the intervention helped through reminding ICS doses, promoting self-monitoring and increasing motivation to take inhalers.<h4>Conclusions</h4>An intervention using electronic reminders and incentives through an app coupled with an EMD was feasible and acceptable to adolescents with asthma. A pilot randomised controlled trial is warranted to better estimate the effect size on adherence, with improved technical support for the EMD.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e053268.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053268; html:https://europepmc.org/articles/PMC8559117; pdf:https://europepmc.org/articles/PMC8559117?pdf=render
 36302124,https://doi.org/10.1080/21645515.2022.2127572,Comparative risk of cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination or infection: A national cohort study using linked electronic health records.,"Ohaeri C, Thomas DR, Salmon J, Cottrell S, Lyons J, Akbari A, Lyons RA, Torabi F, Davies GG, Williams C.",,Human vaccines & immunotherapeutics,2022,2022-10-27,Y,Vaccines; Coronavirus; Cerebral Venous Sinus Thrombosis; Cerebral Venous Thrombosis; Covid19,,,"To inform the public and policy makers, we investigated and compared the risk of cerebral venous sinus thrombosis (CVST) after SARS-Cov-2 vaccination or infection using a national cohort of 2,643,699 individuals aged 17 y and above, alive, and resident in Wales on 1 January 2020 followed up through multiple linked data sources until 28 March 2021. Exposures were first dose of Oxford-ChAdOx1 or Pfizer-BioNTech vaccine or polymerase chain reaction (PCR)-confirmed SARS-Cov-2 infection. The outcome was an incident record of CVST. Hazard ratios (HR) were calculated using multivariable Cox regression, adjusted for confounders. HR from SARS-Cov-2 infection was compared with that for SARS-Cov-2 vaccination. We identified 910,556 (34.4%) records of first SARS-Cov-2 vaccination and 165,862 (6.3%) of SARS-Cov-2 infection. A total of 1,372 CVST events were recorded during the study period, of which 52 (3.8%) and 48 (3.5%) occurred within 28 d after vaccination and infection, respectively. We observed slight non-significant risk of CVST within 28 d of vaccination [aHR: 1.34, 95% CI: 0.95-1.90], which remained after stratifying by vaccine [BNT162b2, aHR: 1.18 (95% CI: 0.63-2.21); ChAdOx1, aHR: 1.40 (95% CI: 0.95-2.05)]. Three times the number of CVST events is observed within 28 d of a positive SARS-Cov-2 test [aHR: 3.02 (95% CI: 2.17-4.21)]. The risk of CVST following SARS-Cov-2 infection is 2.3 times that following SARS-Cov-2 vaccine. This is important information both for those designing COVID-19 vaccination programs and for individuals making their own informed decisions on the risk-benefit of vaccination. This record-linkage approach will be useful in monitoring the safety of future vaccine programs.",,doi:https://doi.org/10.1080/21645515.2022.2127572; doi:https://doi.org/10.1080/21645515.2022.2127572; html:https://europepmc.org/articles/PMC9746546; pdf:https://europepmc.org/articles/PMC9746546?pdf=render
@@ -746,8 +746,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 37609702,https://doi.org/10.1002/pds.5681,Adverse drug reactions and hospital admissions: Large case-control study of patients aged 65-100 years using linked English primary care and hospital data.,"van Staa TP, Pirmohamed M, Sharma A, Ashcroft DM, Buchan I.",,Pharmacoepidemiology and drug safety,2023,2023-08-23,N,Adverse drug reactions; Primary Care; Medicines; Pharmacovigilance; Polypharmacy,,,"<h4>Background</h4>Adverse drug reactions (ADRs) are common and a leading cause of injury. However, information on ADR risks of individual medicines is often limited. The aim of this hypothesis-generating study was to assess the relative importance of ADR-related and emergency hospital admission for large group of medication classes.<h4>Methods</h4>This study was a propensity-matched case-control study in English primary care. Data sources were Clinical Practice Research Databank and Aurum with longitudinal, anonymized, patient level electronic health records (EHRs) from English general practices linked to hospital records. Cases aged 65-100 with ADR-related or emergency hospital admission were matched to up to six controls by age, sex, morbidity and propensity scores for hospital admission risk. Medication groups with systemic administration as listed in the British National Formulary (used by prescribers for medication advice). Prescribing in the 84 days before the index date was assessed. Only medication groups with 50+ cases exposed were analysed. The outcomes of interest were ADR-related and emergency hospital admissions. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CI).<h4>Results</h4>The overall population included 121 546 cases with an ADR-related and 849 769 cases with emergency hospital admission. The percentage of hospitalizations with an ADR-related code for admission diagnosis was 1.83% and 6.58% with an ADR-related code at any time during hospitalization. A total of 137 medication groups was included in the main ADR analyses. Of these, 13 (9.5%) had statistically non-significant adjusted ORs, 58 (42.3%) statistically significant ORs between 1.0 and 1.5, 37 (27.0%) between 1.5-2.0, 18 (13.1%) between 2.0-3.0 and 11 (8.0%) 3.0 or higher. Several classes of antibiotics (including penicillins) were among medicines with largest ORs. Evaluating the 14 medications most often associated with ADRs, a strong association was found between the number of these medicines and the risk of ADR-related hospital admission (adjusted OR of 7.53 (95% CI 7.15-7.93) for those exposed to 6+ of these medicines).<h4>Conclusions and relevance</h4>There is a need for a regular systematic assessment of the harm-benefit ratio of medicines, harvesting the information in large healthcare databases and combining it with causality assessment of individual case histories.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5681; doi:https://doi.org/10.1002/pds.5681
 36525457,https://doi.org/10.1371/journal.pone.0279250,Undergoing radical treatment for prostate cancer and its impact on wellbeing: A qualitative study exploring men's experiences.,"Vyas N, Brunckhorst O, Fox L, Van Hemelrijck M, Muir G, Stewart R, Dasgupta P, Ahmed K.",,PloS one,2022,2022-12-16,Y,,,,"<h4>Introduction</h4>Quality of life in prostate cancer survivorship is becoming increasingly important, with mental and social wellbeing recognised as key components. However, limited global evaluation of psychosocial challenges experienced after treatment exists. Therefore, we aimed to explore the lived experiences of men who underwent radical treatment, and its psychosocial impact.<h4>Material and methods</h4>This qualitative study was conducted using 19 men who had undergone radical treatment (prostatectomy or radiotherapy) for their cancer. Semi-structured interviews were conducted exploring lived experiences of men after treatment. A Structured thematic analysis of collected data was undertaken, with an inductive co-construction of themes through the lens of the biopsychosocial model. Themes generated were considered within a psychological, social, and physical wellbeing framework.<h4>Results</h4>An initial knowledge gap meant mental wellbeing was strongly impacted initially leading to a 'Diagnostic Blow and the Search for Clarity'. Doubt over individuals' future resulted in 'An Uncertain Future' in many men. Once treatment was completed a 'Reflective journey' began, with men considering their outcomes and decisions made. Social wellbeing was also impacted with many identifying the 'Emotional Repercussions' on their relationships and the impact their diagnosis had on their partner and family. Many subsequently sought to increase their support through 'The Social Network and Advocacy', while physical changes led to an increased need for 'Social Planning'. Finally, physical wellbeing was highlighted by a continual acknowledgement of the 'Natural process of ageing' leading to a reluctancy to seek help, whilst simultaneously attempting to improve existing health via 'The Health Kick'.<h4>Conclusions</h4>Radical treatments have a considerable impact on mental and social wellbeing of individuals. Anxiety after diagnosis and significant uncertainty over individual futures exist, with physical complications of treatment leading to social repercussions. Future research should aim to identify forms of support to improve quality of life of these men.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279250&type=printable; doi:https://doi.org/10.1371/journal.pone.0279250; html:https://europepmc.org/articles/PMC9757548; pdf:https://europepmc.org/articles/PMC9757548?pdf=render
 36299367,https://doi.org/10.1183/23120541.00211-2022,Mortality associated with metabolic syndrome in people with COPD managed in primary care.,"Karsanji U, Evans RA, Quint JK, Khunti K, Lawson CA, Petherick E, Greening NJ, Singh SJ, Richardson M, Steiner MC.",,ERJ open research,2022,2022-10-24,Y,,,,"<h4>Objective</h4>The prevalence of metabolic syndrome (MetS) has been reported to be higher in selected populations of people with COPD. The impact of MetS on mortality in COPD is unknown. We used routinely collected healthcare data to estimate the prevalence of MetS in people with COPD managed in primary care and determine its impact on 5-year mortality.<h4>Methods</h4>Records from 103 955 patients with COPD from the Clinical Practice Research Datalink (CPRD-GOLD) between 2009 to 2017 were scrutinised. MetS was defined as the presence of three or more of: obesity, hypertension, lowered high-density lipoprotein cholesterol, elevated triglycerides or type 2 diabetes mellitus (T2DM). Univariate and multivariable Cox regression models were constructed to determine the prognostic impact of MetS on 5-year mortality. Similar univariate models were constructed for individual components of the definition of MetS.<h4>Results</h4>The prevalence of MetS in the COPD cohort was 10.1%. Univariate analyses showed the presence of MetS increased mortality (hazard ratio (HR) 1.19, 95% CI: 1.12-1.27, p<0.001), but this risk was substantially attenuated in the multivariable analysis (HR 1.06, 95% CI: 0.99-1.13, p<i>=</i>0.085). The presence of hypertension (HR 1.70, 95% CI: 1.63-1.77, p<0.001) and T2DM (HR 1.41, 95% CI: 1.34-1.48, p<0.001) increased and obesity (HR 0.74, 95% CI: 0.71-0.78, p<0.001) reduced mortality risk.<h4>Conclusion</h4>MetS in patients with COPD is associated with higher 5-year mortality, but this impact was minimal when adjusted for indices of COPD disease severity and other comorbidities. Individual components of the MetS definition exerted differential impacts on mortality suggesting limitation to the use of MetS as a multicomponent condition in predicting outcome in COPD.",,pdf:https://openres.ersjournals.com/content/erjor/8/4/00211-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00211-2022; html:https://europepmc.org/articles/PMC9589337; pdf:https://europepmc.org/articles/PMC9589337?pdf=render
-35444210,https://doi.org/10.1038/s41698-022-00269-5,Pan-cancer prognostic genetic mutations and clinicopathological factors associated with survival outcomes: a systematic review.,"Gammall J, Lai AG.",,NPJ precision oncology,2022,2022-04-20,Y,,,,"Cancer is a leading cause of death, accounting for almost 10 million deaths annually worldwide. Personalised therapies harnessing genetic and clinical information may improve survival outcomes and reduce the side effects of treatments. The aim of this study is to appraise published evidence on clinicopathological factors and genetic mutations (single nucleotide polymorphisms [SNPs]) associated with prognosis across 11 cancer types: lung, colorectal, breast, prostate, melanoma, renal, glioma, bladder, leukaemia, endometrial, ovarian. A systematic literature search of PubMed/MEDLINE and Europe PMC was conducted from database inception to July 1, 2021. 2497 publications from PubMed/MEDLINE and 288 preprints from Europe PMC were included. Subsequent reference and citation search was conducted and a further 39 articles added. 2824 articles were reviewed by title/abstract and 247 articles were selected for systematic review. Majority of the articles were retrospective cohort studies focusing on one cancer type, 8 articles were on pan-cancer level and 6 articles were reviews. Studies analysing clinicopathological factors included 908,567 patients and identified 238 factors, including age, gender, stage, grade, size, site, subtype, invasion, lymph nodes. Genetic studies included 210,802 patients and identified 440 gene mutations associated with cancer survival, including genes TP53, BRCA1, BRCA2, BRAF, KRAS, BIRC5. We generated a comprehensive knowledge base of biomarkers that can be used to tailor treatment according to patients' unique genetic and clinical characteristics. Our pan-cancer investigation uncovers the biomarker landscape and their combined influence that may help guide health practitioners and researchers across the continuum of cancer care from drug development to long-term survivorship.",,pdf:https://www.nature.com/articles/s41698-022-00269-5.pdf; doi:https://doi.org/10.1038/s41698-022-00269-5; html:https://europepmc.org/articles/PMC9021198; pdf:https://europepmc.org/articles/PMC9021198?pdf=render
 32310142,https://doi.org/10.2196/14306,"Objective Characterization of Activity, Sleep, and Circadian Rhythm Patterns Using a Wrist-Worn Actigraphy Sensor: Insights Into Posttraumatic Stress Disorder.","Tsanas A, Woodward E, Ehlers A.",,JMIR mHealth and uHealth,2020,2020-04-20,Y,Sleep; Posttraumatic Stress Disorder; actigraphy; Wearable Technology; Geneactiv,,,"<h4>Background</h4>Wearables have been gaining increasing momentum and have enormous potential to provide insights into daily life behaviors and longitudinal health monitoring. However, to date, there is still a lack of principled algorithmic framework to facilitate the analysis of actigraphy and objectively characterize day-by-day data patterns, particularly in cohorts with sleep problems.<h4>Objective</h4>This study aimed to propose a principled algorithmic framework for the assessment of activity, sleep, and circadian rhythm patterns in people with posttraumatic stress disorder (PTSD), a mental disorder with long-lasting distressing symptoms such as intrusive memories, avoidance behaviors, and sleep disturbance. In clinical practice, these symptoms are typically assessed using retrospective self-reports that are prone to recall bias. The aim of this study was to develop objective measures from patients' everyday lives, which could potentially considerably enhance the understanding of symptoms, behaviors, and treatment effects.<h4>Methods</h4>Using a wrist-worn sensor, we recorded actigraphy, light, and temperature data over 7 consecutive days from three groups: 42 people diagnosed with PTSD, 43 traumatized controls, and 30 nontraumatized controls. The participants also completed a daily sleep diary over 7 days and the standardized Pittsburgh Sleep Quality Index questionnaire. We developed a novel approach to automatically determine sleep onset and offset, which can also capture awakenings that are crucial for assessing sleep quality. Moreover, we introduced a new intuitive methodology facilitating actigraphy exploration and characterize day-by-day data across 49 activity, sleep, and circadian rhythm patterns.<h4>Results</h4>We demonstrate that the new sleep detection algorithm closely matches the sleep onset and offset against the participants' sleep diaries consistently outperforming an existing open-access widely used approach. Participants with PTSD exhibited considerably more fragmented sleep patterns (as indicated by greater nocturnal activity, including awakenings) and greater intraday variability compared with traumatized and nontraumatized control groups, showing statistically significant (P<.05) and strong associations (|R|>0.3).<h4>Conclusions</h4>This study lays the foundation for objective assessment of activity, sleep, and circadian rhythm patterns using passively collected data from a wrist-worn sensor, facilitating large community studies to monitor longitudinally healthy and pathological cohorts under free-living conditions. These findings may be useful in clinical PTSD assessment and could inform therapy and monitoring of treatment effects.",,doi:https://doi.org/10.2196/14306; doi:https://doi.org/10.2196/14306; html:https://europepmc.org/articles/PMC7199134
+35444210,https://doi.org/10.1038/s41698-022-00269-5,Pan-cancer prognostic genetic mutations and clinicopathological factors associated with survival outcomes: a systematic review.,"Gammall J, Lai AG.",,NPJ precision oncology,2022,2022-04-20,Y,,,,"Cancer is a leading cause of death, accounting for almost 10 million deaths annually worldwide. Personalised therapies harnessing genetic and clinical information may improve survival outcomes and reduce the side effects of treatments. The aim of this study is to appraise published evidence on clinicopathological factors and genetic mutations (single nucleotide polymorphisms [SNPs]) associated with prognosis across 11 cancer types: lung, colorectal, breast, prostate, melanoma, renal, glioma, bladder, leukaemia, endometrial, ovarian. A systematic literature search of PubMed/MEDLINE and Europe PMC was conducted from database inception to July 1, 2021. 2497 publications from PubMed/MEDLINE and 288 preprints from Europe PMC were included. Subsequent reference and citation search was conducted and a further 39 articles added. 2824 articles were reviewed by title/abstract and 247 articles were selected for systematic review. Majority of the articles were retrospective cohort studies focusing on one cancer type, 8 articles were on pan-cancer level and 6 articles were reviews. Studies analysing clinicopathological factors included 908,567 patients and identified 238 factors, including age, gender, stage, grade, size, site, subtype, invasion, lymph nodes. Genetic studies included 210,802 patients and identified 440 gene mutations associated with cancer survival, including genes TP53, BRCA1, BRCA2, BRAF, KRAS, BIRC5. We generated a comprehensive knowledge base of biomarkers that can be used to tailor treatment according to patients' unique genetic and clinical characteristics. Our pan-cancer investigation uncovers the biomarker landscape and their combined influence that may help guide health practitioners and researchers across the continuum of cancer care from drug development to long-term survivorship.",,pdf:https://www.nature.com/articles/s41698-022-00269-5.pdf; doi:https://doi.org/10.1038/s41698-022-00269-5; html:https://europepmc.org/articles/PMC9021198; pdf:https://europepmc.org/articles/PMC9021198?pdf=render
 36745557,https://doi.org/10.1093/bjd/ljac132,"Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis.","Adesanya EI, Matthewman J, Schonmann Y, Hayes JF, Henderson A, Mathur R, Mulick AR, Smith CH, Langan SM, Mansfield KE.",,The British journal of dermatology,2023,2023-03-01,N,,,,"<h4>Background</h4>Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear.<h4>Objectives</h4>To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis.<h4>Methods</h4>We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis.<h4>Results</h4>We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, τ2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, τ2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, τ2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, τ2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, τ2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents).<h4>Conclusions</h4>Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear.",,pdf:https://academic.oup.com/bjd/article-pdf/188/4/460/51790111/ljac132.pdf; doi:https://doi.org/10.1093/bjd/ljac132
 34626176,https://doi.org/10.1093/brain/awab253,Whole-exome sequencing reveals a role of HTRA1 and EGFL8 in brain white matter hyperintensities.,"Malik R, Beaufort N, Frerich S, Gesierich B, Georgakis MK, Rannikmäe K, Ferguson AC, Haffner C, Traylor M, Ehrmann M, Sudlow CLM, Dichgans M.",,Brain : a journal of neurology,2021,2021-10-01,N,Whole-exome Sequencing; White Matter Hyperintensities; Uk Biobank; Htra1; Burden Test,,,"White matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on their volume, the contribution of rare variants to the WMH burden in the general population remains largely unexplored. We conducted a comprehensive analysis of this burden in the UK Biobank using publicly available whole-exome sequencing data (n up to 17 830) and found a splice-site variant in GBE1, encoding 1,4-alpha-glucan branching enzyme 1, to be associated with lower white matter burden on an exome-wide level [c.691+2T>C, β = -0.74, standard error (SE) = 0.13, P = 9.7 × 10-9]. Applying whole-exome gene-based burden tests, we found damaging missense and loss-of-function variants in HTRA1 (frequency of 1 in 275 in the UK Biobank population) to associate with an increased WMH volume (P = 5.5 × 10-6, false discovery rate = 0.04). HTRA1 encodes a secreted serine protease implicated in familial forms of small vessel disease. Domain-specific burden tests revealed that the association with WMH volume was restricted to rare variants in the protease domain (amino acids 204-364; β = 0.79, SE = 0.14, P = 9.4 × 10-8). The frequency of such variants in the UK Biobank population was 1 in 450. The WMH volume was brought forward by ∼11 years in carriers of a rare protease domain variant. A comparison with the effect size of established risk factors for WMH burden revealed that the presence of a rare variant in the HTRA1 protease domain corresponded to a larger effect than meeting the criteria for hypertension (β = 0.26, SE = 0.02, P = 2.9 × 10-59) or being in the upper 99.8% percentile of the distribution of a polygenic risk score based on common genetic variants (β = 0.44, SE = 0.14, P = 0.002). In biochemical experiments, most (6/9) of the identified protease domain variants resulted in markedly reduced protease activity. We further found EGFL8, which showed suggestive evidence for association with WMH volume (P = 1.5 × 10-4, false discovery rate = 0.22) in gene burden tests, to be a direct substrate of HTRA1 and to be preferentially expressed in cerebral arterioles and arteries. In a phenome-wide association study mapping ICD-10 diagnoses to 741 standardized Phecodes, rare variants in the HTRA1 protease domain were associated with multiple neurological and non-neurological conditions including migraine with aura (odds ratio = 12.24, 95%CI: 2.54-35.25; P = 8.3 × 10-5]. Collectively, these findings highlight an important role of rare genetic variation and the HTRA1 protease in determining WMH burden in the general population.",,pdf:https://academic.oup.com/brain/article-pdf/144/9/2670/40880367/awab253.pdf; doi:https://doi.org/10.1093/brain/awab253; html:https://europepmc.org/articles/PMC8557338; pdf:https://europepmc.org/articles/PMC8557338?pdf=render; doi:https://doi.org/10.1093/brain/awab253
 37327673,https://doi.org/10.1016/j.ebiom.2023.104655,HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms.,"Petersen TB, de Bakker M, Asselbergs FW, Harakalova M, Akkerhuis KM, Brugts JJ, van Ramshorst J, Lumbers RT, Ostroff RM, Katsikis PD, van der Spek PJ, Umans VA, Boersma E, Rizopoulos D, Kardys I.",,EBioMedicine,2023,2023-06-14,Y,Proteomics; Phenotypes; Biomarkers; Heart Failure; Unsupervised Machine Learning,,,"<h4>Background</h4>HFrEF is a heterogenous condition with high mortality. We used serial assessments of 4210 circulating proteins to identify distinct novel protein-based HFrEF subphenotypes and to investigate underlying dynamic biological mechanisms. Herewith we aimed to gain pathophysiological insights and fuel opportunities for personalised treatment.<h4>Methods</h4>In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 [IQR:1.1-2.6] years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring, and applied an aptamer-based multiplex proteomic approach. Using unsupervised machine learning methods, we derived clusters from 4210 repeatedly measured proteomic biomarkers. Sets of proteins that drove cluster allocation were analysed via an enrichment analysis. Differences in clinical characteristics and PEP occurrence were evaluated.<h4>Findings</h4>We identified four subphenotypes with different protein profiles, prognosis and clinical characteristics, including age (median [IQR] for subphenotypes 1-4, respectively:70 [64, 76], 68 [60, 79], 57 [47, 65], 59 [56, 66]years), EF (30 [26, 36], 26 [20, 38], 26 [22, 32], 33 [28, 37]%), and chronic renal failure (45%, 65%, 36%, 37%). Subphenotype allocation was driven by subsets of proteins associated with various biological functions, such as oxidative stress, inflammation and extracellular matrix organisation. Clinical characteristics of the subphenotypes were aligned with these associations. Subphenotypes 2 and 3 had the worst prognosis compared to subphenotype 1 (adjHR (95%CI):3.43 (1.76-6.69), and 2.88 (1.37-6.03), respectively).<h4>Interpretation</h4>Four circulating-protein based subphenotypes are present in HFrEF, which are driven by varying combinations of protein subsets, and have different clinical characteristics and prognosis.<h4>Clinical trial registration</h4>ClinicalTrials.gov Identifier: NCT01851538https://clinicaltrials.gov/ct2/show/NCT01851538.<h4>Funding</h4>EU/EFPIA IMI2JU BigData@Heart grant n°116074, Jaap Schouten Foundation and Noordwest Academie.",,pdf:http://www.thelancet.com/article/S2352396423002207/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104655; html:https://europepmc.org/articles/PMC10279550; pdf:https://europepmc.org/articles/PMC10279550?pdf=render
@@ -763,16 +763,16 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 29925668,https://doi.org/10.1136/jech-2017-210370,Emergency hospital admissions associated with a non-randomised housing intervention meeting national housing quality standards: a longitudinal data linkage study.,"Rodgers SE, Bailey R, Johnson R, Berridge D, Poortinga W, Lannon S, Smith R, Lyons RA.",,Journal of epidemiology and community health,2018,2018-06-20,Y,Morbidity; Health Services; Public Health; Housing; Longitudinal Studies,Improving Public Health,,"<h4>Background</h4>We investigated tenant healthcare utilisation associated with upgrading 8558 council houses to a national quality standard. Homes received multiple internal and external improvements and were analysed using repeated measures of healthcare utilisation.<h4>Methods</h4>The primary outcome was emergency hospital admissions for cardiorespiratory conditions and injuries for residents aged 60 years and over. Secondary outcomes included each of the separate conditions, for tenants aged 60 and over, and for all ages. Council home address and intervention records for eight housing cointerventions were anonymously linked to demographic data, hospital admissions and deaths for individuals in a dynamic cohort. Counts of health events were analysed using multilevel regression models to investigate associations between receipt of each housing improvement, adjusting for potential confounding factors and regional trends.<h4>Results</h4>Residents aged 60 years and over living in homes when improvements were made were associated with up to 39% fewer admissions compared with those living in homes that were not upgraded (incidence rate ratio=0.61, 95% CI 0.53 to 0.72). Reduced admissions were associated with electrical systems, windows and doors, wall insulation, and garden paths. There were small non-significant reductions for the primary outcome associated with upgrading heating, adequate loft insulation, new kitchens and new bathrooms.<h4>Conclusion</h4>Results suggest that hospital admissions can be avoided through improving whole home quality standards. This is the first large-scale longitudinal evaluation of a whole home intervention that has evaluated multiple improvement elements using individual-level objective routine health data.",,pdf:https://jech.bmj.com/content/jech/72/10/896.full.pdf; doi:https://doi.org/10.1136/jech-2017-210370; html:https://europepmc.org/articles/PMC6161658; pdf:https://europepmc.org/articles/PMC6161658?pdf=render
 33413610,https://doi.org/10.1186/s13073-020-00822-6,An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets.,"Ward D, Higgins M, Phelan JE, Hibberd ML, Campino S, Clark TG.",,Genome medicine,2021,2021-01-07,Y,Mutation; Epitopes; Surveillance; cross-reactivity; Immuno-informatics; Sars-cov-2; Covid; Human-coronavirus,,,"During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online ""immuno-analytics"" resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid proteins are both vaccine and serological diagnostic targets. Using the tool, the nucleocapsid protein appears to be a sub-optimal target for use in serological platforms. Spike D614G (and nsp12 L314P) mutations were most frequent (> 86%), whilst spike A222V/L18F have recently increased. Also, Orf3a proteins may be a suitable target for serology. The tool can accessed from: http://genomics.lshtm.ac.uk/immuno (online); https://github.com/dan-ward-bio/COVID-immunoanalytics (source code).",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-020-00822-6; doi:https://doi.org/10.1186/s13073-020-00822-6; html:https://europepmc.org/articles/PMC7790334; pdf:https://europepmc.org/articles/PMC7790334?pdf=render
 36962513,https://doi.org/10.1371/journal.pgph.0000502,"Association between mobility, non-pharmaceutical interventions, and COVID-19 transmission in Ghana: A modelling study using mobile phone data.","Gibbs H, Liu Y, Abbott S, Baffoe-Nyarko I, Laryea DO, Akyereko E, Kuma-Aboagye P, Asante IA, Mitjà O, LSHTM CMMID COVID-19 Working Group, Ampofo W, Asiedu-Bekoe F, Marks M, Eggo RM.",,PLOS global public health,2022,2022-09-13,Y,,,,"Governments around the world have implemented non-pharmaceutical interventions to limit the transmission of COVID-19. Here we assess if increasing NPI stringency was associated with a reduction in COVID-19 cases in Ghana. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of how NPI measures are reflected in indicators of human mobility. Further, there is a lack of understanding about how findings from high-income settings correspond to low and middle-income contexts. In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of Rt, a real-time measure of the intensity of COVID-19 transmission. We construct a multilevel generalised linear mixed model, combining local disease surveillance data from subnational districts of Ghana with the timing of NPIs and indicators of human mobility from Google and Vodafone Ghana. We observe a relationship between reductions in human mobility and decreases in Rt during the early stages of the COVID-19 epidemic in Ghana. We find that the strength of this relationship varies through time, decreasing after the most stringent period of interventions in the early epidemic. Our findings demonstrate how the association of NPI and mobility indicators with COVID-19 transmission may vary through time. Further, we demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity to monitor the impact of NPI policies.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000502&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000502; html:https://europepmc.org/articles/PMC10021296; pdf:https://europepmc.org/articles/PMC10021296?pdf=render
-36617894,https://doi.org/10.1080/1354750x.2022.2162966,Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.,"de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.",,"Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals",2023,2023-01-08,N,Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements,,,"<b>Introduction</b>Patients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.<b>Methods</b>We conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.<b>Results</b>Cases and controls had a median (25<sup>th</sup>-75<sup>th</sup>percentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] <i>versus</i> 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (<i>P</i> = 0.339). In controls, the mean cell concentration was significantly (<i>P</i> = 0.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) <i>versus</i> 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).<b>Conclusion</b>Despite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.",,doi:https://doi.org/10.1080/1354750x.2022.2162966; doi:https://doi.org/10.1080/1354750X.2022.2162966
 33112263,https://doi.org/10.1530/eje-20-0296,Pubertal timing in boys and girls born to mothers with gestational diabetes mellitus: a systematic review.,"Subramanian A, Idkowiak J, Toulis KA, Thangaratinam S, Arlt W, Nirantharakumar K.",,European journal of endocrinology,2021,2021-01-01,Y,,,,"<h4>Context</h4>The incidence of gestational diabetes mellitus (GDM) has been on the rise, driven by maternal obesity. In parallel, pubertal tempo has increased in the general population, driven by childhood obesity.<h4>Objective</h4>To evaluate the available evidence on pubertal timing of boys and girls born to mothers with GDM.<h4>Data sources</h4>We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane library and grey literature for observational studies up to October 2019.<h4>Study selection and extraction</h4>Two reviewers independently selected studies, collected data and appraised the studies for risk of bias. Results were tabulated and narratively described as reported in the primary studies.<h4>Results</h4>Seven articles (six for girls and four for boys) were included. Study quality score was mostly moderate (ranging from 4 to 10 out of 11). In girls born to mothers with GDM, estimates suggest earlier timing of pubarche, thelarche and menarche although for each of these outcomes only one study each showed a statistically significant association. In boys, there was some association between maternal GDM and earlier pubarche, but inconsistency in the direction of shift of age at onset of genital and testicular development and first ejaculation. Only a single study analysed growth patterns in children of mothers with GDM, describing a 3-month advancement in the age of attainment of peak height velocity and a slight increase in pubertal tempo.<h4>Conclusions</h4>Pubertal timing may be influenced by the presence of maternal GDM, though current evidence is sparse and of limited quality. Prospective cohort studies should be conducted, ideally coupled with objective biochemical tests.",,pdf:https://eje.bioscientifica.com/downloadpdf/journals/eje/184/1/EJE-20-0296.pdf; doi:https://doi.org/10.1530/EJE-20-0296; html:https://europepmc.org/articles/PMC7707806; pdf:https://europepmc.org/articles/PMC7707806?pdf=render
+36617894,https://doi.org/10.1080/1354750x.2022.2162966,Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.,"de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.",,"Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals",2023,2023-01-08,N,Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements,,,"<b>Introduction</b>Patients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.<b>Methods</b>We conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.<b>Results</b>Cases and controls had a median (25<sup>th</sup>-75<sup>th</sup>percentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] <i>versus</i> 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (<i>P</i> = 0.339). In controls, the mean cell concentration was significantly (<i>P</i> = 0.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) <i>versus</i> 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).<b>Conclusion</b>Despite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.",,doi:https://doi.org/10.1080/1354750x.2022.2162966; doi:https://doi.org/10.1080/1354750X.2022.2162966
 34158612,https://doi.org/10.1038/s41366-021-00846-x,Effects of increased body mass index on employment status: a Mendelian randomisation study.,"Campbell DD, Green M, Davies N, Demou E, Ward J, Howe LD, Harrison S, Johnston KJA, Strawbridge RJ, Popham F, Smith DJ, Munafò MR, Katikireddi SV.",,International journal of obesity (2005),2021,2021-06-22,Y,,,,"<h4>Background</h4>The obesity epidemic may have substantial implications for the global workforce, including causal effects on employment, but clear evidence is lacking. Obesity may prevent people from being in paid work through poor health or through social discrimination. We studied genetic variants robustly associated with body mass index (BMI) to investigate its causal effects on employment.<h4>Dataset/methods</h4>White UK ethnicity participants of working age (men 40-64 years, women 40-59 years), with suitable genetic data were selected in the UK Biobank study (N = 230,791). Employment status was categorised in two ways: first, contrasting being in paid employment with any other status; and second, contrasting being in paid employment with sickness/disability, unemployment, early retirement and caring for home/family. Socioeconomic indicators also investigated were hours worked, household income, educational attainment and Townsend deprivation index (TDI). We conducted observational and two-sample Mendelian randomisation (MR) analyses to investigate the effect of increased BMI on employment-related outcomes.<h4>Results</h4>Regressions showed BMI associated with all the employment-related outcomes investigated. MR analyses provided evidence for higher BMI causing increased risk of sickness/disability (OR 1.08, 95% CI 1.04, 1.11, per 1 Kg/m<sup>2</sup> BMI increase) and decreased caring for home/family (OR 0.96, 95% CI 0.93, 0.99), higher TDI (Beta 0.038, 95% CI 0.018, 0.059), and lower household income (OR 0.98, 95% CI 0.96, 0.99). In contrast, MR provided evidence for no causal effect of BMI on unemployment, early retirement, non-employment, hours worked or educational attainment. There was little evidence for causal effects differing by sex or age. Robustness tests yielded consistent results.<h4>Discussion</h4>BMI appears to exert a causal effect on employment status, largely by affecting an individual's health rather than through increased unemployment arising from social discrimination. The obesity epidemic may be contributing to increased worklessness and therefore could impose a substantial societal burden.",,pdf:https://www.nature.com/articles/s41366-021-00846-x.pdf; doi:https://doi.org/10.1038/s41366-021-00846-x; html:https://europepmc.org/articles/PMC8310793; pdf:https://europepmc.org/articles/PMC8310793?pdf=render
 33710281,https://doi.org/10.1093/ageing/afab060,COVID-19 infection and attributable mortality in UK care homes: cohort study using active surveillance and electronic records (March-June 2020).,"Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hayward A, Shallcross L.",,Age and ageing,2021,2021-06-01,Y,Mortality; Morbidity; Older People; Long-term Care; Covid-19; Sars-cov-2,,,"<h4>Background</h4>epidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic.<h4>Methods</h4>cohort study of 179 UK care homes with 9,339 residents and 11,604 staff. We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality and estimate attributable mortality.<h4>Results</h4>2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff, respectively. Sixty-eight percent (121/179) of care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection.Out of 607 residents with confirmed infection, 217 died (case fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was twofold higher in care homes with outbreaks versus those without (adjusted hazard ratio: 2.2 [1.8; 2.6]).<h4>Conclusions</h4>findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.",,pdf:https://academic.oup.com/ageing/article-pdf/50/4/1019/40971734/afab060.pdf; doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render
-37717030,https://doi.org/10.1186/s13756-023-01280-6,The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.,"Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",,Antimicrobial resistance and infection control,2023,2023-09-16,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"<h4>Background</h4>There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.<h4>Methods</h4>With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.<h4>Results</h4>Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.<h4>Conclusions</h4>Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",,doi:https://doi.org/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render
 35964473,https://doi.org/10.1016/j.socscimed.2022.115237,"""We've all got the virus inside us now"": Disaggregating public health relations and responsibilities for health protection in pandemic London.","Kasstan B, Mounier-Jack S, Gaskell KM, Eggo RM, Marks M, Chantler T.",,Social science & medicine (1982),2022,2022-08-07,Y,Pandemic; Public Health; Judaism; Responsibility; London; Covid-19,,,"The COVID-19 pandemic has disproportionately impacted ethnic minorities in the global north, evidenced by higher rates of transmission, morbidity, and mortality relative to population sizes. Orthodox Jewish neighbourhoods in London had extremely high SARS-CoV-2 seroprevalence rates, reflecting patterns in Israel and the US. The aim of this paper is to examine how responsibilities over health protection are conveyed, and to what extent responsibility is sought by, and shared between, state services, and 'community' stakeholders or representative groups, and families in public health emergencies. The study investigates how public health and statutory services stakeholders, Orthodox Jewish communal custodians and households sought to enact health protection in London during the first year of the pandemic (March 2020-March 2021). Twenty-eight semi-structured interviews were conducted across these cohorts. Findings demonstrate that institutional relations - both their formation and at times fragmentation - were directly shaped by issues surrounding COVID-19 control measures. Exchanges around protective interventions (whether control measures, contact tracing technologies, or vaccines) reveal diverse and diverging attributions of responsibility and authority. The paper develops a framework of public health relations to understand negotiations between statutory services and minority groups over responsiveness and accountability in health protection. Disaggregating public health relations can help social scientists to critique who and what characterises institutional relationships with minority groups, and what ideas of responsibility and responsiveness are projected by differently-positioned stakeholders in health protection.",,doi:https://doi.org/10.1016/j.socscimed.2022.115237; doi:https://doi.org/10.1016/j.socscimed.2022.115237; html:https://europepmc.org/articles/PMC9357441; pdf:https://europepmc.org/articles/PMC9357441?pdf=render
+37717030,https://doi.org/10.1186/s13756-023-01280-6,The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.,"Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",,Antimicrobial resistance and infection control,2023,2023-09-16,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"<h4>Background</h4>There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.<h4>Methods</h4>With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.<h4>Results</h4>Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.<h4>Conclusions</h4>Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",,doi:https://doi.org/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render
 37306981,https://doi.org/10.1001/jamaneurol.2023.1580,Independent Associations of Incident Epilepsy and Enzyme-Inducing and Non-Enzyme-Inducing Antiseizure Medications With the Development of Osteoporosis.,"Josephson CB, Gonzalez-Izquierdo A, Denaxas S, Sajobi TT, Klein KM, Wiebe S.",,JAMA neurology,2023,2023-08-01,N,,,,"<h4>Importance</h4>Both epilepsy and enzyme-inducing antiseizure medications (eiASMs) having varying reports of an association with increased risks for osteoporosis.<h4>Objective</h4>To quantify and model the independent hazards for osteoporosis associated with incident epilepsy and eiASMS and non-eiASMs.<h4>Design, setting, and participants</h4>This open cohort study covered the years 1998 to 2019, with a median (IQR) follow-up of 5 (1.7-11.1) years. Data were collected for 6275 patients enrolled in the Clinical Practice Research Datalink and from hospital electronic health records. No patients who met inclusion criteria (Clinical Practice Research Datalink-acceptable data, aged 18 years or older, follow-up after the Hospital Episode Statistics patient care linkage date of 1998, and free of osteoporosis at baseline) were excluded or declined.<h4>Exposure</h4>Incident adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs.<h4>Main outcomes and measures</h4>The outcome was incident osteoporosis as determined through Cox proportional hazards or accelerated failure time models where appropriate. Incident epilepsy was treated as a time-varying covariate. Analyses controlled for age, sex, socioeconomic status, cancer, 1 or more years of corticosteroid use, body mass index, bariatric surgery, eating disorders, hyperthyroidism, inflammatory bowel disease, rheumatoid arthritis, smoking status, falls, fragility fractures, and osteoporosis screening tests. Subsequent analyses (1) excluded body mass index, which was missing in 30% of patients; (2) applied propensity score matching for receipt of an eiASM; (3) restricted analyses to only those with incident onset epilepsy; and (4) restricted analyses to patients who developed epilepsy at age 65 years or older. Analyses were performed between July 1 and October 31, 2022, and in February 2023 for revisions.<h4>Results</h4>Of 8 095 441 adults identified, 6275 had incident adult-onset epilepsy (3220 female [51%] and 3055 male [49%]; incidence rate, 62 per 100 000 person-years) with a median (IQR) age of 56 (38-73) years. When controlling for osteoporosis risk factors, incident epilepsy was independently associated with a 41% faster time to incident osteoporosis (time ratio [TR], 0.59; 95% CI, 0.52-0.67; P < .001). Both eiASMs (TR, 0.91; 95% CI, 0.87-0.95; P < .001) and non-eiASMs (TR, 0.77; 95% CI, 0.76-0.78; P < .001) were also associated with significant increased risks independent of epilepsy, accounting for 9% and 23% faster times to development of osteoporosis, respectively. The independent associations among epilepsy, eiASMs, and non-eiASMs remained consistent in propensity score-matched analyses, cohorts restricted to adult-onset epilepsy, and cohorts restricted to late-onset epilepsy.<h4>Conclusions and relevance</h4>These findings suggest that epilepsy is independently associated with a clinically meaningful increase in the risk for osteoporosis, as are both eiASMs and non-eiASMs. Routine screening and prophylaxis should be considered in all people with epilepsy.",,doi:https://doi.org/10.1001/jamaneurol.2023.1580
 34266851,https://doi.org/10.1136/bmjhci-2021-100356,Development of a core competency framework for clinical informatics. ,"Davies A, Mueller J, Hassey A, Moulton G.",,BMJ health & care informatics,2021,2021-07-01,Y,,,,"Until this point there was no national core competency framework for clinical informatics in the UK. We report on the final two iterations of work carried out in the formation of a national core competency framework. This follows an initial systematic literature review of existing skills and competencies and a job listing analysis.MethodsAn iterative approach was applied to framework development. Using a mixed-methods design we carried out semi-structured interviews with participants involved in informatics (n=15). The framework was updated based on the interview findings and was subsequently distributed as part of a bespoke online digital survey for wider participation (n=87). The final version of the framework is based on the findings of the survey. Over 102 people reviewed the framework as part of the interview or survey process. This led to a final core competency framework containing 6 primary domains with 36 subdomains containing 111 individual competencies. An iterative mixed-methods approach for competency development involving the target community was appropriate for development of the competency framework. There is some contention around the depth of technical competencies required. Care is also needed to avoid professional burnout, as clinicians and healthcare practitioners already have clinical competencies to maintain. Therefore, how the framework is applied in practice and how practitioners meet the competencies requires careful consideration.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100356.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render
-36446449,https://doi.org/10.1136/bmjopen-2022-061849,Effect of lifting COVID-19 restrictions on utilisation of primary care services in Nepal: a difference-in-differences analysis.,"Kapoor NR, Aryal A, Mehata S, Dulal M, Kruk ME, Bauhoff S, Arsenault C.",,BMJ open,2022,2022-11-29,Y,Primary Care; Health Policy; Covid-19,,,"<h4>Introduction</h4>An increasing number of studies have reported disruptions in health service utilisation due to the COVID-19 pandemic and its associated restrictions. However, little is known about the effect of lifting COVID-19 restrictions on health service utilisation. The objective of this study was to estimate the effect of lifting COVID-19 restrictions on primary care service utilisation in Nepal.<h4>Methods</h4>Data on utilisation of 10 primary care services were extracted from the Health Management Information System across all health facilities in Nepal. We used a difference-in-differences design and linear fixed effects regressions to estimate the effect of lifting COVID-19 restrictions. The treatment group included palikas that had lifted restrictions in place from 17 August 2020 to 16 September 2020 (Bhadra 2077) and the control group included palikas that had maintained restrictions during that period. The pre-period included the 4 months of national lockdown from 24 March 2020 to 22 July 2020 (Chaitra 2076 to Ashar 2077). Models included month and palika fixed effects and controlled for COVID-19 incidence.<h4>Results</h4>We found that lifting COVID-19 restrictions was associated with an average increase per palika of 57.5 contraceptive users (95% CI 14.6 to 100.5), 15.6 antenatal care visits (95% CI 5.3 to 25.9) and 1.6 child pneumonia visits (95% CI 0.2 to 2.9). This corresponded to a 9.4% increase in contraceptive users, 34.2% increase in antenatal care visits and 15.6% increase in child pneumonia visits. Utilisation of most other primary care services also increased after lifting restrictions, but coefficients were not statistically significant.<h4>Conclusions</h4>Despite the ongoing pandemic, lifting restrictions can lead to an increase in some primary care services. Our results point to a causal link between restrictions and health service utilisation and call for policy makers in low- and middle-income countries to carefully consider the trade-offs of strict lockdowns during future COVID-19 waves or future pandemics.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render
 33402395,https://doi.org/10.1136/jech-2020-215204,Hospital readmission among people experiencing homelessness in England: a cohort study of 2772 matched homeless and housed inpatients.,"Lewer D, Menezes D, Cornes M, Blackburn RM, Byng R, Clark M, Denaxas S, Evans H, Fuller J, Hewett N, Kilmister A, Luchenski SA, Manthorpe J, McKee M, Neale J, Story A, Tinelli M, Whiteford M, Wurie F, Yavlinsky A, Hayward A, Aldridge R.",,Journal of epidemiology and community health,2021,2021-01-05,Y,Homelessness; Health Inequalities; Record Linkage; Access To Hlth Care,,,"<h4>Background</h4>Inpatients experiencing homelessness are often discharged to unstable accommodation or the street, which may increase the risk of readmission.<h4>Methods</h4>We conducted a cohort study of 2772 homeless patients discharged after an emergency admission at 78 hospitals across England between November 2013 and November 2016. For each individual, we selected a housed patient who lived in a socioeconomically deprived area, matched on age, sex, hospital, and year of discharge. Counts of emergency readmissions, planned readmissions, and Accident and Emergency (A&E) visits post-discharge were derived from national hospital databases, with a median of 2.8 years of follow-up. We estimated the cumulative incidence of readmission over 12 months, and used negative binomial regression to estimate rate ratios.<h4>Results</h4>After adjusting for health measured at the index admission, homeless patients had 2.49 (95% CI 2.29 to 2.70) times the rate of emergency readmission, 0.60 (95% CI 0.53 to 0.68) times the rate of planned readmission and 2.57 (95% CI 2.41 to 2.73) times the rate of A&E visits compared with housed patients. The 12-month risk of emergency readmission was higher for homeless patients (61%, 95% CI 59% to 64%) than housed patients (33%, 95% CI 30% to 36%); and the risk of planned readmission was lower for homeless patients (17%, 95% CI 14% to 19%) than for housed patients (30%, 95% CI 28% to 32%). While the risk of emergency readmission varied with the reason for admission for housed patients, for example being higher for admissions due to cancers than for those due to accidents, the risk was high across all causes for homeless patients.<h4>Conclusions</h4>Hospital patients experiencing homelessness have high rates of emergency readmission that are not explained by health. This highlights the need for discharge arrangements that address their health, housing and social care needs.",,pdf:https://jech.bmj.com/content/jech/75/7/681.full.pdf; doi:https://doi.org/10.1136/jech-2020-215204; html:https://europepmc.org/articles/PMC8223662; pdf:https://europepmc.org/articles/PMC8223662?pdf=render
+36446449,https://doi.org/10.1136/bmjopen-2022-061849,Effect of lifting COVID-19 restrictions on utilisation of primary care services in Nepal: a difference-in-differences analysis.,"Kapoor NR, Aryal A, Mehata S, Dulal M, Kruk ME, Bauhoff S, Arsenault C.",,BMJ open,2022,2022-11-29,Y,Primary Care; Health Policy; Covid-19,,,"<h4>Introduction</h4>An increasing number of studies have reported disruptions in health service utilisation due to the COVID-19 pandemic and its associated restrictions. However, little is known about the effect of lifting COVID-19 restrictions on health service utilisation. The objective of this study was to estimate the effect of lifting COVID-19 restrictions on primary care service utilisation in Nepal.<h4>Methods</h4>Data on utilisation of 10 primary care services were extracted from the Health Management Information System across all health facilities in Nepal. We used a difference-in-differences design and linear fixed effects regressions to estimate the effect of lifting COVID-19 restrictions. The treatment group included palikas that had lifted restrictions in place from 17 August 2020 to 16 September 2020 (Bhadra 2077) and the control group included palikas that had maintained restrictions during that period. The pre-period included the 4 months of national lockdown from 24 March 2020 to 22 July 2020 (Chaitra 2076 to Ashar 2077). Models included month and palika fixed effects and controlled for COVID-19 incidence.<h4>Results</h4>We found that lifting COVID-19 restrictions was associated with an average increase per palika of 57.5 contraceptive users (95% CI 14.6 to 100.5), 15.6 antenatal care visits (95% CI 5.3 to 25.9) and 1.6 child pneumonia visits (95% CI 0.2 to 2.9). This corresponded to a 9.4% increase in contraceptive users, 34.2% increase in antenatal care visits and 15.6% increase in child pneumonia visits. Utilisation of most other primary care services also increased after lifting restrictions, but coefficients were not statistically significant.<h4>Conclusions</h4>Despite the ongoing pandemic, lifting restrictions can lead to an increase in some primary care services. Our results point to a causal link between restrictions and health service utilisation and call for policy makers in low- and middle-income countries to carefully consider the trade-offs of strict lockdowns during future COVID-19 waves or future pandemics.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render
 37667866,https://doi.org/10.1111/cen.14966,Genetically predicted plasma cortisol and common chronic diseases: A Mendelian randomization study.,"Lee WH, Larsson SC, Wood A, Di Angelantonio E, Butterworth AS, Burgess S, Allara E.",,Clinical endocrinology,2023,2023-09-05,N,Hypertension; Cortisol; Osteoporosis; Type 2 diabetes; chronic diseases; Mendelian Randomization; Major Mental Illness,,,"<h4>Objective</h4>Cushing's syndrome is characterized by hypercortisolaemia and is frequently accompanied by comorbidities such as type 2 diabetes, hypertension, osteoporosis, depression and schizophrenia. It is unclear whether moderate but lifelong hypercortisolaemia is causally associated with these diseases in the general population. We aimed to address this research gap using a Mendelian randomization approach.<h4>Methods</h4>We used three cortisol-associated genetic variants in the SERPINA6/SERPINA1 region as genetic instruments in a two-sample, inverse-variance-weighted Mendelian randomization analysis. We obtained summary-level statistics for cortisol and disease outcomes from publicly available genetic consortia, and meta-analysed them as appropriate. We conducted a multivariable Mendelian randomization analysis to assess potential mediating effects.<h4>Results</h4>A 1 standard deviation higher genetically predicted plasma cortisol was associated with greater odds of hypertension (odds ratio: 1.12; 95% confidence interval [CI]: 1.05-1.18) as well as higher systolic blood pressure (mean difference [MD]: 0.03 SD change; 95% CI: 0.01-0.05) and diastolic blood pressure (MD: 0.03 SD change; 95% CI: 0.01-0.04). There was no evidence of association with type 2 diabetes, osteoporosis, depression and schizophrenia. The association with hypertension was attenuated upon adjustment for waist circumference, suggesting potential mediation through central obesity.<h4>Conclusion</h4>There is strong evidence for a causal association between plasma cortisol and greater risk for hypertension, potentially mediated by obesity.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cen.14966; doi:https://doi.org/10.1111/cen.14966
 33356394,https://doi.org/10.1161/hypertensionaha.120.16547,"Urate, Blood Pressure, and Cardiovascular Disease: Evidence From Mendelian Randomization and Meta-Analysis of Clinical Trials.","Gill D, Cameron AC, Burgess S, Li X, Doherty DJ, Karhunen V, Abdul-Rahim AH, Taylor-Rowan M, Zuber V, Tsao PS, Klarin D, VA Million Veteran Program, Evangelou E, Elliott P, Damrauer SM, Quinn TJ, Dehghan A, Theodoratou E, Dawson J, Tzoulaki I.",,"Hypertension (Dallas, Tex. : 1979)",2021,2020-12-28,Y,Cardiovascular diseases; Blood pressure; Uric acid; Systematic review; Odds Ratio,,,"Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10-1.30]; <i>P</i>=4×10<sup>-5</sup>), peripheral artery disease (1.12 [95% CI, 1.03-1.21]; <i>P</i>=9×10<sup>-3</sup>), and stroke (1.11 [95% CI, 1.05-1.18]; <i>P</i>=2×10<sup>-4</sup>). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, -2.55 mm Hg [95% CI, -4.06 to -1.05]; <i>P</i>=1×10<sup>-3</sup>) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22-0.73]; <i>P</i>=3×10<sup>-3</sup>) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44-1.03]; <i>P</i>=0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.120.16547; doi:https://doi.org/10.1161/HYPERTENSIONAHA.120.16547; html:https://europepmc.org/articles/PMC7803439; pdf:https://europepmc.org/articles/PMC7803439?pdf=render
 36529816,https://doi.org/10.1038/s41598-022-26357-x,Novel multimorbidity clusters in people with eczema and asthma: a population-based cluster analysis.,"Mulick AR, Henderson AD, Prieto-Merino D, Mansfield KE, Matthewman J, Quint JK, Lyons RA, Sheikh A, McAllister DA, Nitsch D, Langan SM.",,Scientific reports,2022,2022-12-18,Y,,,,"Eczema and asthma are allergic diseases and two of the commonest chronic conditions in high-income countries. Their co-existence with other allergic conditions is common, but little research exists on wider multimorbidity with these conditions. We set out to identify and compare clusters of multimorbidity in people with eczema or asthma and people without. Using routinely-collected primary care data from the U.K. Clinical Research Practice Datalink GOLD, we identified adults ever having eczema (or asthma), and comparison groups never having eczema (or asthma). We derived clusters of multimorbidity from hierarchical cluster analysis of Jaccard distances between pairs of diagnostic categories estimated from mixed-effects logistic regressions. We analysed 434,422 individuals with eczema (58% female, median age 47 years) and 1,333,281 individuals without (55% female, 47 years), and 517,712 individuals with asthma (53% female, 44 years) and 1,601,210 individuals without (53% female, 45 years). Age at first morbidity, sex and having eczema/asthma affected the scope of multimorbidity, with women, older age and eczema/asthma being associated with larger morbidity clusters. Injuries, digestive, nervous system and mental health disorders were more commonly seen in eczema and asthma than control clusters. People with eczema and asthma of all ages and both sexes may experience greater multimorbidity than people without eczema and asthma, including conditions not previously recognised as contributing to their disease burden. This work highlights areas where there is a critical need for research addressing the burden and drivers of multimorbidity in order to inform strategies to reduce poor health outcomes.",,pdf:https://www.nature.com/articles/s41598-022-26357-x.pdf; doi:https://doi.org/10.1038/s41598-022-26357-x; html:https://europepmc.org/articles/PMC9760185; pdf:https://europepmc.org/articles/PMC9760185?pdf=render
@@ -798,21 +798,21 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 33813844,https://doi.org/10.1161/hypertensionaha.120.16534,Relationship Between Blood Pressure and Incident Cardiovascular Disease: Linear and Nonlinear Mendelian Randomization Analyses.,"Malik R, Georgakis MK, Vujkovic M, Damrauer SM, Elliott P, Karhunen V, Giontella A, Fava C, Hellwege JN, Shuey MM, Edwards TL, Rogne T, Åsvold BO, Brumpton BM, Burgess S, Dichgans M, Gill D.",,"Hypertension (Dallas, Tex. : 1979)",2021,2021-04-05,Y,Hypertension; Blood pressure; Stroke; coronary artery disease; Primary Prevention,,,[Figure: see text].,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.120.16534; doi:https://doi.org/10.1161/HYPERTENSIONAHA.120.16534; html:https://europepmc.org/articles/PMC8115430; pdf:https://europepmc.org/articles/PMC8115430?pdf=render
 36682888,https://doi.org/10.1111/cch.13097,Adversity profiles of children receiving care and support from social services: A latent-class analysis of school-aged children in Wales.,"Anthony R, Scourfield J, Moore G, Paranjothy S, Evans A, Brophy S, Daniel R, Long S.",,"Child: care, health and development",2023,2023-01-31,N,Care; Child Welfare; Social Services; Latent Class Analysis; Adverse Childhood Experiences,,,"<h4>Background</h4>Children receive care and support from social services due to the risk of harm or impeded development or because of disability. This study aimed to identify typologies of adversity experienced by children receiving care and support from social services and to explore how typologies differ by sociodemographic characteristics.<h4>Methods</h4>This is a cross-sectional study of 'Children Receiving Care and Support' (N = 12 792) during 2017/2018 in Wales, UK. We sought to (1) examine the prevalence of household adversities experienced by children in receipt of care and support from social services; (2) identify typologies of household adversities; and (3) explore how typologies of household adversities differ by family characteristics (demographics, measures of social disadvantage, perinatal and care factors).<h4>Results</h4>We found evidence for multiple risk factor constellations. The four-class solution suggested four distinct classes of adversities: child disability (50.0%), low adversities (20.3%), family poor health (6.7%) and multiple risks (23.0%). Children in the 'multiple risk' class were significantly more likely to be younger, more deprived and 'looked after' by the local authority compared with those in the 'low adversities' class.<h4>Conclusions</h4>Given the presence of different constellations of household adversities, policies and interventions that address multiple risk factors simultaneously may be more effective and have longer-lasting benefits.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cch.13097; doi:https://doi.org/10.1111/cch.13097
 35297226,https://doi.org/10.1002/jcsm.12971,Association of shorter leucocyte telomere length with risk of frailty.,"Bountziouka V, Nelson CP, Codd V, Wang Q, Musicha C, Allara E, Kaptoge S, Di Angelantonio E, Butterworth AS, Thompson JR, Curtis EM, Wood AM, Danesh JN, Harvey NC, Cooper C, Samani NJ.",,"Journal of cachexia, sarcopenia and muscle",2022,2022-03-17,Y,Frailty; Biological Age; Uk Biobank; Leucocyte Telomere Length,,,"<h4>Background</h4>Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty.<h4>Methods</h4>We utilized cross-sectional data from 441 781 UK Biobank participants (aged 40-69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal.<h4>Results</h4>Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10<sup>-33</sup> ), more likely to be female (61%, P = 1.97 × 10<sup>-129</sup> ), and had shorter LTL (-0.13SD vs. 0.03SD, P = 5.43 × 10<sup>-111</sup> ) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 × 10<sup>-12</sup> ; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 10<sup>-30</sup> ). Within each age group (40-49, 50-59, 60-69 years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13).<h4>Conclusions</h4>Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcsm.12971; doi:https://doi.org/10.1002/jcsm.12971; html:https://europepmc.org/articles/PMC9178164; pdf:https://europepmc.org/articles/PMC9178164?pdf=render
-36712153,https://doi.org/10.1093/ehjdh/ztac046,Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomized trial.,"Wang X, Mobley AR, Tica O, Okoth K, Ghosh RE, Myles P, Williams T, Haynes S, Nirantharakumar K, Shukla D, Kotecha D, DaRe2THINK Trial Committees .",,European heart journal. Digital health,2022,2022-09-16,Y,Coding; Anticoagulation; Atrial fibrillation; Randomized controlled trial; Primary Care; Secondary Care; Electronic Healthcare Record,,,"<h4>Aims</h4>Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHRs), allow for large-scale screening and follow up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high-quality and high clinical value research.<h4>Methods and results</h4>The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymized pre screening of the primary-care EHR across England, digital enrolment, remote e-consent, and 'no-visit' follow up by linking all primary- and secondary-care health data with patient-reported outcomes. DaRe2THINK is a pragmatic, healthcare-embedded randomized trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This study outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics (mortality).<h4>Conclusion</h4>Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomized trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at risk.",,pdf:https://academic.oup.com/ehjdh/article-pdf/3/3/426/47117043/ztac046.pdf; doi:https://doi.org/10.1093/ehjdh/ztac046; html:https://europepmc.org/articles/PMC9708037; pdf:https://europepmc.org/articles/PMC9708037?pdf=render
 34190735,https://doi.org/,The changing characteristics of COVID-19 presentations. A regional comparison of SARS-CoV-2 hospitalised patients during the first and second wave.,"Atkin C, Kamwa V, Reddy-Kolanu V, Parekh D, Evison F, Nightingale P, Gallier S, Ball S, Sapey E.",,Acute medicine,2021,2021-01-01,N,,,,"<h4>Background</h4>This study assesses COVID-19 hospitalised patient demography and outcomes during wave 1 and wave 2, prior to new variants of the virus.<h4>Methods</h4>All patients with a positive SARS-CoV-2 swab between 10th March 2020 and 5th July 2020 (wave 1) and 1st September 2020 and 16th November 2020 (wave 2) admitted to University Hospitals Birmingham NHS Foundation Trust were included (n=4856), followed for 28 days.<h4>Results</h4>Wave 2 patients were younger, more ethnically diverse, had less co-morbidities and disease presentation was milder on presentation. After matching for these factors, mortality was reduced, but without differences in intensive care admissions.<h4>Conclusion</h4>Prior to new SARS-CoV-2 variants, outcomes for hospitalised patients with COVID-19 were improving but with similar intensive care needs.",,
+36712153,https://doi.org/10.1093/ehjdh/ztac046,Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomized trial.,"Wang X, Mobley AR, Tica O, Okoth K, Ghosh RE, Myles P, Williams T, Haynes S, Nirantharakumar K, Shukla D, Kotecha D, DaRe2THINK Trial Committees .",,European heart journal. Digital health,2022,2022-09-16,Y,Coding; Anticoagulation; Atrial fibrillation; Randomized controlled trial; Primary Care; Secondary Care; Electronic Healthcare Record,,,"<h4>Aims</h4>Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHRs), allow for large-scale screening and follow up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high-quality and high clinical value research.<h4>Methods and results</h4>The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymized pre screening of the primary-care EHR across England, digital enrolment, remote e-consent, and 'no-visit' follow up by linking all primary- and secondary-care health data with patient-reported outcomes. DaRe2THINK is a pragmatic, healthcare-embedded randomized trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This study outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics (mortality).<h4>Conclusion</h4>Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomized trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at risk.",,pdf:https://academic.oup.com/ehjdh/article-pdf/3/3/426/47117043/ztac046.pdf; doi:https://doi.org/10.1093/ehjdh/ztac046; html:https://europepmc.org/articles/PMC9708037; pdf:https://europepmc.org/articles/PMC9708037?pdf=render
 35898465,https://doi.org/10.3389/fendo.2022.888924,Diabetic Foot Risk Classification at the Time of Type 2 Diabetes Diagnosis and Subsequent Risk of Mortality: A Population-Based Cohort Study.,"Wang Z, Hazlehurst J, Subramanian A, Tahrani AA, Hanif W, Thomas N, Singh P, Wang J, Sainsbury C, Nirantharakumar K, Crowe FL.",,Frontiers in endocrinology,2022,2022-07-11,Y,Mortality; Type 2 diabetes; Diabetic Foot Disease; Diabetic Foot Risk; Foot Risk Examination,,,"<h4>Aim</h4>We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.<h4>Methods</h4>This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.<h4>Results</h4>Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).<h4>Conclusion</h4>Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.",,pdf:https://www.frontiersin.org/articles/10.3389/fendo.2022.888924/pdf; doi:https://doi.org/10.3389/fendo.2022.888924; html:https://europepmc.org/articles/PMC9309507; pdf:https://europepmc.org/articles/PMC9309507?pdf=render
-37549998,https://doi.org/10.1136/bjsports-2022-106460,Device-based measurement of physical activity in cardiovascular healthcare: possibilities and challenges.,"Chico TJ, Stamatakis E, Ciravegna F, Dunn J, Redwood S, Al-Lamee R, Sofat R, Gill J.",,British journal of sports medicine,2023,2023-08-07,N,Cardiovascular diseases; Health; Physical Activity,,,,,doi:https://doi.org/10.1136/bjsports-2022-106460
 32626822,https://doi.org/10.1007/s41109-020-00273-3,Normalised degree variance.,"Smith KM, Escudero J.",,Applied network science,2020,2020-06-22,Y,,,,"Finding graph indices which are unbiased to network size and density is of high importance both within a given field and across fields for enhancing comparability of modern network science studies. The degree variance is an important metric for characterising network degree heterogeneity. Here, we provide an analytically valid normalisation of degree variance to replace previous normalisations which are either invalid or not applicable to all networks. It is shown that this normalisation provides equal values for graphs and their complements; it is maximal in the star graph (and its complement); and its expected value is constant with respect to density for Erdös-Rényi (ER) random graphs of the same size. We strengthen these results with model observations in ER random graphs, random geometric graphs, scale-free networks, random hierarchy networks and resting-state brain networks, showing that the proposed normalisation is generally less affected by both network size and density than previous normalisation attempts. The closed form expression proposed also benefits from high computational efficiency and straightforward mathematical analysis. Analysis of 184 real-world binary networks across different disciplines shows that normalised degree variance is not correlated with average degree and is robust to node and edge subsampling. Comparisons across subdomains of biological networks reveals greater degree heterogeneity among brain connectomes and food webs than in protein interaction networks.",,pdf:https://appliednetsci.springeropen.com/track/pdf/10.1007/s41109-020-00273-3; doi:https://doi.org/10.1007/s41109-020-00273-3; html:https://europepmc.org/articles/PMC7319291; pdf:https://europepmc.org/articles/PMC7319291?pdf=render
 30984881,https://doi.org/10.12688/wellcomeopenres.15151.1,Causes of death among homeless people: a population-based cross-sectional study of linked hospitalisation and mortality data in England.,"Aldridge RW, Menezes D, Lewer D, Cornes M, Evans H, Blackburn RM, Byng R, Clark M, Denaxas S, Fuller J, Hewett N, Kilmister A, Luchenski S, Manthorpe J, McKee M, Neale J, Story A, Tinelli M, Whiteford M, Wurie F, Hayward A.",,Wellcome open research,2019,2019-03-11,Y,Mortality; Data Linkage; Hospital Discharge; Amenable Mortality; Homeless Health; Homeless Healthcare,,,"<b>Background</b>: Homelessness has increased by 165% since 2010 in England, with evidence from many settings that those affected experience high levels of mortality. In this paper we examine the contribution of different causes of death to overall mortality in homeless people recently admitted to hospitals in England with specialist integrated homeless health and care (SIHHC) schemes.  <b>Methods</b>: We undertook an analysis of linked hospital admission records and mortality data for people attending any one of 17 SIHHC schemes between 1st November 2013 and 30th November 2016. Our primary outcome was death, which we analysed in subgroups of 10th version international classification of disease (ICD-10) specific deaths; and deaths from amenable causes. We compared our results to a sample of people living in areas of high social deprivation (IMD5 group). <b>Results</b>: We collected data on 3,882 individual homeless hospital admissions that were linked to 600 deaths. The median age of death was 51.6 years (interquartile range 42.7-60.2) for SIHHC and 71.5 for the IMD5 (60.67-79.0).  The top three underlying causes of death by ICD-10 chapter in the SIHHC group were external causes of death (21.7%; 130/600), cancer (19.0%; 114/600) and digestive disease (19.0%; 114/600).  The percentage of deaths due to an amenable cause after age and sex weighting was 30.2% in the homeless SIHHC group (181/600) compared to 23.0% in the IMD5 group (578/2,512). <b>Conclusion</b>: Nearly one in three homeless deaths were due to causes amenable to timely and effective health care. The high burden of amenable deaths highlights the extreme health harms of homelessness and the need for greater emphasis on prevention of homelessness and early healthcare interventions.",,doi:https://doi.org/10.12688/wellcomeopenres.15151.1; html:https://europepmc.org/articles/PMC6449792; pdf:https://europepmc.org/articles/PMC6449792?pdf=render
+37549998,https://doi.org/10.1136/bjsports-2022-106460,Device-based measurement of physical activity in cardiovascular healthcare: possibilities and challenges.,"Chico TJ, Stamatakis E, Ciravegna F, Dunn J, Redwood S, Al-Lamee R, Sofat R, Gill J.",,British journal of sports medicine,2023,2023-08-07,N,Cardiovascular diseases; Health; Physical Activity,,,,,doi:https://doi.org/10.1136/bjsports-2022-106460
 35793336,https://doi.org/10.1371/journal.pone.0266521,"Spatiotemporal mapping of major trauma in Victoria, Australia.","Beck B, Zammit-Mangion A, Fry R, Smith K, Gabbe B.",,PloS one,2022,2022-07-06,Y,,,,"<h4>Background</h4>Spatiotemporal modelling techniques allow one to predict injury across time and space. However, such methods have been underutilised in injury studies. This study demonstrates the use of statistical spatiotemporal modelling in identifying areas of significantly high injury risk, and areas witnessing significantly increasing risk over time.<h4>Methods</h4>We performed a retrospective review of hospitalised major trauma patients from the Victorian State Trauma Registry, Australia, between 2007 and 2019. Geographical locations of injury events were mapped to the 79 local government areas (LGAs) in the state. We employed Bayesian spatiotemporal models to quantify spatial and temporal patterns, and analysed the results across a range of geographical remoteness and socioeconomic levels.<h4>Results</h4>There were 31,317 major trauma patients included. For major trauma overall, we observed substantial spatial variation in injury incidence and a significant 2.1% increase in injury incidence per year. Area-specific risk of injury by motor vehicle collision was higher in regional areas relative to metropolitan areas, while risk of injury by low fall was higher in metropolitan areas. Significant temporal increases were observed in injury by low fall, and the greatest increases were observed in the most disadvantaged LGAs.<h4>Conclusions</h4>These findings can be used to inform injury prevention initiatives, which could be designed to target areas with relatively high injury risk and with significantly increasing injury risk over time. Our finding that the greatest year-on-year increases in injury incidence were observed in the most disadvantaged areas highlights the need for a greater emphasis on reducing inequities in injury.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266521&type=printable; doi:https://doi.org/10.1371/journal.pone.0266521; html:https://europepmc.org/articles/PMC9258853; pdf:https://europepmc.org/articles/PMC9258853?pdf=render
 35459950,https://doi.org/10.1093/intqhc/mzac031,Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.,"Booton RD, Powell AL, Turner KME, Wood RM.",,International journal for quality in health care : journal of the International Society for Quality in Health Care,2022,2022-05-01,N,Vaccination; Coronavirus; Mathematical Modelling; Bed Management; Hospital Capacity; Covid-19,,,"<h4>Background</h4>Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty.<h4>Objective</h4>The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England.<h4>Methods</h4>An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.<h4>Results</h4>Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity.<h4>Conclusion</h4>Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://academic.oup.com/intqhc/article-pdf/34/2/mzac031/43704475/mzac031.pdf; doi:https://doi.org/10.1093/intqhc/mzac031
 32997638,https://doi.org/10.1109/jbhi.2020.3027987,A Novel Intelligent Computational Approach to Model Epidemiological Trends and Assess the Impact of Non-Pharmacological Interventions for COVID-19.,"Ren J, Yan Y, Zhao H, Ma P, Zabalza J, Hussain Z, Luo S, Dai Q, Zhao S, Sheikh A, Hussain A, Li H.",,IEEE journal of biomedical and health informatics,2020,2020-12-04,Y,,,,"The novel coronavirus disease 2019 (COVID-19) pandemic has led to a worldwide crisis in public health. It is crucial we understand the epidemiological trends and impact of non-pharmacological interventions (NPIs), such as lockdowns for effective management of the disease and control of its spread. We develop and validate a novel intelligent computational model to predict epidemiological trends of COVID-19, with the model parameters enabling an evaluation of the impact of NPIs. By representing the number of daily confirmed cases (NDCC) as a time-series, we assume that, with or without NPIs, the pattern of the pandemic satisfies a series of Gaussian distributions according to the central limit theorem. The underlying pandemic trend is first extracted using a singular spectral analysis (SSA) technique, which decomposes the NDCC time series into the sum of a small number of independent and interpretable components such as a slow varying trend, oscillatory components and structureless noise. We then use a mixture of Gaussian fitting (GF) to derive a novel predictive model for the SSA extracted NDCC incidence trend, with the overall model termed SSA-GF. Our proposed model is shown to accurately predict the NDCC trend, peak daily cases, the length of the pandemic period, the total confirmed cases and the associated dates of the turning points on the cumulated NDCC curve. Further, the three key model parameters, specifically, the amplitude (alpha), mean (mu), and standard deviation (sigma) are linked to the underlying pandemic patterns, and enable a directly interpretable evaluation of the impact of NPIs, such as strict lockdowns and travel restrictions. The predictive model is validated using available data from China and South Korea, and new predictions are made, partially requiring future validation, for the cases of Italy, Spain, the UK and the USA. Comparative results demonstrate that the introduction of consistent control measures across countries can lead to development of similar parametric models, reflected in particular by relative variations in their underlying sigma, alpha and mu values. The paper concludes with a number of open questions and outlines future research directions.",,pdf:https://ieeexplore.ieee.org/ielx7/6221020/9281055/09210178.pdf; doi:https://doi.org/10.1109/JBHI.2020.3027987; html:https://europepmc.org/articles/PMC8545177; pdf:https://europepmc.org/articles/PMC8545177?pdf=render
+33280008,https://doi.org/10.1093/cercor/bhaa345,Hierarchical Complexity of the Macro-Scale Neonatal Brain.,"Blesa M, Galdi P, Cox SR, Sullivan G, Stoye DQ, Lamb GJ, Quigley AJ, Thrippleton MJ, Escudero J, Bastin ME, Smith KM, Boardman JP.",,"Cerebral cortex (New York, N.Y. : 1991)",2021,2021-03-01,Y,Newborn; Network Analysis; Developing Brain; Dmri; Structural Connectome; Hierarchical Complexity,,,"The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period, assess correspondences with hierarchical complexity in adulthood, and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.",,pdf:https://academic.oup.com/cercor/article-pdf/31/4/2071/36458400/bhaa345.pdf; doi:https://doi.org/10.1093/cercor/bhaa345; html:https://europepmc.org/articles/PMC7945030; pdf:https://europepmc.org/articles/PMC7945030?pdf=render
 37705832,https://doi.org/10.5837/bjc.2023.003,SGLT2 inhibitors in CKD and HFpEF: two new large trials and two new meta-analyses.,"Mayne KJ, Preiss D, Herrington WG.",,The British journal of cardiology,2023,2023-02-21,N,Cardiovascular disease; Heart Failure; Chronic Kidney Disease; Sodium-Glucose Co-Transporter 2 (Sglt2) Inhibitor,,,,,doi:https://doi.org/10.5837/bjc.2023.003; html:https://europepmc.org/articles/PMC10495762; pdf:https://europepmc.org/articles/PMC10495762?pdf=render; doi:https://doi.org/10.5837/bjc.2023.003
 37008054,https://doi.org/10.14336/ad.2022.0829,Identifying Dynamic Patterns of Polypharmacy for Patients with Dementia from Primary Care Electronic Health Records: A Machine Learning Driven Longitudinal Study.,"Longo E, Burnett B, Bauermeister S, Zhou SM.",,Aging and disease,2023,2023-04-01,Y,Diagnosis; Dementia; Patient Safety; Machine Learning; Polypharmacy; Electronic Health Records; Exploratory Factor Analysis,,,"It is unclear how medication use evolved before diagnosis of dementia (DoD). This study aims to identify varied patterns of polypharmacy before DoD, their prevalence and possible complications. We collected primary care e-health records for 33,451 dementia patients in Wales from 1990 to 2015. The medication uses in every 5-year period along with 20-years prior to dementia diagnosis were considered. Exploratory factor analysis was used to identify clusters of medicines for every 5-year period. The prevalence of patients taking three or more medications was 82.16%, 69.7%, 41.1% and 5.5% in the Period 1 (0-5 years before DoD) ~ Period 4 (16-20 years before DoD) respectively. The Period 1 showed 3 clusters of polypharmacy - medicines for respiratory/urinary infections, arthropathies and rheumatism, and cardio-vascular disease (CVD) (66.55%); medicines for infections, arthropathies and rheumatism (AR), cardio-metabolic disease (CMD) and depression (22.02%); and medicines for arthropathies, rheumatism and osteoarthritis (2.6%). The Period 2 showed 4 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (69.7%); medicines for CVD and depression (3%); medicines for CMD and arthropathies (0.3%); and medicines for AR, and CVD (2,5%). The Period 3 showed 6 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (41.1%); medicines for CVD, acute-respiratory-infection (ARI), and arthropathies (1.25%); medicines for AR (1.16%); medicines for depression, anxiety (0.06%); medicines for CMD (1.4%); and medicines for dermatologic disorders (0.9%). The Period 4 showed 3 main clusters of polypharmacy - medicines for infections, arthropathy, and CVD (5.5%); medicines for anxiety, ARI (2.4%); and medicines for ARI and CVD (2.1%). As the development towards dementia progressed, the associative diseases tended to cluster with a larger prevalence in each cluster. Farther away before DoD, the clusters of polypharmacy tended to be clearly distinct between each other, resulting in an increasing number of patterns, but in a smaller prevalence.",,doi:https://doi.org/10.14336/ad.2022.0829; doi:https://doi.org/10.14336/AD.2022.0829; html:https://europepmc.org/articles/PMC10017143; pdf:https://europepmc.org/articles/PMC10017143?pdf=render
+31000744,https://doi.org/10.1038/s41598-019-42036-w,"Measuring social, environmental and health inequalities using deep learning and street imagery.","Suel E, Polak JW, Bennett JE, Ezzati M.",,Scientific reports,2019,2019-04-18,Y,,"Applied Analytics, Improving Public Health",,"Cities are home to an increasing majority of the world's population. Currently, it is difficult to track social, economic, environmental and health outcomes in cities with high spatial and temporal resolution, needed to evaluate policies regarding urban inequalities. We applied a deep learning approach to street images for measuring spatial distributions of income, education, unemployment, housing, living environment, health and crime. Our model predicts different outcomes directly from raw images without extracting intermediate user-defined features. To evaluate the performance of the approach, we first trained neural networks on a subset of images from London using ground truth data at high spatial resolution from official statistics. We then compared how trained networks separated the best-off from worst-off deciles for different outcomes in images not used in training. The best performance was achieved for quality of the living environment and mean income. Allocation was least successful for crime and self-reported health (but not objectively measured health). We also evaluated how networks trained in London predict outcomes three other major cities in the UK: Birmingham, Manchester, and Leeds. The transferability analysis showed that networks trained in London, fine-tuned with only 1% of images in other cities, achieved performances similar to ones from trained on data from target cities themselves. Our findings demonstrate that street imagery has the potential complement traditional survey-based and administrative data sources for high-resolution urban surveillance to measure inequalities and monitor the impacts of policies that aim to address them.",,pdf:https://www.nature.com/articles/s41598-019-42036-w.pdf; doi:https://doi.org/10.1038/s41598-019-42036-w; html:https://europepmc.org/articles/PMC6473002; pdf:https://europepmc.org/articles/PMC6473002?pdf=render
 37140153,https://doi.org/10.1093/ehjci/jead093,Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.,"Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,European heart journal. Cardiovascular Imaging,2023,2023-08-01,N,Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes,,,"<h4>Aims</h4>Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.<h4>Methods and results</h4>Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.<h4>Conclusion</h4>Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093
-33280008,https://doi.org/10.1093/cercor/bhaa345,Hierarchical Complexity of the Macro-Scale Neonatal Brain.,"Blesa M, Galdi P, Cox SR, Sullivan G, Stoye DQ, Lamb GJ, Quigley AJ, Thrippleton MJ, Escudero J, Bastin ME, Smith KM, Boardman JP.",,"Cerebral cortex (New York, N.Y. : 1991)",2021,2021-03-01,Y,Newborn; Network Analysis; Developing Brain; Dmri; Structural Connectome; Hierarchical Complexity,,,"The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period, assess correspondences with hierarchical complexity in adulthood, and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.",,pdf:https://academic.oup.com/cercor/article-pdf/31/4/2071/36458400/bhaa345.pdf; doi:https://doi.org/10.1093/cercor/bhaa345; html:https://europepmc.org/articles/PMC7945030; pdf:https://europepmc.org/articles/PMC7945030?pdf=render
 35143670,https://doi.org/10.1093/molbev/msac034,The Carbon Footprint of Bioinformatics.,"Grealey J, Lannelongue L, Saw WY, Marten J, Méric G, Ruiz-Carmona S, Inouye M.",,Molecular biology and evolution,2022,2022-03-01,Y,Bioinformatics; Genomics; Carbon Footprint; Green Algorithms,,,"Bioinformatic research relies on large-scale computational infrastructures which have a nonzero carbon footprint but so far, no study has quantified the environmental costs of bioinformatic tools and commonly run analyses. In this work, we estimate the carbon footprint of bioinformatics (in kilograms of CO2 equivalent units, kgCO2e) using the freely available Green Algorithms calculator (www.green-algorithms.org, last accessed 2022). We assessed 1) bioinformatic approaches in genome-wide association studies (GWAS), RNA sequencing, genome assembly, metagenomics, phylogenetics, and molecular simulations, as well as 2) computation strategies, such as parallelization, CPU (central processing unit) versus GPU (graphics processing unit), cloud versus local computing infrastructure, and geography. In particular, we found that biobank-scale GWAS emitted substantial kgCO2e and simple software upgrades could make it greener, for example, upgrading from BOLT-LMM v1 to v2.3 reduced carbon footprint by 73%. Moreover, switching from the average data center to a more efficient one can reduce carbon footprint by approximately 34%. Memory over-allocation can also be a substantial contributor to an algorithm's greenhouse gas emissions. The use of faster processors or greater parallelization reduces running time but can lead to greater carbon footprint. Finally, we provide guidance on how researchers can reduce power consumption and minimize kgCO2e. Overall, this work elucidates the carbon footprint of common analyses in bioinformatics and provides solutions which empower a move toward greener research.",,pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf; doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?pdf=render
-31000744,https://doi.org/10.1038/s41598-019-42036-w,"Measuring social, environmental and health inequalities using deep learning and street imagery.","Suel E, Polak JW, Bennett JE, Ezzati M.",,Scientific reports,2019,2019-04-18,Y,,"Applied Analytics, Improving Public Health",,"Cities are home to an increasing majority of the world's population. Currently, it is difficult to track social, economic, environmental and health outcomes in cities with high spatial and temporal resolution, needed to evaluate policies regarding urban inequalities. We applied a deep learning approach to street images for measuring spatial distributions of income, education, unemployment, housing, living environment, health and crime. Our model predicts different outcomes directly from raw images without extracting intermediate user-defined features. To evaluate the performance of the approach, we first trained neural networks on a subset of images from London using ground truth data at high spatial resolution from official statistics. We then compared how trained networks separated the best-off from worst-off deciles for different outcomes in images not used in training. The best performance was achieved for quality of the living environment and mean income. Allocation was least successful for crime and self-reported health (but not objectively measured health). We also evaluated how networks trained in London predict outcomes three other major cities in the UK: Birmingham, Manchester, and Leeds. The transferability analysis showed that networks trained in London, fine-tuned with only 1% of images in other cities, achieved performances similar to ones from trained on data from target cities themselves. Our findings demonstrate that street imagery has the potential complement traditional survey-based and administrative data sources for high-resolution urban surveillance to measure inequalities and monitor the impacts of policies that aim to address them.",,pdf:https://www.nature.com/articles/s41598-019-42036-w.pdf; doi:https://doi.org/10.1038/s41598-019-42036-w; html:https://europepmc.org/articles/PMC6473002; pdf:https://europepmc.org/articles/PMC6473002?pdf=render
 36834176,https://doi.org/10.3390/ijerph20043477,"Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.","Chandan JS, Brown KR, Simms-Williams N, Bashir NZ, Camaradou J, Heining D, Turner GM, Rivera SC, Hotham R, Minhas S, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Marshall T, Calvert MJ, Haroon S, Aiyegbusi OL, TLC Study.",,International journal of environmental research and public health,2023,2023-02-16,Y,Rehabilitation; Systematic review; Pvs; Non-pharmacological Intervention; Covid-19; Long Covid; Post-covid-19 Condition; Post-acute Sequelae Of Sars-cov-2 Infection (Pasc); Post-Viral Syndromes,,,"<h4>Background</h4>Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS.<h4>Methods</h4>We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively.<h4>Findings</h4>Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients.<h4>Interpretation</h4>In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS.<h4>Registration</h4>The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.",,pdf:https://www.mdpi.com/1660-4601/20/4/3477/pdf?version=1677135187; doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render
 35765786,https://doi.org/10.7189/jogh.12.04052,"Global, regional, and national prevalence of asthma in 2019: a systematic analysis and modelling study.","Song P, Adeloye D, Salim H, Dos Santos JP, Campbell H, Sheikh A, Rudan I.",,Journal of global health,2022,2022-06-29,Y,,,,"<h4>Background</h4>Asthma has a significant impact on people of all ages, particularly children. A lack of universally accepted case definition and confirmatory tests and a poor understanding of major risks interfere with a global response. We aimed to provide global estimates of asthma prevalence and cases in 2019 across four main epidemiological case definitions - current wheezing, ever wheezing, current asthma, and ever asthma. We further investigated major associated factors to determine regional and national distributions of prevalence and cases for current wheezing and ever asthma.<h4>Methods</h4>We identified relevant population-based studies published between January 1, 1990, and December 31, 2019. Using a multilevel multivariable mixed-effects meta-regression model, we assessed the age- and sex-adjusted associations of asthma with study-level variables, including year, setting, region and socio-demographic index (SDI). Using a random-effects meta-analysis, we then identified risk factors for current wheezing and asthma. From a ""risk factor-based model"", which included current smoking, and biomass exposure for current wheezing, and rural setting, current smoking, biomass exposure, and SDI for ever asthma, we estimated case numbers and prevalence across regions and 201 countries and territories in 2019.<h4>Results</h4>220 population-based studies conducted in 88 countries were retained. In 2019, the global prevalence estimates of asthma in people aged 5-69 years by various definitions, namely current wheezing, ever wheezing, current asthma, and ever asthma were 11.5% (95% confidence interval (CI) = 9.1-14.3), 17.9% (95% CI = 14.2-22.3), 5.4% (95% CI = 3.2-9.0) and 9.8% (95% CI = 7.8-12.2), respectively. These translated to 754.6 million (95% CI = 599. 7-943.4), 1181.3 million (95% CI = 938.0-1,471.0), 357.4 million (95% CI = 213.0-590.8), 645.2 million (95% CI = 513.1-806.2) cases, respectively. The overall prevalence of current wheezing among people aged 5-69 years was the highest in the African Region at 13.2% (95% CI = 10.5-16.5), and the lowest in the Americas Region at 10.0% (95% CI = 8.0-12.5). For ever asthma, the estimated prevalence in those aged 5-69 years was also the highest in the African Region at 11.3% (95% CI = 9.0-14.1), but the lowest in South-East Asia Region (8.8, 95% CI = 7.0-11.0).<h4>Conclusions</h4>Although varying approaches to case identification in different settings make epidemiological estimates of asthma very difficult, this analysis reaffirms asthma as a common global respiratory condition before the COVID-19 pandemic in 2019, with higher prevalence than previously reported in many world settings.",,pdf:https://jogh.org/wp-content/uploads/2022/06/jogh-12-04052.pdf; doi:https://doi.org/10.7189/jogh.12.04052; html:https://europepmc.org/articles/PMC9239324; pdf:https://europepmc.org/articles/PMC9239324?pdf=render
 35459745,https://doi.org/10.1136/thoraxjnl-2021-218374,Ambient heat exposure and COPD hospitalisations in England: a nationwide case-crossover study during 2007-2018.,"Konstantinoudis G, Minelli C, Vicedo-Cabrera AM, Ballester J, Gasparrini A, Blangiardo M.",,Thorax,2022,2022-04-22,Y,Copd Exacerbations; Copd Epidemiology; Copd Exacerbations Mechanisms,,,"<h4>Background</h4>There is emerging evidence suggesting a link between ambient heat exposure and chronic obstructive pulmonary disease (COPD) hospitalisations. Individual and contextual characteristics can affect population vulnerabilities to COPD hospitalisation due to heat exposure. This study quantifies the effect of ambient heat on COPD hospitalisations and examines population vulnerabilities by age, sex and contextual characteristics.<h4>Methods</h4>Individual data on COPD hospitalisation at high geographical resolution (postcodes) during 2007-2018 in England was retrieved from the small area health statistics unit. Maximum temperature at 1 km ×1 km resolution was available from the UK Met Office. We employed a case-crossover study design and fitted Bayesian conditional Poisson regression models. We adjusted for relative humidity and national holidays, and examined effect modification by age, sex, green space, average temperature, deprivation and urbanicity.<h4>Results</h4>After accounting for confounding, we found 1.47% (95% Credible Interval (CrI) 1.19% to 1.73%) increase in the hospitalisation risk for every 1°C increase in temperatures above 23.2°C (lags 0-2 days). We reported weak evidence of an effect modification by sex and age. We found a strong spatial determinant of the COPD hospitalisation risk due to heat exposure, which was alleviated when we accounted for contextual characteristics. 1851 (95% CrI 1 576 to 2 079) COPD hospitalisations were associated with temperatures above 23.2°C annually.<h4>Conclusion</h4>Our study suggests that resources should be allocated to support the public health systems, for instance, through developing or expanding heat-health alerts, to challenge the increasing future heat-related COPD hospitalisation burden.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/04/21/thoraxjnl-2021-218374.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-218374; html:https://europepmc.org/articles/PMC9606528; pdf:https://europepmc.org/articles/PMC9606528?pdf=render
@@ -832,8 +832,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 34543272,https://doi.org/10.1371/journal.pcbi.1009324,Ten simple rules to make your computing more environmentally sustainable.,"Lannelongue L, Grealey J, Bateman A, Inouye M.",,PLoS computational biology,2021,2021-09-20,Y,,,,,,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009324&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009324; html:https://europepmc.org/articles/PMC8452068; pdf:https://europepmc.org/articles/PMC8452068?pdf=render
 35997594,https://doi.org/10.1099/mic.0.001223,Diagnostic MALDI-TOF MS can differentiate between high and low toxic <i>Staphylococcus aureus</i> bacteraemia isolates as a predictor of patient outcome.,"Brignoli T, Recker M, Lee WWY, Dong T, Bhamber R, Albur M, Williams P, Dowsey AW, Massey RC.",,"Microbiology (Reading, England)",2022,2022-08-01,Y,Toxicity; Staphylococcus aureus; Bacteraemia; agr; Maldi-tof Ms Diagnosis,,,"<i>Staphylococcus aureus</i> bacteraemia (SAB) is a major cause of blood-stream infection (BSI) in both healthcare and community settings. While the underlying comorbidities of a patient significantly contributes to their susceptibility to and outcome following SAB, recent studies show the importance of the level of cytolytic toxin production by the infecting bacterium. In this study we demonstrate that this cytotoxicity can be determined directly from the diagnostic MALDI-TOF mass spectrum generated in a routine diagnostic laboratory. With further development this information could be used to guide the management and improve the outcomes for SAB patients.",,pdf:https://research-information.bris.ac.uk/ws/files/338315985/mic001223.pdf; doi:https://doi.org/10.1099/mic.0.001223; html:https://europepmc.org/articles/PMC10323763; pdf:https://europepmc.org/articles/PMC10323763?pdf=render
 37920183,https://doi.org/10.3389/fcvm.2023.1148931,Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure.,"Baudier C, Fougerousse F, Asselbergs FW, Guedj M, Komajda M, Kotecha D, Thomas Lumbers R, Schmidt AF, Tyl B.",,Frontiers in cardiovascular medicine,2023,2023-10-18,Y,"adrenergic receptors; Beta-blockers; Mendelian Randomization; Alpha-blockers; Target Validation, Drug",,,"<h4>Background</h4>The effects of α and ß adrenergic receptor modulation on the risk of developing heart failure (HF) remains uncertain due to a lack of randomized controlled trials. This study aimed to estimate the effects of α and ß adrenergic receptors modulation on the risk of HF and to provide proof of principle for genetic target validation studies in HF.<h4>Methods</h4>Genetic variants within the cis regions encoding the adrenergic receptors α1A, α2B, ß1, and ß2 associated with blood pressure in a 757,601-participant genome-wide association study (GWAS) were selected as instruments to perform a drug target Mendelian randomization study. Effects of these variants on HF risk were derived from the HERMES GWAS (542,362 controls; 40,805 HF cases).<h4>Results</h4>Lower α1A or ß1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74-0.93, <i>P</i> = 0.001) and 0.95 (95% CI 0.93-0.97, <i>P</i> = 8 × 10<sup>-6</sup>). Conversely, lower α2B activity was associated with increased HF risk: OR 1.09 (95% CI 1.05-1.12, <i>P</i> = 3 × 10<sup>-7</sup>). No evidence of an effect of lower ß2 activity on HF risk was found: OR 0.99 (95% CI 0.92-1.07, <i>P</i> = 0.95). Complementary analyses showed that these effects were consistent with those on left ventricular dimensions and acted independently of any potential effect on coronary artery disease.<h4>Conclusions</h4>This study provides genetic evidence that α1A or ß1 receptor inhibition will likely decrease HF risk, while lower α2B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.",,doi:https://doi.org/10.3389/fcvm.2023.1148931; html:https://europepmc.org/articles/PMC10619754; pdf:https://europepmc.org/articles/PMC10619754?pdf=render
-37736873,https://doi.org/10.1002/ehf2.14527,Genetically predicted androgenic profiles and adverse cardiac markers: a sex-specific Mendelian randomization study.,"Chen JY, Ardissino M, Reddy RK, Mason AM, Raisi-Estabragh Z, Di Angelantonio E, Burgess S, Ng FS.",,ESC heart failure,2023,2023-09-22,N,Sex hormones; Testosterone; Heart Failure; Cmr; Mendelian Randomization; Shbg,,,"<h4>Aims</h4>Observational evidence suggests associations between sex hormone levels and heart failure (HF). We used sex-specific genetic variants associated with androgenic sex hormone profiles to investigate the causal relevance of androgenic sex hormone profiles on cardiac structure and function and HF using Mendelian randomization (MR).<h4>Methods and results</h4>Sex-specific uncorrelated genome-wide significant (P < 5 × 10<sup>-8</sup> ) variants predicting sex hormone-binding globulin (SHBG), total testosterone, and bioavailable testosterone were extracted from summary statistics of genome-wide association study (GWAS) on 425 097 participants in the UK Biobank. Sex-specific gene-outcome association estimates were computed for left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively), left ventricular stroke volume (LVSV), cardiac index, and cardiac output in 11 528 female and 14 356 male UK Biobank Imaging Study participants and for incident or prevalent HF in an external cohort of 47 309 cases and 930 014 controls. Inverse-variance weighted MR was the primary analysis method. In females, higher genetically predicted bioavailable testosterone was associated with lower LVEDV [β per nmol/L = -0.11 (-0.19 to -0.03), P = 0.006], lower LVESV [β = -0.09 (-0.17 to -0.01), P = 0.022], lower LVSV [β = -0.11 (-0.18 to -0.03), P = 0.005], lower cardiac output [β = -0.08 (-0.16 to 0.00), P = 0.046], and lower cardiac index [β = -0.08 (-0.16 to -0.01), P = 0.034] and a higher risk of HF [odds ratio 1.10 (1.01-1.19), P = 0.026] on external validation analysis in larger scale, sex-adjusted GWAS data. Higher genetically predicted SHBG was associated with higher LVEDV [β per nmol/L = 0.17 (0.08-0.25), P = 2 × 10<sup>-4</sup> ], higher LVESV [β = 0.13 (0.05-0.22), P = 0.003], and higher LVSV [β = 0.18 (0.08-0.28), P = 2 × 10<sup>-4</sup> ]. In males, higher genetically predicted total and bioavailable testosterone was associated with lower LVESV [β = -0.07 (-0.12 to -0.02), P = 0.007] and LVEF [β = -0.11 (-0.18 to -0.04), P = 0.003], respectively.<h4>Conclusions</h4>This study supports a causal effect of pro-androgenic sex hormone profiles in females on adverse markers of left ventricular structure and function typically associated with HF with preserved ejection fraction and with HF. There was weaker evidence of association in males.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14527; doi:https://doi.org/10.1002/ehf2.14527
 34861180,https://doi.org/10.1016/s2213-2600(21)00491-4,Risk of COVID-19 hospital admission among children aged 5-17 years with asthma in Scotland: a national incident cohort study.,"Shi T, Pan J, Katikireddi SV, McCowan C, Kerr S, Agrawal U, Shah SA, Simpson CR, Ritchie LD, Robertson C, Sheikh A, Public Health Scotland and the EAVE II Collaborators.",,The Lancet. Respiratory medicine,2022,2021-11-30,Y,,,,"<h4>Background</h4>There is an urgent need to inform policy deliberations about whether children with asthma should be vaccinated against SARS-CoV-2 and, if so, which subset of children with asthma should be prioritised. We were asked by the UK's Joint Commission on Vaccination and Immunisation to undertake an urgent analysis to identify which children with asthma were at increased risk of serious COVID-19 outcomes.<h4>Methods</h4>This national incident cohort study was done in all children in Scotland aged 5-17 years who were included in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). We used data from EAVE II to investigate the risk of COVID-19 hospitalisation among children with markers of uncontrolled asthma defined by either previous asthma hospital admission or oral corticosteroid prescription in the previous 2 years. A Cox proportional hazard model was used to derive hazard ratios (HRs) and 95% CIs for the association between asthma and COVID-19 hospital admission, stratified by markers of asthma control (previous asthma hospital admission and number of previous prescriptions for oral corticosteroids within 2 years of the study start date). Analyses were adjusted for age, sex, socioeconomic status, comorbidity, and previous hospital admission.<h4>Findings</h4>Between March 1, 2020, and July 27, 2021, 752 867 children were included in the EAVE II dataset, 63 463 (8·4%) of whom had clinician-diagnosed-and-recorded asthma. Of these, 4339 (6·8%) had RT-PCR confirmed SARS-CoV-2 infection. In those with confirmed infection, 67 (1·5%) were admitted to hospital with COVID-19. Among the 689 404 children without asthma, 40 231 (5·8%) had confirmed SARS-CoV-2 infections, of whom 382 (0·9%) were admitted to hospital with COVID-19. The rate of COVID-19 hospital admission was higher in children with poorly controlled asthma than in those with well controlled asthma or without asthma. When using previous hospital admission for asthma as the marker of uncontrolled asthma, the adjusted HR was 6·40 (95% CI 3·27-12·53) for those with poorly controlled asthma and 1·36 (1·02-1·80) for those with well controlled asthma, compared with those with no asthma. When using oral corticosteroid prescriptions as the marker of uncontrolled asthma, the adjusted HR was 3·38 (1·84-6·21) for those with three or more prescribed courses of corticosteroids, 3·53 (1·87-6·67) for those with two prescribed courses of corticosteroids, 1·52 (0·90-2·57) for those with one prescribed course of corticosteroids, and 1·34 (0·98-1·82) for those with no prescribed course, compared with those with no asthma.<h4>Interpretation</h4>School-aged children with asthma with previous recent hospital admission or two or more courses of oral corticosteroids are at markedly increased risk of COVID-19 hospital admission and should be considered a priority for vaccinations. This would translate into 9124 children across Scotland and an estimated 109 448 children across the UK.<h4>Funding</h4>UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and Scottish Government.",,pdf:http://www.thelancet.com/article/S2213260021004914/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00491-4; html:https://europepmc.org/articles/PMC8631918
+37736873,https://doi.org/10.1002/ehf2.14527,Genetically predicted androgenic profiles and adverse cardiac markers: a sex-specific Mendelian randomization study.,"Chen JY, Ardissino M, Reddy RK, Mason AM, Raisi-Estabragh Z, Di Angelantonio E, Burgess S, Ng FS.",,ESC heart failure,2023,2023-09-22,N,Sex hormones; Testosterone; Heart Failure; Cmr; Mendelian Randomization; Shbg,,,"<h4>Aims</h4>Observational evidence suggests associations between sex hormone levels and heart failure (HF). We used sex-specific genetic variants associated with androgenic sex hormone profiles to investigate the causal relevance of androgenic sex hormone profiles on cardiac structure and function and HF using Mendelian randomization (MR).<h4>Methods and results</h4>Sex-specific uncorrelated genome-wide significant (P < 5 × 10<sup>-8</sup> ) variants predicting sex hormone-binding globulin (SHBG), total testosterone, and bioavailable testosterone were extracted from summary statistics of genome-wide association study (GWAS) on 425 097 participants in the UK Biobank. Sex-specific gene-outcome association estimates were computed for left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively), left ventricular stroke volume (LVSV), cardiac index, and cardiac output in 11 528 female and 14 356 male UK Biobank Imaging Study participants and for incident or prevalent HF in an external cohort of 47 309 cases and 930 014 controls. Inverse-variance weighted MR was the primary analysis method. In females, higher genetically predicted bioavailable testosterone was associated with lower LVEDV [β per nmol/L = -0.11 (-0.19 to -0.03), P = 0.006], lower LVESV [β = -0.09 (-0.17 to -0.01), P = 0.022], lower LVSV [β = -0.11 (-0.18 to -0.03), P = 0.005], lower cardiac output [β = -0.08 (-0.16 to 0.00), P = 0.046], and lower cardiac index [β = -0.08 (-0.16 to -0.01), P = 0.034] and a higher risk of HF [odds ratio 1.10 (1.01-1.19), P = 0.026] on external validation analysis in larger scale, sex-adjusted GWAS data. Higher genetically predicted SHBG was associated with higher LVEDV [β per nmol/L = 0.17 (0.08-0.25), P = 2 × 10<sup>-4</sup> ], higher LVESV [β = 0.13 (0.05-0.22), P = 0.003], and higher LVSV [β = 0.18 (0.08-0.28), P = 2 × 10<sup>-4</sup> ]. In males, higher genetically predicted total and bioavailable testosterone was associated with lower LVESV [β = -0.07 (-0.12 to -0.02), P = 0.007] and LVEF [β = -0.11 (-0.18 to -0.04), P = 0.003], respectively.<h4>Conclusions</h4>This study supports a causal effect of pro-androgenic sex hormone profiles in females on adverse markers of left ventricular structure and function typically associated with HF with preserved ejection fraction and with HF. There was weaker evidence of association in males.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14527; doi:https://doi.org/10.1002/ehf2.14527
 32657853,https://doi.org/10.1097/sap.0000000000002434,"Making the Most of Big Data in Plastic Surgery: Improving Outcomes, Protecting Patients, Informing Service Providers.","Gibson JAG, Dobbs TD, Kouzaris L, Lacey A, Thompson S, Akbari A, Hutchings HA, Lineaweaver WC, Lyons RA, Whitaker IS.",,Annals of plastic surgery,2021,2021-03-01,N,,,,"<h4>Abstract</h4>In medicine, ""big data"" refers to the interdisciplinary analysis of high-volume, diverse clinical and lifestyle information on large patient populations. Recent advancements in data storage and electronic record keeping have enabled the expansion of research in this field. In the United Kingdom, Big data has been highlighted as one of the government's ""8 Great Technologies,"" and the Medical Research Council has invested more than £100 million since 2012 in developing the Health Data Research UK infrastructure. The recent Royal College of Surgeons Commission of the Future of Surgery concluded that analysis of big data is one of the 4 most likely avenues to bring some of the most innovative changes to surgical practice in the 21st century.In this article, we provide an overview of the nascent field of big data analytics in plastic and highlight how it has the potential to improve outcomes, increase safety, and aid service planning.We outline the current resources available, the emerging role of big data within the subspecialties of burns, microsurgery, skin and breast cancer, and how these data can be used. We critically review the limitations and considerations raised with big data, offer suggestions regarding database optimization, and suggest future directions for research in this exciting field.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa53972/Download/53972__17281__0cb520258c2b49cdb0e751a62be92c5d.pdf; doi:https://doi.org/10.1097/SAP.0000000000002434
 32460529,https://doi.org/10.1161/circimaging.119.010389,Novel Approach to Imaging Active Takayasu Arteritis Using Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.,"Tarkin JM, Wall C, Gopalan D, Aloj L, Manavaki R, Fryer TD, Aboagye EO, Bennett MR, Peters JE, Rudd JHF, Mason JC.",,Circulation. Cardiovascular imaging,2020,2020-05-28,N,Positron emission tomography; Vasculitis; Aortic Diseases; Molecular Imaging; Takayasu Arteritis,,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCIMAGING.119.010389; doi:https://doi.org/10.1161/CIRCIMAGING.119.010389; html:https://europepmc.org/articles/PMC7610536; pdf:https://europepmc.org/articles/PMC7610536?pdf=render; doi:https://doi.org/10.1161/circimaging.119.010389
 30240446,https://doi.org/10.1371/journal.pone.0203896,Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response: Meta-analysis of three treatment cohorts.,"Ward J, Graham N, Strawbridge RJ, Ferguson A, Jenkins G, Chen W, Hodgson K, Frye M, Weinshilboum R, Uher R, Lewis CM, Biernacka J, Smith DJ.",,PloS one,2018,2018-09-21,Y,,Better Care,,"There are currently no reliable approaches for correctly identifying which patients with major depressive disorder (MDD) will respond well to antidepressant therapy. However, recent genetic advances suggest that Polygenic Risk Scores (PRS) could allow MDD patients to be stratified for antidepressant response. We used PRS for MDD and PRS for neuroticism as putative predictors of antidepressant response within three treatment cohorts: The Genome-based Therapeutic Drugs for Depression (GENDEP) cohort, and 2 sub-cohorts from the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS (total patient number = 760). Results across cohorts were combined via meta-analysis within a random effects model. Overall, PRS for MDD and neuroticism did not significantly predict antidepressant response but there was a consistent direction of effect, whereby greater genetic loading for both MDD (best MDD result, p < 5*10-5 MDD-PRS at 4 weeks, β = -0.019, S.E = 0.008, p = 0.01) and neuroticism (best neuroticism result, p < 0.1 neuroticism-PRS at 8 weeks, β = -0.017, S.E = 0.008, p = 0.03) were associated with less favourable response. We conclude that the PRS approach may offer some promise for treatment stratification in MDD and should now be assessed within larger clinical cohorts.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0203896&type=printable; doi:https://doi.org/10.1371/journal.pone.0203896; html:https://europepmc.org/articles/PMC6150505; pdf:https://europepmc.org/articles/PMC6150505?pdf=render
@@ -850,11 +850,11 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 37200150,https://doi.org/10.1210/clinem/dgad276,Preconception Management of Hyperthyroidism and Thyroid Status in Subsequent Pregnancy: A Population-Based Cohort Study.,"Minassian C, Allen LA, Okosieme O, Vaidya B, Taylor P.",,The Journal of clinical endocrinology and metabolism,2023,2023-10-01,Y,Pregnancy; Thyroxine; Hyperthyroidism; Thyroid stimulating hormone; TSH; Thyroid function; Ft3; Ft4; Carbimazole; Tri-iodothyronine; Ptu; Cprd,,,"<h4>Context</h4>Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy.<h4>Objective</h4>We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status.<h4>Methods</h4>We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset.<h4>Results</h4>Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole.<h4>Conclusion</h4>The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.",,doi:https://doi.org/10.1210/clinem/dgad276; doi:https://doi.org/10.1210/clinem/dgad276; html:https://europepmc.org/articles/PMC10584009
 36439548,https://doi.org/10.3389/fsurg.2022.870494,Development and validation of an automated basal cell carcinoma histopathology information extraction system using natural language processing.,"Ali SR, Strafford H, Dobbs TD, Fonferko-Shadrach B, Lacey AS, Pickrell WO, Hutchings HA, Whitaker IS.",,Frontiers in surgery,2022,2022-08-24,Y,Electronic Health Records (Ehrs); Natural Language Processing (Nlp); Basal Cell Carcinoma (Bcc); Non-melanoma Skin Cancer (Nmsc); Information Extraction (Ie),,,"<h4>Introduction</h4>Routinely collected healthcare data are a powerful research resource, but often lack detailed disease-specific information that is collected in clinical free text such as histopathology reports. We aim to use natural Language Processing (NLP) techniques to extract detailed clinical and pathological information from histopathology reports to enrich routinely collected data.<h4>Methods</h4>We used the general architecture for text engineering (GATE) framework to build an NLP information extraction system using rule-based techniques. During validation, we deployed our rule-based NLP pipeline on 200 previously unseen, de-identified and pseudonymised basal cell carcinoma (BCC) histopathological reports from Swansea Bay University Health Board, Wales, UK. The results of our algorithm were compared with gold standard human annotation by two independent and blinded expert clinicians involved in skin cancer care.<h4>Results</h4>We identified 11,224 items of information with a mean precision, recall, and F1 score of 86.0% (95% CI: 75.1-96.9), 84.2% (95% CI: 72.8-96.1), and 84.5% (95% CI: 73.0-95.1), respectively. The difference between clinician annotator F1 scores was 7.9% in comparison with 15.5% between the NLP pipeline and the gold standard corpus. Cohen's Kappa score on annotated tokens was 0.85.<h4>Conclusion</h4>Using an NLP rule-based approach for named entity recognition in BCC, we have been able to develop and validate a pipeline with a potential application in improving the quality of cancer registry data, supporting service planning, and enhancing the quality of routinely collected data for research.",,pdf:https://www.frontiersin.org/articles/10.3389/fsurg.2022.870494/pdf; doi:https://doi.org/10.3389/fsurg.2022.870494; html:https://europepmc.org/articles/PMC9683031; pdf:https://europepmc.org/articles/PMC9683031?pdf=render
 32616677,https://doi.org/10.1212/wnl.0000000000009924,Accuracy of identifying incident stroke cases from linked health care data in UK Biobank.,"Rannikmäe K, Ngoh K, Bush K, Al-Shahi Salman R, Doubal F, Flaig R, Henshall DE, Hutchison A, Nolan J, Osborne S, Samarasekera N, Schnier C, Whiteley W, Wilkinson T, Wilson K, Woodfield R, Zhang Q, Allen N, Sudlow CLM.",,Neurology,2020,2020-07-02,Y,,,,"<h4>Objective</h4>In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes.<h4>Methods</h4>In a regional UKB subpopulation (n = 17,249), we identified all participants with ≥1 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type.<h4>Results</h4>Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in >99%. PPVs (95% confidence intervals) were 79% (73%-84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%-90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise.<h4>Conclusions</h4>Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types.",,pdf:https://n.neurology.org/content/neurology/95/6/e697.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009924; html:https://europepmc.org/articles/PMC7455356; pdf:https://europepmc.org/articles/PMC7455356?pdf=render
-37729117,https://doi.org/10.1371/journal.pdig.0000309,Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.,"Fuller GW, Hasan M, Hodkinson P, McAlpine D, Goodacre S, Bath PA, Sbaffi L, Omer Y, Wallis L, Marincowitz C.",,PLOS digital health,2023,2023-09-20,Y,,,,"COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000309&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000309; html:https://europepmc.org/articles/PMC10511129; pdf:https://europepmc.org/articles/PMC10511129?pdf=render
 32103533,https://doi.org/10.1002/sim.8503,Propensity scores using missingness pattern information: a practical guide.,"Blake HA, Leyrat C, Mansfield KE, Seaman S, Tomlinson LA, Carpenter J, Williamson EJ.",,Statistics in medicine,2020,2020-02-27,N,Electronic Health Records; Propensity Score Analysis; Missingness Pattern; Missing Indicator; Missing Confounder Data,,,"Electronic health records are a valuable data source for investigating health-related questions, and propensity score analysis has become an increasingly popular approach to address confounding bias in such investigations. However, because electronic health records are typically routinely recorded as part of standard clinical care, there are often missing values, particularly for potential confounders. In our motivating study-using electronic health records to investigate the effect of renin-angiotensin system blockers on the risk of acute kidney injury-two key confounders, ethnicity and chronic kidney disease stage, have 59% and 53% missing data, respectively. The missingness pattern approach (MPA), a variant of the missing indicator approach, has been proposed as a method for handling partially observed confounders in propensity score analysis. In the MPA, propensity scores are estimated separately for each missingness pattern present in the data. Although the assumptions underlying the validity of the MPA are stated in the literature, it can be difficult in practice to assess their plausibility. In this article, we explore the MPA's underlying assumptions by using causal diagrams to assess their plausibility in a range of simple scenarios, drawing general conclusions about situations in which they are likely to be violated. We present a framework providing practical guidance for assessing whether the MPA's assumptions are plausible in a particular setting and thus deciding when the MPA is appropriate. We apply our framework to our motivating study, showing that the MPA's underlying assumptions appear reasonable, and we demonstrate the application of MPA to this study.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4656008/1/manuscript.pdf; doi:https://doi.org/10.1002/sim.8503; html:https://europepmc.org/articles/PMC7612316; pdf:https://europepmc.org/articles/PMC7612316?pdf=render; doi:https://doi.org/10.1002/sim.8503
+37729117,https://doi.org/10.1371/journal.pdig.0000309,Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.,"Fuller GW, Hasan M, Hodkinson P, McAlpine D, Goodacre S, Bath PA, Sbaffi L, Omer Y, Wallis L, Marincowitz C.",,PLOS digital health,2023,2023-09-20,Y,,,,"COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000309&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000309; html:https://europepmc.org/articles/PMC10511129; pdf:https://europepmc.org/articles/PMC10511129?pdf=render
 37293269,https://doi.org/10.1140/epjds/s13688-023-00394-6,Do poverty and wealth look the same the world over? A comparative study of 12 cities from five high-income countries using street images.,"Suel E, Muller E, Bennett JE, Blakely T, Doyle Y, Lynch J, Mackenbach JD, Middel A, Mizdrak A, Nathvani R, Brauer M, Ezzati M.",,EPJ data science,2023,2023-06-07,Y,Computer vision; Visual Similarity; Urban Inequalities; Street Images,,,"Urbanization and inequalities are two of the major policy themes of our time, intersecting in large cities where social and economic inequalities are particularly pronounced. Large scale street-level images are a source of city-wide visual information and allow for comparative analyses of multiple cities. Computer vision methods based on deep learning applied to street images have been shown to successfully measure inequalities in socioeconomic and environmental features, yet existing work has been within specific geographies and have not looked at how visual environments compare across different cities and countries. In this study, we aim to apply existing methods to understand whether, and to what extent, poor and wealthy groups live in visually similar neighborhoods across cities and countries. We present novel insights on similarity of neighborhoods using street-level images and deep learning methods. We analyzed 7.2 million images from 12 cities in five high-income countries, home to more than 85 million people: Auckland (New Zealand), Sydney (Australia), Toronto and Vancouver (Canada), Atlanta, Boston, Chicago, Los Angeles, New York, San Francisco, and Washington D.C. (United States of America), and London (United Kingdom). Visual features associated with neighborhood disadvantage are more distinct and unique to each city than those associated with affluence. For example, from what is visible from street images, high density poor neighborhoods located near the city center (e.g., in London) are visually distinct from poor suburban neighborhoods characterized by lower density and lower accessibility (e.g., in Atlanta). This suggests that differences between two cities is also driven by historical factors, policies, and local geography. Our results also have implications for image-based measures of inequality in cities especially when trained on data from cities that are visually distinct from target cities. We showed that these are more prone to errors for disadvantaged areas especially when transferring across cities, suggesting more attention needs to be paid to improving methods for capturing heterogeneity in poor environment across cities around the world.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00394-6.",,doi:https://doi.org/10.1140/epjds/s13688-023-00394-6; html:https://europepmc.org/articles/PMC10245348; pdf:https://europepmc.org/articles/PMC10245348?pdf=render
-37563310,https://doi.org/10.1038/s41590-023-01588-w,Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-08-10,Y,,,,"Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-α in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.",,doi:https://doi.org/10.1038/s41590-023-01588-w; html:https://europepmc.org/articles/PMC10457199; pdf:https://europepmc.org/articles/PMC10457199?pdf=render
 35308999,https://doi.org/,Axes of Prognosis: Identifying Subtypes of COVID-19 Outcomes.,"Whitfield E, Coffey C, Zhang H, Shi T, Wu X, Li Q, Wu H.",,AMIA ... Annual Symposium proceedings. AMIA Symposium,2021,2021-01-01,N,,,,"COVID-19 is a disease with vast impact, yet much remains unclear about patient outcomes. Most approaches to risk prediction of COVID-19 focus on binary or tertiary severity outcomes, despite the heterogeneity of the disease. In this work, we identify heterogeneous subtypes of COVID-19 outcomes by considering 'axes' of prognosis. We propose two innovative clustering approaches - 'Layered Axes' and 'Prognosis Space' - to apply on patients' outcome data. We then show how these clusters can help predict a patient's deterioration pathway on their hospital admission, using random forest classification. We illustrate this methodology on a cohort from Wuhan in early 2020. We discover interesting subgroups of poor prognosis, particularly within respiratory patients, and predict respiratory subgroup membership with high accuracy. This work could assist clinicians in identifying appropriate treatments at patients' hospital admission. Moreover, our method could be used to explore subtypes of 'long COVID' and other diseases with heterogeneous outcomes.",,html:https://europepmc.org/articles/PMC8861682; pdf:https://europepmc.org/articles/PMC8861682?pdf=render
+37563310,https://doi.org/10.1038/s41590-023-01588-w,Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-08-10,Y,,,,"Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-α in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.",,doi:https://doi.org/10.1038/s41590-023-01588-w; html:https://europepmc.org/articles/PMC10457199; pdf:https://europepmc.org/articles/PMC10457199?pdf=render
 36538350,https://doi.org/10.2196/41200,Identifying Patterns of Clinical Interest in Clinicians' Treatment Preferences: Hypothesis-free Data Science Approach to Prioritizing Prescribing Outliers for Clinical Review.,"MacKenna B, Curtis HJ, Hopcroft LEM, Walker AJ, Croker R, Macdonald O, Evans SJW, Inglesby P, Evans D, Morley J, Bacon SCJ, Goldacre B.",,JMIR medical informatics,2022,2022-12-20,Y,Prescribing; Clinical Audit; Antipsychotics; Pericyazine; Data Science; Nhs England; Promazine Hydrochloride,,,"<h4>Background</h4>Data analysis is used to identify signals suggestive of variation in treatment choice or clinical outcome. Analyses to date have generally focused on a hypothesis-driven approach.<h4>Objective</h4>This study aimed to develop a hypothesis-free approach to identify unusual prescribing behavior in primary care data. We aimed to apply this methodology to a national data set in a cross-sectional study to identify chemicals with significant variation in use across Clinical Commissioning Groups (CCGs) for further clinical review, thereby demonstrating proof of concept for prioritization approaches.<h4>Methods</h4>Here we report a new data-driven approach to identify unusual prescribing behaviour in primary care data. This approach first applies a set of filtering steps to identify chemicals with prescribing rate distributions likely to contain outliers, then applies two ranking approaches to identify the most extreme outliers amongst those candidates. This methodology has been applied to three months of national prescribing data (June-August 2017).<h4>Results</h4>Our methodology provides rankings for all chemicals by administrative region. We provide illustrative results for 2 antipsychotic drugs of particular clinical interest: promazine hydrochloride and pericyazine, which rank highly by outlier metrics. Specifically, our method identifies that, while promazine hydrochloride and pericyazine are barely used by most clinicians (with national prescribing rates of 11.1 and 6.2 per 1000 antipsychotic prescriptions, respectively), they make up a substantial proportion of antipsychotic prescribing in 2 small geographic regions in England during the study period (with maximum regional prescribing rates of 298.7 and 241.1 per 1000 antipsychotic prescriptions, respectively).<h4>Conclusions</h4>Our hypothesis-free approach is able to identify candidates for audit and review in clinical practice. To illustrate this, we provide 2 examples of 2 very unusual antipsychotics used disproportionately in 2 small geographic areas of England.",,pdf:https://medinform.jmir.org/2022/12/e41200/PDF; doi:https://doi.org/10.2196/41200; html:https://europepmc.org/articles/PMC9812268
 31912053,https://doi.org/,Described Practices for Assessing Fluid Resuscitation in Acute Hospital Care: A Qualitative Study.,"Lloyd E, Ignatowicz A, Sapey E, Lasserson D, Seccombe A.",,Acute medicine,2019,2019-01-01,N,,,,"Fluid resuscitation is a widely-used treatment in acute and emergency medicine, however, the process used to perform a fluid assessment has never been studied. This qualitative study explored how acute physicians describe their approach to assessing for fluid resuscitation. 18 clinicians of varying grades consented to a semi-structured interview. Transcripts were coded and analysed using thematic analysis. Participants described three subtypes of assessment; screening assessment, emergency assessment and formal assessment. Whether a patient was 'sick' was key to determining which assessment they would receive. Marked heterogeneity was noted in the assessment processes, particularly regarding the use of history-taking. Further research is required to determine how the information gathered in these assessments is used to decide when fluid resuscitation is indicated.",,
 34649961,https://doi.org/10.1101/cshperspect.a039230,Human Genomics and Drug Development.,"Schmidt AF, Hingorani AD, Finan C.",,Cold Spring Harbor perspectives in medicine,2022,2022-02-01,N,,,,"Insights into the genetic basis of human disease are helping to address some of the key challenges in new drug development including the very high rates of failure. Here we review the recent history of an emerging, genomics-assisted approach to pharmaceutical research and development, and its relationship to Mendelian randomization (MR), a well-established analytical approach to causal inference. We demonstrate how human genomic data linked to pharmaceutically relevant phenotypes can be used for (1) drug target identification (mapping relevant drug targets to diseases), (2) drug target validation (inferring the likely effects of drug target perturbation), (3) evaluation of the effectiveness and specificity of compound-target engagement (inferring the extent to which the effects of a compound are exclusive to the target and distinguishing between on-target and off-target compound effects), and (4) the selection of end points in clinical trials (the diseases or conditions to be evaluated as trial outcomes). We show how genomics can help identify indication expansion opportunities for licensed drugs and repurposing of compounds developed to clinical phase that proved safe but ineffective for the original intended indication. We outline statistical and biological considerations in using MR for drug target validation (drug target MR) and discuss the obstacles and challenges for scaled applications of these genomics-based approaches.",,pdf:https://discovery.ucl.ac.uk/10138810/1/ForUCLDiscovery.pdf; doi:https://doi.org/10.1101/cshperspect.a039230
@@ -867,9 +867,9 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 35130878,https://doi.org/10.1186/s12916-022-02234-2,"Lifetime risk of cardiovascular-renal disease in type 2 diabetes: a population-based study in 473,399 individuals.","Zhang R, Mamza JB, Morris T, Godfrey G, Asselbergs FW, Denaxas S, Hemingway H, Banerjee A.",,BMC medicine,2022,2022-02-07,Y,Kidney; Type 2 diabetes; lifetime; Attributable Risk; Population Health; cardiovascular,,,"<h4>Background</h4>Cardiovascular and renal diseases (CVRD) are major causes of mortality in individuals with type 2 diabetes (T2D). Studies of lifetime risk have neither considered all CVRD together nor the relative contribution of major risk factors to combined disease burden.<h4>Methods</h4>In a population-based cohort study using national electronic health records, we studied 473,399 individuals with T2D in England 2007-2018. Lifetime risk of individual and combined major adverse renal cardiovascular events, MARCE (including CV death and CVRD: heart failure; chronic kidney disease; myocardial infarction; stroke or peripheral artery disease), were estimated, accounting for baseline CVRD status and competing risk of death. We calculated population attributable risk for individual CVRD components. Ideal cardiovascular health was defined by blood pressure, cholesterol, glucose, smoking, physical activity, diet, and body mass index (i.e. modifiable risk factors).<h4>Results</h4>In individuals with T2D, lifetime risk of MARCE was 80% in those free from CVRD and was 97%, 93%, 98%, 89% and 91% in individuals with heart failure, chronic kidney disease, myocardial infarction, stroke and peripheral arterial disease, respectively at baseline. Among CVRD-free individuals, lifetime risk of chronic kidney disease was highest (54%), followed by CV death (41%), heart failure (29%), stroke (20%), myocardial infarction (19%) and peripheral arterial disease (9%). In those with HF only, 75% of MARCE after index T2D can be attributed to HF after adjusting for age, gender, and comorbidities. Compared with those with > 1, < 3 and ≥3 modifiable health risk behaviours, achieving ideal cardiovascular health could reduce MARCE by approximately 41.5%, 23.6% and 17.2%, respectively, in the T2D population.<h4>Conclusions</h4>Four out of five individuals with T2D free from CVRD, and nearly all those with history of CVRD, will develop MARCE over their lifetime. Early preventive measures in T2D patients are clinical, public health and policy priorities.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02234-2; doi:https://doi.org/10.1186/s12916-022-02234-2; html:https://europepmc.org/articles/PMC8822817; pdf:https://europepmc.org/articles/PMC8822817?pdf=render
 34969173,https://doi.org/10.1002/ejhf.2417,"A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential.","Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway H.",,European journal of heart failure,2022,2022-01-26,Y,Risk factor; epidemiology; Heart Failure; Primary Prevention,,,"<h4>Aims</h4>Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.<h4>Methods and results</h4>We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170 885 individuals aged ≥30 years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule-based phenotypes (ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)-based interventions for HF prevention (RCT-HF), and 6 for cardiovascular disease prevention, but not HF (RCT-CVD), and the remainder had no RCT-based preventive interventions (RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5 years prior to HF diagnosis, 44.3% had ≥4 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT-CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT-0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1 year varied across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs.<h4>Conclusion</h4>One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.2417; doi:https://doi.org/10.1002/ejhf.2417; html:https://europepmc.org/articles/PMC9305958; pdf:https://europepmc.org/articles/PMC9305958?pdf=render
 37456658,https://doi.org/10.12688/hrbopenres.13667.1,Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.,"McCarthy M, Gillies K, Rousseau N, Wade J, Gamble C, Toomey E, Matvienko-Sikar K, Sydes M, Dowling M, Bryant V, Biesty L, Houghton C.",,HRB open research,2023,2023-02-06,Y,data sharing; Qualitative; trials; Focus Groups,,,"<b>Background</b>: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. <b>Methods: </b>Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. <b>Results:</b> Three key themes were identified from our Phase 1 findings: ' <i>Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing'</i>, and ' <i>Future guidance and funding</i>'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. <b>Conclusions:</b> The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.",,doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render
-36936265,https://doi.org/10.1136/bmjmed-2022-000276,"Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY.","Green ACA, Curtis HJ, Higgins R, Nab L, Mahalingasivam V, Smith RM, Mehrkar A, Inglesby P, Drysdale H, DeVito NJ, Croker R, Rentsch CT, Bhaskaran K, Tazare J, Zheng B, Andrews CD, Bacon SCJ, Davy S, Dillingham I, Evans D, Fisher L, Hickman G, Hopcroft LEM, Hulme WJ, Massey J, MacDonald O, Morley J, Morton CE, Park RY, Walker AJ, Ward T, Wiedemann M, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Goldacre B, Tomlinson LA, MacKenna B.",,BMJ medicine,2023,2023-01-13,Y,Therapeutics; Community health services; Public Health; Covid-19,,,"<h4>Objective</h4>To ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.<h4>Design</h4>Retrospective, descriptive cohort study, approved by NHS England.<h4>Setting</h4>Routine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.<h4>Participants</h4>Outpatients with covid-19 at high risk of severe outcomes.<h4>Interventions</h4>Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.<h4>Results</h4>93 870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19 040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95% confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from ≥80 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%).<h4>Conclusions</h4>Using the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged ≥80 years, those living in socioeconomically deprived areas, and care home residents.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render
 31104603,https://doi.org/10.1098/rstb.2018.0276,Outbreak analytics: a developing data science for informing the response to emerging pathogens.,"Polonsky JA, Baidjoe A, Kamvar ZN, Cori A, Durski K, Edmunds WJ, Eggo RM, Funk S, Kaiser L, Keating P, de Waroux OLP, Marks M, Moraga P, Morgan O, Nouvellet P, Ratnayake R, Roberts CH, Whitworth J, Jombart T.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2019,2019-07-01,Y,Methods; Software; epidemics; Infectious; pipeline; Tools,Applied Analytics,,"Despite continued efforts to improve health systems worldwide, emerging pathogen epidemics remain a major public health concern. Effective response to such outbreaks relies on timely intervention, ideally informed by all available sources of data. The collection, visualization and analysis of outbreak data are becoming increasingly complex, owing to the diversity in types of data, questions and available methods to address them. Recent advances have led to the rise of outbreak analytics, an emerging data science focused on the technological and methodological aspects of the outbreak data pipeline, from collection to analysis, modelling and reporting to inform outbreak response. In this article, we assess the current state of the field. After laying out the context of outbreak response, we critically review the most common analytics components, their inter-dependencies, data requirements and the type of information they can provide to inform operations in real time. We discuss some challenges and opportunities and conclude on the potential role of outbreak analytics for improving our understanding of, and response to outbreaks of emerging pathogens. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'. This theme issue is linked with the earlier issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'.",,pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.2018.0276; doi:https://doi.org/10.1098/rstb.2018.0276; html:https://europepmc.org/articles/PMC6558557; pdf:https://europepmc.org/articles/PMC6558557?pdf=render
 31685485,https://doi.org/10.1136/bmjopen-2019-031365,"Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case-control comparison.","Demmler JC, Atkinson MD, Reinhold EJ, Choy E, Lyons RA, Brophy ST.",,BMJ open,2019,2019-11-04,Y,Prevalence; Joint Hypermobility Syndrome; Ehlers-danlos Syndromes; Heritable Disorders Of Connective Tissue; Hypermobility Spectrum Disorder; Health Data Linkage,Improving Public Health,,"<h4>Objectives</h4>To describe the epidemiology of diagnosed hypermobility spectrum disorder (HSD) and Ehlers-Danlos syndromes (EDS) using linked electronic medical records. To examine whether these conditions remain rare and primarily affect the musculoskeletal system.<h4>Design</h4>Nationwide linked electronic cohort and nested case-control study.<h4>Setting</h4>Routinely collected data from primary care and hospital admissions in Wales, UK.<h4>Participants</h4>People within the primary care or hospital data systems with a coded diagnosis of EDS or joint hypermobility syndrome (JHS) between 1 July 1990 and 30 June 2017.<h4>Main outcome measures</h4>Combined prevalence of JHS and EDS in Wales. Additional diagnosis and prescription data in those diagnosed with EDS or JHS compared with matched controls.<h4>Results</h4>We found 6021 individuals (men: 30%, women: 70%) with a diagnostic code of either EDS or JHS. This gives a diagnosed point prevalence of 194.2 per 100 000 in 2016/2017 or roughly 10 cases in a practice of 5000 patients. There was a pronounced gender difference of 8.5 years (95% CI: 7.70 to 9.22) in the mean age at diagnosis. EDS or JHS was not only associated with high odds for other musculoskeletal diagnoses and drug prescriptions but also with significantly higher odds of a diagnosis in other disease categories (eg, mental health, nervous and digestive systems) and higher odds of a prescription in most disease categories (eg, gastrointestinal and cardiovascular drugs) within the 12 months before and after the first recorded diagnosis.<h4>Conclusions</h4>EDS and JHS (since March 2017 classified as EDS or HSD) have historically been considered rare diseases only affecting the musculoskeletal system and soft tissues. These data demonstrate that both these assertions should be reconsidered.","epidemiological study looking at the prevalence of ehlos danlos syndrome and joint hypermobility syndrome, using SAIL database for welsh population. They found a steady increase in the rates of diagnosis for these two diseases, higher odds of being on other medication, and association with other diseases categories.",pdf:https://bmjopen.bmj.com/content/bmjopen/9/11/e031365.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-031365; html:https://europepmc.org/articles/PMC6858200; pdf:https://europepmc.org/articles/PMC6858200?pdf=render
+36936265,https://doi.org/10.1136/bmjmed-2022-000276,"Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY.","Green ACA, Curtis HJ, Higgins R, Nab L, Mahalingasivam V, Smith RM, Mehrkar A, Inglesby P, Drysdale H, DeVito NJ, Croker R, Rentsch CT, Bhaskaran K, Tazare J, Zheng B, Andrews CD, Bacon SCJ, Davy S, Dillingham I, Evans D, Fisher L, Hickman G, Hopcroft LEM, Hulme WJ, Massey J, MacDonald O, Morley J, Morton CE, Park RY, Walker AJ, Ward T, Wiedemann M, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Goldacre B, Tomlinson LA, MacKenna B.",,BMJ medicine,2023,2023-01-13,Y,Therapeutics; Community health services; Public Health; Covid-19,,,"<h4>Objective</h4>To ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.<h4>Design</h4>Retrospective, descriptive cohort study, approved by NHS England.<h4>Setting</h4>Routine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.<h4>Participants</h4>Outpatients with covid-19 at high risk of severe outcomes.<h4>Interventions</h4>Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.<h4>Results</h4>93 870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19 040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95% confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from ≥80 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%).<h4>Conclusions</h4>Using the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged ≥80 years, those living in socioeconomically deprived areas, and care home residents.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render
 36276403,https://doi.org/10.3389/fpubh.2022.875198,The mental health experiences of ethnic minorities in the UK during the Coronavirus pandemic: A qualitative exploration.,"Van Bortel T, Lombardo C, Guo L, Solomon S, Martin S, Hughes K, Weeks L, Crepaz-Keay D, McDaid S, Chantler O, Thorpe L, Morton A, Davidson G, John A, Kousoulis AA.",,Frontiers in public health,2022,2022-10-06,Y,Mental health; United Kingdom; Inequalities; Ethnic Minorities; Covid-19; Coronavirus Pandemic; Bame Ethnicity,,,"<h4>Background</h4>Worldwide, the Coronavirus pandemic has had a major impact on people's health, lives, and livelihoods. However, this impact has not been felt equally across various population groups. People from ethnic minority backgrounds in the UK have been more adversely affected by the pandemic, especially in terms of their physical health. Their mental health, on the other hand, has received less attention. This study aimed to explore the mental health experiences of UK adults from ethnic minorities during the Coronavirus pandemic. This work forms part of our wider long-term UK population study ""Mental Health in the Pandemic.""<h4>Methods</h4>We conducted an exploratory qualitative study with people from ethnic minority communities across the UK. A series of in-depth interviews were conducted with 15 women, 14 men and 1 non-binary person from ethnic minority backgrounds, aged between 18 and 65 years old (mean age = 40). We utilized purposefully selected maximum variation sampling in order to capture as wide a variety of views, perceptions and experiences as possible. Inclusion criteria: adults (18+) from ethnic minorities across the UK; able to provide full consent to participate; able to participate in a video- or phone-call interview. All interviews took place <i>via</i> MS Teams or Zoom. The gathered data were transcribed verbatim and underwent thematic analysis following Braun and Clarke carried out using NVivo 12 software.<h4>Results</h4>The qualitative data analysis yielded seven overarching themes: (1) pandemic-specific mental health and wellbeing experiences; (2) issues relating to the media; (3) coping mechanisms; (4) worries around and attitudes toward vaccination; (5) suggestions for support in moving forward; (6) best and worst experiences during pandemic and lockdowns; (7) biggest areas of change in personal life. Generally, participants' mental health experiences varied with some not being affected by the pandemic in a way related to their ethnicity, some sharing positive experiences and coping strategies (exercising more, spending more time with family, community cohesion), and some expressing negative experiences (eating or drinking more, feeling more isolated, or even racism and abuse, especially toward Asian communities). Concerns were raised around trust issues in relation to the media, the inadequate representation of ethnic minorities, and the spread of fake news especially on social media. Attitudes toward vaccinations varied too, with some people more willing to have the vaccine than others.<h4>Conclusion</h4>This study's findings highlight the diversity in the pandemic mental health experiences of ethnic minorities in the UK and has implications for policy, practice and further research. To enable moving forward beyond the pandemic, our study surfaced the need for culturally appropriate mental health support, financial support (as a key mental health determinant), accurate media representation, and clear communication messaging from the Governments of the UK.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.875198/pdf; doi:https://doi.org/10.3389/fpubh.2022.875198; html:https://europepmc.org/articles/PMC9582845; pdf:https://europepmc.org/articles/PMC9582845?pdf=render
 37740900,https://doi.org/10.1093/ageing/afad176,Interventions for reducing anticholinergic medication burden in older adults-a systematic review and meta-analysis.,"Braithwaite E, Todd OM, Atkin A, Hulatt R, Tadrous R, Alldred DP, Pirmohamed M, Walker L, Lawton R, Clegg A.",,Age and ageing,2023,2023-09-01,Y,Cognition; Meta-analysis; Systematic review; Falls; Older People; Older Adult; Anticholinergic Medication,,,"<h4>Introduction</h4>Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls.<h4>Methods</h4>We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults.<h4>Results</h4>We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n = 647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n = 405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n = 710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n = 461).<h4>Discussion</h4>Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.",,pdf:https://academic.oup.com/ageing/article-pdf/52/9/afad176/51729004/afad176.pdf; doi:https://doi.org/10.1093/ageing/afad176; html:https://europepmc.org/articles/PMC10517713; pdf:https://europepmc.org/articles/PMC10517713?pdf=render
 33516523,https://doi.org/10.1016/j.jaci.2020.12.001,"Atopic eczema in adulthood and mortality: UK population-based cohort study, 1998-2016.","Silverwood RJ, Mansfield KE, Mulick A, Wong AYS, Schmidt SAJ, Roberts A, Smeeth L, Abuabara K, Langan SM.",,The Journal of allergy and clinical immunology,2021,2021-01-27,Y,Activity; Mortality; Cohort study; United Kingdom; Primary Care; Atopic Eczema; Severity; Population-based; Electronic Health Care Records,,,"<h4>Background</h4>Atopic eczema affects up to 10% of adults and is becoming more common globally. Few studies have assessed whether atopic eczema increases the risk of death.<h4>Objective</h4>We aimed to determine whether adults with atopic eczema were at increased risk of death overall and by specific causes and to assess whether the risk varied by atopic eczema severity and activity.<h4>Methods</h4>The study was a population-based matched cohort study using UK primary care electronic health care records from the Clinical Practice Research Datalink with linked hospitalization data from Hospital Episode Statistics and mortality data from the Office for National Statistics from 1998 to 2016.<h4>Results</h4>A total of 526,736 patients with atopic eczema were matched to 2,567,872 individuals without atopic eczema. The median age at entry was 41.8 years, and the median follow-up time was 4.5 years. There was limited evidence of increased hazard for all-cause mortality in those with atopic eczema (hazard ratio = 1.04; 99% CI = 1.03-1.06), but there were somewhat stronger associations (8%-14% increased hazard) for deaths due to infectious, digestive, and genitourinary causes. Differences on the absolute scale were modest owing to low overall mortality rates. Mortality risk increased markedly with eczema severity and activity. For example, patients with severe atopic eczema had a 62% increased hazard (hazard ratio = 1.62; 99% CI = 1.54-1.71) for mortality compared with those without eczema, with the strongest associations for infectious, respiratory, and genitourinary causes.<h4>Conclusion</h4>The increased hazards for all-cause and cause-specific mortality were largely restricted to those with the most severe or predominantly active atopic eczema. Understanding the reasons for these increased hazards for mortality is an urgent priority.",,pdf:http://www.jacionline.org/article/S0091674920317127/pdf; doi:https://doi.org/10.1016/j.jaci.2020.12.001; html:https://europepmc.org/articles/PMC8098860; pdf:https://europepmc.org/articles/PMC8098860?pdf=render
@@ -887,12 +887,12 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 37606853,https://doi.org/10.1007/s00520-023-07944-8,"The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.","Han J, Rolles M, Torabi F, Griffiths R, Bedston S, Akbari A, Burnett B, Lyons J, Greene G, Thomas R, Long T, Arnold C, Huws DW, Lawler M, Lyons RA.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-08-22,Y,Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic,,,"<h4>Purpose</h4>Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care.<h4>Methods</h4>A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds.<h4>Results</h4>We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision.<h4>Conclusions</h4>We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf; doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render
 32864476,https://doi.org/10.23889/ijpds.v5i1.1157,"Prevalence of Down's Syndrome in England, 1998-2013: Comparison of linked surveillance data and electronic health records.","Doidge JC, Morris JK, Harron KL, Stevens S, Gilbert R.",,International journal of population data science,2020,2020-01-01,Y,Prevalence; Data Linkage; Disease Surveillance; Down’s Syndrome; Electronic Health Records; Linkage Error,,,"<h4>Introduction</h4>Disease registers and electronic health records are valuable resources for disease surveillance and research but can be limited by variation in data quality over time. Quality may be limited in terms of the accuracy of clinical information, of the internal linkage that supports person-based analysis of most administrative datasets, or by errors in linkage between multiple datasets.<h4>Objectives</h4>By linking the National Down Syndrome Cytogenetic Register (NDSCR) to Hospital Episode Statistics for England (HES), we aimed to assess the quality of each and establish a consistent approach for analysis of trends in prevalence of Down's syndrome among live births in England.<h4>Methods</h4>Probabilistic record linkage of NDSCR to HES for the period 1998-2013 was supported by linkage of babies to mothers within HES. Comparison of prevalence estimates in England were made using NDSCR only, HES data only, and linked data. Capture-recapture analysis and quantitative bias analysis were used to account for potential errors, including false positive diagnostic codes, unrecorded diagnoses, and linkage error.<h4>Results</h4>Analyses of single-source data indicated increasing live birth prevalence of Down's Syndrome, particularly in the analysis of HES. Linked data indicated a contrastingly stable prevalence of 12.3 (plausible range: 11.6-12.7) cases per 10 000 live births.<h4>Conclusion</h4>Case ascertainment in NDSCR improved slightly over time, creating a picture of slowly increasing prevalence. The emerging epidemic suggested by HES primarily reflects improving linkage within HES (assignment of unique patient identifiers to hospital episodes). Administrative data are valuable but trends should be interpreted with caution, and with assessment of data quality over time. Data linkage with quantitative bias analysis can provide more robust estimation and, in this case, stronger evidence that prevalence is not increasing. Routine linkage of administrative and register data can enhance the value of each.",,pdf:https://ijpds.org/article/download/1157/2531; doi:https://doi.org/10.23889/ijpds.v5i1.1157; html:https://europepmc.org/articles/PMC7115985; pdf:https://europepmc.org/articles/PMC7115985?pdf=render
 31628383,https://doi.org/10.1038/s41598-019-51562-6,Whole genome sequencing of drug resistant Mycobacterium tuberculosis isolates from a high burden tuberculosis region of North West Pakistan.,"Jabbar A, Phelan JE, de Sessions PF, Khan TA, Rahman H, Khan SN, Cantillon DM, Wildner LM, Ali S, Campino S, Waddell SJ, Clark TG.",,Scientific reports,2019,2019-10-18,Y,,,,"Tuberculosis (TB), caused by Mycobacterium tuberculosis bacteria, is a leading infectious cause of mortality worldwide, including in Pakistan. Drug resistant M. tuberculosis is an emerging threat for TB control, making it important to detect the underlying genetic mutations, and thereby inform treatment decision making and prevent transmission. Whole genome sequencing has emerged as the new diagnostic to reliably predict drug resistance within a clinically relevant time frame, and its deployment will have the greatest impact on TB control in highly endemic regions. To evaluate the mutations leading to drug resistance and to assess for evidence of the transmission of resistant strains, 81 M. tuberculosis samples from Khyber Pakhtunkhwa province (North West Pakistan) were subjected to whole genome sequencing and standard drug susceptibility testing for eleven anti-TB drugs. We found the majority of M. tuberculosis isolates were the CAS/Delhi strain-type (lineage 3; n = 57; 70.4%) and multi-drug resistant (MDR; n = 62; 76.5%). The most frequent resistance mutations were observed in the katG and rpoB genes, conferring resistance to isoniazid and rifampicin respectively. Mutations were also observed in genes conferring resistance to other first and second-line drugs, including in pncA (pyrazinamide), embB (ethambutol), gyrA (fluoroquinolones), rrs (aminoglycosides), rpsL, rrs and giB (streptomycin) loci. Whilst the majority of mutations have been reported in global datasets, we describe unreported putative resistance markers in katG, ethA (ethionamide), gyrA and gyrB (fluoroquinolones), and pncA. Analysis of the mutations revealed that acquisition of rifampicin resistance often preceded isoniazid in our isolates. We also observed a high proportion (17.6%) of pre-MDR isolates with fluoroquinolone resistance markers, potentially due to unregulated anti-TB drug use. Our isolates were compared to previously sequenced strains from Pakistan in a combined phylogenetic tree analysis. The presence of lineage 2 was only observed in our isolates. Using a cut-off of less than ten genome-wide mutation differences between isolates, a transmission analysis revealed 18 M. tuberculosis isolates clustering within eight networks, thereby providing evidence of drug-resistant TB transmission in the Khyber Pakhtunkhwa province. Overall, we have demonstrated that drug-resistant TB isolates are circulating and transmitted in North West Pakistan. Further, we have shown the usefulness of whole genome sequencing as a diagnostic tool for characterizing M. tuberculosis isolates, which will assist future epidemiological studies and disease control activities in Pakistan.",,pdf:https://www.nature.com/articles/s41598-019-51562-6.pdf; doi:https://doi.org/10.1038/s41598-019-51562-6; html:https://europepmc.org/articles/PMC6802378; pdf:https://europepmc.org/articles/PMC6802378?pdf=render
-35698725,https://doi.org/10.1016/s2665-9913(22)00098-4,Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.,"MacKenna B, Kennedy NA, Mehrkar A, Rowan A, Galloway J, Matthewman J, Mansfield KE, Bechman K, Yates M, Brown J, Schultze A, Norton S, Walker AJ, Morton CE, Harrison D, Bhaskaran K, Rentsch CT, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Davy S, Green A, Fisher L, Hulme W, Bates C, Curtis HJ, Tazare J, Eggo RM, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson LA, Mathur R, Wong AYS, Forbes H, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Lees CW, Evans SJW, Goldacre B, Smith CH, Langan SM.",,The Lancet. Rheumatology,2022,2022-06-09,Y,,,,"<h4>Background</h4>The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies.<h4>Methods</h4>We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate).<h4>Findings</h4>We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL‑23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·<b>54, 0</b>·<b>95</b>-<b>2</b>·<b>49</b>).<h4>Interpretation</h4>COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy.<h4>Funding</h4>UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2665991322000984/pdf; doi:https://doi.org/10.1016/S2665-9913(22)00098-4; html:https://europepmc.org/articles/PMC9179144; pdf:https://europepmc.org/articles/PMC9179144?pdf=render
-34286192,https://doi.org/10.7861/fhj.2021-0083,Making trials part of good clinical care: lessons from the RECOVERY trial.,"Pessoa-Amorim G, Campbell M, Fletcher L, Horby P, Landray M, Mafham M, Haynes R.",,Future healthcare journal,2021,2021-07-01,N,Recovery; RANDOMISED CONTROLLED TRIALS; evidence-based medicine; Quality-by-design; Covid-19,,,"When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.",,pdf:https://www.rcpjournals.org/content/futurehosp/8/2/e243.full.pdf; doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083
 31951005,https://doi.org/10.1093/jamia/ocz211,On classifying sepsis heterogeneity in the ICU: insight using machine learning.,"Ibrahim ZM, Wu H, Hamoud A, Stappen L, Dobson RJB, Agarossi A.",,Journal of the American Medical Informatics Association : JAMIA,2020,2020-03-01,Y,Sepsis; Machine Learning; Artificial Intelligence In Medicine; Sepsis Prediction; Sepsis Subtypes,Applied Analytics,,"<h4>Objectives</h4>Current machine learning models aiming to predict sepsis from electronic health records (EHR) do not account 20 for the heterogeneity of the condition despite its emerging importance in prognosis and treatment. This work demonstrates the added value of stratifying the types of organ dysfunction observed in patients who develop sepsis in the intensive care unit (ICU) in improving the ability to recognize patients at risk of sepsis from their EHR data.<h4>Materials and methods</h4>Using an ICU dataset of 13 728 records, we identify clinically significant sepsis subpopulations with distinct organ dysfunction patterns. We perform classification experiments with random forest, gradient boost trees, and support vector machines, using the identified subpopulations to distinguish patients who develop sepsis in the ICU from those who do not.<h4>Results</h4>The classification results show that features selected using sepsis subpopulations as background knowledge yield a superior performance in distinguishing septic from non-septic patients regardless of the classification model used. The improved performance is especially pronounced in specificity, which is a current bottleneck in sepsis prediction machine learning models.<h4>Conclusion</h4>Our findings can steer machine learning efforts toward more personalized models for complex conditions including sepsis.",Ibrahim et al. categorized patients in groups based on the type of organ failure. This categorization helped machine based algorithms to correctly identify those at high risk of sepsis.,pdf:https://academic.oup.com/jamia/article-pdf/27/3/437/34153319/ocz211.pdf; doi:https://doi.org/10.1093/jamia/ocz211; html:https://europepmc.org/articles/PMC7025363; pdf:https://europepmc.org/articles/PMC7025363?pdf=render
+34286192,https://doi.org/10.7861/fhj.2021-0083,Making trials part of good clinical care: lessons from the RECOVERY trial.,"Pessoa-Amorim G, Campbell M, Fletcher L, Horby P, Landray M, Mafham M, Haynes R.",,Future healthcare journal,2021,2021-07-01,N,Recovery; RANDOMISED CONTROLLED TRIALS; evidence-based medicine; Quality-by-design; Covid-19,,,"When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.",,pdf:https://www.rcpjournals.org/content/futurehosp/8/2/e243.full.pdf; doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083
+35698725,https://doi.org/10.1016/s2665-9913(22)00098-4,Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.,"MacKenna B, Kennedy NA, Mehrkar A, Rowan A, Galloway J, Matthewman J, Mansfield KE, Bechman K, Yates M, Brown J, Schultze A, Norton S, Walker AJ, Morton CE, Harrison D, Bhaskaran K, Rentsch CT, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Davy S, Green A, Fisher L, Hulme W, Bates C, Curtis HJ, Tazare J, Eggo RM, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson LA, Mathur R, Wong AYS, Forbes H, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Lees CW, Evans SJW, Goldacre B, Smith CH, Langan SM.",,The Lancet. Rheumatology,2022,2022-06-09,Y,,,,"<h4>Background</h4>The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies.<h4>Methods</h4>We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate).<h4>Findings</h4>We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL‑23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·<b>54, 0</b>·<b>95</b>-<b>2</b>·<b>49</b>).<h4>Interpretation</h4>COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy.<h4>Funding</h4>UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2665991322000984/pdf; doi:https://doi.org/10.1016/S2665-9913(22)00098-4; html:https://europepmc.org/articles/PMC9179144; pdf:https://europepmc.org/articles/PMC9179144?pdf=render
 31765395,https://doi.org/10.1371/journal.pone.0225625,Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data.,"Bean DM, Teo J, Wu H, Oliveira R, Patel R, Bendayan R, Shah AM, Dobson RJB, Scott PA.",,PloS one,2019,2019-11-25,Y,,,,"Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 ± 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc ≥2) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.","Bean et al. looked at using clinical notes to calculate risk scores: CHADSVASC and HASBLED for 10,030 AF patients from 2011 to October 2017), they’ve validated their natural language processing algorithm with getting clinicians to calculate the risk in conventional manner for 40 of cases, the two scores were in higher agreement for stroke risk compared to HAS-BLED They’ve concluded on usefulness of NLP method in risk calculation at the large scale.",pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225625&type=printable; doi:https://doi.org/10.1371/journal.pone.0225625; html:https://europepmc.org/articles/PMC6876873; pdf:https://europepmc.org/articles/PMC6876873?pdf=render
-34399584,https://doi.org/10.1161/strokeaha.120.032619,Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases.,"Abraham G, Rutten-Jacobs L, Inouye M.",,Stroke,2021,2021-08-17,N,Genetics; Myocardial infarction; Cardiovascular disease; Stroke; risk assessment,,,"Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.032619; doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619
 33890864,https://doi.org/10.2196/24728,The Value of Routinely Collected Data in Evaluating Home Assessment and Modification Interventions to Prevent Falls in Older People: Systematic Literature Review. ,"Daniels H, Hollinghurst J, Fry R, Clegg A, Hillcoat-Nallétamby S, Nikolova S, Rodgers SE, Williams N, Akbari A.",,JMIR aging,2021,2021-04-23,Y,,,,"Falls in older people commonly occur at home. Home assessment and modification (HAM) interventions can be effective in reducing falls; however, there are some concerns over the validity of evaluation findings. Routinely collected data could improve the quality of HAM evaluations and strengthen their evidence base. The aim of this study is to conduct a systematic review of the evidence of the use of routinely collected data in the evaluations of HAM interventions. We searched the following databases from inception until January 31, 2020: PubMed, Ovid, CINAHL, OpenGrey, CENTRAL, LILACS, and Web of Knowledge. Eligible studies were those evaluating HAMs designed to reduce falls involving participants aged 60 years or more. We included study protocols and full reports. Bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. A total of 7 eligible studies were identified in 8 papers. Government organizations provided the majority of data across studies, with health care providers and third-sector organizations also providing data. Studies used a range of demographic, clinical and health, and administrative data. The purpose of using routinely collected data spanned recruiting and creating a sample, stratification, generating independent variables or covariates, and measuring key study-related outcomes. Nonhome-based modification interventions (eg, in nursing homes) using routinely collected data were not included in this study. We included two protocols, which meant that the results of those studies were not available. MeSH headings were excluded from the PubMed search because of a reduction in specificity. This means that some studies that met the inclusion criteria may not have been identified. Routine data can be used successfully in many aspects of HAM evaluations and can reduce biases and improve other important design considerations. However, the use of these data in these studies is currently not widespread. There are a number of governance barriers to be overcome to allow these types of linkage and to ensure that the use of routinely collected data in evaluations of HAM interventions is exploited to its full potential.",,pdf:https://aging.jmir.org/2021/2/e24728/PDF; doi:https://doi.org/10.2196/24728; html:https://europepmc.org/articles/PMC8105762; pdf:https://europepmc.org/articles/PMC8105762?pdf=render
+34399584,https://doi.org/10.1161/strokeaha.120.032619,Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases.,"Abraham G, Rutten-Jacobs L, Inouye M.",,Stroke,2021,2021-08-17,N,Genetics; Myocardial infarction; Cardiovascular disease; Stroke; risk assessment,,,"Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.032619; doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619
 34169636,https://doi.org/10.1002/pst.2148,Assessing safety at the end of clinical trials using system organ classes: A case and comparative study.,"Carragher R, Robertson C.",,Pharmaceutical statistics,2021,2021-06-24,N,Safety; False Discovery Rate; Adverse Events; System Organ Class; Bayesian Hierarchy,,,"Recent approaches to the statistical analysis of adverse event (AE) data in clinical trials have proposed the use of groupings of related AEs, such as by system organ class (SOC). These methods have opened up the possibility of scanning large numbers of AEs while controlling for multiple comparisons, making the comparative performance of the different methods in terms of AE detection and error rates of interest to investigators. We apply two Bayesian models and two procedures for controlling the false discovery rate (FDR), which use groupings of AEs, to real clinical trial safety data. We find that while the Bayesian models are appropriate for the full data set, the error controlling methods only give similar results to the Bayesian methods when low incidence AEs are removed. A simulation study is used to compare the relative performances of the methods. We investigate the differences between the methods over full trial data sets, and over data sets with low incidence AEs and SOCs removed. We find that while the removal of low incidence AEs increases the power of the error controlling procedures, the estimated power of the Bayesian methods remains relatively constant over all data sizes. Automatic removal of low-incidence AEs however does have an effect on the error rates of all the methods, and a clinically guided approach to their removal is needed. Overall we found that the Bayesian approaches are particularly useful for scanning the large amounts of AE data gathered.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pst.2148; doi:https://doi.org/10.1002/pst.2148
 37309807,https://doi.org/10.1093/ehjci/jead123,Characterizing the hypertensive cardiovascular phenotype in the UK Biobank.,"Elghazaly H, McCracken C, Szabo L, Malcolmson J, Manisty CH, Davies AH, Piechnik SK, Harvey NC, Neubauer S, Mohiddin SA, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2023,2023-09-01,Y,Ethnicity; Cardiovascular Magnetic Resonance; Population Health; Women’s Health; Antihypertensive Therapies,,,"<h4>Aims</h4>To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations.<h4>Methods and results</h4>We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control.<h4>Conclusion</h4>Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead123/50578622/jead123.pdf; doi:https://doi.org/10.1093/ehjci/jead123; html:https://europepmc.org/articles/PMC10531143; pdf:https://europepmc.org/articles/PMC10531143?pdf=render
 32444447,https://doi.org/10.1136/archdischild-2019-317902,Emergency paediatric critical care in England: describing trends using routine hospital data.,"Lewis KM, Parekh SM, Ramnarayan P, Gilbert R, Hardelid P, Wijlaars L.",,Archives of disease in childhood,2020,2020-05-22,Y,epidemiology; Intensive Care,,,"<h4>Objective</h4>To determine trends in emergency admission rates requiring different levels of critical care in hospitals with and without a paediatric intensive care unit (PICU).<h4>Design</h4>Birth cohort study created from Hospital Episode Statistics.<h4>Setting</h4>National Health Service funded hospitals in England.<h4>Patients</h4>8 577 680 singleton children born between 1 May 2003 and 31 April 2017.<h4>Outcome measures</h4>Using procedure and diagnostic codes, we assigned indicators of high dependency care (eg, non-invasive ventilation) or intensive care (eg, invasive ventilation) to emergency admissions.<h4>Interventions</h4>Children were followed up until their fifth birthday to estimate high dependency and intensive care admission rates in hospitals with and without a PICU. We tested the yearly trend of high dependency and intensive care admissions to hospitals without a PICU using logistic regression models.<h4>Results</h4>Emergency admissions requiring high dependency care in hospitals without a PICU increased from 3.30 (95% CI 3.09 to 3.51) per 10 000 child-years in 2008/2009 to 7.58 (95% CI 7.28 to 7.89) in 2016/2017 and overtook hospitals with a PICU in 2015/2016. The odds of an admission requiring high dependency care to a hospital without a PICU compared with a hospital with a PICU increased by 9% per study year (OR 1.09, 95% CI 1.08 to 1.10). The same trend was not present for admissions requiring intensive care (OR 1.01, 95% CI 0.99 to 1.03).<h4>Conclusions</h4>Between 2008/2009 and 2016/2017, an increasing proportion of admissions with indicators of high dependency care took place in hospitals without a PICU.",,pdf:https://adc.bmj.com/content/archdischild/105/11/1061.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317902; html:https://europepmc.org/articles/PMC7588403; pdf:https://europepmc.org/articles/PMC7588403?pdf=render
@@ -903,11 +903,11 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 32462176,https://doi.org/10.1093/ehjci/jeaa088,A head-to-head comparison of speckle tracking echocardiography and feature tracking cardiovascular magnetic resonance imaging in right ventricular deformation.,"Taha K, Bourfiss M, Te Riele ASJM, Cramer MM, van der Heijden JF, Asselbergs FW, Velthuis BK, Teske AJ.",,European heart journal. Cardiovascular Imaging,2021,2021-07-01,Y,Right Ventricle; Strain Imaging; Speckle Tracking; Arvc; Feature Tracking; Deformation Imaging,,,"<h4>Aims</h4>Speckle tracking echocardiography (STE) and feature tracking cardiovascular magnetic resonance imaging (FT-CMR) are advanced imaging techniques which are both used for quantification of global and regional myocardial strain. Direct comparisons of STE and FT-CMR regarding right ventricular (RV) strain analysis are limited. We aimed to study clinical performance, correlation and agreement of RV strain by these techniques, using arrhythmogenic right ventricular cardiomyopathy (ARVC) as a model for RV disease.<h4>Methods and results</h4>We enrolled 110 subjects, including 34 patients with definite ARVC, 30 preclinical relatives of ARVC patients, and 46 healthy control subjects. Global and regional RV longitudinal peak strain (PS) were measured by STE and FT-CMR. Both modalities showed reduced strain values in ARVC patients compared to ARVC relatives (STE global PS: P < 0.001; FT-CMR global PS: P < 0.001) and reduced strain values in ARVC relatives compared to healthy control subjects (STE global PS: P = 0.042; FT-CMR global PS: P = 0.084). There was a moderate, albeit significant correlation between RV strain values obtained by STE and FT-CMR [global PS r = 0.578 (95% confidence interval 0.427-0.697), P < 0.001]. Agreement between the techniques was weak (limits of agreement for global PS: ±11.8%). Correlation and agreement both deteriorated when regional strain was studied.<h4>Conclusion</h4>RV STE and FT-CMR show a similar trend within the spectrum of ARVC and have significant correlation, but inter-modality agreement is weak. STE and FT-CMR may therefore both individually have added value for assessment of RV function, but RV PS values obtained by these techniques currently cannot be used interchangeably in clinical practice.",,pdf:https://academic.oup.com/ehjcimaging/article-pdf/22/8/950/39199744/jeaa088.pdf; doi:https://doi.org/10.1093/ehjci/jeaa088; html:https://europepmc.org/articles/PMC8291671; pdf:https://europepmc.org/articles/PMC8291671?pdf=render
 33414147,https://doi.org/10.1136/bmjopen-2020-041536,Estimating the COVID-19 epidemic trajectory and hospital capacity requirements in South West England: a mathematical modelling framework.,"Booton RD, MacGregor L, Vass L, Looker KJ, Hyams C, Bright PD, Harding I, Lazarus R, Hamilton F, Lawson D, Danon L, Pratt A, Wood R, Brooks-Pollock E, Turner KME.",,BMJ open,2021,2021-01-07,Y,Infection control; epidemiology; Public Health,,,"<h4>Objectives</h4>To develop a regional model of COVID-19 dynamics for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West England (SW) as an example case.<h4>Design</h4>Open-source age-structured variant of a susceptible-exposed-infectious-recovered compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths.<h4>Setting</h4>SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.<h4>Participants</h4>Publicly available data on patients with COVID-19.<h4>Primary and secondary outcome measures</h4>The expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction ('R') number over time.<h4>Results</h4>SW model projections indicate that, as of 11 May 2020 (when 'lockdown' measures were eased), 5793 (95% credible interval (CrI) 2003 to 12 051) individuals were still infectious (0.10% of the total SW population, 95% CrI 0.04% to 0.22%), and a total of 189 048 (95% CrI 141 580 to 277 955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95% CrI 2.5% to 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on 11 May 2020 was predicted to be 701 (95% CrI 169 to 1543) and 110 (95% CrI 8 to 464), respectively. The R value in SW was predicted to be 2.6 (95% CrI 2.0 to 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95% CrI 1.8 to 2.9) and lockdown/school closures further reducing the R value to 0.6 (95% CrI 0.5 to 0.7).<h4>Conclusions</h4>The developed model has proved a valuable asset for regional healthcare services. The model will be used further in the SW as the pandemic evolves, and-as open-source software-is portable to healthcare systems in other geographies.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render
 33249608,https://doi.org/10.1111/opo.12765,Authors' Reply.,"Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.",,Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists),2021,2020-11-29,N,,,,,,doi:https://doi.org/10.1111/opo.12765
-35921096,https://doi.org/10.1001/jamacardio.2022.2333,Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.,"Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.",,JAMA cardiology,2022,2022-09-01,N,,,,"<h4>Importance</h4>Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.<h4>Objective</h4>To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.<h4>Design, setting, and participants</h4>Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.<h4>Exposures</h4>Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.<h4>Main outcomes and measures</h4>Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.<h4>Results</h4>Data for 425 354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229 399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P = .34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P = .83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).<h4>Conclusions and relevance</h4>Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.",,doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333
 31416346,https://doi.org/10.1161/circulationaha.119.041980,Machine Learning to Predict the Likelihood of Acute Myocardial Infarction.,"Than MP, Pickering JW, Sandoval Y, Shah ASV, Tsanas A, Apple FS, Blankenberg S, Cullen L, Mueller C, Neumann JT, Twerenbold R, Westermann D, Beshiri A, Mills NL, MI3 Collaborative.",,Circulation,2019,2019-08-16,Y,Troponin; Myocardial infarction; acute coronary syndrome; Machine Learning,Applied Analytics,,"<h4>Background</h4>Variations in cardiac troponin concentrations by age, sex, and time between samples in patients with suspected myocardial infarction are not currently accounted for in diagnostic approaches. We aimed to combine these variables through machine learning to improve the assessment of risk for individual patients.<h4>Methods</h4>A machine learning algorithm (myocardial-ischemic-injury-index [MI<sup>3</sup>]) incorporating age, sex, and paired high-sensitivity cardiac troponin I concentrations, was trained on 3013 patients and tested on 7998 patients with suspected myocardial infarction. MI<sup>3</sup> uses gradient boosting to compute a value (0-100) reflecting an individual's likelihood of a diagnosis of type 1 myocardial infarction and estimates the sensitivity, negative predictive value, specificity and positive predictive value for that individual. Assessment was by calibration and area under the receiver operating characteristic curve. Secondary analysis evaluated example MI<sup>3</sup> thresholds from the training set that identified patients as low risk (99% sensitivity) and high risk (75% positive predictive value), and performance at these thresholds was compared in the test set to the 99th percentile and European Society of Cardiology rule-out pathways.<h4>Results</h4>Myocardial infarction occurred in 404 (13.4%) patients in the training set and 849 (10.6%) patients in the test set. MI<sup>3</sup> was well calibrated with a very high area under the receiver operating characteristic curve of 0.963 [0.956-0.971] in the test set and similar performance in early and late presenters. Example MI<sup>3</sup> thresholds identifying low- and high-risk patients in the training set were 1.6 and 49.7, respectively. In the test set, MI<sup>3</sup> values were <1.6 in 69.5% with a negative predictive value of 99.7% (99.5-99.8%) and sensitivity of 97.8% (96.7-98.7%), and were ≥49.7 in 10.6% with a positive predictive value of 71.8% (68.9-75.0%) and specificity of 96.7% (96.3-97.1%). Using these thresholds, MI<sup>3</sup> performed better than the European Society of Cardiology 0/3-hour pathway (sensitivity, 82.5% [74.5-88.8%]; specificity, 92.2% [90.7-93.5%]) and the 99th percentile at any time point (sensitivity, 89.6% [87.4-91.6%]); specificity, 89.3% [88.6-90.0%]).<h4>Conclusions</h4>Using machine learning, MI<sup>3</sup> provides an individualized and objective assessment of the likelihood of myocardial infarction, which can be used to identify low- and high-risk patients who may benefit from earlier clinical decisions.<h4>Clinical trial registration</h4>URL: https://www.anzctr.org.au. Unique identifier: ACTRN12616001441404.",,doi:https://doi.org/10.1161/circulationaha.119.041980; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041980; html:https://europepmc.org/articles/PMC6749969; pdf:https://europepmc.org/articles/PMC6749969?pdf=render
+35921096,https://doi.org/10.1001/jamacardio.2022.2333,Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.,"Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.",,JAMA cardiology,2022,2022-09-01,N,,,,"<h4>Importance</h4>Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.<h4>Objective</h4>To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.<h4>Design, setting, and participants</h4>Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.<h4>Exposures</h4>Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.<h4>Main outcomes and measures</h4>Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.<h4>Results</h4>Data for 425 354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229 399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P = .34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P = .83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).<h4>Conclusions and relevance</h4>Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.",,doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333
 33704068,https://doi.org/10.7554/elife.64827,Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death.,"Gisby J, Clarke CL, Medjeral-Thomas N, Malik TH, Papadaki A, Mortimer PM, Buang NB, Lewis S, Pereira M, Toulza F, Fagnano E, Mawhin MA, Dutton EE, Tapeng L, Richard AC, Kirk PD, Behmoaras J, Sandhu E, McAdoo SP, Prendecki MF, Pickering MC, Botto M, Willicombe M, Thomas DC, Peters JE.",,eLife,2021,2021-03-11,Y,Human; Cytokines; Proteomics; Inflammation; Medicine; Biomarkers; immunology; Longitudinal; End-stage Kidney Disease; Covid-19,,,"End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.",,doi:https://doi.org/10.7554/elife.64827; doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?pdf=render
-36644660,https://doi.org/10.1177/20552076221128677,Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.,"Gardner C, Wake D, Brodie D, Silverstein A, Young S, Cunningham S, Sainsbury C, Ilia M, Lucas A, Willis T, Halligan J.",,Digital health,2023,2023-01-08,Y,Artificial intelligence; Internet; Diabetes; Qualitative; risk factors; Machine Learning; Health Informatics; Behaviour Change; Personalised Medicine; Digital Health,,,"The prevalence of type 2 diabetes in North West London (NWL) is relatively high compared to other parts of the United Kingdom with outcomes suboptimal. This presents a need for more effective strategies to identify people living with type 2 diabetes who need additional support. An emerging subset of web-based interventions for diabetes self-management and population management has used artificial intelligence and machine learning models to stratify the risk of complications from diabetes and identify patients in need of immediate support. In this study, two prototype risk prediction tools on the MyWay Diabetes and MyWay Clinical platforms were evaluated with six clinicians and six people living with type 2 diabetes in NWL using the think aloud method. The results of the sessions with people living with type 2 diabetes showed that the concept of the tool was intuitive, however, more instruction on how to correctly use the risk prediction tool would be valuable. The feedback from the sessions with clinicians was that the data presented in the tool aligned with the key diabetes targets in NWL, and that this would be useful for identifying and inviting patients to the practice who are overdue for tests and at risk of complications. The findings of the evaluation have been used to support the development of the prototype risk predictions tools. This study demonstrates the value of conducting usability testing on web-based interventions designed to support the targeted management of type 2 diabetes in local communities.",,doi:https://doi.org/10.1177/20552076221128677; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render
 32954362,https://doi.org/10.1038/s43016-020-0093-y,Nutriome-metabolome relationships provide insights into dietary intake and metabolism.,"Posma JM, Garcia-Perez I, Frost G, Aljuraiban GS, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson JK.",,Nature food,2020,2020-06-22,N,,,,"Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with <sup>1</sup>H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497842; doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y
+36644660,https://doi.org/10.1177/20552076221128677,Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.,"Gardner C, Wake D, Brodie D, Silverstein A, Young S, Cunningham S, Sainsbury C, Ilia M, Lucas A, Willis T, Halligan J.",,Digital health,2023,2023-01-08,Y,Artificial intelligence; Internet; Diabetes; Qualitative; risk factors; Machine Learning; Health Informatics; Behaviour Change; Personalised Medicine; Digital Health,,,"The prevalence of type 2 diabetes in North West London (NWL) is relatively high compared to other parts of the United Kingdom with outcomes suboptimal. This presents a need for more effective strategies to identify people living with type 2 diabetes who need additional support. An emerging subset of web-based interventions for diabetes self-management and population management has used artificial intelligence and machine learning models to stratify the risk of complications from diabetes and identify patients in need of immediate support. In this study, two prototype risk prediction tools on the MyWay Diabetes and MyWay Clinical platforms were evaluated with six clinicians and six people living with type 2 diabetes in NWL using the think aloud method. The results of the sessions with people living with type 2 diabetes showed that the concept of the tool was intuitive, however, more instruction on how to correctly use the risk prediction tool would be valuable. The feedback from the sessions with clinicians was that the data presented in the tool aligned with the key diabetes targets in NWL, and that this would be useful for identifying and inviting patients to the practice who are overdue for tests and at risk of complications. The findings of the evaluation have been used to support the development of the prototype risk predictions tools. This study demonstrates the value of conducting usability testing on web-based interventions designed to support the targeted management of type 2 diabetes in local communities.",,doi:https://doi.org/10.1177/20552076221128677; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render
 36013179,https://doi.org/10.3390/jpm12081230,Grip Strength Trajectories and Cognition in English and Chilean Older Adults: A Cross-Cohort Study.,"Angel B, Ajnakina O, Albala C, Lera L, Márquez C, Leipold L, Bilovich A, Dobson R, Bendayan R.",,Journal of personalized medicine,2022,2022-07-27,Y,Cognition; Longitudinal study; Older Adults; Grip Strength,,,"Growing evidence about the link between cognitive and physical decline suggests the early changes in physical functioning as a potential biomarker for cognitive impairment. Thus, we compared grip-strength trajectories over 12-16 years in three groups classified according to their cognitive status (two stable patterns, normal and impaired cognitive performance, and a declining pattern) in two representative UK and Chilean older adult samples. The samples consisted of 7069 UK (ELSA) and 1363 Chilean participants (ALEXANDROS). Linear Mixed models were performed. Adjustments included socio-demographics and health variables. The Declined and Impaired group had significantly lower grip-strength at baseline when compared to the Non-Impaired. In ELSA, the Declined and Impaired showed a faster decline in their grip strength compared to the Non-Impaired group but differences disappeared in the fully adjusted models. In ALEXANDROS, the differences were only found between the Declined and Non-Impaired and they were partially attenuated by covariates. Our study provides robust evidence of the association between grip strength and cognitive performance and how socio-economic factors might be key to understanding this association and their variability across countries. This has implications for future epidemiological research, as hand-grip strength measurements have the potential to be used as an indicator of cognitive performance.",,pdf:https://www.mdpi.com/2075-4426/12/8/1230/pdf?version=1659687887; doi:https://doi.org/10.3390/jpm12081230; html:https://europepmc.org/articles/PMC9410389; pdf:https://europepmc.org/articles/PMC9410389?pdf=render
 36581539,https://doi.org/10.1016/j.jpsychires.2022.12.015,"Corrigendum ""Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting"" [J. Psychiatr. Res. 153 (2022) 167-173].","Farran D, Bean D, Wang T, Msosa Y, Casetta C, Dobson R, Teo JT, Scott P, Gaughran F.",,Journal of psychiatric research,2023,2022-12-28,N,,,,,,doi:https://doi.org/10.1016/j.jpsychires.2022.12.015; doi:https://doi.org/10.1016/j.jpsychires.2022.12.015
 37395705,https://doi.org/10.1167/tvst.12.7.3,Reliability of Optical Coherence Tomography Angiography Retinal Blood Flow Analyses.,"Courtie EF, Gilani A, Capewell N, Kale AU, Hui BTK, Liu X, Montesano G, Teussink M, Denniston AK, Veenith T, Blanch RJ.",,Translational vision science & technology,2023,2023-07-01,Y,,,,"<h4>Purpose</h4>Investigate the association between the optical coherence tomography angiography (OCTA) metrics derived from different analysis programs to understand the comparability of studies using these different approaches.<h4>Methods</h4>Secondary analysis of a prospective observational study (March 2018-September 2021). Forty-four right eyes and 42 left eyes from 44 patients were included. Patients were either undergoing upper gastrointestinal surgery with a critical care stay planned or were already in the critical care unit with sepsis. OCTA scans were obtained in an ophthalmology department or critical care setting. Fourteen OCTA metrics were compared within and between the programs, and agreement was measured by Pearson's R coefficient and intraclass correlation coefficient.<h4>Results</h4>Correlation was highest between all Heidelberg metrics and Fractalyse (all >0.84), and lowest between Matlab skeletonized or foveal avascular zone metrics and all other measures (e.g., skeletal fractal dimension and vessel density at -0.02). Agreement between eyes was moderate to excellent in all metrics (0.60-0.90).<h4>Conclusions</h4>The significant variability between metrics and programs used for OCTA analysis demonstrates that they are not interchangeable and supports a recommendation for perfusion density metrics to be reported as standard.<h4>Translational relevance</h4>Agreement between different OCTA analyses is variable and not interchangeable. The high agreement between non-skeletonized vessel density metrics suggests that these should be routinely reported.",,doi:https://doi.org/10.1167/tvst.12.7.3; doi:https://doi.org/10.1167/tvst.12.7.3; html:https://europepmc.org/articles/PMC10324418; pdf:https://europepmc.org/articles/PMC10324418?pdf=render
@@ -918,23 +918,23 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 34435642,https://doi.org/10.1093/eurheartj/ehab350,Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices.,"Bhuva AN, Moralee R, Brunker T, Lascelles K, Cash L, Patel KP, Lowe M, Sekhri N, Alpendurada F, Pennell DJ, Schilling R, Lambiase PD, Chow A, Moon JC, Litt H, Baksi AJ, Manisty CH.",,European heart journal,2022,2022-07-01,Y,Pacemaker; Magnetic Resonance Imaging; Defibrillator,,,"<h4>Aims</h4>Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified 'non-MR conditional' due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads.<h4>Methods and results</h4>Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1-8.3).<h4>Conclusions</h4>There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehab350/39932149/ehab350.pdf; doi:https://doi.org/10.1093/eurheartj/ehab350; html:https://europepmc.org/articles/PMC9259370; pdf:https://europepmc.org/articles/PMC9259370?pdf=render
 37337639,https://doi.org/10.1002/ctm2.1291,Trans-ethnic polygenic risk scores for body mass index: An international hundred K+ cohorts consortium study.,"Qu HQ, Connolly JJ, Kraft P, Long J, Pereira A, Flatley C, Turman C, Prins B, Mentch F, Lotufo PA, Magnus P, Stampfer MJ, Tamimi R, Eliassen AH, Zheng W, Knudsen GPS, Helgeland O, Butterworth AS, Hakonarson H, Sleiman PM, IHCC consortium.",,Clinical and translational medicine,2023,2023-06-01,Y,Obesity; Population admixture; body mass index; Polygenic Risk Score; Trans-ethnic,,,"<h4>Background</h4>While polygenic risk scores hold significant promise in estimating an individual's risk of developing a complex trait such as obesity, their application in the clinic has, to date, been limited by a lack of data from non-European populations. As a collaboration model of the International Hundred K+ Cohorts Consortium (IHCC), we endeavored to develop a globally applicable trans-ethnic PRS for body mass index (BMI) through this relatively new international effort.<h4>Methods</h4>The polygenic risk score (PRS) model was developed, trained and tested at the Center for Applied Genomics (CAG) of The Children's Hospital of Philadelphia (CHOP) based on a BMI meta-analysis from the GIANT consortium. The validated PRS models were subsequently disseminated to the participating sites. Scores were generated by each site locally on their cohorts and summary statistics returned to CAG for final analysis.<h4>Results</h4>We show that in the absence of a well powered trans-ethnic GWAS from which to derive marker SNPs and effect estimates for PRS, trans-ethnic scores can be generated from European ancestry GWAS using Bayesian approaches such as LDpred, by adjusting the summary statistics using trans-ethnic linkage disequilibrium reference panels. The ported trans-ethnic scores outperform population specific-PRS across all non-European ancestry populations investigated including East Asians and three-way admixed Brazilian cohort.<h4>Conclusions</h4>Here we show that for a truly polygenic trait such as BMI adjusting the summary statistics of a well powered European ancestry study using trans-ethnic LD reference results in a score that is predictive across a range of ancestries including East Asians and three-way admixed Brazilians.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1291; doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render
 32908801,https://doi.org/10.1167/tvst.9.9.38,Merging Information From Infrared and Autofluorescence Fundus Images for Monitoring of Chorioretinal Atrophic Lesions.,"Ometto G, Montesano G, Sadeghi Afgeh S, Lazaridis G, Liu X, Keane PA, Crabb DP, Denniston AK.",,Translational vision science & technology,2020,2020-08-25,Y,Autofluorescence; Segmentation; infrared; Uveitis; Multimodal,,,"<h4>Purpose</h4>To develop a method for automated detection and progression analysis of chorioretinal atrophic lesions using the combined information of standard infrared (IR) and autofluorescence (AF) fundus images.<h4>Methods</h4>Eighteen eyes (from 16 subjects) with punctate inner choroidopathy were analyzed. Macular IR and blue AF images were acquired in all eyes with a Spectralis HRA+OCT device (Heidelberg Engineering, Heidelberg, Germany). Two clinical experts manually segmented chorioretinal lesions on the AF image. AF images were aligned to the corresponding IR. Two random forest models were trained to classify pixels of lesions, one based on the AF image only, the other based on the aligned IR-AF. The models were validated using a leave-one-out cross-validation and were tested against the manual segmentation to compare their performance. A time series from one eye was identified and used to evaluate the method based on the IR-AF in a case study.<h4>Results</h4>The method based on the AF images correctly classified 95% of the pixels (i.e., in vs. out of the lesion) with a Dice's coefficient of 0.80. The method based on the combined IR-AF correctly classified 96% of the pixels with a Dice's coefficient of 0.84.<h4>Conclusions</h4>The automated segmentation of chorioretinal lesions using IR and AF shows closer alignment to manual segmentation than the same method based on AF only. Merging information from multimodal images improves the automatic and objective segmentation of chorioretinal lesions even when based on a small dataset.<h4>Translational relevance</h4>Merged information from multimodal images improves segmentation performance of chorioretinal lesions.",,doi:https://doi.org/10.1167/tvst.9.9.38; doi:https://doi.org/10.1167/tvst.9.9.38; html:https://europepmc.org/articles/PMC7453042; pdf:https://europepmc.org/articles/PMC7453042?pdf=render
-37067859,https://doi.org/10.1136/bmjmed-2022-000245,Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.,"Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .",,BMJ medicine,2023,2023-02-14,Y,epidemiology; Heart Failure; Cardiology; Covid-19,,,"<h4>Objective</h4>To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.<h4>Design</h4>Registry based observational study.<h4>Setting</h4>74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.<h4>Participants</h4>All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).<h4>Main outcome measures</h4>Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.<h4>Results</h4>Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).<h4>Conclusions</h4>In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render
 33692093,https://doi.org/10.1136/heartjnl-2020-318557,Improving the diagnosis of heart failure in patients with atrial fibrillation.,"Bunting KV, Gill SK, Sitch A, Mehta S, O'Connor K, Lip GY, Kirchhof P, Strauss VY, Rahimi K, Camm AJ, Stanbury M, Griffith M, Townend JN, Gkoutos GV, Karwath A, Steeds RP, Kotecha D, RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial group.",,Heart (British Cardiac Society),2021,2021-03-10,Y,Atrial fibrillation; Echocardiography; Heart Failure; Systolic; Diastolic,,,"<h4>Objective</h4>To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval.<h4>Methods</h4>Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides.<h4>Results</h4>160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e' with natriuretic peptide levels.<h4>Conclusions</h4>Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF.",,pdf:https://heart.bmj.com/content/heartjnl/107/11/902.full.pdf; doi:https://doi.org/10.1136/heartjnl-2020-318557; html:https://europepmc.org/articles/PMC8142420; pdf:https://europepmc.org/articles/PMC8142420?pdf=render
+37067859,https://doi.org/10.1136/bmjmed-2022-000245,Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.,"Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .",,BMJ medicine,2023,2023-02-14,Y,epidemiology; Heart Failure; Cardiology; Covid-19,,,"<h4>Objective</h4>To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.<h4>Design</h4>Registry based observational study.<h4>Setting</h4>74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.<h4>Participants</h4>All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).<h4>Main outcome measures</h4>Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.<h4>Results</h4>Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).<h4>Conclusions</h4>In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render
 35135774,https://doi.org/10.1136/bmjopen-2021-055603,"Observational retrospective study calculating health service costs of patients receiving surgery for chronic rhinosinusitis in England, using linked patient-level primary and secondary care electronic data.","Clarke CS, Williamson E, Denaxas S, Carpenter JR, Thomas M, Blackshaw H, Schilder AGM, Philpott CM, Hopkins C, Morris S, MACRO programme team.",,BMJ open,2022,2022-02-08,Y,Otolaryngology; Clinical Trials; Health Economics,,,"<h4>Objectives</h4>Chronic rhinosinusitis (CRS) symptoms are experienced by an estimated 11% of UK adults, and symptoms have major impacts on quality of life. Data from UK and elsewhere suggest high economic burden of CRS, but detailed cost information and economic analyses regarding surgical pathway are lacking. This paper estimates healthcare costs for patients receiving surgery for CRS in England.<h4>Design</h4>Observational retrospective study examining cost of healthcare of patients receiving CRS surgery.<h4>Setting</h4>Linked electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics databases in England.<h4>Participants</h4>A phenotyping algorithm using medical ontology terms identified 'definite' CRS cases who received CRS surgery. Patients were registered with a general practice in England. Data covered the period 1997-2016. A cohort of 13 462 patients had received surgery for CRS, with 9056 (67%) having confirmed nasal polyps.<h4>Outcome measures</h4>Information was extracted on numbers and types of primary care prescriptions and consultations, and inpatient and outpatient hospital investigations and procedures. Resource use was costed using published sources.<h4>Results</h4>Total National Health Service costs in CRS surgery patients were £2173 over 1 year including surgery. Total costs per person-quarter were £1983 in the quarter containing surgery, mostly comprising surgical inpatient care costs (£1902), and around £60 per person-quarter in the 2 years before and after surgery, of which half were outpatient costs. Outpatient and primary care costs were low compared with the peak in inpatient costs at surgery. The highest outpatient expenditure was on CT scans, peaking in the quarter preceding surgery.<h4>Conclusions</h4>We present the first study of costs to the English healthcare system for patients receiving surgery for CRS. The total aggregate costs provide a further impetus for trials to evaluate the relative benefit of surgical intervention.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055603.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055603; html:https://europepmc.org/articles/PMC8830221; pdf:https://europepmc.org/articles/PMC8830221?pdf=render
 35896705,https://doi.org/10.1038/s41598-022-16639-9,Estimation of biological heart age using cardiovascular magnetic resonance radiomics.,"Raisi-Estabragh Z, Salih A, Gkontra P, Atehortúa A, Radeva P, Boscolo Galazzo I, Menegaz G, Harvey NC, Lekadir K, Petersen SE.",,Scientific reports,2022,2022-07-27,Y,,,,"We developed a novel interpretable biological heart age estimation model using cardiovascular magnetic resonance radiomics measures of ventricular shape and myocardial character. We included 29,996 UK Biobank participants without cardiovascular disease. Images were segmented using an automated analysis pipeline. We extracted 254 radiomics features from the left ventricle, right ventricle, and myocardium of each study. We then used Bayesian ridge regression with tenfold cross-validation to develop a heart age estimation model using the radiomics features as the model input and chronological age as the model output. We examined associations of radiomics features with heart age in men and women, observing sex-differential patterns. We subtracted actual age from model estimated heart age to calculate a ""heart age delta"", which we considered as a measure of heart aging. We performed a phenome-wide association study of 701 exposures with heart age delta. The strongest correlates of heart aging were measures of obesity, adverse serum lipid markers, hypertension, diabetes, heart rate, income, multimorbidity, musculoskeletal health, and respiratory health. This technique provides a new method for phenotypic assessment relating to cardiovascular aging; further studies are required to assess whether it provides incremental risk information over current approaches.",,pdf:https://www.nature.com/articles/s41598-022-16639-9.pdf; doi:https://doi.org/10.1038/s41598-022-16639-9; html:https://europepmc.org/articles/PMC9329281; pdf:https://europepmc.org/articles/PMC9329281?pdf=render
 32060159,https://doi.org/10.1136/bmjopen-2019-034396,Data-driven discovery of changes in clinical code usage over time: a case-study on changes in cardiovascular disease recording in two English electronic health records databases (2001-2015).,"Rockenschaub P, Nguyen V, Aldridge RW, Acosta D, García-Gómez JM, Sáez C.",,BMJ open,2020,2020-02-13,Y,Cardiovascular disease; Data Quality; Electronic Health Records; Clinical Coding; Statistics & Research Methods,The Human Phenome,,"<h4>Objectives</h4>To demonstrate how data-driven variability methods can be used to identify changes in disease recording in two English electronic health records databases between 2001 and 2015.<h4>Design</h4>Repeated cross-sectional analysis that applied data-driven temporal variability methods to assess month-by-month changes in routinely collected medical data. A measure of difference between months was calculated based on joint distributions of age, gender, socioeconomic status and recorded cardiovascular diseases. Distances between months were used to identify temporal trends in data recording.<h4>Setting</h4>400 English primary care practices from the Clinical Practice Research Datalink (CPRD GOLD) and 451 hospital providers from the Hospital Episode Statistics (HES).<h4>Main outcomes</h4>The proportion of patients (CPRD GOLD) and hospital admissions (HES) with a recorded cardiovascular disease (CPRD GOLD: coronary heart disease, heart failure, peripheral arterial disease, stroke; HES: International Classification of Disease codes I20-I69/G45).<h4>Results</h4>Both databases showed gradual changes in cardiovascular disease recording between 2001 and 2008. The recorded prevalence of included cardiovascular diseases in CPRD GOLD increased by 47%-62%, which partially reversed after 2008. For hospital records in HES, there was a relative decrease in angina pectoris (-34.4%) and unspecified stroke (-42.3%) over the same time period, with a concomitant increase in chronic coronary heart disease (+14.3%). Multiple abrupt changes in the use of myocardial infarction codes in hospital were found in March/April 2010, 2012 and 2014, possibly linked to updates of clinical coding guidelines.<h4>Conclusions</h4>Identified temporal variability could be related to potentially non-medical causes such as updated coding guidelines. These artificial changes may introduce temporal correlation among diagnoses inferred from routine data, violating the assumptions of frequently used statistical methods. Temporal variability measures provide an objective and robust technique to identify, and subsequently account for, those changes in electronic health records studies without any prior knowledge of the data collection process.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/2/e034396.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-034396; html:https://europepmc.org/articles/PMC7045100; pdf:https://europepmc.org/articles/PMC7045100?pdf=render
 34985035,https://doi.org/10.1097/htr.0000000000000741,Epidemiology and 6- and 12-Month Outcomes of Intimate Partner Violence and Other Violence-Related Traumatic Brain Injury in Major Trauma: A Population-Based Trauma Registry Study.,"Gabbe BJ, Braaf S, Cameron PA, Berecki-Gisolf J.",,The Journal of head trauma rehabilitation,2022,2022-01-01,N,,,,"<h4>Objective</h4>To compare the epidemiology, in-hospital outcomes, and 6-month and 12-month patient-reported, outcomes of major trauma patients with intimate partner violence (IPV)-related traumatic brain injury (TBI) with other interpersonal violence (OV)-related TBI.<h4>Setting</h4>Victoria, Australia.<h4>Participants</h4>Adult (≥18 years) major trauma cases with TBI (concussion, skull fracture, or intracranial injury), injured through IPV or OV, between July 2010 and June 2020, and included on the population-based Victorian State Trauma Registry. There were 133 adult major trauma cases due to IPV and 1796 due to OV. The prevalence of TBI was 39% (n = 52) in the IPV group and 56% (n = 1010) in the OV group.<h4>Design</h4>Registry-based cohort study.<h4>Main measures</h4>Trauma care indicators and 6- and 12-month patient-reported outcomes (self-reported disability, Glasgow Outcome Scale-Extended, EQ-5D-3L, and return to work).<h4>Results</h4>The annual incidence (95% CI) of major trauma involving TBI was 0.11 (0.08-0.14) per 100 000 population for IPV and 2.11 (1.98-2.24) per 100 000 for OV. A higher proportion of IPV-related cases were women (73% vs 5%), had sustained a severe TBI (Glasgow Coma Scale score 3-8; 27% vs 15%), were admitted to intensive care (56% vs 37%), and died in hospital (14% vs 5%). The median (interquartile range) time to definitive care (4.7 hours vs 3.3 hours) and head computed tomographic scan (5.0 hours vs 3.1 hours) was longer in the IPV group. Follow-up rates at 6 and 12 months were 71% and 69%, respectively. The 6- and 12-month outcomes were generally poorer in the IPV-related group.<h4>Conclusion</h4>The incidence of IPV-related major trauma with TBI was low. However, the prevalence of severe TBI, the time to key aspects of clinical care, in-hospital mortality, and longer-term work-related disability were higher. However, power to detect differences was low due to the small number of IPV-related cases compared with the OV group.",,doi:https://doi.org/10.1097/HTR.0000000000000741
-37827807,https://doi.org/10.1136/bmjresp-2023-001806,Observational cohort study protocol: neutrophil function and energetics in adults with pneumonia and sepsis - Pneumonia Metabolism in Ageing (PUMA).,"Grudzinska FS, Faniyi AA, Scott A, Sapey E, Thickett DR.",,BMJ open respiratory research,2023,2023-10-01,Y,Pneumonia; innate immunity; Bacterial Infection; respiratory infection; Neutrophil Biology,,,"<h4>Introduction</h4>Community-acquired pneumonia has high mortality and is associated with significant healthcare costs. In older adults with community-acquired pneumonia neutrophil dysfunction has been identified and is associated with poor outcomes for patients. Immunometabolism is a rapidly developing field which links immune cell function to metabolism. This study aims to explore neutrophil metabolism in community-acquired pneumonia.<h4>Methods and analysis</h4>Pneumonia Metabolism in Ageing study is a prospective observational study recruiting older adults hospitalised with community-acquired pneumonia to examine neutrophil function and metabolic status. Controls will be older adults with no acute illness. The primary endpoint is neutrophil chemotaxis.<h4>Ethics and dissemination</h4>The study has ethical approval from the Research Ethics Committee Wales, reference 19/WA/0299. This study involves participants who may lack the capacity to consent to research involvement, in this situation, personal or professional assent will be sought. The results from this study will be submitted for publication in peer-reviewed journals and disseminated at local and international conferences.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001806.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001806; html:https://europepmc.org/articles/PMC10582892; pdf:https://europepmc.org/articles/PMC10582892?pdf=render
 34847088,https://doi.org/10.1097/ede.0000000000001429,The Authors Respond.,"Katsoulis M, De Stavola B, Lai AG, Gomes M, Diaz-Ordaz K.",,"Epidemiology (Cambridge, Mass.)",2022,2022-01-01,N,,,,,,html:https://journals.lww.com/epidem/Fulltext/2022/01000/The_Authors_Respond.22.aspx; doi:https://doi.org/10.1097/EDE.0000000000001429
 34671274,https://doi.org/10.3389/fphys.2021.730736,Comparing Non-invasive Inverse Electrocardiography With Invasive Endocardial and Epicardial Electroanatomical Mapping During Sinus Rhythm.,"Roudijk RW, Boonstra MJ, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, van Dam PM, Loh P.",,Frontiers in physiology,2021,2021-10-04,Y,Cardiac Arrhythmia; Sudden Cardiac Death; Electroanatomical Mapping; Electrocardiographic Imaging (Ecgi); Non-invasive Mapping; Equivalent Dipole Layer; Inverse Problem Of Electrocardiography,,,"This study presents a novel non-invasive equivalent dipole layer (EDL) based inverse electrocardiography (<i>i</i>ECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our <i>i</i>ECG approach with invasive electro-anatomical mapping (EAM) during sinus rhythm with the objective of enabling functional substrate imaging and sudden cardiac death risk stratification in patients with cardiomyopathy. Thirteen patients (77% males, 48 ± 20 years old) referred for endocardial and epicardial EAM underwent 67-electrode body surface potential mapping and CT imaging. The EDL-based <i>i</i>ECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with <i>i</i>ECG-LAT maps using absolute differences and Pearson's correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between <i>i</i>ECG-LAT maps and EAM was 0.54 ± 0.19 [0.49-0.59] for epicardial activation, 0.50 ± 0.27 [0.41-0.58] for right ventricular endocardial activation and 0.44 ± 0.29 [0.32-0.56] for left ventricular endocardial activation. The absolute difference in timing between <i>i</i>ECG maps and EAM was 17.4 ± 7.2 ms for epicardial maps, 19.5 ± 7.7 ms for right ventricular endocardial maps, 27.9 ± 8.7 ms for left ventricular endocardial maps. The absolute distance between right ventricular endocardial breakthrough sites was 30 ± 16 mm and 31 ± 17 mm for the left ventricle. The absolute distance for latest epicardial activation was median 12.8 [IQR: 2.9-29.3] mm. This first in-human quantitative comparison of <i>i</i>ECG and invasive LAT-maps on both the endocardial and epicardial surface during sinus rhythm showed improved agreement, although with considerable absolute difference and moderate correlation coefficient. Non-invasive <i>i</i>ECG requires further refinements to facilitate clinical implementation and risk stratification.",,pdf:https://www.frontiersin.org/articles/10.3389/fphys.2021.730736/pdf; doi:https://doi.org/10.3389/fphys.2021.730736; html:https://europepmc.org/articles/PMC8521153; pdf:https://europepmc.org/articles/PMC8521153?pdf=render
+37827807,https://doi.org/10.1136/bmjresp-2023-001806,Observational cohort study protocol: neutrophil function and energetics in adults with pneumonia and sepsis - Pneumonia Metabolism in Ageing (PUMA).,"Grudzinska FS, Faniyi AA, Scott A, Sapey E, Thickett DR.",,BMJ open respiratory research,2023,2023-10-01,Y,Pneumonia; innate immunity; Bacterial Infection; respiratory infection; Neutrophil Biology,,,"<h4>Introduction</h4>Community-acquired pneumonia has high mortality and is associated with significant healthcare costs. In older adults with community-acquired pneumonia neutrophil dysfunction has been identified and is associated with poor outcomes for patients. Immunometabolism is a rapidly developing field which links immune cell function to metabolism. This study aims to explore neutrophil metabolism in community-acquired pneumonia.<h4>Methods and analysis</h4>Pneumonia Metabolism in Ageing study is a prospective observational study recruiting older adults hospitalised with community-acquired pneumonia to examine neutrophil function and metabolic status. Controls will be older adults with no acute illness. The primary endpoint is neutrophil chemotaxis.<h4>Ethics and dissemination</h4>The study has ethical approval from the Research Ethics Committee Wales, reference 19/WA/0299. This study involves participants who may lack the capacity to consent to research involvement, in this situation, personal or professional assent will be sought. The results from this study will be submitted for publication in peer-reviewed journals and disseminated at local and international conferences.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001806.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001806; html:https://europepmc.org/articles/PMC10582892; pdf:https://europepmc.org/articles/PMC10582892?pdf=render
 37645022,https://doi.org/10.1183/20734735.0058-2023,The impact of poor housing and indoor air quality on respiratory health in children.,"Holden KA, Lee AR, Hawcutt DB, Sinha IP.",,"Breathe (Sheffield, England)",2023,2023-06-01,Y,,,,"It is becoming increasingly apparent that poor housing quality affects indoor air quality, significantly impacting on respiratory health in children and young people. Exposure to damp and/or mould in the home, cold homes and the presence of pests and pollutants all have a significant detrimental impact on child respiratory health. There is a complex relationship between features of poor-quality housing, such as being in a state of disrepair, poor ventilation, overcrowding and being cold, that favour an environment resulting in poor indoor air quality. Children living in rented (private or public) housing are more likely to come from lower-income backgrounds and are most at risk of living in substandard housing posing a serious threat to respiratory health. Children have the right to safe and adequate housing, and research has shown that either rehousing or making modifications to poor-quality housing to improve indoor air quality results in improved respiratory health. Urgent action is needed to address this threat to health. All stakeholders should understand the relationship between poor-quality housing and respiratory health in children and act, working with families, to redress this modifiable risk factor.<h4>Educational aims</h4>The reader should understand how housing quality and indoor air quality affect respiratory health in children.The reader should understand which children are at most risk of living in poor-quality housing.The reader should understand what policy recommendations have been made and what actions need to be undertaken to improve housing quality and respiratory health in children and young people.",,doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render
 37532769,https://doi.org/10.1038/s42003-023-05171-9,Direct inference and control of genetic population structure from RNA sequencing data.,"Fachrul M, Karkey A, Shakya M, Judd LM, Harshegyi T, Sim KS, Tonks S, Dongol S, Shrestha R, Salim A, STRATAA study group, Baker S, Pollard AJ, Khor CC, Dolecek C, Basnyat B, Dunstan SJ, Holt KE, Inouye M.",,Communications biology,2023,2023-08-02,Y,,,,"RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.",,pdf:https://www.nature.com/articles/s42003-023-05171-9.pdf; doi:https://doi.org/10.1038/s42003-023-05171-9; html:https://europepmc.org/articles/PMC10397182; pdf:https://europepmc.org/articles/PMC10397182?pdf=render
 36580444,https://doi.org/10.1371/journal.pmed.1004141,Associations of genetically predicted fatty acid levels across the phenome: A mendelian randomisation study.,"Zagkos L, Dib MJ, Pinto R, Gill D, Koskeridis F, Drenos F, Markozannes G, Elliott P, Zuber V, Tsilidis K, Dehghan A, Tzoulaki I.",,PLoS medicine,2022,2022-12-29,Y,,,,"<h4>Background</h4>Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.<h4>Methods and findings</h4>The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.<h4>Conclusions</h4>Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004141&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004141; html:https://europepmc.org/articles/PMC9799317; pdf:https://europepmc.org/articles/PMC9799317?pdf=render
 35792838,https://doi.org/10.1093/bioinformatics/btac453,Flashfm-ivis: interactive visualization for fine-mapping of multiple quantitative traits.,"Zhou F, Butterworth AS, Asimit JL.",,"Bioinformatics (Oxford, England)",2022,2022-09-01,Y,,,,"<h4>Summary</h4>flashfm-ivis provides a suite of interactive visualization plots to view potential causal genetic variants that underlie associations that are shared or distinct between multiple quantitative traits and compares results between single- and multi-trait fine-mapping. Unique features include network diagrams that show joint effects between variants for each trait and regional association plots that integrate fine-mapping results, all with user-controlled zoom features for an interactive exploration of potential causal variants across traits.<h4>Availability and implementation</h4>flashfm-ivis is an open-source software under the MIT license. It is available as an interactive web-based tool (http://shiny.mrc-bsu.cam.ac.uk/apps/flashfm-ivis/) and as an R package. Code and documentation are available at https://github.com/fz-cambridge/flashfm-ivis and https://zenodo.org/record/6376244#.YjnarC-l2X0. Additional features can be downloaded as standalone R libraries to encourage reuse.<h4>Supplementary information</h4>Supplementary information are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/38/17/4238/49889636/btac453.pdf; doi:https://doi.org/10.1093/bioinformatics/btac453; html:https://europepmc.org/articles/PMC9438951; pdf:https://europepmc.org/articles/PMC9438951?pdf=render
 36369983,https://doi.org/10.1093/eurheartj/ehac650,Fit for the future: empowering clinical trials with digital technology.,"Kotecha D, DeVore AD, Asselbergs FW.",,European heart journal,2023,2023-01-01,N,,,,,,doi:https://doi.org/10.1093/eurheartj/ehac650
 32946551,https://doi.org/10.1093/ageing/afaa158,Do home modifications reduce care home admissions for older people? A matched control evaluation of the Care & Repair Cymru service in Wales.,"Hollinghurst J, Fry R, Akbari A, Watkins A, Williams N, Hillcoat-Nallétamby S, Lyons RA, Clegg A, Rodgers SE.",,Age and ageing,2020,2020-10-01,Y,Frailty; Interventions; Older People; Care Homes; Administrative Data,,,"<h4>Background</h4>home advice and modification interventions aim to promote independent living for those living in the community, but quantitative evidence of their effectiveness is limited.<h4>Aim</h4>assess the risk of care home admissions for people with different frailty levels receiving home advice and modification interventions against a control group who do not.<h4>Study design and setting</h4>matched control evaluation using linked longitudinal data from the Secure Anonymised Information Linkage (SAIL) Databank, comprising people aged 60-95, registered with a SAIL contributing general practice. The intervention group received the Care & Repair Cymru (C & RC) service, a home advice and modification service available to residents in Wales.<h4>Methods</h4>frailty, age and gender were used in propensity score matching to assess the Hazard Ratio (HR) of care home admissions within a 1-, 3- and 5-year period for the intervention group (N = 93,863) compared to a matched control group (N = 93,863). Kaplan-Meier curves were used to investigate time to a care home admission.<h4>Results</h4>the intervention group had an increased risk of a care home admission at 1-, 3- and 5-years [HR (95%CI)] for those classified as fit [1-year: 2.02 (1.73, 2.36), 3-years: 1.87 (1.72, 2.04), 5-years: 1.99 (1.86, 2.13)] and mildly frail [1-year: 1.25 (1.09, 1.42), 3-years: 1.25 (1.17, 1.34), 5-years: 1.30 (1.23, 1.38)], but a reduced risk of care home admission for moderately [1-year: 0.66 (0.58, 0.75), 3-years: 0.75 (0.70, 0.80), 5-years: 0.83 (0.78, 0.88)] and severely frail individuals [1-year: 0.44 (0.37, 0.54), 3-years: 0.54 (0.49, 0.60), 5-years: 0.60(0.55, 0.66)].<h4>Conclusions</h4>HRs indicated that the C & RC service helped to prevent care home admissions for moderately and severely frail individuals. The HRs generally increased with follow-up duration.",,pdf:https://academic.oup.com/ageing/article-pdf/49/6/1056/33993322/afaa158.pdf; doi:https://doi.org/10.1093/ageing/afaa158; html:https://europepmc.org/articles/PMC7583515; pdf:https://europepmc.org/articles/PMC7583515?pdf=render
-34516619,https://doi.org/10.1093/ehjci/jeab178,Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers.,"Taha K, Verstraelen TE, de Brouwer R, de Bruin-Bon RHACM, Cramer MJ, Te Rijdt WP, Bouma BJ, de Boer RA, Doevendans PA, Asselbergs FW, Wilde AAM, van den Berg MP, Teske AJ.",,European heart journal. Cardiovascular Imaging,2022,2022-10-01,Y,Risk stratification; ventricular arrhythmia; Phospholamban; Mechanical Dispersion; Deformation Imaging; Genetic Cardiomyopathy,,,"<h4>Aims</h4>Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers.<h4>Methods and results</h4>We included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the '45/45' rule: (i) normal left ventricular (LV) function, defined as preserved LVEF ≥45% with normal LVMD ≤45 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF ≥45% with abnormal LVMD &gt;45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF &lt;45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8-6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92-100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15-27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57-162.84)].<h4>Conclusion</h4>LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The '45/45' rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab178/40357499/jeab178.pdf; doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render
 32763878,https://doi.org/10.2196/18690,Notifications to Improve Engagement With an Alcohol Reduction App: Protocol for a Micro-Randomized Trial.,"Bell L, Garnett C, Qian T, Perski O, Potts HWW, Williamson E.",,JMIR research protocols,2020,2020-08-07,Y,Alcohol; Engagement; Mhealth; Mobile Health; Excessive Alcohol Consumption; Smartphone App; Push Notifications; Digital Behavior Change; Micro-randomized Trial,,,"<h4>Background</h4>Drink Less is a behavior change app that aims to help users in the general adult population reduce hazardous and harmful alcohol consumption. The app includes a daily push notification, delivered at 11 am, asking users to ""Please complete your mood and drinking diaries."" Previous analysis of Drink Less engagement data suggests the current notification strongly influences how users engage with the app in the subsequent hour. To exploit a potential increase of vulnerability of excess drinking and opportunity to engage with the app in the evenings, we changed the delivery time from 11 am to 8 pm. We now aim to further optimise the content and sequence of notifications, testing 30 new evidence-informed notifications targeting the user's perceived usefulness of the app.<h4>Objective</h4>The primary objective is to assess whether sending a notification at 8 pm increases behavioral engagement (opening the app) in the subsequent hour. Secondary objectives include comparing the effect of the new bank of messages with the standard message and effect moderation over time. We also aim to more generally understand the role notifications have on the overall duration, depth, and frequency of engagement with Drink Less over the first 30 days after download.<h4>Methods</h4>This is a protocol for a micro-randomized trial with two additional parallel arms. Inclusion criteria are Drink Less users who (1) consent to participate in the trial; (2) self-report a baseline Alcohol Use Disorders Identification Test score of 8 or above; (3) reside in the United Kingdom; (4) age ≥18 years and; (5) report interest in drinking less alcohol. In the micro-randomized trial, participants will be randomized daily at 8 pm to receive no notification, a notification with text from the new message bank, or the standard message. The primary outcome is the time-varying, binary outcome of ""Did the user open the app in the hour from 8 pm to 9 pm?"". The primary analysis will estimate the marginal relative risk for the notifications using an estimator developed for micro-randomized trials with binary outcomes. Participants randomized to the parallel arms will receive no notifications (Secondary Arm A), or the standard notification delivered daily at 11 am (Secondary Arm B) over 30 days, allowing the comparison of overall engagement between different notification delivery strategies.<h4>Results</h4>Approval was granted by the University College of London's Departmental Research Ethics Committee (CEHP/2016/556) on October 11, 2019, and The London School of Hygiene and Tropical Medicine Interventions Research Ethics Committee (17929) on November 27, 2019. Recruitment began on January 2, 2020, and is ongoing.<h4>Conclusions</h4>Understanding how push notifications may impact engagement with a behavior change app can lead to further improvements in engagement, and ultimately help users reduce their alcohol consumption. This understanding may also be generalizable to other apps that target a variety of behavior changes.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/18690.",,pdf:https://www.researchprotocols.org/2020/8/e18690/PDF; doi:https://doi.org/10.2196/18690; html:https://europepmc.org/articles/PMC7442945
+34516619,https://doi.org/10.1093/ehjci/jeab178,Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers.,"Taha K, Verstraelen TE, de Brouwer R, de Bruin-Bon RHACM, Cramer MJ, Te Rijdt WP, Bouma BJ, de Boer RA, Doevendans PA, Asselbergs FW, Wilde AAM, van den Berg MP, Teske AJ.",,European heart journal. Cardiovascular Imaging,2022,2022-10-01,Y,Risk stratification; ventricular arrhythmia; Phospholamban; Mechanical Dispersion; Deformation Imaging; Genetic Cardiomyopathy,,,"<h4>Aims</h4>Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers.<h4>Methods and results</h4>We included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the '45/45' rule: (i) normal left ventricular (LV) function, defined as preserved LVEF ≥45% with normal LVMD ≤45 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF ≥45% with abnormal LVMD &gt;45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF &lt;45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8-6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92-100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15-27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57-162.84)].<h4>Conclusion</h4>LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The '45/45' rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab178/40357499/jeab178.pdf; doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render
 37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"<h4>Background</h4>Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.<h4>Objective</h4>This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.<h4>Methods</h4>Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.<h4>Results</h4>A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.<h4>Conclusions</h4>Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627
 34328624,https://doi.org/10.1007/s11695-021-05493-9,30-Day Morbidity and Mortality of Bariatric Surgery During the COVID-19 Pandemic: a Multinational Cohort Study of 7704 Patients from 42 Countries.,"Singhal R, Ludwig C, Rudge G, Gkoutos GV, Tahrani A, Mahawar K, GENEVA Collaborators, Pędziwiatr M, Major P, Zarzycki P, Pantelis A, Lapatsanis DP, Stravodimos G, Matthys C, Focquet M, Vleeschouwers W, Spaventa AG, Zerrweck C, Vitiello A, Berardi G, Musella M, Sanchez-Meza A, Cantu FJ, Mora F, Cantu MA, Katakwar A, Reddy DN, Elmaleh H, Hassan M, Elghandour A, Elbanna M, Osman A, Khan A, Layani L, Kiran N, Velikorechin A, Solovyeva M, Melali H, Shahabi S, Agrawal A, Shrivastava A, Sharma A, Narwaria B, Narwaria M, Raziel A, Sakran N, Susmallian S, Karagöz L, Akbaba M, Pişkin SZ, Balta AZ, Senol Z, Manno E, Iovino MG, Osman A, Qassem M, Arana-Garza S, Povoas HP, Vilas-Boas ML, Naumann D, Super J, Li A, Ammori BJ, Balamoun H, Salman M, Nasta AM, Goel R, Sánchez-Aguilar H, Herrera MF, Abou-Mrad A, Cloix L, Mazzini GS, Kristem L, Lazaro A, Campos J, Bernardo J, González J, Trindade C, Viveiros O, Ribeiro R, Goitein D, Hazzan D, Segev L, Beck T, Reyes H, Monterrubio J, García P, Benois M, Kassir R, Contine A, Elshafei M, Aktas S, Weiner S, Heidsieck T, Level L, Pinango S, Ortega PM, Moncada R, Valenti V, Vlahović I, Boras Z, Liagre A, Martini F, Juglard G, Motwani M, Saggu SS, Al Moman H, López LAA, Cortez MAC, Zavala RA, D'Haese C, Kempeneers I, Himpens J, Lazzati A, Paolino L, Bathaei S, Bedirli A, Yavuz A, Büyükkasap Ç, Özaydın S, Kwiatkowski A, Bartosiak K, Walędziak M, Santonicola A, Angrisani L, Iovino P, Palma R, Iossa A, Boru CE, De Angelis F, Silecchia G, Hussain A, Balchandra S, Coltell IB, Pérez JL, Bohra A, Awan AK, Madhok B, Leeder PC, Awad S, Al-Khyatt W, Shoma A, Elghadban H, Ghareeb S, Mathews B, Kurian M, Larentzakis A, Vrakopoulou GZ, Albanopoulos K, Bozdag A, Lale A, Kirkil C, Dincer M, Bashir A, Haddad A, Hijleh LA, Zilberstein B, de Marchi DD, Souza WP, Brodén CM, Gislason H, Shah K, Ambrosi A, Pavone G, Tartaglia N, Kona SLK, Kalyan K, Perez CEG, Botero MAF, Covic A, Timofte D, Maxim M, Faraj D, Tseng L, Liem R, Ören G, Dilektasli E, Yalcin I, AlMukhtar H, Al Hadad M, Mohan R, Arora N, Bedi D, Rives-Lange C, Chevallier JM, Poghosyan T, Sebbag H, Zinaï L, Khaldi S, Mauchien C, Mazza D, Dinescu G, Rea B, Pérez-Galaz F, Zavala L, Besa A, Curell A, Balibrea JM, Vaz C, Galindo L, Silva N, Caballero JLE, Sebastian SO, Marchesini JCD, da Fonseca Pereira RA, Sobottka WH, Fiolo FE, Turchi M, Coelho ACJ, Zacaron AL, Barbosa A, Quinino R, Menaldi G, Paleari N, Martinez-Duartez P, de Aragon Ramírez de Esparza GM, Esteban VS, Torres A, Garcia-Galocha JL, Josa M, Pacheco-Garcia JM, Mayo-Ossorio MA, Chowbey P, Soni V, de Vasconcelos Cunha HA, Castilho MV, Ferreira RMA, Barreiro TA, Charalabopoulos A, Sdralis E, Davakis S, Bomans B, Dapri G, Van Belle K, Takieddine M, Vaneukem P, Karaca ESA, Karaca FC, Sumer A, Peksen C, Savas OA, Chousleb E, Elmokayed F, Fakhereldin I, Aboshanab HM, Swelium T, Gudal A, Gamloo L, Ugale A, Ugale S, Boeker C, Reetz C, Hakami IA, Mall J, Alexandrou A, Baili E, Bodnar Z, Maleckas A, Gudaityte R, Guldogan CE, Gundogdu E, Ozmen MM, Thakkar D, Dukkipati N, Shah PS, Shah SS, Shah SS, Adil MT, Jambulingam P, Mamidanna R, Whitelaw D, Adil MT, Jain V, Veetil DK, Wadhawan R, Torres A, Torres M, Tinoco T, Leclercq W, Romeijn M, van de Pas K, Alkhazraji AK, Taha SA, Ustun M, Yigit T, Inam A, Burhanulhaq M, Pazouki A, Eghbali F, Kermansaravi M, Jazi AHD, Mahmoudieh M, Mogharehabed N, Tsiotos G, Stamou K, Barrera Rodriguez FJ, Rojas Navarro MA, Torres OM, Martinez SL, Tamez ERM, Millan Cornejo GA, Flores JEG, Mohammed DA, Elfawal MH, Shabbir A, Guowei K, So JB, Kaplan ET, Kaplan M, Kaplan T, Pham D, Rana G, Kappus M, Gadani R, Kahitan M, Pokharel K, Osborne A, Pournaras D, Hewes J, Napolitano E, Chiappetta S, Bottino V, Dorado E, Schoettler A, Gaertner D, Fedtke K, Aguilar-Espinosa F, Aceves-Lozano S, Balani A, Nagliati C, Pennisi D, Rizzi A, Frattini F, Foschi D, Benuzzi L, Parikh C, Shah H, Pinotti E, Montuori M, Borrelli V, Dargent J, Copaescu CA, Hutopila I, Smeu B, Witteman B, Hazebroek E, Deden L, Heusschen L, Okkema S, Aufenacker T, den Hengst W, Vening W, van der Burgh Y, Ghazal A, Ibrahim H, Niazi M, Alkhaffaf B, Altarawni M, Cesana GC, Anselmino M, Uccelli M, Olmi S, Stier C, Akmanlar T, Sonnenberg T, Schieferbein U, Marcolini A, Awruch D, Vicentin M, de Souza Bastos EL, Gregorio SA, Ahuja A, Mittal T, Bolckmans R, Wiggins T, Baratte C, Wisnewsky JA, Genser L, Chong L, Taylor L, Ward S, Chong L, Taylor L, Hi MW, Heneghan H, Fearon N, Plamper A, Rheinwalt K, Heneghan H, Geoghegan J, Ng KC, Fearon N, Kaseja K, Kotowski M, Samarkandy TA, Leyva-Alvizo A, Corzo-Culebro L, Wang C, Yang W, Dong Z, Riera M, Jain R, Hamed H, Said M, Zarzar K, Garcia M, Türkçapar AG, Şen O, Baldini E, Conti L, Wietzycoski C, Lopes E, Pintar T, Salobir J, Aydin C, Atici SD, Ergin A, Ciyiltepe H, Bozkurt MA, Kizilkaya MC, Onalan NBD, Zuber MNBA, Wong WJ, Garcia A, Vidal L, Beisani M, Pasquier J, Vilallonga R, Sharma S, Parmar C, Lee L, Sufi P, Sinan H, Saydam M.",,Obesity surgery,2021,2021-07-30,Y,Pandemic; Obesity Surgery; Bariatric Surgery; Revisional Surgery; Covid-19; Sars-cov-2,,,"<h4>Background</h4>There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates.<h4>Methods</h4>We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020.<h4>Results</h4>Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country.<h4>Conclusions</h4>BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak.",,pdf:https://link.springer.com/content/pdf/10.1007/s11695-021-05493-9.pdf; doi:https://doi.org/10.1007/s11695-021-05493-9; html:https://europepmc.org/articles/PMC8323543; pdf:https://europepmc.org/articles/PMC8323543?pdf=render
 34798287,https://doi.org/10.1016/j.jclinepi.2021.11.023,Missing data is poorly handled and reported in prediction model studies using machine learning: a literature review.,"Nijman S, Leeuwenberg AM, Beekers I, Verkouter I, Jacobs J, Bots ML, Asselbergs FW, Moons K, Debray T.",,Journal of clinical epidemiology,2022,2021-11-16,N,Prediction; Literature review; Reporting; Missing Data; Machine Learning,,,"<h4>Objectives</h4>Missing data is a common problem during the development, evaluation, and implementation of prediction models. Although machine learning (ML) methods are often said to be capable of circumventing missing data, it is unclear how these methods are used in medical research. We aim to find out if and how well prediction model studies using machine learning report on their handling of missing data.<h4>Study design and setting</h4>We systematically searched the literature on published papers between 2018 and 2019 about primary studies developing and/or validating clinical prediction models using any supervised ML methodology across medical fields. From the retrieved studies information about the amount and nature (e.g. missing completely at random, potential reasons for missingness) of missing data and the way they were handled were extracted.<h4>Results</h4>We identified 152 machine learning-based clinical prediction model studies. A substantial amount of these 152 papers did not report anything on missing data (n = 56/152). A majority (n = 96/152) reported details on the handling of missing data (e.g., methods used), though many of these (n = 46/96) did not report the amount of the missingness in the data. In these 96 papers the authors only sometimes reported possible reasons for missingness (n = 7/96) and information about missing data mechanisms (n = 8/96). The most common approach for handling missing data was deletion (n = 65/96), mostly via complete-case analysis (CCA) (n = 43/96). Very few studies used multiple imputation (n = 8/96) or built-in mechanisms such as surrogate splits (n = 7/96) that directly address missing data during the development, validation, or implementation of the prediction model.<h4>Conclusion</h4>Though missing values are highly common in any type of medical research and certainly in the research based on routine healthcare data, a majority of the prediction model studies using machine learning does not report sufficient information on the presence and handling of missing data. Strategies in which patient data are simply omitted are unfortunately the most often used methods, even though it is generally advised against and well known that it likely causes bias and loss of analytical power in prediction model development and in the predictive accuracy estimates. Prediction model researchers should be much more aware of alternative methodologies to address missing data.",,pdf:http://www.jclinepi.com/article/S0895435621003759/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.11.023
@@ -947,15 +947,15 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 33503030,https://doi.org/10.1371/journal.pone.0245636,Classification of road traffic injury collision characteristics using text mining analysis: Implications for road injury prevention.,"Giummarra MJ, Beck B, Gabbe BJ.",,PloS one,2021,2021-01-27,Y,,,,"Road traffic injuries are a leading cause of morbidity and mortality globally. Understanding circumstances leading to road traffic injury is crucial to improve road safety, and implement countermeasures to reduce the incidence and severity of road trauma. We aimed to characterise crash characteristics of road traffic collisions in Victoria, Australia, and to examine the relationship between crash characteristics and fault attribution. Data were extracted from the Victorian State Trauma Registry for motor vehicle drivers, motorcyclists, pedal cyclists and pedestrians with a no-fault compensation claim, aged > = 16 years and injured 2010-2016. People with intentional injury, serious head injury, no compensation claim/missing injury event description or who died < = 12-months post-injury were excluded, resulting in a sample of 2,486. Text mining of the injury event using QDA Miner and Wordstat was used to classify crash circumstances for each road user group. Crashes in which no other was at fault included circumstances involving lost control or avoiding a hazard, mechanical failure or medical conditions. Collisions in which another was predominantly at fault occurred at intersections with another vehicle entering from an adjacent direction, and head-on collisions. Crashes with higher prevalence of unknown fault included multi-vehicle collisions, pedal cyclists injured in rear-end collisions, and pedestrians hit while crossing the road or navigating slow traffic areas. We discuss several methods to promote road safety and to reduce the incidence and severity of road traffic injuries. Our recommendations take into consideration the incidence and impact of road trauma for different types of road users, and include engineering and infrastructure controls through to interventions targeting or accommodating human behaviour.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0245636&type=printable; doi:https://doi.org/10.1371/journal.pone.0245636; html:https://europepmc.org/articles/PMC7840051; pdf:https://europepmc.org/articles/PMC7840051?pdf=render
 35673545,https://doi.org/10.12688/wellcomeopenres.17231.2,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study.,"Cann A, Clarke C, Brown J, Thomson T, Prendecki M, Moshe M, Badhan A, Simmons B, Klaber B, Elliott P, Darzi A, Riley S, Ashby D, Martin P, Gleeson S, Willicombe M, Kelleher P, Ward H, Barclay WS, Cooke GS.",,Wellcome open research,2021,2021-01-01,Y,Antibodies; Seroprevalence; Lateral Flow; Neutralisation; Lfia; Covid-19; Sars-cov-2,,,"<b>Background:</b> Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. <b>Methods:</b> This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay <b>Results:</b> The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) <b>Conclusions:</b> Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.",,doi:https://doi.org/10.12688/wellcomeopenres.17231.2; html:https://europepmc.org/articles/PMC9152464; pdf:https://europepmc.org/articles/PMC9152464?pdf=render
 35987738,https://doi.org/10.1016/j.jcmg.2022.06.017,Benefits of Machine Learning to Predict Survival Using Stress Perfusion CMR and Basic Clinical Information.,"Petersen SE, Aung N.",,JACC. Cardiovascular imaging,2022,2022-08-17,N,Machine Learning; Cardiovascular Magnetic Resonance; Vasodilator Stress Perfusion,,,,,doi:https://doi.org/10.1016/j.jcmg.2022.06.017
-36825398,https://doi.org/10.1097/mcp.0000000000000948,Effectiveness and safety of coronavirus disease 2019 vaccines.,"Shi T, Robertson C, Sheikh A.",,Current opinion in pulmonary medicine,2023,2023-02-24,Y,,,,"<h4>Purpose of review</h4>To review and summarise recent evidence on the effectiveness of coronavirus disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 hospitalisation and death in adults as well as in specific population groups, namely pregnant women, and children and adolescents. We also sought to summarise evidence on vaccine safety in relation to cardiovascular and neurological complications. In order to do so, we drew primarily on evidence from two our own data platforms and supplement these with insights from related large population-based studies and systematic reviews.<h4>Recent findings</h4>All studies showed high vaccine effectiveness against confirmed SARS-CoV-2 infection and in particular against COVID-19 hospitalisation and death. However, vaccine effectiveness against symptomatic COVID-19 infection waned over time. These studies also found that booster vaccines would be needed to maintain high vaccine effectiveness against severe COVID-19 outcomes. Rare cardiovascular and neurological complications have been reported in association with COVID-19 vaccines.<h4>Summary</h4>The findings from this paper support current recommendations that vaccination remains the safest way for adults, pregnant women, children and adolescents to be protected against COVID-19. There is a need to continue to monitor the effectiveness and safety of COVID-19 vaccines as these continue to be deployed in the evolving pandemic.",,html:https://journals.lww.com/co-pulmonarymedicine/Fulltext/9900/Effectiveness_and_safety_of_coronavirus_disease.53.aspx; doi:https://doi.org/10.1097/MCP.0000000000000948; html:https://europepmc.org/articles/PMC10090353; pdf:https://europepmc.org/articles/PMC10090353?pdf=render
 32896935,https://doi.org/10.1002/cbm.2166,Are Liaison and Diversion interventions in policing delivering the planned impact: A longitudinal evaluation in two constabularies?,"Kane E, Evans E, Mitsch J, Jilani T.",,Criminal behaviour and mental health : CBMH,2020,2020-09-08,N,Mental health; Outcomes; Offending; Policing; Liaison & Diversion,,,"Liaison and Diversion (L&D) has twin objectives: improving mental health outcomes and reducing re-offending. Early diversion from police custody seems promising, but evidence of benefit is required to sustain such programmes. To test the hypothesis that contact with L&D services while in police custody would lead to improved mental health outcomes and a reduction in type and level of offending, we used a pre-post service use design. National Health Service (NHS) records in two counties were searched for evidence that patients had been involved with L&D services while in police custody during the period July 2009-December 2017. We defined January 2009-July 2014 as the pre-intervention period and any time after contact as the post-intervention period. Data from the Police National Computer were gathered for each period for these individuals, to assess their pre-post L&D contact offending histories. NHS Trust data were similarly gathered to assess their pre-post use of mental health legislation. 4,462 individuals were identified who had used L&D services in police custody. There were statistically significant reductions in the amount of offending following contact with the L&D service (whether one or two contacts), regardless of offence type. Statistically significant reductions were also observed in use of the four most commonly used legislative powers for detaining patients in hospital on mental disorder grounds, regardless of offending status (prolific/non-prolific). Our results indicate positive associations between the L&D interventions and change in offending and use of compulsory hospital detention. Whilst our research does not allow a direct causal relationship to be established in either area, the findings go beyond other impact assessments of L&D which have either been with small samples or relied only on qualitative data or expert opinion.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cbm.2166; doi:https://doi.org/10.1002/cbm.2166
+36825398,https://doi.org/10.1097/mcp.0000000000000948,Effectiveness and safety of coronavirus disease 2019 vaccines.,"Shi T, Robertson C, Sheikh A.",,Current opinion in pulmonary medicine,2023,2023-02-24,Y,,,,"<h4>Purpose of review</h4>To review and summarise recent evidence on the effectiveness of coronavirus disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 hospitalisation and death in adults as well as in specific population groups, namely pregnant women, and children and adolescents. We also sought to summarise evidence on vaccine safety in relation to cardiovascular and neurological complications. In order to do so, we drew primarily on evidence from two our own data platforms and supplement these with insights from related large population-based studies and systematic reviews.<h4>Recent findings</h4>All studies showed high vaccine effectiveness against confirmed SARS-CoV-2 infection and in particular against COVID-19 hospitalisation and death. However, vaccine effectiveness against symptomatic COVID-19 infection waned over time. These studies also found that booster vaccines would be needed to maintain high vaccine effectiveness against severe COVID-19 outcomes. Rare cardiovascular and neurological complications have been reported in association with COVID-19 vaccines.<h4>Summary</h4>The findings from this paper support current recommendations that vaccination remains the safest way for adults, pregnant women, children and adolescents to be protected against COVID-19. There is a need to continue to monitor the effectiveness and safety of COVID-19 vaccines as these continue to be deployed in the evolving pandemic.",,html:https://journals.lww.com/co-pulmonarymedicine/Fulltext/9900/Effectiveness_and_safety_of_coronavirus_disease.53.aspx; doi:https://doi.org/10.1097/MCP.0000000000000948; html:https://europepmc.org/articles/PMC10090353; pdf:https://europepmc.org/articles/PMC10090353?pdf=render
 31711534,https://doi.org/10.1186/s13326-019-0216-2,Combining string and phonetic similarity matching to identify misspelt names of drugs in medical records written in Portuguese.,"Tissot H, Dobson R.",,Journal of biomedical semantics,2019,2019-11-12,Y,Similarity Search; Phonetic Similarity; Misspelt Names Of Drugs,,,"<h4>Background</h4>There is an increasing amount of unstructured medical data that can be analysed for different purposes. However, information extraction from free text data may be particularly inefficient in the presence of spelling errors. Existing approaches use string similarity methods to search for valid words within a text, coupled with a supporting dictionary. However, they are not rich enough to encode both typing and phonetic misspellings.<h4>Results</h4>Experimental results showed a joint string and language-dependent phonetic similarity is more accurate than traditional string distance metrics when identifying misspelt names of drugs in a set of medical records written in Portuguese.<h4>Conclusion</h4>We present a hybrid approach to efficiently perform similarity match that overcomes the loss of information inherit from using either exact match search or string based similarity search methods.",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0216-2; doi:https://doi.org/10.1186/s13326-019-0216-2; html:https://europepmc.org/articles/PMC6849162; pdf:https://europepmc.org/articles/PMC6849162?pdf=render
 34427560,https://doi.org/10.1684/ejd.2021.4108,"The association between immunosuppression and skin cancer in solid organ transplant recipients: a control-matched cohort study of 2,852 patients.","Gibson JAG, Cordaro A, Dobbs TD, Griffiths R, Akbari A, Whitaker S, Hutchings HA, Lyons RA, Whitaker IS.",,European journal of dermatology : EJD,2021,2021-12-01,N,Transplant; Oncology; immunosuppression; Skin Cancer,,,"Skin cancer is more common in transplant recipients, although the quoted incidence is variable. This study investigated the incidence of skin cancer in solid organ transplant recipients (OTRs) in a national cohort and the effect of pharmacotherapeutic agents Transplant patients were identified from Patient Episode Database for Wales (PEDW) using Office of Population Census and Surveys Classifications of Interventions and Procedures-4 (OPCS-4) codes. Controls were matched to cases according to age, sex and socioeconomic status. Skin cancer data were obtained from linkage with other national data sources. Incidence was calculated per 100,000 person-years at risk (PYAR). Negative binomial regression was used to calculate adjusted incidence rate ratios (IRRs) for each organ type. During 2000-2018, 2,852 Welsh patients underwent solid organ transplantation. A total of 13,527 controls were matched from the general population. The incidence of skin cancer within the OTR cohort was 1203.2 per 100,000 PYAR vs 133.9 in the matched control group. Age, male gender and azathioprine use were all associated with an increased risk of skin cancer. Contemporary immunomodulators such as tacrolimus and mycophenolate were associated with a reduction in skin cancer risk when compared to their predecessors, cyclosporin and azathioprine. The highest adjusted IRR was observed in heart transplant recipients (IRR: 10.82; 95% CI: 3.64-32.19) and the lowest in liver transplant recipients (IRR: 2.86; 95% CI: 1.15-7.13). This study highlights the need for long-term routine skin cancer surveillance for all OTRs and the importance of using contemporary immunomodulators, when possible, for risk reduction.",,doi:https://doi.org/10.1684/ejd.2021.4108
 34629034,https://doi.org/10.1080/02640414.2021.1928409,Are individual and social factors specific to the home associated with children's behaviour and physical environment at home.,"Sheldrick MPR, Maitland C, Mackintosh KA, Rosenberg M, Griffiths LJ, Fry R, Stratton G.",,Journal of sports sciences,2021,2021-10-09,N,Youth; Family; House; Sedentary Time; Moderate-vigorous Physical Activity,,,"This study used linear regression analyses to investigate the influence of parent-reported home-specific social and individual factors on: (i) 235 children's home-based objectively measured overall sitting time, breaks in sitting, and PA, and; (ii) the home physical environment via an audit. Parental importance assigned to active play for children was positively associated with PA equipment (accessibility and availability), as well as light physical activity (LPA) and sitting breaks on both weekdays and weekend days. Parental preference for being active at home and limits on screen-time were associated with less household media equipment and portable media equipment, respectively. Greater parental importance placed on playing electronic games/using computers for fun was associated with less LPA and more sitting on weekdays. Further, children who preferred being sedentary sat more and engaged in less moderate-vigorous physical activity (MVPA) on weekdays. Parental and child preferences and priorities, as well as parental rules for activity at home, were associated with children's home-based sitting and PA, especially on weekdays. Such factors were also associated with the physical environment in the expected directions. The findings suggest interventions need to target social and individual factors, alongside adapting the physical environment to create homes more promotive of physical activity.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56833/Download/56833__19829__9b0bb77f67e84342b525fbccaba98e67.pdf; doi:https://doi.org/10.1080/02640414.2021.1928409
 34610958,https://doi.org/10.1136/emermed-2019-209368,Association between anticoagulants and mortality and functional outcomes in older patients with major trauma. ,"Sato N, Cameron P, Mclellan S, Beck B, Gabbe B.",,Emergency medicine journal : EMJ,2021,2021-10-05,N,,,,"The number of trauma patients taking anticoagulants and antiplatelet agents is increasing as society ages. However, there have been limited and inconsistent reports of the association between anticoagulants and mortality and functional outcomes. This study aimed to quantify the association between anticoagulant/antiplatelet medication at the time of injury and both short-term and longer-term outcomes in older major trauma patients. This was a population-based registry study using data from the Victorian State Trauma Registry from July 2017 to June 2018. We included patients with major trauma aged 65 years and older. The outcomes of interest were in-hospital mortality, hospital length of stay, intensive care unit length of stay and the Extended Glasgow Outcome Scale (GOS-E) at 6 months after injury. We examined the association between the outcomes and anticoagulants/antiplatelet agents at the time of injury and used multivariable logistic regression models to account for known confounders. There were 1323 older adults eligible for inclusion in the study, of which 249 (18.8%) were taking anticoagulants (n=8 were taking both anticoagulants and antiplatelet agents), 380 (28.7%) were taking antiplatelet agents and 694 (52.5%) were not using either. Any anticoagulant use was associated with higher odds of in-hospital mortality (adjusted OR (AOR), 2.38; 95% CI 1.58 to 3.59) compared with not using anticoagulants. No differences were observed in the GOS-E at 6 months after injury between any anticoagulants use, antiplatelet use and no anticoagulant use (anticoagulant AOR, 0.71; 95% CI 0.48 to 1.05, antiplatelet AOR, 1.02; 95% CI 0.73 to 1.42). Anticoagulant use at the time of injury was associated with higher odds of in-hospital mortality but did not adversely impact functional outcomes at 6 months after injury. These findings demonstrate the importance of seeking an accurate history of anticoagulant use and its indication, as well as the immediate initiation of reversal therapies.",,doi:https://doi.org/10.1136/emermed-2019-209368
 32728709,https://doi.org/10.1093/pubmed/fdaa115,Are children who are home from school at an increased risk of child maltreatment?,"Syed S, Gilbert R.",,"Journal of public health (Oxford, England)",2021,2021-04-01,N,,,,,,pdf:https://discovery.ucl.ac.uk/10110375/1/Syed%20and%20Gilbert%20%282020%29.%20Are%20children%20who%20are%20home%20from%20school%20at%20an%20increased%20risk%20of%20child%20maltreatment.pdf; doi:https://doi.org/10.1093/pubmed/fdaa115
-36942567,https://doi.org/10.1161/circep.122.011585,Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.,"Dickow J, Kany S, Roth Cardoso V, Ellinor PT, Gkoutos GV, Van Houten HK, Kirchhof P, Metzner A, Noseworthy PA, Yao X, Rillig A.",,Circulation. Arrhythmia and electrophysiology,2023,2023-03-21,N,Atrial fibrillation; Stroke; Catheter ablation; Heart Failure; Comorbidity,,,"<h4>Background</h4>A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden.<h4>Methods</h4>We identified 109 739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11 625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4); (2) ERC and lower comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 2-3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 0-1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC.<h4>Results</h4>In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72-0.95]; <i>P</i>=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; <i>P</i>=0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54-1.57]; <i>P</i>=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; <i>P</i>=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- <i>P</i>=0.027) but not in OptumLabs (interaction-<i>P</i>=0.720). ERC was not associated with an increased risk for the primary safety outcome.<h4>Conclusions</h4>ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4).",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.122.011585; doi:https://doi.org/10.1161/CIRCEP.122.011585
 31329239,https://doi.org/10.1093/jamia/ocz105,UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER.,"Denaxas S, Gonzalez-Izquierdo A, Direk K, Fitzpatrick NK, Fatemifar G, Banerjee A, Dobson RJB, Howe LJ, Kuan V, Lumbers RT, Pasea L, Patel RS, Shah AD, Hingorani AD, Sudlow C, Hemingway H.",,Journal of the American Medical Informatics Association : JAMIA,2019,2019-12-01,Y,Phenotyping; Medical Informatics; Personalized Medicine; Electronic Health Records,The Human Phenome,,"<h4>Objective</h4>Electronic health records (EHRs) are a rich source of information on human diseases, but the information is variably structured, fragmented, curated using different coding systems, and collected for purposes other than medical research. We describe an approach for developing, validating, and sharing reproducible phenotypes from national structured EHR in the United Kingdom with applications for translational research.<h4>Materials and methods</h4>We implemented a rule-based phenotyping framework, with up to 6 approaches of validation. We applied our framework to a sample of 15 million individuals in a national EHR data source (population-based primary care, all ages) linked to hospitalization and death records in England. Data comprised continuous measurements (for example, blood pressure; medication information; coded diagnoses, symptoms, procedures, and referrals), recorded using 5 controlled clinical terminologies: (1) read (primary care, subset of SNOMED-CT [Systematized Nomenclature of Medicine Clinical Terms]), (2) International Classification of Diseases-Ninth Revision and Tenth Revision (secondary care diagnoses and cause of mortality), (3) Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures, Fourth Revision (hospital surgical procedures), and (4) DM+D prescription codes.<h4>Results</h4>Using the CALIBER phenotyping framework, we created algorithms for 51 diseases, syndromes, biomarkers, and lifestyle risk factors and provide up to 6 validation approaches. The EHR phenotypes are curated in the open-access CALIBER Portal (https://www.caliberresearch.org/portal) and have been used by 40 national and international research groups in 60 peer-reviewed publications.<h4>Conclusions</h4>We describe a UK EHR phenomics approach within the CALIBER EHR data platform with initial evidence of validity and use, as an important step toward international use of UK EHR data for health research.",,doi:https://doi.org/10.1093/jamia/ocz105; doi:https://doi.org/10.1093/jamia/ocz105; html:https://europepmc.org/articles/PMC6857510; pdf:https://europepmc.org/articles/PMC6857510?pdf=render
+36942567,https://doi.org/10.1161/circep.122.011585,Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.,"Dickow J, Kany S, Roth Cardoso V, Ellinor PT, Gkoutos GV, Van Houten HK, Kirchhof P, Metzner A, Noseworthy PA, Yao X, Rillig A.",,Circulation. Arrhythmia and electrophysiology,2023,2023-03-21,N,Atrial fibrillation; Stroke; Catheter ablation; Heart Failure; Comorbidity,,,"<h4>Background</h4>A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden.<h4>Methods</h4>We identified 109 739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11 625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4); (2) ERC and lower comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 2-3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 0-1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC.<h4>Results</h4>In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72-0.95]; <i>P</i>=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; <i>P</i>=0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54-1.57]; <i>P</i>=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; <i>P</i>=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- <i>P</i>=0.027) but not in OptumLabs (interaction-<i>P</i>=0.720). ERC was not associated with an increased risk for the primary safety outcome.<h4>Conclusions</h4>ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4).",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.122.011585; doi:https://doi.org/10.1161/CIRCEP.122.011585
 34939031,https://doi.org/10.1093/braincomms/fcab241,Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia.,"Vuksanović V, Staff RT, Morson S, Ahearn T, Bracoud L, Murray AD, Bentham P, Kipps CM, Harrington CR, Wischik CM.",,Brain communications,2021,2021-10-21,Y,Neurodegeneration; Brain Networks; Behavioural Variant Frontotemporal Dementia; Rich Club; Anatomical Subtypes,,,"The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke's Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome.",,pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab241/41829863/fcab241.pdf; doi:https://doi.org/10.1093/braincomms/fcab241; html:https://europepmc.org/articles/PMC8688778; pdf:https://europepmc.org/articles/PMC8688778?pdf=render
 35151869,https://doi.org/10.1016/j.jbi.2022.104010,Patient-centric characterization of multimorbidity trajectories in patients with severe mental illnesses: A temporal bipartite network modeling approach.,"Wang T, Bendayan R, Msosa Y, Pritchard M, Roberts A, Stewart R, Dobson R.",,Journal of biomedical informatics,2022,2022-02-11,Y,Network Evolution; Multimorbidity; Severe Mental Illnesses; Disease Trajectories; Temporal Bipartite Network; Ehr Data Linkage,,,"Multimorbidity is a major factor contributing to increased mortality among people with severe mental illnesses (SMI). Previous studies either focus on estimating prevalence of a disease in a population without considering relationships between diseases or ignore heterogeneity of individual patients in examining disease progression by looking merely at aggregates across a whole cohort. Here, we present a temporal bipartite network model to jointly represent detailed information on both individual patients and diseases, which allows us to systematically characterize disease trajectories from both patient and disease centric perspectives. We apply this approach to a large set of longitudinal diagnostic records for patients with SMI collected through a data linkage between electronic health records from a large UK mental health hospital and English national hospital administrative database. We find that the resulting diagnosis networks show disassortative mixing by degree, suggesting that patients affected by a small number of diseases tend to suffer from prevalent diseases. Factors that determine the network structures include an individual's age, gender and ethnicity. Our analysis on network evolution further shows that patients and diseases become more interconnected over the illness duration of SMI, which is largely driven by the process that patients with similar attributes tend to suffer from the same conditions. Our analytic approach provides a guide for future patient-centric research on multimorbidity trajectories and contributes to achieving precision medicine.",,doi:https://doi.org/10.1016/j.jbi.2022.104010; doi:https://doi.org/10.1016/j.jbi.2022.104010; html:https://europepmc.org/articles/PMC8894882
 36501061,https://doi.org/10.3390/nu14235031,Associations of Genetically Predicted Vitamin B<sub>12</sub> Status across the Phenome.,"Dib MJ, Ahmadi KR, Zagkos L, Gill D, Morris B, Elliott P, Dehghan A, Tzoulaki I.",,Nutrients,2022,2022-11-26,Y,Vitamin B12; Deficiency; epidemiology; Mendelian Randomisation; Pernicious Anaemia,,,"Variation in vitamin B<sub>12</sub> levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B<sub>12</sub> status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B<sub>12</sub> levels, serving as genetic instruments for vitamin B<sub>12</sub> status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B<sub>12</sub> status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B<sub>12</sub> status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B<sub>12</sub> status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B<sub>12</sub> status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20-0.50) and pernicious anaemia (0.29, 0.19-0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B<sub>12</sub> status is potentially protective of risk of vitamin B<sub>12</sub> deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B<sub>12</sub> status in disease diagnosis, progression and management remains to be investigated.",,pdf:https://www.mdpi.com/2072-6643/14/23/5031/pdf?version=1669449806; doi:https://doi.org/10.3390/nu14235031; html:https://europepmc.org/articles/PMC9740080; pdf:https://europepmc.org/articles/PMC9740080?pdf=render
@@ -969,8 +969,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 34506014,https://doi.org/10.1007/s11605-020-04612-8,"The Impact of a Centralised Pancreatic Cancer Service: a Case Study of Wales, UK.","Mowbray NG, Griffiths R, Akbari A, Hutchings H, Jenkins G, Al-Sarireh B.",,Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract,2022,2021-09-10,N,Pancreatic cancer; Pancreatic Surgery; Centralisation,,,"<h4>Introduction</h4>The centralisation of pancreatic cancer (PC) services still varies worldwide. This study aimed to assess the impact that a centralisation has had on patients in South Wales, UK.<h4>Methods</h4>A retrospective cohort analysis of patients in South Wales, UK, with PC prior to (2004-2009), and after (2010-2014) the formation of a specialist centre. Patients were identified using record linkage of electronic health records.<h4>Results</h4>The overall survival (OS) of all 3413 patients with PC increased from a median (IQR) 10 weeks (3-31) to 11 weeks (4-35), p = 0.038, after centralisation. The OS of patients undergoing surgical resection or chemotherapy alone did not improve (93 weeks (39-203) vs. 90 weeks (50-95), p = 0.764 and 33 weeks (20-57) vs. 33 weeks (19-58), p = 0.793). Surgical resection and chemotherapy rates increased (6.1% vs. 9.2%, p < 0.001 and 19.7% vs. 27.0%, p < 0.001). The 30-day mortality rate trended downwards (7.2% vs. 3.6%, p = 0.186). The percentage of patients who received no treatment reduced (75.2% vs. 69.6%, p < 0.001).<h4>Conclusion</h4>The centralisation of PC services in South Wales is associated with a small increase in OS and a larger increase in PC treatment utilisation. It is concerning that many patients still fail to receive any treatments.",,doi:https://doi.org/10.1007/s11605-020-04612-8
 37119604,https://doi.org/10.1016/j.canep.2023.102367,"Whole-population trends in pathology-confirmed cancer incidence in Northern Ireland, Scotland and Wales during the SARS-CoV-2 pandemic: A retrospective observational study.","Greene GJ, Thomson CS, Donnelly D, Chung D, Bhatti L, Gavin AT, Lawler M, Huws DW, Rolles MJ, Bennée F, Morrison DS.",,Cancer epidemiology,2023,2023-04-21,Y,Pandemic; Population-based Incidence; Covid-19; Sars-cov-2; Pathology-Confirmed Cancer,,,"<h4>Introduction</h4>The COVID-19 epidemic interrupted normal cancer diagnosis procedures. Population-based cancer registries report incidence at least 18 months after it happens. Our goal was to make more timely estimates by using pathologically confirmed cancers (PDC) as a proxy for incidence. We compared the 2020 and 2021 PDC with the 2019 pre-pandemic baseline in Scotland, Wales, and Northern Ireland (NI).<h4>Methods</h4>Numbers of female breast (ICD-10 C50), lung (C33-34), colorectal (C18-20), gynaecological (C51-58), prostate (C61), head and neck (C00-C14, C30-32), upper gastro-intestinal (C15-16), urological (C64-68), malignant melanoma (C43), and non-melanoma skin (NMSC) (C44) cancers were counted. Multiple pairwise comparisons generated incidence rate ratios (IRR).<h4>Results</h4>Data were accessible within 5 months of the pathological diagnosis date. Between 2019 and 2020, the number of pathologically confirmed malignancies (excluding NMSC) decreased by 7315 (14.1 %). Scotland experienced early monthly declines of up to 64 % (colorectal cancers, April 2020 versus April 2019). Wales experienced the greatest overall change in 2020, but Northern Ireland experienced the quickest recovery. The pandemic's effects varied by cancer type, with no significant change in lung cancer diagnoses in Wales in 2020 (IRR 0.97 (95 % CI 0.90-1.05)), followed by an increase in 2021 (IRR 1.11 (1.03-1.20).<h4>Conclusion</h4>PDC are useful in reporting cancer incidence quicker than cancer registrations. Temporal and geographical differences between participating countries mirrored differences in responses to the COVID-19 pandemic, indicating face validity and the potential for quick cancer diagnosis assessment. To verify their sensitivity and specificity against the gold standard of cancer registrations, however, additional research is required.",,doi:https://doi.org/10.1016/j.canep.2023.102367; html:https://europepmc.org/articles/PMC10121133; pdf:https://europepmc.org/articles/PMC10121133?pdf=render
 35440465,https://doi.org/10.3399/bjgp.2021.0689,Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study.,"Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Warfarin; Factor Xa Inhibitors; Dabigatran; Covid-19,,,"<h4>Background</h4>Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited.<h4>Aim</h4>To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of 2.<h4>Design and setting</h4>On behalf of NHS England, a population-based cohort study was conducted.<h4>Method</h4>The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice.<h4>Results</h4>Of 71 103 people with atrial fibrillation and a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use.<h4>Conclusion</h4>Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.",,pdf:https://bjgp.org/content/bjgp/early/2022/04/19/BJGP.2021.0689.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?pdf=render
-34631820,https://doi.org/10.3389/fcvm.2021.716577,New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.,"Rauseo E, Izquierdo Morcillo C, Raisi-Estabragh Z, Gkontra P, Aung N, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2021-09-23,Y,Myocardial infarction; Stroke; Cerebrovascular disease; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Radiomics; Brain-heart Axis,,,"<b>Background:</b> Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions. <b>Objective:</b> To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. <b>Methods:</b> We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (<i>n</i> = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired <i>t</i>-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. <b>Results:</b> In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found. <b>Conclusions:</b> This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.716577/pdf; doi:https://doi.org/10.3389/fcvm.2021.716577; html:https://europepmc.org/articles/PMC8494975; pdf:https://europepmc.org/articles/PMC8494975?pdf=render
 33820530,https://doi.org/10.1186/s12916-021-01940-7,"Machine learning for subtype definition and risk prediction in heart failure, acute coronary syndromes and atrial fibrillation: systematic review of validity and clinical utility.","Banerjee A, Chen S, Fatemifar G, Zeina M, Lumbers RT, Mielke J, Gill S, Kotecha D, Freitag DF, Denaxas S, Hemingway H.",,BMC medicine,2021,2021-04-06,Y,Subtype; Cardiovascular disease; Systematic review; Machine Learning; Informatics; Risk Prediction,,,"<h4>Background</h4>Machine learning (ML) is increasingly used in research for subtype definition and risk prediction, particularly in cardiovascular diseases. No existing ML models are routinely used for cardiovascular disease management, and their phase of clinical utility is unknown, partly due to a lack of clear criteria. We evaluated ML for subtype definition and risk prediction in heart failure (HF), acute coronary syndromes (ACS) and atrial fibrillation (AF).<h4>Methods</h4>For ML studies of subtype definition and risk prediction, we conducted a systematic review in HF, ACS and AF, using PubMed, MEDLINE and Web of Science from January 2000 until December 2019. By adapting published criteria for diagnostic and prognostic studies, we developed a seven-domain, ML-specific checklist.<h4>Results</h4>Of 5918 studies identified, 97 were included. Across studies for subtype definition (n = 40) and risk prediction (n = 57), there was variation in data source, population size (median 606 and median 6769), clinical setting (outpatient, inpatient, different departments), number of covariates (median 19 and median 48) and ML methods. All studies were single disease, most were North American (n = 61/97) and only 14 studies combined definition and risk prediction. Subtype definition and risk prediction studies respectively had limitations in development (e.g. 15.0% and 78.9% of studies related to patient benefit; 15.0% and 15.8% had low patient selection bias), validation (12.5% and 5.3% externally validated) and impact (32.5% and 91.2% improved outcome prediction; no effectiveness or cost-effectiveness evaluations).<h4>Conclusions</h4>Studies of ML in HF, ACS and AF are limited by number and type of included covariates, ML methods, population size, country, clinical setting and focus on single diseases, not overlap or multimorbidity. Clinical utility and implementation rely on improvements in development, validation and impact, facilitated by simple checklists. We provide clear steps prior to safe implementation of machine learning in clinical practice for cardiovascular diseases and other disease areas.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-01940-7; doi:https://doi.org/10.1186/s12916-021-01940-7; html:https://europepmc.org/articles/PMC8022365; pdf:https://europepmc.org/articles/PMC8022365?pdf=render
+34631820,https://doi.org/10.3389/fcvm.2021.716577,New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.,"Rauseo E, Izquierdo Morcillo C, Raisi-Estabragh Z, Gkontra P, Aung N, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2021-09-23,Y,Myocardial infarction; Stroke; Cerebrovascular disease; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Radiomics; Brain-heart Axis,,,"<b>Background:</b> Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions. <b>Objective:</b> To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. <b>Methods:</b> We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (<i>n</i> = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired <i>t</i>-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. <b>Results:</b> In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found. <b>Conclusions:</b> This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.716577/pdf; doi:https://doi.org/10.3389/fcvm.2021.716577; html:https://europepmc.org/articles/PMC8494975; pdf:https://europepmc.org/articles/PMC8494975?pdf=render
 35188950,https://doi.org/10.1001/jamaneurol.2021.5420,Risk Factors and Prognosis of Early Posttraumatic Seizures in Moderate to Severe Traumatic Brain Injury.,"Laing J, Gabbe B, Chen Z, Perucca P, Kwan P, O'Brien TJ.",,JAMA neurology,2022,2022-04-01,N,,,,"<h4>Importance</h4>Early posttraumatic seizures (EPS) that may occur following a traumatic brain injury (TBI) are associated with poorer outcomes and development of posttraumatic epilepsy (PTE).<h4>Objective</h4>To evaluate risk factors for EPS, associated morbidity and mortality, and contribution to PTE.<h4>Design, setting, and participants</h4>Data were collected from an Australian registry-based cohort study of adults (age ≥18 years) with moderate to severe TBI from January 2005 to December 2019, with 2-year follow-up. The statewide trauma registry, conducted on an opt-out basis in Victoria (population 6.5 million), had 15 152 patients with moderate to severe TBI identified via Abbreviated Injury Scale (AIS) head severity score, with an opt-out rate less than 0.5% (opt-out n = 136).<h4>Main outcomes and measures</h4>EPS were identified via International Statistical Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes recorded after the acute admission. Outcome measures also included in-hospital metrics, 2-year outcomes including PTE, and post-discharge mortality. Adaptive least absolute shrinkage and selection operator (LASSO) regression was used to build a prediction model for risk factors of EPS.<h4>Results</h4>Among the 15 152 participants (10 457 [69%] male; median [IQR] age, 60 [35-79] y), 416 (2.7%) were identified with EPS, including 27 (0.2%) with status epilepticus. Significant risk factors on multivariable analysis for developing EPS were younger age, higher Charlson Comorbidity Index, TBI sustained from a low fall, subdural hemorrhage, subarachnoid hemorrhage, higher Injury Severity Score, and greater head injury severity, measured using the AIS and Glasgow Coma Score. After adjustment for confounders, EPS were associated with increased ICU admission and ICU length of stay, ventilation and duration, hospital length of stay, and discharge to inpatient rehabilitation rather than home, but not in-hospital mortality. Outcomes in TBI admission survivors at 24 months, including mortality (relative risk [RR] = 2.14; 95% CI, 1.32-3.46; P = .002), development of PTE (RR = 2.91; 95% CI, 2.22-3.81; P < .001), and use of antiseizure medications (RR = 2.44; 95% CI, 1.98-3.02; P < .001), were poorer for cases with EPS after adjustment for confounders. The prediction model for EPS had an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.66-0.79), sensitivity of 66%, and specificity of 73% in the validation set.<h4>Discussion</h4>We identified important risk factors for EPS following moderate to severe TBI. Early posttraumatic seizures were associated with longer ICU and hospital admissions, ICU ventilation, and poorer 24-month outcomes including mortality and development of PTE.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420; html:https://europepmc.org/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420
 37394283,https://doi.org/10.1002/ehf2.14444,Survival after HeartMate 3 left ventricular assist device implantation: real-world data from Europe.,"Numan L, Schramm R, Oerlemans MIFJ, van der Kaaij NP, Aarts E, Ramjankhan FZ, Oppelaar AM, Morshuis M, Guenther SPW, Zimpfer D, Riebandt J, Wiedemann D, Asselbergs FW, Van Laake LW.",,ESC heart failure,2023,2023-07-02,Y,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14444; doi:https://doi.org/10.1002/ehf2.14444; html:https://europepmc.org/articles/PMC10375103; pdf:https://europepmc.org/articles/PMC10375103?pdf=render
 35642867,https://doi.org/10.1111/bjhp.12606,"Perceived threat of COVID-19, attitudes towards vaccination, and vaccine hesitancy: A prospective longitudinal study in the UK.","Phillips R, Gillespie D, Hallingberg B, Evans J, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Sheils E, Ashfield-Watt P, Akbari A, Hughes K, Thomas-Jones E, James D, Wood F.",,British journal of health psychology,2022,2022-06-01,Y,Risk Perception; Behaviour Change; Vaccine Hesitancy; Covid-19; Sars Cov2,,,"<h4>Objectives</h4>Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID-19, COVID-19 vaccinations, and vaccine hesitancy and change in these variables over a 9-month period in a UK cohort.<h4>Methods</h4>The COPE study cohort (n = 11,113) was recruited via an online survey at enrolment in March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow-up data were available for 6942 people at 3 months (June/July 2020) and 5037 at 12 months (March/April 2021) post-enrolment. Measures included demographics, perceived threat of COVID-19, perceived control, intention to accept or decline a COVID-19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross-sectionally at 3 and 12 months to assess the association between motivational factors and vaccine hesitancy. Longitudinal changes in motivational variables for vaccine-hesitant and non-hesitant groups were examined using mixed-effect analysis of variance models.<h4>Results</h4>Fear of COVID-19, perceived susceptibility to COVID-19, and perceived personal control over COVID-19 infection transmission decreased between the 3- and 12-month surveys. Vaccine hesitancy at 12 months was independently associated with low fear of the disease and more negative attitudes towards COVID-19 vaccination. Specific barriers to COVID-19 vaccine uptake included concerns about safety and efficacy in light of its rapid development, mistrust of government and pharmaceutical companies, dislike of coercive policies, and perceived lack of relaxation in COVID-19-related restrictions as the vaccination programme progressed.<h4>Conclusions</h4>Decreasing fear of COVID-19, perceived susceptibility to the disease, and perceptions of personal control over reducing infection-transmission may impact future COVID-19 vaccination uptake.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa60128/Download/60128__24479__4d74009536e649b0b17180e2bfd80435.pdf; doi:https://doi.org/10.1111/bjhp.12606; html:https://europepmc.org/articles/PMC9347957; pdf:https://europepmc.org/articles/PMC9347957?pdf=render
@@ -978,9 +978,9 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 37669576,https://doi.org/10.1016/j.schres.2023.08.024,Unraveling ethnic disparities in antipsychotic prescribing among patients with psychosis: A retrospective cohort study based on electronic clinical records.,"Wang T, Codling D, Bhugra D, Msosa Y, Broadbent M, Patel R, Roberts A, McGuire P, Stewart R, Dobson R, Harland R.",,Schizophrenia research,2023,2023-09-03,N,Psychopharmacology; Psychosis; Ethnicity; Electronic Health Records; Healthcare Inequality; Antipsychotic Prescription,,,"<h4>Background</h4>Previous studies have shown mixed evidence on ethnic disparities in antipsychotic prescribing among patients with psychosis in the UK, partly due to small sample sizes. This study aimed to examine the current state of antipsychotic prescription with respect to patient ethnicity among the entire population known to a large UK mental health trust with non-affective psychosis, adjusting for multiple potential risk factors.<h4>Methods</h4>This retrospective cohort study included all patients (N = 19,291) who were aged 18 years or over at their first diagnoses of non-affective psychosis (identified with the ICD-10 codes of F20-F29) recorded in electronic health records (EHRs) at the South London and Maudsley NHS Trust until March 2021. The most recently recorded antipsychotic treatments and patient attributes were extracted from EHRs, including both structured fields and free-text fields processed using natural language processing applications. Multivariable logistic regression models were used to calculate the odds ratios (OR) for antipsychotic prescription according to patient ethnicity, adjusted for multiple potential contributing factors, including demographic (age and gender), clinical (diagnoses, duration of illness, service use and history of cannabis use), socioeconomic factors (level of deprivation and own-group ethnic density in the area of residence) and temporal changes in clinical guidelines (date of prescription).<h4>Results</h4>The cohort consisted of 43.10 % White, 8.31 % Asian, 40.80 % Black, 2.64 % Mixed, and 5.14 % of patients from Other ethnicity. Among them, 92.62 % had recorded antipsychotic receipt, where 24.05 % for depot antipsychotics and 81.72 % for second-generation antipsychotic (SGA) medications. Most ethnic minority groups were not significantly different from White patients in receiving any antipsychotic. Among those receiving antipsychotic prescribing, Black patients were more likely to be prescribed depot (adjusted OR 1.29, 95 % confidence interval (CI) 1.14-1.47), but less likely to receive SGA (adjusted OR 0.85, 95 % CI 0.74-0.97), olanzapine (OR 0.82, 95 % CI 0.73-0.92) and clozapine (adjusted OR 0.71, 95 % CI 0.6-0.85) than White patients. All the ethnic minority groups were less likely to be prescribed olanzapine than the White group.<h4>Conclusions</h4>Black patients with psychosis had a distinct pattern in antipsychotic prescription, with less use of SGA, including olanzapine and clozapine, but more use of depot antipsychotics, even when adjusting for the effects of multiple demographic, clinical and socioeconomic factors. Further research is required to understand the sources of these ethnic disparities and eliminate care inequalities.",,doi:https://doi.org/10.1016/j.schres.2023.08.024
 34871122,https://doi.org/10.1080/09638288.2021.2008526,Pain and mental health symptom patterns and treatment trajectories following road trauma: a registry-based cohort study.,"Huang S, Dipnall JF, Gabbe BJ, Giummarra MJ.",,Disability and rehabilitation,2022,2021-12-06,N,Injury; Recovery; Pain; Mental health; Healthcare Use,,,"<h4>Purpose</h4>This study aimed to characterise recovery from pain and mental health symptoms, and identify whether treatment use facilitates recovery.<h4>Methods</h4>Victorian State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry participants without neurotrauma who had transport injury claims with the Transport Accident Commission from 2007 to 2014 were included (<i>n</i> = 5908). Latent transition analysis of pain Numeric Rating Scale, SF-12, and EQ-5D-3L pain and mental health items from 6 to 12 months, and 12 to 24 months post-injury were used to identify symptom transitions.<h4>Results</h4>Four transition groups were identified: transition to low problems by 12-months; transition to low problems at 24-months; stable low problems; and no transition from problems. Group-based trajectory modelling of pain and mental health treatments found three treatment trajectories: low/no treatment, a moderate treatment that declined to low treatment 3-12 months post-injury, and increasing treatment over time. Predictors of pain and mental health recovery transitions, identified using multinomial logistic regression, were primarily found to be non-modifiable socioeconomic and health-related characteristics (e.g., higher education, working pre-injury, and not having comorbidities), and low treatment trajectories.<h4>Conclusions</h4>Targeted and collaborative rehabilitation should be considered for people at risk of persistent pain or mental health symptoms to optimise their recovery, particularly patients with socioeconomic disadvantage.IMPLICATIONS FOR REHABILITATIONTwo-thirds of people experience pain and/or mental health within the first 24-months after hospitalization for road trauma, of whom only 6-7% recover by 12-months, and a further 6% recover by 24-months post-injury.There were three main trajectories of administrative records of treatments received in the first two years after injury: 76 and 83% had low treatment, 18 and 12% had moderate then declining treatment levels, and 6 and 5% had stable high treatment for pain or mental health, respectively.People who recovered from pain or mental health symptoms generally had lower treatment and higher socioeconomic position, highlighting that coordinated rehabilitation care should be prioritized for people living with socioeconomic disadvantage.",,doi:https://doi.org/10.1080/09638288.2021.2008526
 33707775,https://doi.org/10.1038/s41591-021-01266-0,Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.,"Pietzner M, Stewart ID, Raffler J, Khaw KT, Michelotti GA, Kastenmüller G, Wareham NJ, Langenberg C.",,Nature medicine,2021,2021-03-11,N,,,,"Multimorbidity, the simultaneous presence of multiple chronic conditions, is an increasing global health problem and research into its determinants is of high priority. We used baseline untargeted plasma metabolomics profiling covering >1,000 metabolites as a comprehensive readout of human physiology to characterize pathways associated with and across 27 incident noncommunicable diseases (NCDs) assessed using electronic health record hospitalization and cancer registry data from over 11,000 participants (219,415 person years). We identified 420 metabolites shared between at least 2 NCDs, representing 65.5% of all 640 significant metabolite-disease associations. We integrated baseline data on over 50 diverse clinical risk factors and characteristics to identify actionable shared pathways represented by those metabolites. Our study highlights liver and kidney function, lipid and glucose metabolism, low-grade inflammation, surrogates of gut microbial diversity and specific health-related behaviors as antecedents of common NCD multimorbidity with potential for early prevention. We integrated results into an open-access webserver ( https://omicscience.org/apps/mwasdisease/ ) to facilitate future research and meta-analyses.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127079; doi:https://doi.org/10.1038/s41591-021-01266-0; html:https://europepmc.org/articles/PMC8127079; pdf:https://europepmc.org/articles/PMC8127079?pdf=render; doi:https://doi.org/10.1038/s41591-021-01266-0
+34270458,https://doi.org/10.4269/ajtmh.21-0482,The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.,"Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",,The American journal of tropical medicine and hygiene,2021,2021-07-16,Y,,,,"The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",,pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render
 37658971,https://doi.org/10.1007/s11897-023-00626-w,Multimorbidity in Heart Failure: Leveraging Cluster Analysis to Guide Tailored Treatment Strategies.,"van de Veerdonk MC, Savarese G, Handoko ML, Beulens JWJ, Asselbergs F, Uijl A.",,Current heart failure reports,2023,2023-09-02,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Treatment Response; Precision Medicine,,,"<h4>Review purpose</h4>This review summarises key findings on treatment effects within phenotypical clusters of patients with heart failure (HF), making a distinction between patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).<h4>Findings</h4>Treatment response differed among clusters; ACE inhibitors were beneficial in all HFrEF phenotypes, while only some studies show similar beneficial prognostic effects in HFpEF patients. Beta-blockers had favourable effects in all HFrEF patients but not in HFpEF phenotypes and tended to worsen prognosis in older, cardiorenal patients. Mineralocorticoid receptor antagonists had more favourable prognostic effects in young, obese males and metabolic HFpEF patients. While a phenotype-guided approach is a promising solution for individualised treatment strategies, there are several aspects that still require improvements before such an approach could be implemented in clinical practice. Stronger evidence from clinical trials and real-world data may assist in establishing a phenotype-guided treatment approach for patient with HF in the future.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00626-w.pdf; doi:https://doi.org/10.1007/s11897-023-00626-w; html:https://europepmc.org/articles/PMC10589138; pdf:https://europepmc.org/articles/PMC10589138?pdf=render
 37884627,https://doi.org/10.1038/s41591-023-02608-w,The value of standards for health datasets in artificial intelligence-based applications.,"Arora A, Alderman JE, Palmer J, Ganapathi S, Laws E, McCradden MD, Oakden-Rayner L, Pfohl SR, Ghassemi M, McKay F, Treanor D, Rostamzadeh N, Mateen B, Gath J, Adebajo AO, Kuku S, Matin R, Heller K, Sapey E, Sebire NJ, Cole-Lewis H, Calvert M, Denniston A, Liu X.",,Nature medicine,2023,2023-10-26,N,,,,"Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).",,doi:https://doi.org/10.1038/s41591-023-02608-w
-34270458,https://doi.org/10.4269/ajtmh.21-0482,The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.,"Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",,The American journal of tropical medicine and hygiene,2021,2021-07-16,Y,,,,"The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",,pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render
 37679551,https://doi.org/10.1038/s41590-023-01635-6,Author Correction: Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-11-01,Y,,,,,,doi:https://doi.org/10.1038/s41590-023-01635-6; html:https://europepmc.org/articles/PMC10602847; pdf:https://europepmc.org/articles/PMC10602847?pdf=render
 37225263,https://doi.org/10.1136/bmjgast-2023-001139,Delphi consensus survey: the opinions of patients living with refractory ulcerative proctitis and the health care professionals who care for them.,"Kyriacou M, Radford S, Moran GW, Focus group collaborators group.",,BMJ open gastroenterology,2023,2023-05-01,Y,Ulcerative colitis; Inflammatory Bowel Disease; Adjuvant Treatment,,,"<h4>Background</h4>Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive condition but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance, resulting in many patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions related to refractory proctitis disease burden and best practice for management.<h4>Methods</h4>A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease from the UK. A brainstorming stage involving a focus group where the participants came up with an initial list of statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the importance of the statements and provide any additional comments or clarifications. Calculation of mean scores, analysis of comments and revisions were performed to produce a final list of statements.<h4>Results</h4>In total, 14 statements were suggested by the focus group at the initial brainstorming stage. Following completion of three Delphi survey rounds, all 14 statements reached consensus following appropriate revision.<h4>Conclusions</h4>We established consensus on the thoughts and opinions related to refractory proctitis from both the experts who manage this disease and the patients living with it. This represents the first step towards developing clinical research data and ultimately the evidence needed for best practice management guidance of this condition.",,pdf:https://bmjopengastro.bmj.com/content/bmjgast/10/1/e001139.full.pdf; doi:https://doi.org/10.1136/bmjgast-2023-001139; html:https://europepmc.org/articles/PMC10230891; pdf:https://europepmc.org/articles/PMC10230891?pdf=render
 31477110,https://doi.org/10.1186/s12913-019-4286-8,Weekend admissions and mortality for major acute disorders across England and Wales: record linkage cohort studies.,"Roberts SE, John A, Lewis KE, Brown J, Lyons RA, Williams JG.",,BMC health services research,2019,2019-09-02,Y,Mortality; Weekend Admissions; Acute Disorders,Improving Public Health,,"<h4>Background</h4>To establish which major disorders are susceptible to increased mortality following acute admissions on weekends, compared with week days, and how this may be explained.<h4>Methods</h4>Cohorts based on national administrative inpatient and mortality data for 14,168,443 hospitalised patients in England and 913,068 in Wales who were admitted for 66 disorders that were associated with at least 200 deaths within 30 days of acute admission. The main outcome measure was the weekend mortality effect (defined as the conventional mortality odds ratio for admissions on weekends compared with week days).<h4>Results</h4>There were large, statistically significant weekend mortality effects (> 20%) in England for 22 of the 66 conditions and in both countries for 14. These 14 were 4 of 13 cancers (oesophageal, colorectal, lung and lymphomas); 4 of 13 circulatory disorders (angina, abdominal aortic aneurysm, peripheral vascular disease and arterial embolism & thrombosis); one of 8 respiratory disorders (pleural effusion); 2 of 12 gastrointestinal disorders (alcoholic and other liver disease); 2 of 3 ageing-related disorders (Alzheimer's disease and dementia); none of 7 trauma conditions; and one of 10 other disorders (acute renal failure). Across the disorders, 64% of the variation in weekend mortality effects in England and Wales was explained by reductions in admission rates at weekends and the medical disease category.<h4>Conclusions</h4>The effect of weekend admission on 30 day mortality is seen mainly for cancers, some circulatory disorders, liver disease and a few other conditions which are mainly ageing- or cancer-related. Most of the increased mortality is associated with reduced admission rates at weekends and the medical disease category.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-019-4286-8; doi:https://doi.org/10.1186/s12913-019-4286-8; html:https://europepmc.org/articles/PMC6720086; pdf:https://europepmc.org/articles/PMC6720086?pdf=render
@@ -1002,8 +1002,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 34544691,https://doi.org/10.3399/bjgp.2021.0153,Identifying symptoms associated with diagnosis of pancreatic exocrine and neuroendocrine neoplasms: a nested case-control study of the UK primary care population.,"Liao W, Clift AK, Patone M, Coupland C, González-Izquierdo A, Pereira SP, Hippisley-Cox J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-10-28,Y,Symptom; Early diagnosis; Pancreatic neoplasms; Primary Health Care; Pancreatic Ductal Adenocarcinoma (Pdac); Pancreatic Neuroendocrine Neoplasms (Pnen),,,"<h4>Background</h4>Pancreatic cancer has the worst survival rate among all cancers. Almost 70% of patients in the UK were diagnosed at Stage IV.<h4>Aim</h4>This study aimed to investigate the symptoms associated with the diagnoses of pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine neoplasms (PNEN), and comparatively characterise the symptomatology between the two tumour types to inform earlier diagnosis.<h4>Design and setting</h4>A nested case-control study in primary care was conducted using data from the QResearch<sup>®</sup> database. Patients aged ≥25 years and diagnosed with PDAC or PNEN during 2000 to 2019 were included as cases. Up to 10 controls from the same general practice were matched with each case by age, sex, and calendar year using incidence density sampling.<h4>Method</h4>Conditional logistic regression was used to investigate the association between the 42 shortlisted symptoms and the diagnoses of PDAC and (or) PNEN in different timeframes relative to the index date, adjusting for patients' sociodemographic characteristics, lifestyle, and relevant comorbidities.<h4>Results</h4>A total of 23 640 patients were identified as diagnosed with PDAC and 596 with PNEN. Of the symptoms identified, 23 were significantly associated with PDAC, and nine symptoms with PNEN. The two alarm symptoms for both tumours were jaundice and gastrointestinal bleeding. The two newly identified symptoms for PDAC were thirst and dark urine. The risk of unintentional weight loss may be longer than 2 years before the diagnosis of PNEN.<h4>Conclusion</h4>PDAC and PNEN have overlapping symptom profiles. The QCancer<sup>®</sup> (pancreas) risk prediction model could be updated by including the newly identified symptoms and comorbidities, which could help GPs identify high-risk patients for timely investigation in primary care.",,pdf:https://bjgp.org/content/bjgp/71/712/e836.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0153; html:https://europepmc.org/articles/PMC8463137; pdf:https://europepmc.org/articles/PMC8463137?pdf=render
 36660920,https://doi.org/10.1093/ehjci/jeac270,The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.,"Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2023,2023-06-01,Y,Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes,,,"<h4>Aims</h4>We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.<h4>Methods and results</h4>In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.<h4>Conclusions</h4>We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac270/48798234/jeac270.pdf; doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render
 35266090,https://doi.org/10.1007/s12471-022-01677-9,The benefit of vaccination against COVID-19 outweighs the potential risk of myocarditis and pericarditis.,"Klamer TA, Linschoten M, Asselbergs FW.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2022,2022-03-09,Y,Side effect; Myocarditis; pericarditis; Covid-19; Coronavirus Disease 2019; Covid-19 Vaccination,,,"Vaccines against coronavirus 2019 disease (COVID-19) have shown to be greatly effective in preventing viral spread, serious illness and death from this infectious disease and are therefore critical for the management of the COVID-19 pandemic. However, the listing of myocarditis and pericarditis as possible rare side effects of the messenger RNA (mRNA) vaccines against COVID-19 by regulatory agencies has sparked discussion on the vaccines' safety. The most important published cohort studies to date demonstrat that myocarditis is a very rare side effect after COVID-19 mRNA vaccination, with an incidence of approximately 1-4 cases per 100,000 vaccinated persons. Young males (16-29 years) appear to be at highest risk, predominantly after receiving the second dose. The disease course is self-limiting in a vast majority of cases: 95% of patients show a rapid resolution of symptoms and normalisation of cardiac biomarkers, electro- and echocardiographic findings within days. Importantly, the available data suggest that the incidence rate of myocarditis in the context of COVID-19 is much greater than the risk of this side effect following vaccination. We conclude that the benefit of vaccination against COVID-19 outweighs the potential risk of myocarditis and pericarditis in both adolescents and adults. Prospective follow-up of patients who have developed these complications after vaccination is required to assess long-term outcomes.",,pdf:https://link.springer.com/content/pdf/10.1007/s12471-022-01677-9.pdf; doi:https://doi.org/10.1007/s12471-022-01677-9; html:https://europepmc.org/articles/PMC8906525; pdf:https://europepmc.org/articles/PMC8906525?pdf=render
-37798805,https://doi.org/10.1186/s13063-023-07576-7,"Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-10-05,Y,Legislation; data sharing; Consultation,,,"In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals ""to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines"". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render
 35616501,https://doi.org/10.1177/14791641221088824,Sleep behaviours and associated habits and the progression of pre-diabetes to type 2 diabetes mellitus in adults: A systematic review and meta-analysis.,"Mostafa SA, Mena SC, Antza C, Balanos G, Nirantharakumar K, Tahrani AA.",,Diabetes & vascular disease research,2022,2022-05-01,Y,Type 2 diabetes mellitus; Sleep disorders; Systematic review; Pre-diabetes,,,"<h4>Introduction</h4>Certain sleep behaviours increase risk of type 2 diabetes mellitus (T2DM) in the general population, but whether they contribute to the progression from pre-diabetes to T2DM is uncertain. We conducted a systematic review to assess this.<h4>Methods</h4>Structured searches were performed on bibliographic databases (MEDLINE, EMBASE and CINAHL) from inception to 26/04/2021 for longitudinal studies/trials consisting of adults⩾18 years with pre-diabetes and sleep behaviours (short or long sleep duration (SD), late chronotype, insomnia, obstructive sleep apnoea, daytime napping and/or night-shift employment) that reported on incident T2DM or glycaemic changes. The Newcastle-Ottawa Scale was used for quality assessment.<h4>Results</h4>Six studies were included. Meta-analysis of three studies (<i>n</i> = 20,139) demonstrated that short SD was associated with greater risk of progression to T2DM, hazard ratio (HR) 1.59 (95% CI 1.29-1.97), I<sup>2</sup> heterogeneity score 0%, <i>p</i> < 0.0001, but not for long SD, HR 1.50 (0.86-2.62), I<sup>2</sup> heterogeneity 77%, <i>p</i> = 0.15. The systematic review showed insomnia and night-shift duty were associated with higher progression to T2DM. Studies were rated as moderate-to-high quality.<h4>Conclusions</h4>Progression from pre-diabetes to T2DM increases with short SD, but only limited data exists for insomnia and night-shift duty. Whether manipulating sleep could reduce progression from pre-diabetes to T2DM needs to be examined.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152198; doi:https://doi.org/10.1177/14791641221088824; html:https://europepmc.org/articles/PMC9152198; pdf:https://europepmc.org/articles/PMC9152198?pdf=render
+37798805,https://doi.org/10.1186/s13063-023-07576-7,"Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-10-05,Y,Legislation; data sharing; Consultation,,,"In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals ""to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines"". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render
 33328049,https://doi.org/10.1016/s2589-7500(20)30219-3,Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension.,"Cruz Rivera S, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group.",,The Lancet. Digital health,2020,2020-09-09,Y,,,,"The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the design and risk of bias for a planned clinical trial.",,pdf:http://www.thelancet.com/article/S2589750020302193/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30219-3; html:https://europepmc.org/articles/PMC8212701; pdf:https://europepmc.org/articles/PMC8212701?pdf=render
 35271547,https://doi.org/10.1097/ta.0000000000003592,Does patient preference for online or telephone follow-up impact on response rates and data completeness following injury?,"Gabbe BJ, Hart MJ, Brown A, McLellan S, Morgan MJ, Beck B, de Steiger RS, Cameron PA.",,The journal of trauma and acute care surgery,2022,2022-03-08,N,,,,"<h4>Background</h4>Routine collection of patient-reported outcomes is needed to better understand recovery, benchmark between trauma centers and systems, and monitor outcomes over time. A key component of follow-up methodology is the mode of administration of outcome measures with multiple options available. We aimed to quantify patient preference and compare the response rates and data completeness for telephone and online completion in trauma patients.<h4>Methods</h4>A registry-based cohort study of adult (16 years and older) patients registered to the Victorian State Trauma Registry and Victorian Orthopedic Trauma Outcomes Registry from April 2020 to December 2020 was undertaken. Survivors to discharge were contacted by telephone and offered the option of telephone or online completion of 6-month follow-up using the five-level EuroQol five-dimension (EQ-5D-5L) questionnaire and the 12-item World Health Organization Disability Assessment Schedule (WHODAS). The online and telephone groups were compared for differences in characteristics, follow-up rates, and data completeness. Multivariable logistic regression was used to identify predictors of choosing online completion.<h4>Results</h4>Of the 3,886 patients, 51% (n = 1,994) chose online follow-up, and the follow-up rates were lower for online (77%), compared with telephone (89%), follow-up. Younger age, higher socioeconomic status, and preferred language other than English were associated with higher adjusted odds of choosing online completion. Admission to intensive care was associated with lower adjusted odds of choosing online completion. Completion rate for the EQ-5D-5L utility score was 97% for both groups. A valid total 12-WHODAS score could be calculated for 63% of online respondents compared with 86% for the telephone group.<h4>Conclusion</h4>More than half of trauma patients opted for online completion. Completion rates did differ depending on the questionnaire and telephone follow-up rates were higher. Nevertheless, given the wide diversity of the trauma population, the high rate of online uptake, and potential resource constraints, the study findings largely support the use of dual methods for follow-up.<h4>Level of evidence</h4>Prognostic/Epidemiological, Level III.",,doi:https://doi.org/10.1097/TA.0000000000003592
 37311637,https://doi.org/10.1136/bmjopen-2023-071973,Number and timing of primary cleft lip and palate repair surgeries in England: whole nation study of electronic health records before and during the COVID-19 pandemic.,"Etoori D, Park MH, Blackburn RM, Fitzsimons KJ, Butterworth S, Medina J, Mc Grath-Lone L, Russell C, van der Meulen J.",,BMJ open,2023,2023-06-13,Y,epidemiology; Paediatric Surgery; Covid-19,,,"<h4>Objective</h4>To quantify differences in number and timing of first primary cleft lip and palate (CLP) repair procedures during the first year of the COVID-19 pandemic (1 April 2020 to 31 March 2021; 2020/2021) compared with the preceding year (1 April 2019 to 31 March 2020; 2019/2021).<h4>Design</h4>National observational study of administrative hospital data.<h4>Setting</h4>National Health Service hospitals in England.<h4>Study population</h4>Children <5 years undergoing primary repair for an orofacial cleft Population Consensus and Surveys Classification of Interventions and Procedures-fourth revisions (OPCS-4) codes F031, F291).<h4>Main exposure</h4>Procedure date (2020/2021 vs 2019/2020).<h4>Main outcomes</h4>Numbers and timing (age in months) of first primary CLP procedures.<h4>Results</h4>1716 CLP primary repair procedures were included in the analysis. In 2020/2021, 774 CLP procedures were carried out compared with 942 in 2019/2020, a reduction of 17.8% (95% CI 9.5% to 25.4%). The reduction varied over time in 2020/2021, with no surgeries at all during the first 2 months (April and May 2020). Compared with 2019/2020, first primary lip repair procedures performed in 2020/2021 were delayed by 1.6 months on average (95% CI 0.9 to 2.2 months). Delays in primary palate repairs were smaller on average but varied across the nine geographical regions.<h4>Conclusion</h4>There were significant reductions in the number and delays in timing of first primary CLP repair procedures in England during the first year of the pandemic, which may affect long-term outcomes.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e071973.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-071973; html:https://europepmc.org/articles/PMC10276964; pdf:https://europepmc.org/articles/PMC10276964?pdf=render
@@ -1012,15 +1012,15 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 32182948,https://doi.org/10.3390/cells9030665,"Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases.","Martin TC, Ilieva KM, Visconti A, Beaumont M, Kiddle SJ, Dobson RJB, Mangino M, Lim EM, Pezer M, Steves CJ, Bell JT, Wilson SG, Lauc G, Roederer M, Walsh JP, Spector TD, Karagiannis SN.",,Cells,2020,2020-03-09,Y,Apoptosis; Genetic Variants; Antibody-dependent Cell-mediated Cytotoxicity (Adcc); Multi-omic; Autoimmune Thyroid Diseases (Aitd); Anti-thyroid Peroxidase Antibody (Tpoab),Understanding the Causes of Disease,inflammatory and immune system,"The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335<sup>-</sup> CD314<sup>+</sup> CD158b<sup>+</sup> NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD.",,pdf:https://www.mdpi.com/2073-4409/9/3/665/pdf?version=1584361130; doi:https://doi.org/10.3390/cells9030665; html:https://europepmc.org/articles/PMC7140647; pdf:https://europepmc.org/articles/PMC7140647?pdf=render
 33655079,https://doi.org/10.12688/wellcomeopenres.16304.2,Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.,"Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.",,Wellcome open research,2020,2020-01-01,Y,Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Swab Test; Covid-19,,,"<b>Background:</b> Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. <b>Methods:</b> In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. <b>Results:</b> Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. <b>Conclusions:</b> Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.",,doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render
 32771960,https://doi.org/10.1016/j.ijmedinf.2020.104237,Core competencies for clinical informaticians: A systematic review.,"Davies A, Mueller J, Moulton G.",,International journal of medical informatics,2020,2020-07-24,N,Bioinformatics; Health; Clinical; Pharmacy; Skills; Informatics; Requirements; Core Competencies; Healthcare Data Science,,,"<h4>Background</h4>Building on initial work carried out by the Faculty of Clinical Informatics (FCI) in the UK, the creation of a national competency framework for Clinical Informatics is required for the definition of clinical informaticians' professional attributes and skills. We aimed to systematically review the academic literature relating to competencies, skills and existing course curricula in the clinical and health related informatics domains.<h4>Methods</h4>Two independent reviewers searched Web of Science, EMBASE, ERIC, PubMed and CINAHL. Publications were included if they reported details of relevant competencies, skills and existing course curricula. We report findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.<h4>Results</h4>A total of 82 publications were included. The most frequently used method was surveys (30 %) followed by narrative descriptions (28 %). Most of the publications describe curriculum design (23 %) followed by competency definition (18 %) and skills, qualifications & training (18 %). Core skills surrounding data, information systems and information management appear to be cross-cutting across the various informatics disciplines with Bioinformatics and Pharmacy Informatics expressing the most unique competency requirements.<h4>Conclusion</h4>We identified eight key domains that cut across the different sub-disciplines of health informatics, including data, information management, human factors, project management, research skills/knowledge, leadership and management, systems development and evaluation, and health/healthcare. Some informatics disciplines such as Nursing Informatics appear to be further ahead at achieving widespread competency standardisation. Attempts at standardisation for competencies should be tempered with flexibility to allow for local variation and requirements.",,doi:https://doi.org/10.1016/j.ijmedinf.2020.104237
-37230417,https://doi.org/10.1016/j.jtha.2023.05.012,C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study.,"Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",,Journal of thrombosis and haemostasis : JTH,2023,2023-05-23,N,,,,,,doi:https://doi.org/10.1016/j.jtha.2023.05.012
 31442537,https://doi.org/10.1016/j.jaad.2019.08.039,Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study.,"Schmidt SAJ, Olsen M, Schmidt M, Vestergaard C, Langan SM, Deleuran MS, Riis JL.",,Journal of the American Academy of Dermatology,2020,2019-08-20,Y,Validation; Atrial fibrillation; Atrial flutter; Cohort study; risk factors; Atopic Dermatitis,Understanding the Causes of Disease,,"<h4>Background</h4>Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation.<h4>Objective</h4>To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation.<h4>Methods</h4>Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review.<h4>Results</h4>We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors.<h4>Limitations</h4>Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data.<h4>Conclusion</h4>Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low.",,pdf:http://www.jaad.org/article/S0190962219326143/pdf; doi:https://doi.org/10.1016/j.jaad.2019.08.039; html:https://europepmc.org/articles/PMC7704103; pdf:https://europepmc.org/articles/PMC7704103?pdf=render
 34726481,https://doi.org/10.1126/science.abl9551,"Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant.","Elliott P, Haw D, Wang H, Eales O, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Prosolek SJ, COVID-19 Genomics UK (COG-UK) Consortium11‡, Ashby D, Donnelly CA, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S.",,"Science (New York, N.Y.)",2021,2021-12-17,N,,,,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.",,pdf:https://www.science.org/history/7d0b03b2-b465-410e-a40d-7300157d8b54/science.abl9551.v1.pdf; doi:https://doi.org/10.1126/science.abl9551
+37230417,https://doi.org/10.1016/j.jtha.2023.05.012,C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study.,"Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",,Journal of thrombosis and haemostasis : JTH,2023,2023-05-23,N,,,,,,doi:https://doi.org/10.1016/j.jtha.2023.05.012
 33990383,https://doi.org/10.1136/gutjnl-2020-323546,Multicentre derivation and validation of a colitis-associated colorectal cancer risk prediction web tool.,"Curtius K, Kabir M, Al Bakir I, Choi CHR, Hartono JL, Johnson M, East JE, Oxford IBD Cohort Study Investigators, Lindsay JO, Vega R, Thomas-Gibson S, Warusavitarne J, Wilson A, Graham TA, Hart A.",,Gut,2022,2021-05-14,Y,Dysplasia; Ulcerative colitis; Colorectal Cancer; Clinical Decision Making,,,"<h4>Objective</h4>Patients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in patients with UC with LGD and create a visual web tool to effectively communicate the risk.<h4>Design</h4>In our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk.<h4>Results</h4>Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD >1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up.<h4>Conclusion</h4>Multicohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator ( <i>www.UC-CaRE.uk</i> ) can support treatment decision-making.",,pdf:https://gut.bmj.com/content/gutjnl/71/4/705.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-323546; html:https://europepmc.org/articles/PMC8921573; pdf:https://europepmc.org/articles/PMC8921573?pdf=render
 37218687,https://doi.org/10.1093/ehjqcco/qcad029,Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.,"Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Quality of care & clinical outcomes,2023,2023-05-22,N,Myocardial infarction; Stroke; Sex differences; risk factors,,,"<h4>Aim</h4>This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.<h4>Methods</h4>Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.<h4>Results</h4>Among the 363 313 participants (53.5% women), 8 470 experienced MI (29.9% women) and 7 705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].<h4>Conclusion</h4>Older age, hypertension and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029
 35650647,https://doi.org/10.1186/s41512-022-00124-y,A scoping methodological review of simulation studies comparing statistical and machine learning approaches to risk prediction for time-to-event data.,"Smith H, Sweeting M, Morris T, Crowther MJ.",,Diagnostic and prognostic research,2022,2022-06-02,Y,Survival analysis; Machine Learning; Simulation Studies; Clinical Risk Prediction; Prognostic Modelling,,,"<h4>Background</h4>There is substantial interest in the adaptation and application of so-called machine learning approaches to prognostic modelling of censored time-to-event data. These methods must be compared and evaluated against existing methods in a variety of scenarios to determine their predictive performance. A scoping review of how machine learning methods have been compared to traditional survival models is important to identify the comparisons that have been made and issues where they are lacking, biased towards one approach or misleading.<h4>Methods</h4>We conducted a scoping review of research articles published between 1 January 2000 and 2 December 2020 using PubMed. Eligible articles were those that used simulation studies to compare statistical and machine learning methods for risk prediction with a time-to-event outcome in a medical/healthcare setting. We focus on data-generating mechanisms (DGMs), the methods that have been compared, the estimands of the simulation studies, and the performance measures used to evaluate them.<h4>Results</h4>A total of ten articles were identified as eligible for the review. Six of the articles evaluated a method that was developed by the authors, four of which were machine learning methods, and the results almost always stated that this developed method's performance was equivalent to or better than the other methods compared. Comparisons were often biased towards the novel approach, with the majority only comparing against a basic Cox proportional hazards model, and in scenarios where it is clear it would not perform well. In many of the articles reviewed, key information was unclear, such as the number of simulation repetitions and how performance measures were calculated.<h4>Conclusion</h4>It is vital that method comparisons are unbiased and comprehensive, and this should be the goal even if realising it is difficult. Fully assessing how newly developed methods perform and how they compare to a variety of traditional statistical methods for prognostic modelling is imperative as these methods are already being applied in clinical contexts. Evaluations of the performance and usefulness of recently developed methods for risk prediction should be continued and reporting standards improved as these methods become increasingly popular.",,pdf:https://diagnprognres.biomedcentral.com/track/pdf/10.1186/s41512-022-00124-y; doi:https://doi.org/10.1186/s41512-022-00124-y; html:https://europepmc.org/articles/PMC9161606; pdf:https://europepmc.org/articles/PMC9161606?pdf=render
 35260393,https://doi.org/10.1136/bmjgh-2021-008099,Overcoming disruptions in essential health services during the COVID-19 pandemic in Mexico. ,"Doubova SV, Robledo-Aburto ZA, Duque-Molina C, Borrayo-Sánchez G, González-León M, Avilés-Hernández R, Contreras-Sánchez SE, Leslie HH, Kruk M, Pérez-Cuevas R, Arsenault C.",,BMJ global health,2022,2022-03-01,Y,,,,,,pdf:https://gh.bmj.com/content/bmjgh/7/3/e008099.full.pdf; doi:https://doi.org/10.1136/bmjgh-2021-008099; html:https://europepmc.org/articles/PMC8905410; pdf:https://europepmc.org/articles/PMC8905410?pdf=render
-34873584,https://doi.org/10.1016/j.eclinm.2021.101212,Disentangling post-vaccination symptoms from early COVID-19.,"Canas LS, Österdahl MF, Deng J, Hu C, Selvachandran S, Polidori L, May A, Molteni E, Murray B, Chen L, Kerfoot E, Klaser K, Antonelli M, Hammers A, Spector T, Ourselin S, Steves C, Sudre CH, Modat M, Duncan EL.",,EClinicalMedicine,2021,2021-12-01,Y,"Vaccination; Side-effects; Early Detection; Mobile Technology; Self-reported Symptoms; Roc, Receiver Operating Curve; Severe Acute Respiratory Syndrome‐Related Coronavirus 2 (Sars-Cov-2); Bmem, Bayesian Mixed-effect Model; Css, Covid Symptoms Study; Di, Data Invalid; Kcl, King's College London; Lfat, Lateral Flow Antigen Test; Nhs Uk, National Health Service Of The United Kingdom; O-az, Oxford-astrazeneca Adenovirus-vectored Vaccine; Pb, Pfizer-bointech Mrna Vaccine; Sars-cov-2, Severe Acute Respiratory Syndrome-related Coronavirus-2; Uk, United Kingdom Of Great Britain And Nothern Ireland; Auc, Area Under The Curve; Bmi, Body Mass Index; Ci, Confidence Interval; Lr, Logistic Regression; Iqr, Inter Quartile Range; Rf, Random Forest; Covid-19, Coronavirus Disease 2019; Covid-19 Detection; Rtpcr, Reverse Transcription Polymerase Chain Reaction",,,"<h4>Background</h4>Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app.<h4>Methods</h4>We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects <i>per se</i> from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering UK testing criteria.<h4>Findings</h4>Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue).<h4>Interpretation</h4>Post-vaccination symptoms <i>per se</i> cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread.<h4>Funding</h4>UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Chronic Disease Research Foundation, Zoe Limited.",,doi:https://doi.org/10.1016/j.eclinm.2021.101212; doi:https://doi.org/10.1016/j.eclinm.2021.101212; html:https://europepmc.org/articles/PMC8635464; pdf:https://europepmc.org/articles/PMC8635464?pdf=render
 32065794,https://doi.org/10.3233/jad-191163,Working Towards a Blood-Derived Gene Expression Biomarker Specific for Alzheimer's Disease.,"Patel H, Iniesta R, Stahl D, Dobson RJB, Newhouse SJ.",,Journal of Alzheimer's disease : JAD,2020,2020-01-01,Y,Human; Biomarkers; Alzheimer’s disease; Dementia; Gene Expression; Neurodegenerative Disorders; Machine Learning; Microarray Analysis; Age-related Memory Disorders,,,"<h4>Background</h4>The typical approach to identify blood-derived gene expression signatures as a biomarker for Alzheimer's disease (AD) have relied on training classification models using AD and healthy controls only. This may inadvertently result in the identification of markers for general illness rather than being disease-specific.<h4>Objective</h4>Investigate whether incorporating additional related disorders in the classification model development process can lead to the discovery of an AD-specific gene expression signature.<h4>Methods</h4>Two types of XGBoost classification models were developed. The first used 160 AD and 127 healthy controls and the second used the same 160 AD with 6,318 upsampled mixed controls consisting of Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, bipolar disorder, schizophrenia, coronary artery disease, rheumatoid arthritis, chronic obstructive pulmonary disease, and cognitively healthy subjects. Both classification models were evaluated in an independent cohort consisting of 127 AD and 687 mixed controls.<h4>Results</h4>The AD versus healthy control models resulted in an average 48.7% sensitivity (95% CI = 34.7-64.6), 41.9% specificity (95% CI = 26.8-54.3), 13.6% PPV (95% CI = 9.9-18.5), and 81.1% NPV (95% CI = 73.3-87.7). In contrast, the mixed control models resulted in an average of 40.8% sensitivity (95% CI = 27.5-52.0), 95.3% specificity (95% CI = 93.3-97.1), 61.4% PPV (95% CI = 53.8-69.6), and 89.7% NPV (95% CI = 87.8-91.4).<h4>Conclusions</h4>This early work demonstrates the value of incorporating additional related disorders into the classification model developmental process, which can result in models with improved ability to distinguish AD from a heterogeneous aging population. However, further improvement to the sensitivity of the test is still required.",,pdf:https://content.iospress.com:443/download/journal-of-alzheimers-disease/jad191163?id=journal-of-alzheimers-disease%2Fjad191163; doi:https://doi.org/10.3233/JAD-191163; html:https://europepmc.org/articles/PMC7175937; pdf:https://europepmc.org/articles/PMC7175937?pdf=render
+34873584,https://doi.org/10.1016/j.eclinm.2021.101212,Disentangling post-vaccination symptoms from early COVID-19.,"Canas LS, Österdahl MF, Deng J, Hu C, Selvachandran S, Polidori L, May A, Molteni E, Murray B, Chen L, Kerfoot E, Klaser K, Antonelli M, Hammers A, Spector T, Ourselin S, Steves C, Sudre CH, Modat M, Duncan EL.",,EClinicalMedicine,2021,2021-12-01,Y,"Vaccination; Side-effects; Early Detection; Mobile Technology; Self-reported Symptoms; Roc, Receiver Operating Curve; Severe Acute Respiratory Syndrome‐Related Coronavirus 2 (Sars-Cov-2); Bmem, Bayesian Mixed-effect Model; Css, Covid Symptoms Study; Di, Data Invalid; Kcl, King's College London; Lfat, Lateral Flow Antigen Test; Nhs Uk, National Health Service Of The United Kingdom; O-az, Oxford-astrazeneca Adenovirus-vectored Vaccine; Pb, Pfizer-bointech Mrna Vaccine; Sars-cov-2, Severe Acute Respiratory Syndrome-related Coronavirus-2; Uk, United Kingdom Of Great Britain And Nothern Ireland; Auc, Area Under The Curve; Bmi, Body Mass Index; Ci, Confidence Interval; Lr, Logistic Regression; Iqr, Inter Quartile Range; Rf, Random Forest; Covid-19, Coronavirus Disease 2019; Covid-19 Detection; Rtpcr, Reverse Transcription Polymerase Chain Reaction",,,"<h4>Background</h4>Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app.<h4>Methods</h4>We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects <i>per se</i> from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering UK testing criteria.<h4>Findings</h4>Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue).<h4>Interpretation</h4>Post-vaccination symptoms <i>per se</i> cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread.<h4>Funding</h4>UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Chronic Disease Research Foundation, Zoe Limited.",,doi:https://doi.org/10.1016/j.eclinm.2021.101212; doi:https://doi.org/10.1016/j.eclinm.2021.101212; html:https://europepmc.org/articles/PMC8635464; pdf:https://europepmc.org/articles/PMC8635464?pdf=render
 34230034,https://doi.org/10.1136/bmjresp-2021-000967,Increase in recruitment upon integration of trial into a clinical care pathway: an observational study. ,"Yip KP, Gompertz S, Snelson C, Willson J, Madathil S, Huq SS, Rauf F, Salmon N, Tengende J, Tracey J, Cooper B, Filby K, Ball S, Parekh D, Dosanjh DPS.",,BMJ open respiratory research,2021,2021-07-01,Y,,,,"Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers. A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP. On integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence. Integrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/8/1/e000967.full.pdf; doi:https://doi.org/10.1136/bmjresp-2021-000967; html:https://europepmc.org/articles/PMC8261886; pdf:https://europepmc.org/articles/PMC8261886?pdf=render
 32046816,https://doi.org/10.2807/1560-7917.es.2020.25.5.2000080,Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV).,"Quilty BJ, Clifford S, CMMID nCoV working group2, Flasche S, Eggo RM.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-02-01,Y,Surveillance; Effectiveness; Interventions; Emerging Infections; 2019-Ncov; Airport Screening; Thermal Scanning,,,"We evaluated effectiveness of thermal passenger screening for 2019-nCoV infection at airport exit and entry to inform public health decision-making. In our baseline scenario, we estimated that 46% (95% confidence interval: 36 to 58) of infected travellers would not be detected, depending on incubation period, sensitivity of exit and entry screening, and proportion of asymptomatic cases. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/5/eurosurv-25-5-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.5.2000080&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000080; html:https://europepmc.org/articles/PMC7014668; pdf:https://europepmc.org/articles/PMC7014668?pdf=render
 35471746,https://doi.org/10.1186/s13613-022-01011-x,The resilient intensive care unit.,"Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.",,Annals of intensive care,2022,2022-04-26,Y,,,,"<h4>Background</h4>The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.<h4>Methods</h4>In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.<h4>Results</h4>We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.<h4>Conclusions</h4>The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.",,pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render
@@ -1028,23 +1028,23 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 36357675,https://doi.org/10.1038/s41591-022-02046-0,Rare and common genetic determinants of metabolic individuality and their effects on human health.,"Surendran P, Stewart ID, Au Yeung VPW, Pietzner M, Raffler J, Wörheide MA, Li C, Smith RF, Wittemans LBL, Bomba L, Menni C, Zierer J, Rossi N, Sheridan PA, Watkins NA, Mangino M, Hysi PG, Di Angelantonio E, Falchi M, Spector TD, Soranzo N, Michelotti GA, Arlt W, Lotta LA, Denaxas S, Hemingway H, Gamazon ER, Howson JMM, Wood AM, Danesh J, Wareham NJ, Kastenmüller G, Fauman EB, Suhre K, Butterworth AS, Langenberg C.",,Nature medicine,2022,2022-11-10,Y,,,,"Garrod's concept of 'chemical individuality' has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant-metabolite associations (P < 1.25 × 10<sup>-11</sup>) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant-metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYD and SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships.",,pdf:https://www.nature.com/articles/s41591-022-02046-0.pdf; doi:https://doi.org/10.1038/s41591-022-02046-0; html:https://europepmc.org/articles/PMC9671801; pdf:https://europepmc.org/articles/PMC9671801?pdf=render
 32301135,https://doi.org/10.1111/opo.12685,Delayed attendance at routine eye examinations is associated with increased probability of general practitioner referral: a record linkage study in Northern Ireland.,"Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.",,Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists),2020,2020-04-16,N,epidemiology; Public Health; Optometry Services,,,"<h4>Purpose</h4>To investigate relationships between health and socio-economic status with delayed attendance at routine eye examinations and risk of subsequent general practitioner (GP) referral in Northern Ireland.<h4>Methods</h4>We constructed a cohort of 132 046 community dwelling individuals aged ≥60 years, drawing contextual information from the 2011 Northern Ireland Census. Using linked administrative records of routine eye examinations between 2009 and 2014, we calculated 311 999 examination intervals. Multinomial models were used to estimate associations between contextual factors and examination interval (classified into three groups: early recall, on-time, delayed attendance). Associations between examination interval and referral risk were estimated using logistic regression.<h4>Results</h4>Delayed attendance was recorded for 129 857 (41.6%) examination intervals, 53 759 (17.2%) delayed by ≥6 months. Female sex, poor general or mental health were each associated with delay, as were longer distances to optometry services among those aged ≥70 years (longest vs shortest: Relative Risk Ratio = 1.21 [1.14, 1.28]). Low income and residence in social housing were associated with reduced delay risk. There were 3347 (3.5%) and 11 401 (5.3%) GP referrals in the 60-69 and ≥70 years age groups respectively. Delayed attendance was associated with increased referral risk in both groups (Odds Ratios: 60-69 years = 1.30 [1.04, 1.61]; ≥70 years = 1.07 [1.01, 1.13]).<h4>Conclusions</h4>Poor health and longer distances to optometry services were associated with delayed attendance at routine eye examinations but low income was not. Delayed attendance was associated with increased GP referral risk, indicative of missed opportunities to detect potentially serious eye conditions.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/opo.12685; doi:https://doi.org/10.1111/opo.12685
 37124165,https://doi.org/10.1016/j.ufug.2023.127934,"Effects of the onset of the COVID-19 pandemic restrictions on park crime in London, England: An interrupted time series analysis.","Hajna S, Cummins S.",,Urban forestry & urban greening,2023,2023-04-11,Y,Parks; Crimes; Covid-19,,,"<h4>Introduction</h4>Park crimes may have increased during the COVID-19 pandemic as a result of lockdowns that limited the number of capable guardians in public spaces. Despite this, the impacts of the lockdowns on park crimes remain unknown. To help us understand the societal impacts of policies implemented during this period, we assessed how the onset of the COVID-19 restrictions impacted urban park crime levels in London, England.<h4>Methods</h4>We identified crimes that occurred in publicly accessible parks and gardens in the Greater London Authority (England, UK) between March 1, 2019 and February 28, 2021 by overlaying open-access crime data with greenspace data supplied by the Greater Information for Greater London service. Using interrupted time series analyses, we estimated seasonality-adjusted associations between the onset of COVID-19 restrictions and park crimes.<h4>Results</h4>Overall (1565.7, 95% confidence intervals [CI] 1021.9 to 2109.5) and antisocial behaviour crimes (1772.7, 95% CI 823.6-2721.7) increased in London parks during the first full month of COVID-19 restrictions (April 2020). There were no notable trends in park crimes in London prior to the onset of restrictions, but overall and antisocial behaviour crimes decreased after the onset of restrictions at a rate of 156.4 (95% CI -220.25 to -92.51) and 164.7 (95% CI -280.68 to -48.74) crimes/months, respectively.<h4>Conclusions</h4>Overall park crimes increased during the first full month of the COVID-19 restrictions, largely driven by an increase in antisocial behaviours. Additional research is needed to identify the specific misdemeanours that accounted for this rise in antisocial behaviours and to investigate their downstream impacts (e.g. increases in policing costs or decreases in perceived park safety).",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render
-37133927,https://doi.org/10.2196/45534,"Understanding Views Around the Creation of a Consented, Donated Databank of Clinical Free Text to Develop and Train Natural Language Processing Models for Research: Focus Group Interviews With Stakeholders.","Fitzpatrick NK, Dobson R, Roberts A, Jones K, Shah AD, Nenadic G, Ford E.",,JMIR medical informatics,2023,2023-05-03,Y,Consent; Governance; Electronic Health Records; Natural Language Processing; Free Text; Databank; Public Involvement; Unstructured Text,,,"<h4>Background</h4>Information stored within electronic health records is often recorded as unstructured text. Special computerized natural language processing (NLP) tools are needed to process this text; however, complex governance arrangements make such data in the National Health Service hard to access, and therefore, it is difficult to use for research in improving NLP methods. The creation of a donated databank of clinical free text could provide an important opportunity for researchers to develop NLP methods and tools and may circumvent delays in accessing the data needed to train the models. However, to date, there has been little or no engagement with stakeholders on the acceptability and design considerations of establishing a free-text databank for this purpose.<h4>Objective</h4>This study aimed to ascertain stakeholder views around the creation of a consented, donated databank of clinical free text to help create, train, and evaluate NLP for clinical research and to inform the potential next steps for adopting a partner-led approach to establish a national, funded databank of free text for use by the research community.<h4>Methods</h4>Web-based in-depth focus group interviews were conducted with 4 stakeholder groups (patients and members of the public, clinicians, information governance leads and research ethics members, and NLP researchers).<h4>Results</h4>All stakeholder groups were strongly in favor of the databank and saw great value in creating an environment where NLP tools can be tested and trained to improve their accuracy. Participants highlighted a range of complex issues for consideration as the databank is developed, including communicating the intended purpose, the approach to access and safeguarding the data, who should have access, and how to fund the databank. Participants recommended that a small-scale, gradual approach be adopted to start to gather donations and encouraged further engagement with stakeholders to develop a road map and set of standards for the databank.<h4>Conclusions</h4>These findings provide a clear mandate to begin developing the databank and a framework for stakeholder expectations, which we would aim to meet with the databank delivery.",,pdf:https://medinform.jmir.org/2023/1/e45534/PDF; doi:https://doi.org/10.2196/45534; html:https://europepmc.org/articles/PMC10193205
 35487738,https://doi.org/10.1136/bmjopen-2021-057017,Variation in the estimated prevalence of multimorbidity: systematic review and meta-analysis of 193 international studies.,"Ho IS, Azcoaga-Lorenzo A, Akbari A, Davies J, Hodgins P, Khunti K, Kadam U, Lyons R, McCowan C, Mercer SW, Nirantharakumar K, Guthrie B.",,BMJ open,2022,2022-04-29,Y,epidemiology; Geriatric Medicine; General Medicine (See Internal Medicine),,,"<h4>Objective</h4>(1) To estimate the pooled prevalence of multimorbidity in all age groups, globally. (2) To examine how measurement of multimorbidity impacted the estimated prevalence.<h4>Methods</h4>In this systematic review and meta-analysis, we conducted searches in nine bibliographic databases (PsycINFO, Embase, Global Health, Medline, Scopus, Web of Science, Cochrane Library, CINAHL and ProQuest Dissertations and Theses Global) for prevalence studies published between database inception and 21 January 2020. Studies reporting the prevalence of multimorbidity (in all age groups and in community, primary care, care home and hospital settings) were included. Studies with an index condition or those that did not include people with no long-term conditions in the denominator were excluded. Retrieved studies were independently reviewed by two reviewers, and relevant data were extracted using predesigned pro forma. We used meta-analysis to pool the estimated prevalence of multimorbidity across studies, and used random-effects meta-regression and subgroup analysis to examine the association of heterogeneous prevalence estimates with study and measure characteristics.<h4>Results</h4>13 807 titles were screened, of which 193 met inclusion criteria for meta-analysis. The pooled prevalence of multimorbidity was 42.4% (95% CI 38.9% to 46.0%) with high heterogeneity (I<sup>2</sup> >99%). In adjusted meta-regression models, participant mean age and the number of conditions included in a measure accounted for 47.8% of heterogeneity in effect sizes. The estimated prevalence of multimorbidity was significantly higher in studies with older adults and those that included larger numbers of conditions. There was no significant difference in estimated prevalence between low-income or middle-income countries (36.8%) and high-income countries (44.3%), or between self-report (40.0%) and administrative/clinical databases (52.7%).<h4>Conclusions</h4>The pooled prevalence of multimorbidity was significantly higher in older populations and when studies included a larger number of baseline conditions. The findings suggest that, to improve study comparability and quality of reporting, future studies should use a common core conditions set for multimorbidity measurement and report multimorbidity prevalence stratified by sociodemographics.<b>PROSPERO registration number</b>CRD42020172409.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057017.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057017; html:https://europepmc.org/articles/PMC9058768; pdf:https://europepmc.org/articles/PMC9058768?pdf=render
+37133927,https://doi.org/10.2196/45534,"Understanding Views Around the Creation of a Consented, Donated Databank of Clinical Free Text to Develop and Train Natural Language Processing Models for Research: Focus Group Interviews With Stakeholders.","Fitzpatrick NK, Dobson R, Roberts A, Jones K, Shah AD, Nenadic G, Ford E.",,JMIR medical informatics,2023,2023-05-03,Y,Consent; Governance; Electronic Health Records; Natural Language Processing; Free Text; Databank; Public Involvement; Unstructured Text,,,"<h4>Background</h4>Information stored within electronic health records is often recorded as unstructured text. Special computerized natural language processing (NLP) tools are needed to process this text; however, complex governance arrangements make such data in the National Health Service hard to access, and therefore, it is difficult to use for research in improving NLP methods. The creation of a donated databank of clinical free text could provide an important opportunity for researchers to develop NLP methods and tools and may circumvent delays in accessing the data needed to train the models. However, to date, there has been little or no engagement with stakeholders on the acceptability and design considerations of establishing a free-text databank for this purpose.<h4>Objective</h4>This study aimed to ascertain stakeholder views around the creation of a consented, donated databank of clinical free text to help create, train, and evaluate NLP for clinical research and to inform the potential next steps for adopting a partner-led approach to establish a national, funded databank of free text for use by the research community.<h4>Methods</h4>Web-based in-depth focus group interviews were conducted with 4 stakeholder groups (patients and members of the public, clinicians, information governance leads and research ethics members, and NLP researchers).<h4>Results</h4>All stakeholder groups were strongly in favor of the databank and saw great value in creating an environment where NLP tools can be tested and trained to improve their accuracy. Participants highlighted a range of complex issues for consideration as the databank is developed, including communicating the intended purpose, the approach to access and safeguarding the data, who should have access, and how to fund the databank. Participants recommended that a small-scale, gradual approach be adopted to start to gather donations and encouraged further engagement with stakeholders to develop a road map and set of standards for the databank.<h4>Conclusions</h4>These findings provide a clear mandate to begin developing the databank and a framework for stakeholder expectations, which we would aim to meet with the databank delivery.",,pdf:https://medinform.jmir.org/2023/1/e45534/PDF; doi:https://doi.org/10.2196/45534; html:https://europepmc.org/articles/PMC10193205
 37712381,https://doi.org/10.7189/jogh.13.04101,Understanding and reporting odds ratios as rate-ratio estimates in case-control studies.,"Kerr S, Greenland S, Jeffrey K, Millington T, Bedston S, Ritchie L, Simpson CR, Fagbamigbe AF, Kurdi A, Robertson C, Sheikh A, Rudan I.",,Journal of global health,2023,2023-09-15,Y,,,,"<h4>Background</h4>We noted that there remains some confusion in the health-science literature on reporting sample odds ratios as estimated rate ratios in case-control studies.<h4>Methods</h4>We recap historical literature that definitively answered the question of when sample odds ratios (ORs) from a case-control study are consistent estimators for population rate ratios. We use numerical examples to illustrate the magnitude of the disparity between sample ORs in a case-control study and population rate ratios when sufficient conditions for them to be equal are not satisfied.<h4>Results</h4>We stress that in a case-control study, sampling controls from those still at risk at the time of outcome event of the index case is not sufficient for a sample OR to be a consistent estimator for an intelligible rate ratio. In such studies, constancy of the exposure prevalence together with constancy of the hazard ratio (HR) (i.e., the instantaneous rate ratio) over time is sufficient for this result if sampling time is not controlled; if time is controlled, constancy of the HR will suffice. We present numerical examples to illustrate how failure to satisfy these conditions adds a small systematic error to sample ORs as estimates of population rate ratios.<h4>Conclusions</h4>We recommend that researchers understand and critically evaluate all conditions used to interpret their estimates as consistent for a population parameter in case-control studies.",,pdf:https://jogh.org/wp-content/uploads/2023/09/jogh-13-04101.pdf; doi:https://doi.org/10.7189/jogh.13.04101; html:https://europepmc.org/articles/PMC10502767; pdf:https://europepmc.org/articles/PMC10502767?pdf=render
-37706486,https://doi.org/10.1080/09638288.2023.2254235,Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.,"Giummarra MJ, Reeder S, Williams S, Devlin A, Knol R, Ponsford J, Arnold CA, Konstantatos A, Gabbe BJ, Clarke H, Katz J, Mitchell F, Robinson E, Zatzick D.",,Disability and rehabilitation,2023,2023-09-14,N,Trauma; Injury; Recovery; Pain; Hospitalization; Ptsd; Brief Intervention,,,"<h4>Purpose</h4>To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury.<h4>Materials and methods</h4>Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (<i>n</i> = 15) or intervention (<i>n</i> = 17) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability.<h4>Results</h4>Intervention participants received a median of 7 h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months.<h4>Conclusions</h4>Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/09638288.2023.2254235?needAccess=true; doi:https://doi.org/10.1080/09638288.2023.2254235
 34639581,https://doi.org/10.3390/ijerph181910265,Identifying Prenatal and Postnatal Determinants of Infant Growth: A Structural Equation Modelling Based Cohort Analysis. ,"Morgan K, Zhou SM, Hill R, Lyons RA, Paranjothy S, Brophy ST.",,International journal of environmental research and public health,2021,2021-09-29,Y,,,,"The growth and maturation of infants reflect their overall health and nutritional status. The purpose of this study is to examine the associations of prenatal and early postnatal factors with infant growth (IG). A data-driven model was constructed by structural equation modelling to examine the relationships between pre- and early postnatal environmental factors and IG at age 12 months. The IG was a latent variable created from infant weight and waist circumference. Data were obtained on 274 mother-child pairs during pregnancy and the postnatal periods. Maternal pre-pregnancy BMI emerged as an important predictor of IG with both direct and indirect (mediated through infant birth weight) effects. Infants who gained more weight from birth to 6 months and consumed starchy foods daily at age 12 months, were more likely to be larger by age 12 months. Infant physical activity (PA) levels also emerged as a determinant. The constructed model provided a reasonable fit (χ2 (11) = 21.5, p < 0.05; RMSEA = 0.07; CFI = 0.94; SRMR = 0.05) to the data with significant pathways for all examined variables. Promoting healthy weight amongst women of child bearing age is important in preventing childhood obesity, and increasing daily infant PA is as important as a healthy infant diet.",,pdf:https://www.mdpi.com/1660-4601/18/19/10265/pdf?version=1633013750; doi:https://doi.org/10.3390/ijerph181910265; html:https://europepmc.org/articles/PMC8507693; pdf:https://europepmc.org/articles/PMC8507693?pdf=render
+37706486,https://doi.org/10.1080/09638288.2023.2254235,Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.,"Giummarra MJ, Reeder S, Williams S, Devlin A, Knol R, Ponsford J, Arnold CA, Konstantatos A, Gabbe BJ, Clarke H, Katz J, Mitchell F, Robinson E, Zatzick D.",,Disability and rehabilitation,2023,2023-09-14,N,Trauma; Injury; Recovery; Pain; Hospitalization; Ptsd; Brief Intervention,,,"<h4>Purpose</h4>To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury.<h4>Materials and methods</h4>Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (<i>n</i> = 15) or intervention (<i>n</i> = 17) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability.<h4>Results</h4>Intervention participants received a median of 7 h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months.<h4>Conclusions</h4>Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/09638288.2023.2254235?needAccess=true; doi:https://doi.org/10.1080/09638288.2023.2254235
 33653753,https://doi.org/10.1136/bmjopen-2020-043290,Temporal trends in heart failure medication prescription in a population-based cohort study.,"Uijl A, Vaartjes I, Denaxas S, Hemingway H, Shah A, Cleland J, Grobbee D, Hoes A, Asselbergs FW, Koudstaal S.",,BMJ open,2021,2021-03-02,Y,Heart Failure; Public Health; Cardiac Epidemiology,,,"<h4>Objective</h4>We examined temporal heart failure (HF) prescription patterns in a large representative sample of real-world patients in the UK, using electronic health records (EHR).<h4>Methods</h4>From primary and secondary care EHR, we identified 85 732 patients with a HF diagnosis between 2002 and 2015. Almost 50% of patients with HF were women and the median age was 79.1 (IQR 70.2-85.7) years, with age at diagnosis increasing over time.<h4>Results</h4>We found several trends in pharmacological HF management, including increased beta blocker prescriptions over time (29% in 2002-2005 and 54% in 2013-2015), which was not observed for mineralocorticoid receptor-antagonists (MR-antagonists) (18% in 2002-2005 and 18% in 2013-2015); higher prescription rates of loop diuretics in women and elderly patients together with lower prescription rates of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, beta blockers or MR-antagonists in these patients; little change in medication prescription rates occurred after 6 months of HF diagnosis and, finally, patients hospitalised for HF who had no recorded follow-up in primary care had considerably lower prescription rates compared with patients with a HF diagnosis in primary care with or without HF hospitalisation.<h4>Conclusion</h4>In the general population, the use of MR-antagonists for HF remained low and did not change throughout 13 years of follow-up. For most patients, few changes were seen in pharmacological management of HF in the 6 months following diagnosis.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/3/e043290.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043290; html:https://europepmc.org/articles/PMC7929882; pdf:https://europepmc.org/articles/PMC7929882?pdf=render
 36648036,https://doi.org/10.1016/j.jcmg.2022.06.011,Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank.,"Raisi-Estabragh Z, McCracken C, Hann E, Condurache DG, Harvey NC, Munroe PB, Ferreira VM, Neubauer S, Piechnik SK, Petersen SE.",,JACC. Cardiovascular imaging,2023,2022-09-14,Y,Mortality; Cardiovascular disease; Cardiac Magnetic Resonance; Native T1 Mapping; Incident Events,,,"<h4>Background</h4>Cardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.<h4>Objectives</h4>The associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.<h4>Methods</h4>Native T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.<h4>Results</h4>Higher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10<sup>-9</sup>) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10<sup>-4</sup>). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10<sup>-4</sup>), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10<sup>-11</sup>), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10<sup>-5</sup>), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).<h4>Conclusions</h4>This large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.",,doi:https://doi.org/10.1016/j.jcmg.2022.06.011; doi:https://doi.org/10.1016/j.jcmg.2022.06.011; html:https://europepmc.org/articles/PMC10102720; pdf:https://europepmc.org/articles/PMC10102720?pdf=render
-36545688,https://doi.org/10.1192/bjb.2022.83,EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.,"Hemmings A, Sharpe H, Allen K, Bartel H, Campbell IC, Desrivières S, Dobson RJB, Folarin AA, French T, Kelly J, Micali N, Raman S, Treasure J, Abbas R, Heslop B, Street T, Schmidt U.",,BJPsych bulletin,2022,2022-12-22,N,Eating Disorders; Risk And Resilience; Prevention And Early Intervention; Youth Engagement; Interdisciplinary Working,,,"EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/C1E5FCC67F1D627908A5495EED02577B/S2056469422000833a.pdf/div-class-title-edify-eating-disorders-delineating-illness-and-recovery-trajectories-to-inform-personalised-prevention-and-early-intervention-in-young-people-project-outline-div.pdf; doi:https://doi.org/10.1192/bjb.2022.83
 34781301,https://doi.org/10.1159/000520674,"Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.","Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.",,Cardiology,2022,2021-11-15,N,Data Sources; cardiovascular; Real-world Data; Real-world Evidence,,,"<h4>Background</h4>Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).<h4>Methods</h4>We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.<h4>Results</h4>Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.<h4>Conclusions</h4>This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.",,pdf:https://www.karger.com/Article/Pdf/520674; doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674
+36545688,https://doi.org/10.1192/bjb.2022.83,EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.,"Hemmings A, Sharpe H, Allen K, Bartel H, Campbell IC, Desrivières S, Dobson RJB, Folarin AA, French T, Kelly J, Micali N, Raman S, Treasure J, Abbas R, Heslop B, Street T, Schmidt U.",,BJPsych bulletin,2022,2022-12-22,N,Eating Disorders; Risk And Resilience; Prevention And Early Intervention; Youth Engagement; Interdisciplinary Working,,,"EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/C1E5FCC67F1D627908A5495EED02577B/S2056469422000833a.pdf/div-class-title-edify-eating-disorders-delineating-illness-and-recovery-trajectories-to-inform-personalised-prevention-and-early-intervention-in-young-people-project-outline-div.pdf; doi:https://doi.org/10.1192/bjb.2022.83
 36137640,https://doi.org/10.1136/bmjopen-2022-064586,Myocardial infarction and stroke subsequent to urinary tract infection (MISSOURI): protocol for a self-controlled case series using linked electronic health records.,"Reeve NF, Best V, Gillespie D, Hughes K, Lugg-Widger FV, Cannings-John R, Torabi F, Wootton M, Akbari A, Ahmed H.",,BMJ open,2022,2022-09-22,Y,Myocardial infarction; Stroke; Urinary tract infections,,,"<h4>Introduction</h4>There is increasing interest in the relationship between acute infections and acute cardiovascular events. Most previous research has focused on understanding whether the risk of acute cardiovascular events increases following a respiratory tract infection. The relationship between urinary tract infections (UTIs) and acute cardiovascular events is less well studied. Therefore, the aim of this study is to determine whether there is a causal relationship between UTI and acute myocardial infarction (MI) or stroke.<h4>Methods and analysis</h4>We will undertake a self-controlled case series study using linked anonymised general practice, hospital admission and microbiology data held within the Secure Anonymised Information Linkage (SAIL) Databank. Self-controlled case series is a relatively novel study design where individuals act as their own controls, thereby inherently controlling for time-invariant confounders. Only individuals who experience an exposure and outcome of interest are included.We will identify individuals in the SAIL Databank who have a hospital admission record for acute MI or stroke during the study period of 2010-2020. Individuals will need to be aged 30-100 during the study period and be Welsh residents for inclusion. UTI will be identified using general practice, microbiology and hospital admissions data. We will calculate the incidence of MI and stroke in predefined risk periods following an UTI and in 'baseline' periods (without UTI exposure) and use conditional Poisson regression models to derive incidence rate ratios.<h4>Ethics and dissemination</h4>Data access, research permissions and approvals have been obtained from the SAIL independent Information Governance Review Panel, project number 0972. Findings will be disseminated through conferences, blogs, social media threads and peer-reviewed journals. Results will be of interest internationally to primary and secondary care clinicians who manage UTIs and may inform future clinical trials of preventative therapy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e064586.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064586; html:https://europepmc.org/articles/PMC9511592; pdf:https://europepmc.org/articles/PMC9511592?pdf=render
 31666244,https://doi.org/10.1136/archdischild-2019-317271,Behavioural difficulties in early childhood and risk of adolescent injury.,"Bandyopadhyay A, Tingay K, Akbari A, Griffiths L, Bedford H, Cortina-Borja M, Walton S, Dezateux C, Lyons RA, Brophy S.",,Archives of disease in childhood,2020,2019-10-30,Y,Hospital Admission; Routine Data; Strengths And Difficulties Questionnaire; A&e Attendance; Longitudinal Data Linkage,,,"<h4>Objective</h4>To evaluate long-term associations between early childhood hyperactivity and conduct problems (CP), measured using Strengths and Difficulties Questionnaire (SDQ) and risk of injury in early adolescence.<h4>Design</h4>Data linkage between a longitudinal birth cohort and routinely collected electronic health records.<h4>Setting</h4>Consenting Millennium Cohort Study (MCS) participants residing in Wales and Scotland.<h4>Patients</h4>3119 children who participated in the age 5 MCS interview.<h4>Main outcome measures</h4>Children with parent-reported SDQ scores were linked with hospital admission and Accident & Emergency (A&E) department records for injuries between ages 9 and 14 years. Negative binomial regression models adjusting for number of people in the household, lone parent, residential area, household poverty, maternal age and academic qualification, child sex, physical activity level and country of interview were fitted in the models.<h4>Results</h4>46% of children attended A&E or were admitted to hospital for injury, and 11% had high/abnormal scores for hyperactivity and CP. High/abnormal or borderline hyperactivity were not significantly associated with risk of injury, incidence rate ratio (IRR) with 95% CI of the high/abnormal and borderline were 0.92 (95% CI 0.74 to 1.14) and 1.16 (95% CI 0.88 to 1.52), respectively. Children with borderline CP had higher injury rates compared with those without CP (IRR 1.31, 95% CI 1.09 to 1.57).<h4>Conclusions</h4>Children with high/abnormal hyperactivity or CP scores were not at increased risk of injury; however, those with borderline CP had higher injury rates. Further research is needed to understand if those with difficulties receive treatment and support, which may reduce the likelihood of injuries.",,pdf:https://adc.bmj.com/content/archdischild/105/3/282.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317271; html:https://europepmc.org/articles/PMC7041499; pdf:https://europepmc.org/articles/PMC7041499?pdf=render
 32128788,https://doi.org/10.1111/bjd.18889,The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.,"Wong AYS, Frøslev T, Dearing L, Forbes HJ, Mulick A, Mansfield KE, Silverwood RJ, Kjaersgaard A, Sørensen HT, Smeeth L, Lewin A, Schmidt SAJ, Langan SM.",,The British journal of dermatology,2020,2020-03-03,Y,,,,"<h4>Background</h4>Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited.<h4>Objectives</h4>This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma.<h4>Methods</h4>We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis.<h4>Results</h4>In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60).<h4>Conclusions</h4>We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.",,doi:https://doi.org/10.1111/bjd.18889; doi:https://doi.org/10.1111/bjd.18889; html:https://europepmc.org/articles/PMC7587014; pdf:https://europepmc.org/articles/PMC7587014?pdf=render
-37284234,https://doi.org/10.1140/epjds/s13688-023-00391-9,"The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.","Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",,EPJ data science,2023,2023-06-05,Y,Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19,,,"Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming ""digital residents."" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",,doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render
 35403174,https://doi.org/10.14218/jctp.2022.00003,Changing Trends in the Proportional Incidence and Five-year Net Survival of Screened and Non-screened Breast Cancers among Women During 1995-2011 in England.,"Wu H, Wong K, Lu SE, Broggio J, Zhang L.",,Journal of clinical and translational pathology,2022,2022-03-18,Y,Screening; Breast cancer; incidence; trends; Net Survival,,,"<h4>Background and objectives</h4>Uptake of breast cancer screening has been decreasing in England since 2007. However, the associated factors are unclear. On the other hand, survival among breast cancer patients have recently increased. We conducted a quasi-experimental analysis to test whether the trend-change in proportional incidence of non-screened cancers coincided with that in five-year net-survival.<h4>Methods</h4>We extracted population-based proportional incidence and age-standardized five-year net-survival data from Public Health England that included English women with invasive breast cancer diagnosed during 1995-2011 (linked to death certificates, followed through 2016). Piece-wise log-linear models with change-point/joinpoint were used to estimate temporal trends.<h4>Results</h4>Among 254,063 women in England with invasive breast cancer diagnosed during 1995-2011, there was downward-to-upward trend-change in proportional incidence of non-screened breast cancers (annual percent change [APC]=5.6 after 2007 versus APC=-3.5 before 2007, <i>p</i><0.001) in diagnosis-year 2007, when a steeper upward-trend in age-standardized five-year net survival started (APC=5.7 after 2007/2008 versus APC=0.3 before 2007/2008, <i>p<</i>0.001). Net-survival difference of screened versus non-screened cancers also significantly narrowed (18% in 2007/2008 versus 5% in 2011). Similar associations were found in all strata of race, cancer stage, grade, and histology, except in Black patients or patients with stage I, stage III, or grade I cancer.<h4>Conclusions</h4>There was a downward-to-upward trend-change in proportional incidence of non-screened breast cancers in 2007 that coincided with a steeper upward-trend in age-standardized five-year net survival among English women in 2007. Survival benefits of breast cancer screening decreased during 2007-2011. The data support reduction of breast cancer screening in some patients, but future validation studies are warranted.",,pdf:https://publinestorage.blob.core.windows.net/journals/JCTP.2022.2(1).23.00003.pdf; doi:https://doi.org/10.14218/jctp.2022.00003; html:https://europepmc.org/articles/PMC8994161; pdf:https://europepmc.org/articles/PMC8994161?pdf=render
+37284234,https://doi.org/10.1140/epjds/s13688-023-00391-9,"The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.","Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",,EPJ data science,2023,2023-06-05,Y,Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19,,,"Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming ""digital residents."" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",,doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render
 33168126,https://doi.org/10.1192/bjo.2020.42,Impact of schizophrenia genetic liability on the association between schizophrenia and physical illness: data-linkage study.,"Kendall KM, John A, Lee SC, Rees E, Pardiñas AF, Banos MDP, Owen MJ, O'Donovan MC, Kirov G, Lloyd K, Jones I, Legge SE, Walters JTR.",,BJPsych open,2020,2020-11-10,Y,Genetics; Schizophrenia; Physical Health; Psychotic Disorders,,,"<h4>Background</h4>Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.<h4>Aims</h4>To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.<h4>Method</h4>We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.<h4>Results</h4>Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.<h4>Conclusions</h4>This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00360A347FCC91E2E9D0B39FBDCE887/S2056472420000423a.pdf/div-class-title-impact-of-schizophrenia-genetic-liability-on-the-association-between-schizophrenia-and-physical-illness-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjo.2020.42; html:https://europepmc.org/articles/PMC7745237; pdf:https://europepmc.org/articles/PMC7745237?pdf=render
-33475522,https://doi.org/10.2196/18229,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: Protocol for a Systematic Review.,"Fundikira LS, Chillo P, van Laake LW, Mutagaywa RK, Schmidt AF, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,JMIR research protocols,2021,2021-01-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiomyopathy; Cardiovascular risk factors; Heart Failure,,,"<h4>Background</h4>Cardiomyopathies, defined as diseases involving mainly the heart muscles, are linked to an estimated 5.9 of 100,000 deaths globally. In sub-Saharan Africa, cardiomyopathies constitute 21.4% of heart failure cases, with dilated cardiomyopathy (DCM) being the most common form. The etiology of DCM is heterogeneous and is broadly categorized as genetic or nongenetic, as well as a mixed disease in which genetics interact with intrinsic and environmental factors. Factors such as age, gender, family history, and ethnicity are nonmodifiable, whereas modifiable risk factors include poor nutrition, physical inactivity, and excessive alcohol consumption, among others. However, the relative contribution of the different risk factors to the etiology of DCM is not known in sub-Saharan Africa, and the prevalence of DCM among heart failure patients has not been systematically studied in the region.<h4>Objective</h4>The aim of this review is to synthesize available literature from sub-Saharan Africa on the prevalence of DCM among patients with heart failure, as well as the literature on factors associated with DCM. This paper outlines the protocol that will be followed to conduct the systematic review.<h4>Methods</h4>A limited search of the PubMed database will be performed to identify relevant keywords contained in the title, abstract, and subject descriptors using initial search terms ""heart failure,"" ""cardiomyopathy,"" and ""sub-Saharan Africa."" These search terms and their synonyms will then be used in an extensive search in PubMed, and will address the first research question on prevalence. To address the second research question on risk factors, the terms ""heart failure,"" ""cardiomyopathy,"" and ""cardiovascular risk factors"" in ""Sub-Saharan Africa"" will be used, listing them one by one. Articles published from 2000 and in the English language will be included. Indexed articles in PubMed and Embase will be included, as well as the first 300 articles retrieved from a Google Scholar search. Collected data will be organized in Endnote and then uploaded to the Rayyan web app for systematic reviews. Two reviewers will independently select articles against the inclusion criteria. Discrepancies in reviewer selections will be resolved by an arbitrator. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for reporting systematic reviews will be applied. A map of sub-Saharan Africa with colors to show disease prevalence in each country will be included. For quantitative data, where possible, odds ratios (for categorical outcome data) or standardized mean differences (for continuous data) and their 95% CIs will be calculated.<h4>Results</h4>The primary outcomes will be the prevalence of DCM among patients with heart failure and cardiovascular risk factors associated with DCM in sub-Saharan Africa. The literature search will begin on January 1, 2021, and data analysis is expected to be completed by April 30, 2021.<h4>Conclusions</h4>This review will provide information on the current status of the prevalence and associated factors of DCM, and possibly identify gaps, including paucity of data or conflicting results that need to be addressed to improve our understanding of DCM in sub-Saharan Africa.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/18229.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i1e18229_app1.pdf&filename=7e28e6f3581cda60eb7faa74a1bb7968.pdf; doi:https://doi.org/10.2196/18229; html:https://europepmc.org/articles/PMC7862000
 30659777,https://doi.org/10.1111/ijpo.12505,Are children with clinical obesity at increased risk of inpatient hospital admissions? An analysis using linked electronic health records in the UK millennium cohort study.,"Griffiths LJ, Cortina-Borja M, Bandyopadhyay A, Tingay K, De Stavola BL, Bedford H, Akbari A, Firman N, Lyons RA, Dezateux C.",,Pediatric obesity,2019,2019-01-18,Y,Obesity; Cohort study; Record Linkage; Health Service Utilization,Improving Public Health,,"<h4>Background</h4>Few studies have examined health service utilization of children with overweight or obesity by using linked electronic health records (EHRs).<h4>Objective/methods</h4>We analysed EHRs from 3269 children (1678 boys; 51.3% [weighted]) participating in the Millennium Cohort Study, living in Wales or Scotland at age seven whose parents consented to record linkage. We used height and weight measurements at age five to categorize children as obese (>98th centile) or overweight (>91st centile) (UK1990 clinical reference standards) and linked to hospital admissions, up to age 14 years, in the Patient Episode Database for Wales and Scottish Morbidity Records. Negative binomial regression models compared rates of inpatient admissions by weight status at age five.<h4>Results</h4>At age five, 11.5% and 6.7% of children were overweight or obese, respectively; 1221 (38%) children were subsequently admitted to hospital at least once. Admissions were not increased among children with overweight or obesity (adjusted rate ratio [RR], 95% confidence interval [CI]: 0.87, 0.68-1.10 and 1.16, 0.87-1.54, respectively).<h4>Conclusions</h4>In this nationally representative cohort of children in Wales and Scotland, those with overweight or obesity at entry to primary school did not have increased rates of hospital admissions in later childhood and early adolescence.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ijpo.12505; doi:https://doi.org/10.1111/ijpo.12505; html:https://europepmc.org/articles/PMC6563186; pdf:https://europepmc.org/articles/PMC6563186?pdf=render
+33475522,https://doi.org/10.2196/18229,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: Protocol for a Systematic Review.,"Fundikira LS, Chillo P, van Laake LW, Mutagaywa RK, Schmidt AF, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,JMIR research protocols,2021,2021-01-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiomyopathy; Cardiovascular risk factors; Heart Failure,,,"<h4>Background</h4>Cardiomyopathies, defined as diseases involving mainly the heart muscles, are linked to an estimated 5.9 of 100,000 deaths globally. In sub-Saharan Africa, cardiomyopathies constitute 21.4% of heart failure cases, with dilated cardiomyopathy (DCM) being the most common form. The etiology of DCM is heterogeneous and is broadly categorized as genetic or nongenetic, as well as a mixed disease in which genetics interact with intrinsic and environmental factors. Factors such as age, gender, family history, and ethnicity are nonmodifiable, whereas modifiable risk factors include poor nutrition, physical inactivity, and excessive alcohol consumption, among others. However, the relative contribution of the different risk factors to the etiology of DCM is not known in sub-Saharan Africa, and the prevalence of DCM among heart failure patients has not been systematically studied in the region.<h4>Objective</h4>The aim of this review is to synthesize available literature from sub-Saharan Africa on the prevalence of DCM among patients with heart failure, as well as the literature on factors associated with DCM. This paper outlines the protocol that will be followed to conduct the systematic review.<h4>Methods</h4>A limited search of the PubMed database will be performed to identify relevant keywords contained in the title, abstract, and subject descriptors using initial search terms ""heart failure,"" ""cardiomyopathy,"" and ""sub-Saharan Africa."" These search terms and their synonyms will then be used in an extensive search in PubMed, and will address the first research question on prevalence. To address the second research question on risk factors, the terms ""heart failure,"" ""cardiomyopathy,"" and ""cardiovascular risk factors"" in ""Sub-Saharan Africa"" will be used, listing them one by one. Articles published from 2000 and in the English language will be included. Indexed articles in PubMed and Embase will be included, as well as the first 300 articles retrieved from a Google Scholar search. Collected data will be organized in Endnote and then uploaded to the Rayyan web app for systematic reviews. Two reviewers will independently select articles against the inclusion criteria. Discrepancies in reviewer selections will be resolved by an arbitrator. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for reporting systematic reviews will be applied. A map of sub-Saharan Africa with colors to show disease prevalence in each country will be included. For quantitative data, where possible, odds ratios (for categorical outcome data) or standardized mean differences (for continuous data) and their 95% CIs will be calculated.<h4>Results</h4>The primary outcomes will be the prevalence of DCM among patients with heart failure and cardiovascular risk factors associated with DCM in sub-Saharan Africa. The literature search will begin on January 1, 2021, and data analysis is expected to be completed by April 30, 2021.<h4>Conclusions</h4>This review will provide information on the current status of the prevalence and associated factors of DCM, and possibly identify gaps, including paucity of data or conflicting results that need to be addressed to improve our understanding of DCM in sub-Saharan Africa.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/18229.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i1e18229_app1.pdf&filename=7e28e6f3581cda60eb7faa74a1bb7968.pdf; doi:https://doi.org/10.2196/18229; html:https://europepmc.org/articles/PMC7862000
 31504435,https://doi.org/10.1093/eurheartj/ehz569,Obesity causes cardiovascular diseases: adding to the weight of evidence.,"Hingorani AD, Finan C, Schmidt AF.",,European heart journal,2020,2020-01-01,N,,,,,,pdf:https://academic.oup.com/eurheartj/article-pdf/41/2/227/31731687/ehz569.pdf; doi:https://doi.org/10.1093/eurheartj/ehz569
 31529485,https://doi.org/10.1111/bjd.18526,"The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.","Gibson JAG, Dobbs TD, Griffiths R, Song J, Akbari A, Whitaker S, Watkins A, Langan SM, Hutchings HA, Lyons RA, Whitaker IS.",,The British journal of dermatology,2020,2019-12-01,Y,,Improving Public Health,,"<h4>Background</h4>Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce.<h4>Objectives</h4>To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival.<h4>Methods</h4>We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome.<h4>Results</h4>During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90).<h4>Conclusions</h4>Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.","This study investiages whether there is a smoking and socioeconomic status is linked to the risk of developing melanoma (a skin cancer). They used a Welsh database to find data on individuals who had melanoma and linked this data with smoking status and socioeconomic status on other national databases. They found that melanoma was less likely in those who smoked, but was associated with less chance of survival (due to health problems other than melanoma). Those in higher socioeconomic status had overall higher likelihood of survival.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18526; doi:https://doi.org/10.1111/bjd.18526; html:https://europepmc.org/articles/PMC7383980; pdf:https://europepmc.org/articles/PMC7383980?pdf=render
 34194954,https://doi.org/10.1002/advs.202100707,Green Algorithms: Quantifying the Carbon Footprint of Computation.,"Lannelongue L, Grealey J, Inouye M.",,"Advanced science (Weinheim, Baden-Wurttemberg, Germany)",2021,2021-05-02,Y,Climate change; Green Computing; Computational Research,,,"Climate change is profoundly affecting nearly all aspects of life on earth, including human societies, economies, and health. Various human activities are responsible for significant greenhouse gas (GHG) emissions, including data centers and other sources of large-scale computation. Although many important scientific milestones are achieved thanks to the development of high-performance computing, the resultant environmental impact is underappreciated. In this work, a methodological framework to estimate the carbon footprint of any computational task in a standardized and reliable way is presented and metrics to contextualize GHG emissions are defined. A freely available online tool, Green Algorithms (www.green-algorithms.org) is developed, which enables a user to estimate and report the carbon footprint of their computation. The tool easily integrates with computational processes as it requires minimal information and does not interfere with existing code, while also accounting for a broad range of hardware configurations. Finally, the GHG emissions of algorithms used for particle physics simulations, weather forecasts, and natural language processing are quantified. Taken together, this study develops a simple generalizable framework and freely available tool to quantify the carbon footprint of nearly any computation. Combined with recommendations to minimize unnecessary CO<sub>2</sub> emissions, the authors hope to raise awareness and facilitate greener computation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202100707; doi:https://doi.org/10.1002/advs.202100707; html:https://europepmc.org/articles/PMC8224424; pdf:https://europepmc.org/articles/PMC8224424?pdf=render
@@ -1057,15 +1057,15 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 34974610,https://doi.org/10.1093/eurheartj/ehab874,The year in cardiovascular medicine 2021: digital health and innovation.,"Vardas PE, Asselbergs FW, van Smeden M, Friedman P.",,European heart journal,2022,2022-01-01,N,Cardiovascular Medicine; Machine Learning; Big Data; Digital Health; Ai-ecg; Ai-wearables,,,"This article presents some of the most important developments in the field of digital medicine that have appeared over the last 12 months and are related to cardiovascular medicine. The article consists of three main sections, as follows: (i) artificial intelligence-enabled cardiovascular diagnostic tools, techniques, and methodologies, (ii) big data and prognostic models for cardiovascular risk protection, and (iii) wearable devices in cardiovascular risk assessment, cardiovascular disease prevention, diagnosis, and management. To conclude the article, the authors present a brief further prospective on this new domain, highlighting existing gaps that are specifically related to artificial intelligence technologies, such as explainability, cost-effectiveness, and, of course, the importance of proper regulatory oversight for each clinical implementation.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/4/271/46630082/ehab874.pdf; doi:https://doi.org/10.1093/eurheartj/ehab874
 35537476,https://doi.org/10.1177/01410768221095245,Indirect effects of the pandemic: highlighting the need for data-driven policy and preparedness.,"Banerjee A, Sudlow C, Lawler M.",,Journal of the Royal Society of Medicine,2022,2022-05-10,Y,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221095245; doi:https://doi.org/10.1177/01410768221095245; html:https://europepmc.org/articles/PMC9234890; pdf:https://europepmc.org/articles/PMC9234890?pdf=render
 36332947,https://doi.org/10.1136/bmjopen-2022-061843,Numbers and types of neurological emergencies in England and the influence of socioeconomic deprivation: a retrospective analysis of hospital episode statistics data.,"Jackson M, Szczepaniak M, Wall J, Maskery M, Mummery C, Morrish P, Williams A, Knight J, Emsley HCA.",,BMJ open,2022,2022-11-04,Y,Epilepsy; Neurology; Public Health,,,"<h4>Objectives</h4>In this first large-scale analysis of neurological emergency admissions in England, we determine the number and types of emergency admissions with neurological emergency diagnostic codes, how many are under the care of a neurologist or neurosurgeon and how such admissions vary by levels of deprivation.<h4>Design</h4>Retrospective empirical research employing a derived list of neurological emergency diagnostic codes SETTING: This study used the Hospital Episode Statistics data set for the financial year 2019/2020 based on 17 million in-year inpatient admissions in England including 6.5 million (100%) emergency admissions with any diagnosis codes.<h4>Results</h4>There were 1.4 million (21.2%) emergency inpatient admissions with a mention of any neurological code, approx. 248 455 (3.8%) with mention of a specific neurological emergency code from the derived list, and 72 485 (1.1%) included such a code as the primary reason for admission. The highest number of in-year admissions for adults was for epilepsy (145 995), with epilepsy as the primary diagnostic code in 15 945 (10.9%). Acute nerve root/spinal cord syndrome (41 215), head injury (29 235) and subarachnoid haemorrhage (18 505) accounted for the next three highest number of admissions. 3230 (1.4%) in-year emergency hospital admissions with mention of a neurological emergency code were under the care of a neurologist or neurosurgeon, with only 1315 (0.9%) admissions with mention of an epilepsy code under a neurologist. There was significant variation for epilepsy and functional neurological disorders (FNDs) in particular by Index of Multiple Deprivation decile. The association between deprivation and epilepsy and FND was significant with p-values of 2.5e-6 and 1.5e-8, respectively.<h4>Conclusions</h4>This study has identified important findings in relation to the burden of neurological emergency admissions but further work is needed, with greater clinical engagement in diagnostic coding, to better understand the implications for workforce and changes to service delivery needing to be implemented.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061843.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061843; html:https://europepmc.org/articles/PMC9639083; pdf:https://europepmc.org/articles/PMC9639083?pdf=render
-37634573,https://doi.org/10.1016/j.cardfail.2023.08.008,Does Heterogeneity Exist in Treatment Associations With Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?,"Uijl A, Koudstaal S, Stolfo D, Dahlström U, Vaartjes I, Grobbee RE, Asselbergs FW, Lund LH, Savarese G.",,Journal of cardiac failure,2023,2023-08-25,N,Personalized Medicine; Beta-blockers; Hfpef; Renin–angiotensin System Inhibitors; Phenotype Clusters,,,"<h4>Background</h4>We explored the association between use of renin-angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF).<h4>Methods and results</h4>We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation-hypertensive (32%), older-atrial fibrillation (24%), obese-diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin-angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P = .03) and non-CV hospitalisation (P = .001). In the young-low comorbidity burden and atrial fibrillation-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar.<h4>Conclusions</h4>In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.",,doi:https://doi.org/10.1016/j.cardfail.2023.08.008
 36350810,https://doi.org/10.1371/journal.pone.0276781,"Primary hypertension, anti-hypertensive medications and the risk of severe COVID-19 in UK Biobank.","Pavey H, Kulkarni S, Wood A, Ben-Shlomo Y, Sever P, McEniery C, Wilkinson I.",,PloS one,2022,2022-11-09,Y,,,,"Hypertension appears to be one of the commonest comorbidities in COVID-19 patients, although whether hypertensive individuals have a higher risk of severe COVID-19 compared with non-hypertensives is unclear. It is also unclear whether the absolute level of systolic blood pressure, or the type of anti-hypertensive medication is related to this risk. Analyses were conducted using data from the UK Biobank and linked health records. Logistic regression models were fitted to assess the impact of hypertension, systolic blood pressure (SBP) and medications on the risk of severe COVID-19. 16,134 individuals tested positive for severe acute respiratory syndrome-coronavirus, 22% (n = 3,584) developed severe COVID-19 and 40% (n = 6,517) were hypertensive. Hypertension was associated with 22% higher odds of severe COVID-19 (Odds ratio (OR) 1.22; 95% confidence interval (CI) 1.12, 1.33), compared with normotension after adjusting for confounding variables. In those taking anti-hypertensive medications, elevated SBP showed a dose-response relationship with severe COVID-19 (150-159mmHg versus 120-129mmHg (OR 1.91; 95% CI 1.44, 2.53), &gt;180+mmHg versus 120-129mmHg (OR 1.93; 95% CI 1.06, 3.51)). SBP &lt;120mmHg was associated with greater odds of severe COVID-19 (OR 1.40; 95% CI 1.11, 1.78). Angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers were not associated with altered risk of severe COVID-19. Hypertension is an important risk factor for COVID-19. A better understanding of the underlying mechanisms is warranted in case of more severe strains or other viruses in the future.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0276781&type=printable; doi:https://doi.org/10.1371/journal.pone.0276781; html:https://europepmc.org/articles/PMC9645600; pdf:https://europepmc.org/articles/PMC9645600?pdf=render
-37286615,https://doi.org/10.1038/s41598-023-36214-0,Combining machine learning with Cox models to identify predictors for incident post-menopausal breast cancer in the UK Biobank.,"Liu X, Morelli D, Littlejohns TJ, Clifton DA, Clifton L.",,Scientific reports,2023,2023-06-07,Y,,,,"We aimed to identify potential novel predictors for breast cancer among post-menopausal women, with pre-specified interest in the role of polygenic risk scores (PRS) for risk prediction. We utilised an analysis pipeline where machine learning was used for feature selection, prior to risk prediction by classical statistical models. An ""extreme gradient boosting"" (XGBoost) machine with Shapley feature-importance measures were used for feature selection among [Formula: see text] 1.7 k features in 104,313 post-menopausal women from the UK Biobank. We constructed and compared the ""augmented"" Cox model (incorporating the two PRS, known and novel predictors) with a ""baseline"" Cox model (incorporating the two PRS and known predictors) for risk prediction. Both of the two PRS were significant in the augmented Cox model ([Formula: see text]). XGBoost identified 10 novel features, among which five showed significant associations with post-menopausal breast cancer: plasma urea (HR = 0.95, 95% CI 0.92-0.98, [Formula: see text]), plasma phosphate (HR = 0.68, 95% CI 0.53-0.88, [Formula: see text]), basal metabolic rate (HR = 1.17, 95% CI 1.11-1.24, [Formula: see text]), red blood cell count (HR = 1.21, 95% CI 1.08-1.35, [Formula: see text]), and creatinine in urine (HR = 1.05, 95% CI 1.01-1.09, [Formula: see text]). Risk discrimination was maintained in the augmented Cox model, yielding C-index 0.673 vs 0.667 (baseline Cox model) with the training data and 0.665 vs 0.664 with the test data. We identified blood/urine biomarkers as potential novel predictors for post-menopausal breast cancer. Our findings provide new insights to breast cancer risk. Future research should validate novel predictors, investigate using multiple PRS and more precise anthropometry measures for better breast cancer risk prediction.",,doi:https://doi.org/10.1038/s41598-023-36214-0; doi:https://doi.org/10.1038/s41598-023-36214-0; html:https://europepmc.org/articles/PMC10247810; pdf:https://europepmc.org/articles/PMC10247810?pdf=render
+37634573,https://doi.org/10.1016/j.cardfail.2023.08.008,Does Heterogeneity Exist in Treatment Associations With Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?,"Uijl A, Koudstaal S, Stolfo D, Dahlström U, Vaartjes I, Grobbee RE, Asselbergs FW, Lund LH, Savarese G.",,Journal of cardiac failure,2023,2023-08-25,N,Personalized Medicine; Beta-blockers; Hfpef; Renin–angiotensin System Inhibitors; Phenotype Clusters,,,"<h4>Background</h4>We explored the association between use of renin-angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF).<h4>Methods and results</h4>We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation-hypertensive (32%), older-atrial fibrillation (24%), obese-diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin-angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P = .03) and non-CV hospitalisation (P = .001). In the young-low comorbidity burden and atrial fibrillation-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar.<h4>Conclusions</h4>In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.",,doi:https://doi.org/10.1016/j.cardfail.2023.08.008
 36587850,https://doi.org/10.1016/j.jaci.2022.12.810,The gut microbiome is a significant risk factor for future chronic lung disease.,"Liu Y, Teo SM, Méric G, Tang HHF, Zhu Q, Sanders JG, Vázquez-Baeza Y, Verspoor K, Vartiainen VA, Jousilahti P, Lahti L, Niiranen T, Havulinna AS, Knight R, Salomaa V, Inouye M.",,The Journal of allergy and clinical immunology,2023,2022-12-29,Y,Gut; Asthma; COPD; Metagenomics; Microbiome,,,"<h4>Background</h4>The gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults.<h4>Objective</h4>We sought to investigate the association and predictive capacity of the gut microbiome for incident asthma and chronic obstructive pulmonary disease (COPD).<h4>Methods</h4>Shallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N = 7115 adults) with linked national administrative health register-derived classifications for incident asthma and COPD up to 15 years after baseline. Generalized linear models and Cox regressions were used to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index, and smoking status.<h4>Results</h4>A total of 695 and 392 statistically significant associations were found between baseline taxonomic groups and incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome abundance predicted incident asthma and COPD in the validation data sets with mean area under the curves of 0.608 and 0.780, respectively. Cox analysis showed that the baseline gut microbiome achieved higher predictive performance than individual conventional risk factors, with C-indices of 0.623 for asthma and 0.817 for COPD. The integration of the gut microbiome and conventional risk factors further improved prediction capacities.<h4>Conclusions</h4>The gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors.",,doi:https://doi.org/10.1016/j.jaci.2022.12.810; doi:https://doi.org/10.1016/j.jaci.2022.12.810; html:https://europepmc.org/articles/PMC10109092; pdf:https://europepmc.org/articles/PMC10109092?pdf=render
+37286615,https://doi.org/10.1038/s41598-023-36214-0,Combining machine learning with Cox models to identify predictors for incident post-menopausal breast cancer in the UK Biobank.,"Liu X, Morelli D, Littlejohns TJ, Clifton DA, Clifton L.",,Scientific reports,2023,2023-06-07,Y,,,,"We aimed to identify potential novel predictors for breast cancer among post-menopausal women, with pre-specified interest in the role of polygenic risk scores (PRS) for risk prediction. We utilised an analysis pipeline where machine learning was used for feature selection, prior to risk prediction by classical statistical models. An ""extreme gradient boosting"" (XGBoost) machine with Shapley feature-importance measures were used for feature selection among [Formula: see text] 1.7 k features in 104,313 post-menopausal women from the UK Biobank. We constructed and compared the ""augmented"" Cox model (incorporating the two PRS, known and novel predictors) with a ""baseline"" Cox model (incorporating the two PRS and known predictors) for risk prediction. Both of the two PRS were significant in the augmented Cox model ([Formula: see text]). XGBoost identified 10 novel features, among which five showed significant associations with post-menopausal breast cancer: plasma urea (HR = 0.95, 95% CI 0.92-0.98, [Formula: see text]), plasma phosphate (HR = 0.68, 95% CI 0.53-0.88, [Formula: see text]), basal metabolic rate (HR = 1.17, 95% CI 1.11-1.24, [Formula: see text]), red blood cell count (HR = 1.21, 95% CI 1.08-1.35, [Formula: see text]), and creatinine in urine (HR = 1.05, 95% CI 1.01-1.09, [Formula: see text]). Risk discrimination was maintained in the augmented Cox model, yielding C-index 0.673 vs 0.667 (baseline Cox model) with the training data and 0.665 vs 0.664 with the test data. We identified blood/urine biomarkers as potential novel predictors for post-menopausal breast cancer. Our findings provide new insights to breast cancer risk. Future research should validate novel predictors, investigate using multiple PRS and more precise anthropometry measures for better breast cancer risk prediction.",,doi:https://doi.org/10.1038/s41598-023-36214-0; doi:https://doi.org/10.1038/s41598-023-36214-0; html:https://europepmc.org/articles/PMC10247810; pdf:https://europepmc.org/articles/PMC10247810?pdf=render
 34459398,https://doi.org/10.3233/jad-210462,Assessing Genetic Overlap and Causality Between Blood Plasma Proteins and Alzheimer's Disease.,"Handy A, Lord J, Green R, Xu J, Aarsland D, Velayudhan L, Hye A, Dobson R, Proitsi P, Alzheimer’s Disease Neuroimaging initiative, AddNeuroMed, and the GERAD1 Consortium.",,Journal of Alzheimer's disease : JAD,2021,2021-01-01,Y,Apolipoprotein E; Blood proteins; Alzheimer’s disease; C-reactive Protein; Apolipoprotein B-100; Insulin-like Growth Factor Binding Protein 2; Vitamin D-binding Protein; Mendelian Randomization Analysis; Polygenic Trait,,,"<h4>Background</h4>Blood plasma proteins have been associated with Alzheimer's disease (AD), but understanding which proteins are on the causal pathway remains challenging.<h4>Objective</h4>Investigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian randomization (MR).<h4>Methods</h4>Following a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritized proteins with and without the apolipoprotein E region (APOE+/-PRS) and tested for association with AD status across three cohorts (n = 6,244). An AD PRS was also tested for association with protein levels in one cohort (n = 410). Proteins showing association with AD were taken forward for MR.<h4>Results</h4>For APOE ɛ3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p < 0.00017). No protein APOE- PRS or AD PRS (APOE+/-) passed pBonf. However, vitamin D-binding protein (protein PRS APOE-, p = 0.009) and insulin-like growth factor-binding protein 2 (AD APOE- PRS p = 0.025, protein APOE- PRS p = 0.045) displayed suggestive signals and were selected for MR. In bi-directional MR, none of the five proteins demonstrated a causal association (p < 0.05) in either direction.<h4>Conclusion</h4>Apolipoproteins and CRP PRS are associated with AD and provide a genetic signal linked to a specific, accessible risk factor. While evidence of causality was limited, this study was conducted in a moderate sample size and provides a framework for larger samples with greater statistical power.",,pdf:https://content.iospress.com:443/download/journal-of-alzheimers-disease/jad210462?id=journal-of-alzheimers-disease%2Fjad210462; doi:https://doi.org/10.3233/JAD-210462; html:https://europepmc.org/articles/PMC8609677; pdf:https://europepmc.org/articles/PMC8609677?pdf=render
 32249120,https://doi.org/10.1016/j.schres.2020.03.044,"Area deprivation, urbanicity, severe mental illness and social drift - A population-based linkage study using routinely collected primary and secondary care data.","Lee SC, DelPozo-Banos M, Lloyd K, Jones I, Walters JTR, Owen MJ, O'Donovan M, John A.",,Schizophrenia research,2020,2020-04-02,N,Schizophrenia; Bipolar disorder; Deprivation; Severe Mental Illness; Urbanicity; Social Drift,Improving Public Health,mental health,"We investigated whether associations between area deprivation, urbanicity and elevated risk of severe mental illnesses (SMIs, including schizophrenia and bipolar disorder) is accounted for by social drift or social causation. We extracted primary and secondary care electronic health records from 2004 to 2015 from a population of 3.9 million. We identified prevalent and incident individuals with SMIs and their level of deprivation and urbanicity using the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator. The presence of social drift was determined by whether odds ratios (ORs) from logistic regression is greater than the incidence rate ratios (IRRs) from Poisson regression. Additionally, we performed longitudinal analysis to measure the proportion of change in deprivation level and rural/urban residence 10 years after an incident diagnosis of SMI and compared it to the general population using standardised rate ratios (SRRs). Prevalence and incidence of SMIs were significantly associated with deprivation and urbanicity (all ORs and IRRs significantly >1). ORs and IRRs were similar across all conditions and cohorts (ranging from 1.1 to 1.4). Results from the longitudinal analysis showed individuals with SMIs are more likely to move compared to the general population. However, they did not preferentially move to more deprived or urban areas. There was little evidence of downward social drift over a 10-year period. These findings have implications for the allocation of resources, service configuration and access to services in deprived communities, as well as, for broader public health interventions addressing poverty, and social and environmental contexts.",,doi:https://doi.org/10.1016/j.schres.2020.03.044; doi:https://doi.org/10.1016/j.schres.2020.03.044
 31744503,https://doi.org/10.1186/s12916-019-1438-y,"Bleeding in cardiac patients prescribed antithrombotic drugs: electronic health record phenotyping algorithms, incidence, trends and prognosis.","Pasea L, Chung SC, Pujades-Rodriguez M, Shah AD, Alvarez-Madrazo S, Allan V, Teo JT, Bean D, Sofat R, Dobson R, Banerjee A, Patel RS, Timmis A, Denaxas S, Hemingway H.",,BMC medicine,2019,2019-11-20,Y,Phenotype; Bleeding; Prognosis; Antithrombotic Therapy; Electronic Health Records,The Human Phenome,,"<h4>Background</h4>Clinical guidelines and public health authorities lack recommendations on scalable approaches to defining and monitoring the occurrence and severity of bleeding in populations prescribed antithrombotic therapy.<h4>Methods</h4>We examined linked primary care, hospital admission and death registry electronic health records (CALIBER 1998-2010, England) of patients with newly diagnosed atrial fibrillation, acute myocardial infarction, unstable angina or stable angina with the aim to develop algorithms for bleeding events. Using the developed bleeding phenotypes, Kaplan-Meier plots were used to estimate the incidence of bleeding events and we used Cox regression models to assess the prognosis for all-cause mortality, atherothrombotic events and further bleeding.<h4>Results</h4>We present electronic health record phenotyping algorithms for bleeding based on bleeding diagnosis in primary or hospital care, symptoms, transfusion, surgical procedures and haemoglobin values. In validation of the phenotype, we estimated a positive predictive value of 0.88 (95% CI 0.64, 0.99) for hospitalised bleeding. Amongst 128,815 patients, 27,259 (21.2%) had at least 1 bleeding event, with 5-year risks of bleeding of 29.1%, 21.9%, 25.3% and 23.4% following diagnoses of atrial fibrillation, acute myocardial infarction, unstable angina and stable angina, respectively. Rates of hospitalised bleeding per 1000 patients more than doubled from 1.02 (95% CI 0.83, 1.22) in January 1998 to 2.68 (95% CI 2.49, 2.88) in December 2009 coinciding with the increased rates of antiplatelet and vitamin K antagonist prescribing. Patients with hospitalised bleeding and primary care bleeding, with or without markers of severity, were at increased risk of all-cause mortality and atherothrombotic events compared to those with no bleeding. For example, the hazard ratio for all-cause mortality was 1.98 (95% CI 1.86, 2.11) for primary care bleeding with markers of severity and 1.99 (95% CI 1.92, 2.05) for hospitalised bleeding without markers of severity, compared to patients with no bleeding.<h4>Conclusions</h4>Electronic health record bleeding phenotyping algorithms offer a scalable approach to monitoring bleeding in the population. Incidence of bleeding has doubled in incidence since 1998, affects one in four cardiovascular disease patients, and is associated with poor prognosis. Efforts are required to tackle this iatrogenic epidemic.",A phenotyping algorithm is presented to monitor bleeding in primary and hospital care. Model is well presented in the document and has potential to be scalable and applied to other conditions.,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-019-1438-y; doi:https://doi.org/10.1186/s12916-019-1438-y; html:https://europepmc.org/articles/PMC6864929; pdf:https://europepmc.org/articles/PMC6864929?pdf=render
-37438684,https://doi.org/10.1186/s12874-023-01935-3,Estimating medication adherence from Electronic Health Records: comparing methods for mining and processing asthma treatment prescriptions.,"Tibble H, Sheikh A, Tsanas A.",,BMC medical research methodology,2023,2023-07-12,Y,Adherence; Asthma; Compliance; corticosteroid; Electronic Health Records,,,"<h4>Background</h4>Medication adherence is usually defined as the extent of the agreement between the medication regimen agreed to by patients with their healthcare provider and the real-world implementation. Proactive identification of those with poor adherence may be useful to identify those with poor disease control and offers the opportunity for ameliorative action. Adherence can be estimated from Electronic Health Records (EHRs) by comparing medication dispensing records to the prescribed regimen. Several methods have been developed in the literature to infer adherence from EHRs, however there is no clear consensus on what should be considered the gold standard in each use case. Our objectives were to critically evaluate different measures of medication adherence in a large longitudinal Scottish EHR dataset. We used asthma, a chronic condition with high prevalence and high rates of non-adherence, as a case study.<h4>Methods</h4>Over 1.6 million asthma controllers were prescribed for our cohort of 91,334 individuals, between January 2009 and March 2017. Eight adherence measures were calculated, and different approaches to estimating the amount of medication supply available at any time were compared.<h4>Results</h4>Estimates from different measures of adherence varied substantially. Three of the main drivers of the differences between adherence measures were the expected duration (if taken as in accordance with the dose directions), whether there was overlapping supply between prescriptions, and whether treatment had been discontinued. However, there are also wider, study-related, factors which are crucial to consider when comparing the adherence measures.<h4>Conclusions</h4>We evaluated the limitations of various medication adherence measures, and highlight key considerations about the underlying data, condition, and population to guide researchers choose appropriate adherence measures. This guidance will enable researchers to make more informed decisions about the methodology they employ, ensuring that adherence is captured in the most meaningful way for their particular application needs.",,pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-023-01935-3; doi:https://doi.org/10.1186/s12874-023-01935-3; html:https://europepmc.org/articles/PMC10337150; pdf:https://europepmc.org/articles/PMC10337150?pdf=render
 32518842,https://doi.org/10.12688/wellcomeopenres.15786.1,Inferring the number of COVID-19 cases from recently reported deaths.,"Jombart T, van Zandvoort K, Russell TW, Jarvis CI, Gimma A, Abbott S, Clifford S, Funk S, Gibbs H, Liu Y, Pearson CAB, Bosse NI, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Eggo RM, Kucharski AJ, Edmunds WJ.",,Wellcome open research,2020,2020-04-27,Y,Estimation; Statistics; epidemics; outbreak; Modelling; Covid-19; Sars-cov-2,,,"We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.",,doi:https://doi.org/10.12688/wellcomeopenres.15786.1; doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render
+37438684,https://doi.org/10.1186/s12874-023-01935-3,Estimating medication adherence from Electronic Health Records: comparing methods for mining and processing asthma treatment prescriptions.,"Tibble H, Sheikh A, Tsanas A.",,BMC medical research methodology,2023,2023-07-12,Y,Adherence; Asthma; Compliance; corticosteroid; Electronic Health Records,,,"<h4>Background</h4>Medication adherence is usually defined as the extent of the agreement between the medication regimen agreed to by patients with their healthcare provider and the real-world implementation. Proactive identification of those with poor adherence may be useful to identify those with poor disease control and offers the opportunity for ameliorative action. Adherence can be estimated from Electronic Health Records (EHRs) by comparing medication dispensing records to the prescribed regimen. Several methods have been developed in the literature to infer adherence from EHRs, however there is no clear consensus on what should be considered the gold standard in each use case. Our objectives were to critically evaluate different measures of medication adherence in a large longitudinal Scottish EHR dataset. We used asthma, a chronic condition with high prevalence and high rates of non-adherence, as a case study.<h4>Methods</h4>Over 1.6 million asthma controllers were prescribed for our cohort of 91,334 individuals, between January 2009 and March 2017. Eight adherence measures were calculated, and different approaches to estimating the amount of medication supply available at any time were compared.<h4>Results</h4>Estimates from different measures of adherence varied substantially. Three of the main drivers of the differences between adherence measures were the expected duration (if taken as in accordance with the dose directions), whether there was overlapping supply between prescriptions, and whether treatment had been discontinued. However, there are also wider, study-related, factors which are crucial to consider when comparing the adherence measures.<h4>Conclusions</h4>We evaluated the limitations of various medication adherence measures, and highlight key considerations about the underlying data, condition, and population to guide researchers choose appropriate adherence measures. This guidance will enable researchers to make more informed decisions about the methodology they employ, ensuring that adherence is captured in the most meaningful way for their particular application needs.",,pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-023-01935-3; doi:https://doi.org/10.1186/s12874-023-01935-3; html:https://europepmc.org/articles/PMC10337150; pdf:https://europepmc.org/articles/PMC10337150?pdf=render
 36134690,https://doi.org/10.1242/dev.200654,Coupled myovascular expansion directs cardiac growth and regeneration.,"DeBenedittis P, Karpurapu A, Henry A, Thomas MC, McCord TJ, Brezitski K, Prasad A, Baker CE, Kobayashi Y, Shah SH, Kontos CD, Tata PR, Lumbers RT, Karra R.",,"Development (Cambridge, England)",2022,2022-09-22,N,Mouse; Cardiomyocyte proliferation; Heart regeneration; Myovascular,,,"Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled. We show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion of Vegfr2 from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density after cryoinjury with virus encoding Vegfa enhances regeneration. Using Mendelian randomization, we demonstrate that circulating VEGFA levels are positively linked with human myocardial mass, suggesting that Vegfa can stimulate human cardiac growth. Our work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration.",,pdf:https://journals.biologists.com/dev/article-pdf/149/18/dev200654/2167548/dev200654.pdf; doi:https://doi.org/10.1242/dev.200654
 35595677,https://doi.org/10.1016/s2589-7500(22)00061-9,Identifying adverse childhood experiences with electronic health records of linked mothers and children in England: a multistage development and validation study.,"Syed S, Gonzalez-Izquierdo A, Allister J, Feder G, Li L, Gilbert R.",,The Lancet. Digital health,2022,2022-05-17,N,,,,"<h4>Background</h4>Electronic health records (EHRs) of mothers and children provide an opportunity to identify adverse childhood experiences (ACEs) during crucial periods of childhood development, yet well developed indicators of ACEs remain scarce. We aimed to develop clinically relevant indicators of ACEs for linked EHRs of mothers and children using a multistage prediction model of child maltreatment and maternal intimate partner violence (IPV).<h4>Methods</h4>In this multistage development and validation study, we developed a representative population-based birth cohort of mothers and children in England, followed from up to 2 years before birth to up to 5 years after birth across the Clinical Practice Research Datalink (CPRD) GOLD (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics mortality register. We included livebirths in England between July 1, 2004, and June 30, 2016, to mothers aged 16-55 years, who had registered with a general practitioner (GP) that met CPRD quality standards before 21 weeks of gestation. The primary outcome (reference standard) was any child maltreatment or maternal IPV in either the mother's or child's record from 2 years before birth (maternal IPV only) to 5 years after birth. We used seven prediction models, combined with expert ratings, to systematically develop indicators. We validated the final indicators by integrating results from machine learning models, survival analyses, and clustering analyses in the validation cohort.<h4>Findings</h4>We included data collected between July 1, 2002, and June 27, 2018. Of 376 006 eligible births, we included 211 393 mother-child pairs (422 786 patients) from 400 practices, of whom 126 837 mother-child pairs (60·0%; 240 practices) were randomly assigned to a derivation cohort and 84 556 pairs (40·0%; 160 practices) to a validation cohort. We included 63 indicators in six ACE domains: maternal mental health problems, maternal substance misuse, adverse family environments, child maltreatment, maternal IPV, and high-risk presentations of child maltreatment. Excluding the seven indicators in the reference standard, 56 indicators showed high discriminative validity for the reference standard of any child maltreatment or maternal IPV between 2 years before and 5 years after birth (validation cohort, area under the receiver operating characteristic curve 0·85 [95% CI 0·84-0·86]). During the 2 years before birth and 5 years after birth, the overall period prevalence of maternal IPV and child maltreatment (reference standard) was 2·3% (2876 of 126 837 pairs) in the derivation cohort and 2·3% (1916 of 84 556 pairs) in the validation cohort. During the 2 years before and after birth, the period prevalence was 39·1% (95% CI 38·7-39·5; 34 773 pairs) for any of the 63 ACE indicators, 22·2% (21·8-22·5%; 20 122 pairs) for maternal mental health problems, 15·7% (15·4-16·0%; 14 549 pairs) for adverse family environments, 8·1% (7·8-8·3%; 6808 pairs) for high-risk presentations of child maltreatment, 6·9% (6·7-7·2%; 7856 pairs) for maternal substance misuse, and 3·0% (2·9-3·2%; 2540 pairs) for any child maltreatment (2·4% [2·3-5·6%; 2051 pairs]) and maternal IPV (1·0% [0·8-1·0%; 875 pairs]). 62·6% (21 785 of 34 773 pairs) of ACEs were recorded in primary care only, and 72·3% (25 140 cases) were recorded in the maternal record only.<h4>Interpretation</h4>We developed clinically relevant indicators for identifying ACEs using the EHRs of mothers and children presenting to general practices and hospital admissions. Over 70% of ACEs were identified via maternal records and were recorded in primary care by GPs within 2 years of birth, reinforcing the importance of reviewing parental and carer records to inform clinical responses to children. ACE indicators can contribute to longitudinal surveillance informing public health policy and resource allocation. Further evaluation is required to determine how ACE indicators can be used in clinical practice.<h4>Funding</h4>None.",,pdf:http://www.thelancet.com/article/S2589750022000619/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00061-9
 35038301,https://doi.org/10.2196/30523,Requirements for a Bespoke Intensive Care Unit Dashboard in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Davidson B, Ferrer Portillo KM, Wac M, McWilliams C, Bourdeaux C, Craddock I.",,JMIR human factors,2022,2022-04-13,Y,Development; Monitoring; Design; Disease monitoring; ICU; Interview; Intensive Care; Critical Care; Ehealth; Dashboard; Human-centered Design; Covid-19,,,"<h4>Background</h4>Intensive care units (ICUs) around the world are in high demand due to patients with COVID-19 requiring hospitalization. As researchers at the University of Bristol, we were approached to develop a bespoke data visualization dashboard to assist two local ICUs during the pandemic that will centralize disparate data sources in the ICU to help reduce the cognitive load on busy ICU staff in the ever-evolving pandemic.<h4>Objective</h4>The aim of this study was to conduct interviews with ICU staff in University Hospitals Bristol and Weston National Health Service Foundation Trust to elicit requirements for a bespoke dashboard to monitor the high volume of patients, particularly during the COVID-19 pandemic.<h4>Methods</h4>We conducted six semistructured interviews with clinical staff to obtain an overview of their requirements for the dashboard and to ensure its ultimate suitability for end users. Interview questions aimed to understand the job roles undertaken in the ICU, potential uses of the dashboard, specific issues associated with managing COVID-19 patients, key data of interest, and any concerns about the introduction of a dashboard into the ICU.<h4>Results</h4>From our interviews, we found the following design requirements: (1) a flexible dashboard, where the functionality can be updated quickly and effectively to respond to emerging information about the management of this new disease; (2) a mobile dashboard, which allows staff to move around on wards with a dashboard, thus potentially replacing paper forms to enable detailed and consistent data entry; (3) a customizable and intuitive dashboard, where individual users would be able to customize the appearance of the dashboard to suit their role; (4) real-time data and trend analysis via informative data visualizations that help busy ICU staff to understand a patient's clinical trajectory; and (5) the ability to manage tasks and staff, tracking both staff and patient movements, handovers, and task monitoring to ensure the highest quality of care.<h4>Conclusions</h4>The findings of this study confirm that digital solutions for ICU use would potentially reduce the cognitive load of ICU staff and reduce clinical errors at a time of notably high demand of intensive health care.",,pdf:https://humanfactors.jmir.org/2022/2/e30523/PDF; doi:https://doi.org/10.2196/30523; html:https://europepmc.org/articles/PMC9009380
@@ -1076,8 +1076,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 33342219,https://doi.org/10.1161/circoutcomes.120.007085,Estimating the Effect of Reduced Attendance at Emergency Departments for Suspected Cardiac Conditions on Cardiac Mortality During the COVID-19 Pandemic.,"Katsoulis M, Gomes M, Lai AG, Henry A, Denaxas S, Lagiou P, Nafilyan V, Humberstone B, Banerjee A, Hemingway H, Lumbers RT.",,Circulation. Cardiovascular quality and outcomes,2021,2020-12-20,Y,"Cardiovascular diseases; Coronavirus; Pandemic; Heart Disease; Death, Sudden, Cardiac",,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCOUTCOMES.120.007085; doi:https://doi.org/10.1161/CIRCOUTCOMES.120.007085; html:https://europepmc.org/articles/PMC7819531; pdf:https://europepmc.org/articles/PMC7819531?pdf=render
 35508365,https://doi.org/10.1136/injuryprev-2021-044513,Prevalence of alcohol and other drug use in patients presenting to hospital for fall-related injuries: a systematic review.,"Lau G, Ang JY, Kim N, Gabbe BJ, Mitra B, Dietze PM, Reeder S, Beck B.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2022,2022-05-04,N,Drugs; Alcohol; Fall; Systematic review; Metanalysis,,,"<h4>Background</h4>Alcohol and other drug (AOD) use is a key preventable risk factor for serious injuries. Prevention strategies to date have largely focused on transport injuries, despite AOD use being a significant risk factor for other injury causes, including falls. This systematic review aimed to report the prevalence of AOD use in patients presenting to hospital for fall-related injuries.<h4>Methods</h4>This systematic review includes studies published in English after the year 2010 that objectively measured the prevalence of AOD use in patients presenting to hospital for a fall-related injury. Screening, data extraction and risk of bias assessments were completed by two independent reviewers. Data were presented using narrative synthesis and, where appropriate, meta-analyses.<h4>Results</h4>A total of 12 707 records were screened. Full texts were retrieved for 2042 records, of which 29 were included. Four studies reported the combined prevalence of any alcohol and/or drug use, generating a pooled prevalence estimate of 37% (95% CI 25% to 49%). Twenty-two records reported on the prevalence of acute alcohol use alone and nine reported specifically on the prevalence of drugs other than alcohol, with prevalence ranging from 2% to 57% and 7% to 46%, respectively. The variation in prevalence estimates likely resulted from differences in toxicology testing methods across studies.<h4>Conclusions</h4>AOD exposure was common in hospitalised fall-related injuries. However, research addressing prevalence across different types of falls and the use of drugs other than alcohol was limited. Future research should address these areas to improve our understanding of which populations should be targeted in AOD and injury prevention strategies .<h4>Prospero registration number</h4>CRD42020188746.",,doi:https://doi.org/10.1136/injuryprev-2021-044513
 36403308,https://doi.org/10.1016/j.media.2022.102678,DragNet: Learning-based deformable registration for realistic cardiac MR sequence generation from a single frame.,"Zakeri A, Hokmabadi A, Bi N, Wijesinghe I, Nix MG, Petersen SE, Frangi AF, Taylor ZA, Gooya A.",,Medical image analysis,2023,2022-11-02,N,Uncertainty Estimation; Uk Biobank; Deep Learning; Deformable Temporal Image Registration; Sequential Image Data Generation; Variational Recurrent Neural Networks,,,"Deformable image registration (DIR) can be used to track cardiac motion. Conventional DIR algorithms aim to establish a dense and non-linear correspondence between independent pairs of images. They are, nevertheless, computationally intensive and do not consider temporal dependencies to regulate the estimated motion in a cardiac cycle. In this paper, leveraging deep learning methods, we formulate a novel hierarchical probabilistic model, termed DragNet, for fast and reliable spatio-temporal registration in cine cardiac magnetic resonance (CMR) images and for generating synthetic heart motion sequences. DragNet is a variational inference framework, which takes an image from the sequence in combination with the hidden states of a recurrent neural network (RNN) as inputs to an inference network per time step. As part of this framework, we condition the prior probability of the latent variables on the hidden states of the RNN utilised to capture temporal dependencies. We further condition the posterior of the motion field on a latent variable from hierarchy and features from the moving image. Subsequently, the RNN updates the hidden state variables based on the feature maps of the fixed image and the latent variables. Different from traditional methods, DragNet performs registration on unseen sequences in a forward pass, which significantly expedites the registration process. Besides, DragNet enables generating a large number of realistic synthetic image sequences given only one frame, where the corresponding deformations are also retrieved. The probabilistic framework allows for computing spatio-temporal uncertainties in the estimated motion fields. Our results show that DragNet performance is comparable with state-of-the-art methods in terms of registration accuracy, with the advantage of offering analytical pixel-wise motion uncertainty estimation across a cardiac cycle and being a motion generator. We will make our code publicly available.",,doi:https://doi.org/10.1016/j.media.2022.102678; doi:https://doi.org/10.1016/j.media.2022.102678
-37269003,https://doi.org/10.1186/s13643-023-02261-x,Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.,"Shahzad H, Mahmood S, McGee S, Hubbard J, Haque S, Paudyal V, Denniston AK, Hill LJ, Jalal Z.",,Systematic reviews,2023,2023-06-02,Y,Meta-analysis; Intravitreal; Anti-vegf; Non-adherence; Macular; Non-persistence; Covid-19,,,"<h4>Background</h4>Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes.<h4>Methods</h4>Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors.<h4>Results</h4>Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown.<h4>Discussion</h4>Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence.<h4>Systematic review registration</h4>PROSPERO CRD42020216205.",,doi:https://doi.org/10.1186/s13643-023-02261-x; doi:https://doi.org/10.1186/s13643-023-02261-x; html:https://europepmc.org/articles/PMC10237080; pdf:https://europepmc.org/articles/PMC10237080?pdf=render
 32979970,https://doi.org/10.1016/s0140-6736(20)31966-8,Models for mortality require tailoring in the context of the COVID-19 pandemic - Authors' reply.,"Banerjee A, Pasea L, Denaxas S, Williams B, Hemingway H.",,"Lancet (London, England)",2020,2020-09-01,Y,,,,,,pdf:http://www.thelancet.com/article/S0140673620319668/pdf; doi:https://doi.org/10.1016/S0140-6736(20)31966-8; html:https://europepmc.org/articles/PMC7515579; pdf:https://europepmc.org/articles/PMC7515579?pdf=render
+37269003,https://doi.org/10.1186/s13643-023-02261-x,Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.,"Shahzad H, Mahmood S, McGee S, Hubbard J, Haque S, Paudyal V, Denniston AK, Hill LJ, Jalal Z.",,Systematic reviews,2023,2023-06-02,Y,Meta-analysis; Intravitreal; Anti-vegf; Non-adherence; Macular; Non-persistence; Covid-19,,,"<h4>Background</h4>Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes.<h4>Methods</h4>Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors.<h4>Results</h4>Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown.<h4>Discussion</h4>Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence.<h4>Systematic review registration</h4>PROSPERO CRD42020216205.",,doi:https://doi.org/10.1186/s13643-023-02261-x; doi:https://doi.org/10.1186/s13643-023-02261-x; html:https://europepmc.org/articles/PMC10237080; pdf:https://europepmc.org/articles/PMC10237080?pdf=render
 30969971,https://doi.org/10.1371/journal.pone.0213435,Are active children and young people at increased risk of injuries resulting in hospital admission or accident and emergency department attendance? Analysis of linked cohort and electronic hospital records in Wales and Scotland.,"Griffiths LJ, Cortina-Borja M, Tingay K, Bandyopadhyay A, Akbari A, DeStavola BL, Bedford H, Lyons RA, Dezateux C.",,PloS one,2019,2019-04-10,Y,,Improving Public Health,,"<h4>Introduction</h4>Children and young people (CYP) are encouraged to increase time spent being physically active, especially in moderate and vigorous intensity pursuits. However, there is limited evidence on the prospective association of activity levels with injuries resulting in use of hospital services. We examined the relationship between objectively-measured physical activity (PA) and subsequent injuries resulting in hospital admissions or accident and emergency department (A&E) attendances, using linked electronic hospital records (EHR) from a nationally representative prospective cohort of CYP in Wales and Scotland.<h4>Methods</h4>We analysed accelerometer-based estimates of moderate to vigorous (MVPA) and vigorous PA (VPA) from 1,585 (777 [46%] boys) seven-year-old Millennium Cohort Study members, living in Wales or Scotland, whose parents consented to linkage of cohort records to EHRs up until their 14th birthday. Negative binomial regression models adjusted by potential individual, household and area-level confounders, were fitted to estimate associations between average daily minutes of MVPA, and VPA (in 10-minute increments), and number of injury-related hospital admissions and/or A&E attendances from age nine to 14 years.<h4>Results</h4>CYP spent a median of 59.5 and 18.1 minutes in MVPA and VPA/day respectively, with boys significantly more active than girls; 47.3% of children experienced at least one injury-related admission or A&E attendance during the study period. Rates of injury-related hospital admission and/or A&E attendance were positively associated with MVPA and VPA in boys but not in girls: respective adjusted incidence rate ratios (95% CI) for boys: 1.09 (1.01, 1.17) and 1.16 (1.00, 1.34), and for girls: 0.94 (0.86, 1.03) and 0.85 (0.69, 1.04).<h4>Conclusion</h4>Boys but not girls who engage in more intense PA at age seven years are at higher risk of injury-related hospital admission or A&E attendance when aged nine to 14 years than their less active peers. This may reflect gender differences in the type and associated risks of activities undertaken. EHRs can make a useful contribution to injury surveillance and prevention if routinely augmented with information on context and setting of the injuries sustained. Injury prevention initiatives should not discourage engagement in PA and outdoor play given their over-riding health and social benefits.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0213435&type=printable; doi:https://doi.org/10.1371/journal.pone.0213435; html:https://europepmc.org/articles/PMC6457613; pdf:https://europepmc.org/articles/PMC6457613?pdf=render
 34125897,https://doi.org/10.1093/nar/gkab449,DGLinker: flexible knowledge-graph prediction of disease-gene associations.,"Hu J, Lepore R, Dobson RJB, Al-Chalabi A, M Bean D, Iacoangeli A.",,Nucleic acids research,2021,2021-07-01,Y,,,,"As a result of the advent of high-throughput technologies, there has been rapid progress in our understanding of the genetics underlying biological processes. However, despite such advances, the genetic landscape of human diseases has only marginally been disclosed. Exploiting the present availability of large amounts of biological and phenotypic data, we can use our current understanding of disease genetics to train machine learning models to predict novel genetic factors associated with the disease. To this end, we developed DGLinker, a webserver for the prediction of novel candidate genes for human diseases given a set of known disease genes. DGLinker has a user-friendly interface that allows non-expert users to exploit biomedical information from a wide range of biological and phenotypic databases, and/or to upload their own data, to generate a knowledge-graph and use machine learning to predict new disease-associated genes. The webserver includes tools to explore and interpret the results and generates publication-ready figures. DGLinker is available at https://dglinker.rosalind.kcl.ac.uk. The webserver is free and open to all users without the need for registration.",,doi:https://doi.org/10.1093/nar/gkab449; doi:https://doi.org/10.1093/nar/gkab449; html:https://europepmc.org/articles/PMC8262728; pdf:https://europepmc.org/articles/PMC8262728?pdf=render
 37538142,https://doi.org/10.1093/ehjdh/ztad037,Predicting left ventricular hypertrophy from the 12-lead electrocardiogram in the UK Biobank imaging study using machine learning.,"Naderi H, Ramírez J, van Duijvenboden S, Pujadas ER, Aung N, Wang L, Anwar Ahmed Chahal C, Lekadir K, Petersen SE, Munroe PB.",,European heart journal. Digital health,2023,2023-06-01,Y,Electrocardiogram; Left ventricular hypertrophy; Cardiovascular Screening; Machine Learning; Cardiovascular Magnetic Resonance Imaging,,,"<h4>Aims</h4>Left ventricular hypertrophy (LVH) is an established, independent predictor of cardiovascular disease. Indices derived from the electrocardiogram (ECG) have been used to infer the presence of LVH with limited sensitivity. This study aimed to classify LVH defined by cardiovascular magnetic resonance (CMR) imaging using the 12-lead ECG for cost-effective patient stratification.<h4>Methods and results</h4>We extracted ECG biomarkers with a known physiological association with LVH from the 12-lead ECG of 37 534 participants in the UK Biobank imaging study. Classification models integrating ECG biomarkers and clinical variables were built using logistic regression, support vector machine (SVM) and random forest (RF). The dataset was split into 80% training and 20% test sets for performance evaluation. Ten-fold cross validation was applied with further validation testing performed by separating data based on UK Biobank imaging centres. QRS amplitude and blood pressure (<i>P</i> < 0.001) were the features most strongly associated with LVH. Classification with logistic regression had an accuracy of 81% [sensitivity 70%, specificity 81%, Area under the receiver operator curve (AUC) 0.86], SVM 81% accuracy (sensitivity 72%, specificity 81%, AUC 0.85) and RF 72% accuracy (sensitivity 74%, specificity 72%, AUC 0.83). ECG biomarkers enhanced model performance of all classifiers, compared to using clinical variables alone. Validation testing by UK Biobank imaging centres demonstrated robustness of our models.<h4>Conclusion</h4>A combination of ECG biomarkers and clinical variables were able to predict LVH defined by CMR. Our findings provide support for the ECG as an inexpensive screening tool to risk stratify patients with LVH as a prelude to advanced imaging.",,doi:https://doi.org/10.1093/ehjdh/ztad037; html:https://europepmc.org/articles/PMC10393938; pdf:https://europepmc.org/articles/PMC10393938?pdf=render
@@ -1086,18 +1086,18 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 35776955,https://doi.org/10.1093/ehjqcco/qcac039,One step closer to quantifying 'clinical likelihood' in pre-test probability.,"Weir-McCall JR, Williams MC, Wood A.",,European heart journal. Quality of care & clinical outcomes,2022,2022-09-01,N,,,,,,doi:https://doi.org/10.1093/ehjqcco/qcac039; html:https://europepmc.org/articles/PMC9442847; pdf:https://europepmc.org/articles/PMC9442847?pdf=render; doi:https://doi.org/10.1093/ehjqcco/qcac039
 32894757,https://doi.org/10.1093/ageing/afaa138,Short physical performance battery as a practical tool to assess mortality risk in chronic obstructive pulmonary disease.,"Fermont JM, Mohan D, Fisk M, Bolton CE, Macnee W, Cockcroft JR, McEniery C, Fuld J, Cheriyan J, Tal-Singer R, Müllerova H, Wood AM, Wilkinson IB, Polkey MI, ERICA consortium.",,Age and ageing,2021,2021-05-01,Y,Mortality; Skeletal muscle; Biomarkers; Older People; chronic obstructive pulmonary disease,,,"<h4>Rationale</h4>chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and common in older adults. The BODE Index is the most recognised mortality risk score in COPD but includes a 6-minute walk test (6MWT) that is seldom available in practise; the BODE Index may be better adopted if the 6MWT was replaced.<h4>Objectives</h4>we investigated whether a modified BODE Index in which 6MWT was replaced by an alternative measure of physical capacity, specifically the short physical performance battery (SPPB) or components, retained its predictive ability for mortality in individuals with COPD.<h4>Methods</h4>we analysed 630 COPD patients from the ERICA cohort study for whom UK Office for National Statistics verified mortality data were available. Variables tested at baseline included spirometry, 6MWT, SPPB and its components (4-m gait speed test [4MGS], chair stand and balance). Predictive models were developed using stratified multivariable Cox regression, and assessed by C-indices and calibration plots with 10-fold cross-validation and replication.<h4>Results</h4>during median 2 years of follow-up, 60 (10%) individuals died. There was no significant difference between the discriminative ability of BODE6MWT (C-index 0.709, 95% confidence interval [CI], 0.680-0.737), BODESPPB (C-index 0.683, 95% CI, 0.647-0.712), BODE4MGS (C-index 0.676, 95% CI, 0.643-0.700) and BODEBALANCE (C-index 0.686, 95% CI, 0.651-0.713) for predicting mortality.<h4>Conclusions</h4>the SPPB, and its 4MGS and balance components, can potentially be used as an alternative to the 6MWT in the BODE Index without significant loss of predictive ability in all-cause mortality.",,pdf:https://academic.oup.com/ageing/article-pdf/50/3/795/37807880/afaa138.pdf; doi:https://doi.org/10.1093/ageing/afaa138; html:https://europepmc.org/articles/PMC8098797; pdf:https://europepmc.org/articles/PMC8098797?pdf=render
 37563721,https://doi.org/10.1186/s13063-023-07473-z,Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.,"McMahon A, Kaptoge S, Walker M, Mehenny S, Gilchrist PT, Sambrook J, Akhtar N, Sweeting M, Wood AM, Stirrups K, Chung R, Fahle S, Johnson E, Cullen D, Godfrey R, Duthie S, Allen L, Harvey P, Berkson M, Allen E, Watkins NA, Bradley JR, Kingston N, Miflin G, Armitage J, Roberts DJ, Danesh J, Di Angelantonio E.",,Trials,2023,2023-08-10,Y,Cross-over; Blood donors; Blood Donation; Factorial Design; Vasovagal Reactions; Cluster Randomised Trial; Stepped-wedge,,,"<h4>Background</h4>Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.<h4>Methods</h4>STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (""cluster"") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.<h4>Discussion</h4>The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.<h4>Trial registration</h4>ISRCTN: 10412338. Registration date: October 24, 2019.",,doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render
-36810251,https://doi.org/10.1172/jci.insight.156643,Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.,"Tsakok T, Saklatvala J, Rispens T, Loeff FC, de Vries A, Allen MH, Barbosa IA, Baudry D, Dasandi T, Duckworth M, Meynell F, Russell A, Chapman A, McBride S, McKenna K, Perera G, Ramsay H, Ramesh R, Sands K, Shipman A, Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) Study Group, Burden AD, Griffiths CE, Reynolds NJ, Warren RB, Mahil S, Barker J, Dand N, Smith C, Simpson MA.",,JCI insight,2023,2023-02-22,Y,Genetics; Drug therapy; Molecular genetics; Therapeutics; adaptive immunity,,,"Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.",,pdf:http://insight.jci.org/articles/view/156643/files/pdf; doi:https://doi.org/10.1172/jci.insight.156643; html:https://europepmc.org/articles/PMC9977494; pdf:https://europepmc.org/articles/PMC9977494?pdf=render
 30999919,https://doi.org/10.1186/s12911-019-0805-0,Identifying clinically important COPD sub-types using data-driven approaches in primary care population based electronic health records.,"Pikoula M, Quint JK, Nissen F, Hemingway H, Smeeth L, Denaxas S.",,BMC medical informatics and decision making,2019,2019-04-18,Y,Cluster analysis; Electronic Health Records; Copd Exacerbations; Copd Epidemiology,The Human Phenome,,"<h4>Background</h4>COPD is a highly heterogeneous disease composed of different phenotypes with different aetiological and prognostic profiles and current classification systems do not fully capture this heterogeneity. In this study we sought to discover, describe and validate COPD subtypes using cluster analysis on data derived from electronic health records.<h4>Methods</h4>We applied two unsupervised learning algorithms (k-means and hierarchical clustering) in 30,961 current and former smokers diagnosed with COPD, using linked national structured electronic health records in England available through the CALIBER resource. We used 15 clinical features, including risk factors and comorbidities and performed dimensionality reduction using multiple correspondence analysis. We compared the association between cluster membership and COPD exacerbations and respiratory and cardiovascular death with 10,736 deaths recorded over 146,466 person-years of follow-up. We also implemented and tested a process to assign unseen patients into clusters using a decision tree classifier.<h4>Results</h4>We identified and characterized five COPD patient clusters with distinct patient characteristics with respect to demographics, comorbidities, risk of death and exacerbations. The four subgroups were associated with 1) anxiety/depression; 2) severe airflow obstruction and frailty; 3) cardiovascular disease and diabetes and 4) obesity/atopy. A fifth cluster was associated with low prevalence of most comorbid conditions.<h4>Conclusions</h4>COPD patients can be sub-classified into groups with differing risk factors, comorbidities, and prognosis, based on data included in their primary care records. The identified clusters confirm findings of previous clustering studies and draw attention to anxiety and depression as important drivers of the disease in young, female patients.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0805-0; doi:https://doi.org/10.1186/s12911-019-0805-0; html:https://europepmc.org/articles/PMC6472089; pdf:https://europepmc.org/articles/PMC6472089?pdf=render
+36810251,https://doi.org/10.1172/jci.insight.156643,Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.,"Tsakok T, Saklatvala J, Rispens T, Loeff FC, de Vries A, Allen MH, Barbosa IA, Baudry D, Dasandi T, Duckworth M, Meynell F, Russell A, Chapman A, McBride S, McKenna K, Perera G, Ramsay H, Ramesh R, Sands K, Shipman A, Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) Study Group, Burden AD, Griffiths CE, Reynolds NJ, Warren RB, Mahil S, Barker J, Dand N, Smith C, Simpson MA.",,JCI insight,2023,2023-02-22,Y,Genetics; Drug therapy; Molecular genetics; Therapeutics; adaptive immunity,,,"Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.",,pdf:http://insight.jci.org/articles/view/156643/files/pdf; doi:https://doi.org/10.1172/jci.insight.156643; html:https://europepmc.org/articles/PMC9977494; pdf:https://europepmc.org/articles/PMC9977494?pdf=render
 33655501,https://doi.org/10.1111/bjd.19885,Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.,"Mulick AR, Mansfield KE, Silverwood RJ, Budu-Aggrey A, Roberts A, Custovic A, Pearce N, Irvine AD, Smeeth L, Abuabara K, Langan SM.",,The British journal of dermatology,2021,2021-05-09,N,,,,"<h4>Background</h4>Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity.<h4>Objectives</h4>To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables.<h4>Methods</h4>We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results.<h4>Results</h4>There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other.<h4>Conclusions</h4>Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660846/7/Mulick_etal_2021_Four-childhood-atopic-dermatitis-subtypes.pdf; doi:https://doi.org/10.1111/bjd.19885; html:https://europepmc.org/articles/PMC8410876; pdf:https://europepmc.org/articles/PMC8410876?pdf=render; doi:https://doi.org/10.1111/bjd.19885
-37730605,https://doi.org/10.1186/s12889-023-16523-9,Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.,"Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",,BMC public health,2023,2023-09-20,Y,Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19,,,"<h4>Background</h4>The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.<h4>Methods</h4>The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.<h4>Results</h4>Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.<h4>Conclusions</h4>The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?pdf=render
 36691123,https://doi.org/10.1136/bmjopen-2022-063199,Feasibility of a new electronic patient-reported outcome (ePRO) system for an advanced therapy clinical trial in immune-mediated inflammatory disease (PROmics): protocol for a qualitative feasibility study.,"Hughes SE, McMullan C, Rowe A, Retzer A, Malpass R, Bathurst C, Davies EH, Frost C, McNamara G, Harding R, Price G, Wilson R, Walker A, Newsome PN, Calvert M.",,BMJ open,2022,2022-09-06,Y,information technology; immunology; Hepatology; Inflammatory Bowel Disease; Rheumatology,,,"<h4>Introduction</h4>The use of electronic patient-reported outcome (ePRO) systems to capture PRO data in clinical trials is increasing; however, their feasibility, acceptability and utility in clinical trials of advanced therapy medicinal products (ATMPs) are not yet well understood. This protocol describes a qualitative study that aims to evaluate the feasibility and acceptability of ePRO data capture using a trial-specific ePRO system (the PROmics system) within an advanced therapy trial involving patients with immune-mediated inflammatory disease (rheumatoid arthritis, lupus, primary sclerosing cholangitis (PSC) and Crohn's disease).<h4>Methods and analysis</h4>This protocol for a remote, qualitative, interview-based feasibility study is embedded within the POLARISE trial, a single-arm, phase II, multisite ATMP basket trial in the UK. 10-15 patients enrolled in the POLARISE trial and 10-15 research team members at the trial sites will be recruited. Participants will take part in semistructured interviews which will be transcribed verbatim and analysed thematically according to the framework method. Data collection and analysis will occur concurrently and iteratively. Researcher triangulation will be used to achieve a consensus-based analysis, enhancing rigour and trustworthiness.<h4>Ethics and dissemination</h4>This study was approved by the London-West London and GTAC Research Ethics Committee (Ref: 21/LO/0475). Informed consent will be obtained from all participants prior to data collection. The study findings will be published in peer-review journals and disseminated via conference presentations and other media. Our patient and public involvement and engagement group and ATMP stakeholder networks will be consulted to maximise dissemination and impact.<h4>Trial registration number</h4>ISRCTN80103507.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e063199.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063199; html:https://europepmc.org/articles/PMC9453996; pdf:https://europepmc.org/articles/PMC9453996?pdf=render
+37730605,https://doi.org/10.1186/s12889-023-16523-9,Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.,"Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",,BMC public health,2023,2023-09-20,Y,Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19,,,"<h4>Background</h4>The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.<h4>Methods</h4>The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.<h4>Results</h4>Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.<h4>Conclusions</h4>The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?pdf=render
 36264615,https://doi.org/10.1161/circgen.122.003704,Prevalence and Disease Expression of Pathogenic and Likely Pathogenic Variants Associated With Inherited Cardiomyopathies in the General Population.,"Bourfiss M, van Vugt M, Alasiri AI, Ruijsink B, van Setten J, Schmidt AF, Dooijes D, Puyol-Antón E, Velthuis BK, van Tintelen JP, Te Riele ASJM, Baas AF, Asselbergs FW.",,Circulation. Genomic and precision medicine,2022,2022-10-20,Y,Genetics; Dilated cardiomyopathy; hypertrophic cardiomyopathy; Arrhythmogenic Right Ventricular Cardiomyopathy; Whole Exome Sequencing,,,"<h4>Background</h4>Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population.<h4>Methods</h4>We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200 643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analyzed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analyzed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data.<h4>Results</h4>We found a prevalence of 1:578, 1:251, and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared with controls, cardiovascular mortality was higher in DCM G+ (odds ratio 1.67 [95% CI 1.04; 2.59], <i>P</i>=0.030), but similar in ARVC and HCM G+ (<i>P</i>≥0.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (odds ratio 3.66 [95% CI 2.24; 5.81], <i>P</i>=4.9×10<sup>-7</sup>) and HCM G+ (odds ratio 3.03 [95% CI 1.98; 4.56], <i>P</i>=5.8×10<sup>-7</sup>), but comparable in ARVC G+ (<i>P</i>=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (<i>P</i>=3.3×10<sup>-4</sup>). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (<i>P</i>=0.009).<h4>Conclusions</h4>In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM, or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.",,pdf:https://discovery.ucl.ac.uk/10160737/3/Asselbergs_hcg-15-e003704.pdf; doi:https://doi.org/10.1161/CIRCGEN.122.003704; html:https://europepmc.org/articles/PMC9770140; pdf:https://europepmc.org/articles/PMC9770140?pdf=render
 36529028,https://doi.org/10.1016/j.ijmedinf.2022.104942,Defining clinical subtypes of adult asthma using electronic health records: Analysis of a large UK primary care database with external validation.,"Horne EMF, McLean S, Alsallakh MA, Davies GA, Price DB, Sheikh A, Tsanas A.",,International journal of medical informatics,2023,2022-12-07,N,Cluster analysis; Asthma; Electronic Health Records,,,"<h4>Introduction</h4>Asthma is one of the commonest chronic conditions in the world. Subtypes of asthma have been defined, typically from clinical datasets on small, well-characterised subpopulations of asthma patients. We sought to define asthma subtypes from large longitudinal primary care electronic health records (EHRs) using cluster analysis.<h4>Methods</h4>In this retrospective cohort study, we extracted asthma subpopulations from the Optimum Patient Care Research Database (OPCRD) to robustly train and test algorithms, and externally validated findings in the Secure Anonymised Information Linkage (SAIL) Databank. In both databases, we identified adults with an asthma diagnosis code recorded in the three years prior to an index date. Train and test datasets were selected from OPCRD using an index date of Jan 1, 2016. Two internal validation datasets were selected from OPCRD using index dates of Jan 1, 2017 and 2018. Three external validation datasets were selected from SAIL using index dates of Jan 1, 2016, 2017 and 2018. Each dataset comprised 50,000 randomly selected non-overlapping patients. Subtypes were defined by applying multiple correspondence analysis and k-means cluster analysis to the train dataset, and were validated in the internal and external validation datasets.<h4>Results</h4>We defined six asthma subtypes with clear clinical interpretability: low inhaled corticosteroid (ICS) use and low healthcare utilisation (30% of patients); low-to-medium ICS use (36%); low-to-medium ICS use and comorbidities (12%); varied ICS use and comorbid chronic obstructive pulmonary disease (4%); high (10%) and very high ICS use (7%). The subtypes were replicated with high accuracy in internal (91-92%) and external (84-86%) datasets.<h4>Conclusion</h4>Asthma subtypes derived and validated in large independent EHR databases were primarily defined by level of ICS use, level of healthcare use, and presence of comorbidities. This has important clinical implications towards defining asthma subtypes, facilitating patient stratification, and developing more personalised monitoring and treatment strategies.",,doi:https://doi.org/10.1016/j.ijmedinf.2022.104942; doi:https://doi.org/10.1016/j.ijmedinf.2022.104942
 33096553,https://doi.org/10.1093/ajcn/nqaa266,"Association between diet and periodontitis: a cross-sectional study of 10,000 NHANES participants.","Wright DM, McKenna G, Nugent A, Winning L, Linden GJ, Woodside JV.",,The American journal of clinical nutrition,2020,2020-12-01,N,Diet; Periodontitis; Nhanes; Robust Regression; Treelet Transformation,,,"<h4>Background</h4>Periodontitis is a major cause of tooth loss globally. Risk factors include age, smoking, and diabetes. Intake of specific nutrients has been associated with periodontitis risk but there has been little research into the influence of overall diet, potentially more relevant when formulating dietary recommendations.<h4>Objectives</h4>We aimed to investigate potential associations between diet and periodontitis using novel statistical techniques for dietary pattern analysis.<h4>Methods</h4>Two 24-h dietary recalls and periodontal examination data from the cross-sectional US NHANES, 2009-2014 (n = 10,010), were used. Dietary patterns were extracted using treelet transformation, a data-driven hierarchical clustering and dimension reduction technique. Associations between each pattern [treelet component (TC)] and extent of periodontitis [proportion of sites with clinical attachment loss (CAL) ≥ 3 mm] were estimated using robust logistic quantile regression, adjusting for age, sex, ethnicity, education level, smoking, BMI, and diabetes.<h4>Results</h4>Eight TCs explained 21% of the variation in diet, 1 of which (TC1) was associated with CAL extent. High TC1 scores represented a diet rich in salad, fruit, vegetables, poultry and seafood, and plain water or tea to drink. There was a substantial negative gradient in CAL extent from the lowest to the highest decile of TC1 (median proportion of sites with CAL ≥ 3 mm: decile 1 = 19.1%, decile 10 = 8.1%; OR, decile 10 compared with decile 1: 0.67; 95% CI: 0.46, 0.99).<h4>Conclusions</h4>Most dietary patterns identified were not associated with periodontitis extent. One pattern, however, rich in salad, fruit, and vegetables and with plain water or tea to drink, was associated with lower CAL extent. Treelet transformation may be a useful approach for calculating dietary patterns in nutrition research.",,pdf:https://academic.oup.com/ajcn/article-pdf/112/6/1485/34844146/nqaa266.pdf; doi:https://doi.org/10.1093/ajcn/nqaa266
-36713101,https://doi.org/10.1093/ehjdh/ztab082,A data mining-based cross-industry process for predicting major bleeding in mechanical circulatory support.,"Felix SEA, Bagheri A, Ramjankhan FR, Spruit MR, Oberski D, de Jonge N, van Laake LW, Suyker WJL, Asselbergs FW.",,European heart journal. Digital health,2021,2021-10-01,Y,Prediction; Bleeding; data mining; Mechanical Circulatory Support; Cross-Industry Standard Process For Data Mining (Crisp-Dm),,,"<h4>Aims</h4>Over a third of patients, treated with mechanical circulatory support (MCS) for end-stage heart failure, experience major bleeding. Currently, the prediction of a major bleeding in the near future is difficult because of many contributing factors. Predictive analytics using data mining could help calculating the risk of bleeding; however, its application is generally reserved for experienced researchers on this subject. We propose an easily applicable data mining tool to predict major bleeding in MCS patients.<h4>Methods and results</h4>All data of electronic health records of MCS patients in the University Medical Centre Utrecht were included. Based on the cross-industry standard process for data mining (CRISP-DM) methodology, an application named Auto-Crisp was developed. Auto-Crisp was used to evaluate the predictive models for a major bleeding in the next 3, 7, and 30 days after the first 30 days post-operatively following MCS implantation. The performance of the predictive models is investigated by the area under the curve (AUC) evaluation measure. In 25.6% of 273 patients, a total of 142 major bleedings occurred during a median follow-up period of 542 [interquartile range (IQR) 205-1044] days. The best predictive models assessed by Auto-Crisp had AUC values of 0.792, 0.788, and 0.776 for bleedings in the next 3, 7, and 30 days, respectively.<h4>Conclusion</h4>The Auto-Crisp-based predictive model created in this study had an acceptable performance to predict major bleeding in MCS patients in the near future. However, further validation of the application is needed to evaluate Auto-Crisp in other research projects.",,pdf:https://academic.oup.com/ehjdh/article-pdf/2/4/635/41972750/ztab082.pdf; doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render
 29457906,https://doi.org/10.1021/acs.jproteome.7b00879,Optimized Phenotypic Biomarker Discovery and Confounder Elimination via Covariate-Adjusted Projection to Latent Structures from Metabolic Spectroscopy Data.,"Posma JM, Garcia-Perez I, Ebbels TMD, Lindon JC, Stamler J, Elliott P, Holmes E, Nicholson JK.",,Journal of proteome research,2018,2018-02-27,Y,Chemometrics; multivariate data analysis; Biomarker Discovery; Sampling Bias; Covariate Adjustment; Metabolic Phenotyping; Random Matrix Theory; Reanalysis; Monte Carlo Cross-validation; Confounder Elimination,Applied Analytics,,"Metabolism is altered by genetics, diet, disease status, environment, and many other factors. Modeling either one of these is often done without considering the effects of the other covariates. Attributing differences in metabolic profile to one of these factors needs to be done while controlling for the metabolic influence of the rest. We describe here a data analysis framework and novel confounder-adjustment algorithm for multivariate analysis of metabolic profiling data. Using simulated data, we show that similar numbers of true associations and significantly less false positives are found compared to other commonly used methods. Covariate-adjusted projections to latent structures (CA-PLS) are exemplified here using a large-scale metabolic phenotyping study of two Chinese populations at different risks for cardiovascular disease. Using CA-PLS, we find that some previously reported differences are actually associated with external factors and discover a number of previously unreported biomarkers linked to different metabolic pathways. CA-PLS can be applied to any multivariate data where confounding may be an issue and the confounder-adjustment procedure is translatable to other multivariate regression techniques.",,pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.7b00879; doi:https://doi.org/10.1021/acs.jproteome.7b00879; html:https://europepmc.org/articles/PMC5891819; pdf:https://europepmc.org/articles/PMC5891819?pdf=render
-36721180,https://doi.org/10.1186/s12961-022-00956-6,Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.,"Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",,Health research policy and systems,2023,2023-01-31,Y,Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19,,,"COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.",,pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render
+36713101,https://doi.org/10.1093/ehjdh/ztab082,A data mining-based cross-industry process for predicting major bleeding in mechanical circulatory support.,"Felix SEA, Bagheri A, Ramjankhan FR, Spruit MR, Oberski D, de Jonge N, van Laake LW, Suyker WJL, Asselbergs FW.",,European heart journal. Digital health,2021,2021-10-01,Y,Prediction; Bleeding; data mining; Mechanical Circulatory Support; Cross-Industry Standard Process For Data Mining (Crisp-Dm),,,"<h4>Aims</h4>Over a third of patients, treated with mechanical circulatory support (MCS) for end-stage heart failure, experience major bleeding. Currently, the prediction of a major bleeding in the near future is difficult because of many contributing factors. Predictive analytics using data mining could help calculating the risk of bleeding; however, its application is generally reserved for experienced researchers on this subject. We propose an easily applicable data mining tool to predict major bleeding in MCS patients.<h4>Methods and results</h4>All data of electronic health records of MCS patients in the University Medical Centre Utrecht were included. Based on the cross-industry standard process for data mining (CRISP-DM) methodology, an application named Auto-Crisp was developed. Auto-Crisp was used to evaluate the predictive models for a major bleeding in the next 3, 7, and 30 days after the first 30 days post-operatively following MCS implantation. The performance of the predictive models is investigated by the area under the curve (AUC) evaluation measure. In 25.6% of 273 patients, a total of 142 major bleedings occurred during a median follow-up period of 542 [interquartile range (IQR) 205-1044] days. The best predictive models assessed by Auto-Crisp had AUC values of 0.792, 0.788, and 0.776 for bleedings in the next 3, 7, and 30 days, respectively.<h4>Conclusion</h4>The Auto-Crisp-based predictive model created in this study had an acceptable performance to predict major bleeding in MCS patients in the near future. However, further validation of the application is needed to evaluate Auto-Crisp in other research projects.",,pdf:https://academic.oup.com/ehjdh/article-pdf/2/4/635/41972750/ztab082.pdf; doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render
 32975552,https://doi.org/10.1001/jamapediatrics.2020.4573,Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis.,"Viner RM, Mytton OT, Bonell C, Melendez-Torres GJ, Ward J, Hudson L, Waddington C, Thomas J, Russell S, van der Klis F, Koirala A, Ladhani S, Panovska-Griffiths J, Davies NG, Booy R, Eggo RM.",,JAMA pediatrics,2021,2021-02-01,N,,,,"<h4>Importance</h4>The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior.<h4>Objective</h4>To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults.<h4>Data sources</h4>PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts.<h4>Study selection</h4>Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded.<h4>Data extraction and synthesis</h4>PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken.<h4>Main outcomes and measures</h4>Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults.<h4>Results</h4>A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults.<h4>Conclusions and relevance</h4>In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.",,pdf:https://jamanetwork.com/journals/jamapediatrics/articlepdf/2771181/jamapediatrics_viner_2020_oi_200071_1611604170.25358.pdf; doi:https://doi.org/10.1001/jamapediatrics.2020.4573; html:https://europepmc.org/articles/PMC7519436; doi:https://doi.org/10.1001/jamapediatrics.2020.4573
+36721180,https://doi.org/10.1186/s12961-022-00956-6,Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.,"Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",,Health research policy and systems,2023,2023-01-31,Y,Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19,,,"COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.",,pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render
 37101398,https://doi.org/10.1002/ejhf.2868,Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction.,"Schroeder M, Lim YMF, Savarese G, Suzart-Woischnik K, Baudier C, Dyszynski T, Vaartjes I, Eijkemans MJC, Uijl A, Herrera R, Vradi E, Brugts JJ, Brunner-La Rocca HP, Blanc-Guillemaud V, Waechter S, Couvelard F, Tyl B, Fatoba S, Hoes AW, Lund LH, Gerlinger C, Asselbergs FW, Grobbee DE, Cronin M, Koudstaal S.",,European journal of heart failure,2023,2023-05-18,N,Heart Failure; Randomized Clinical Trial; Females; Enrichment Strategies; Standardized Mortality Ratios; Real-world Evidence,,,"<h4>Aims</h4>In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.<h4>Methods and results</h4>Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).<h4>Conclusion</h4>Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.",,doi:https://doi.org/10.1002/ejhf.2868; doi:https://doi.org/10.1002/ejhf.2868
 36809311,https://doi.org/10.1093/ejendo/lvad024,The ultra-acute steroid response to traumatic injury: a cohort study.,"Bentley C, Hazeldine J, Bravo L, Taylor AE, Gilligan LC, Shaheen F, Acharjee A, Gkoutos G, Foster MA, Arlt W, Lord JM.",,European journal of endocrinology,2023,2023-03-01,N,Steroids; Mass spectrometry; Glucocorticoids; Major Trauma; 11-Oxygenated Androgens,,,"<h4>Objective</h4>Trauma-induced steroid changes have been studied post-hospital admission, resulting in a lack of understanding of the speed and extent of the immediate endocrine response to injury. The Golden Hour study was designed to capture the ultra-acute response to traumatic injury.<h4>Design</h4>We conducted an observational cohort study including adult male trauma patients <60 years, with blood samples drawn ≤1 h of major trauma by pre-hospital emergency responders.<h4>Methods</h4>We recruited 31 adult male trauma patients (mean age 28 [range 19-59] years) with a mean injury severity score (ISS) of 16 (IQR 10-21). The median time to first sample was 35 (range 14-56) min, with follow-up samples collected 4-12 and 48-72 h post-injury. Serum steroids in patients and age- and sex-matched healthy controls (HCs) (n = 34) were analysed by tandem mass spectrometry.<h4>Results</h4>Within 1 h of injury, we observed an increase in glucocorticoid and adrenal androgen biosynthesis. Cortisol and 11-hydroxyandrostendione increased rapidly, whilst cortisone and 11-ketoandrostenedione decreased, reflective of increased cortisol and 11-oxygenated androgen precursor biosynthesis by 11β-hydroxylase and increased cortisol activation by 11β-hydroxysteroid dehydrogenase type 1. Active classic gonadal androgens testosterone and 5α-dihydrotestosterone decreased, whilst the active 11-oxygenated androgen 11-ketotestosterone maintained pre-injury levels.<h4>Conclusions</h4>Changes in steroid biosynthesis and metabolism occur within minutes of traumatic injury. Studies that address whether ultra-early changes in steroid metabolism are associated with patient outcomes are now required.",,pdf:https://academic.oup.com/ejendo/article-pdf/188/3/290/49630912/lvad024.pdf; doi:https://doi.org/10.1093/ejendo/lvad024
 35684987,https://doi.org/10.1111/camh.12571,Assessing the feasibility of a web-based outcome measurement system in child and adolescent mental health services - myHealthE a randomised controlled feasibility pilot study.,"Morris AC, Ibrahim Z, Heslin M, Moghraby OS, Stringaris A, Grant IM, Zalewski L, Pritchard M, Stewart R, Hotopf M, Pickles A, Dobson RJB, Simonoff E, Downs J.",,Child and adolescent mental health,2023,2022-06-09,Y,Child And Adolescent Mental Health; Remote Monitoring; Acceptability; Patient-reported Outcome Measures,,,"<h4>Background</h4>Interest in internet-based patient reported outcome measure (PROM) collection is increasing. The NHS myHealthE (MHE) web-based monitoring system was developed to address the limitations of paper-based PROM completion. MHE provides a simple and secure way for families accessing Child and Adolescent Mental Health Services to report clinical information and track their child's progress. This study aimed to assess whether MHE improves the completion of the Strengths and Difficulties Questionnaire (SDQ) compared with paper collection. Secondary objectives were to explore caregiver satisfaction and application acceptability.<h4>Methods</h4>A 12-week single-blinded randomised controlled feasibility pilot trial of MHE was conducted with 196 families accessing neurodevelopmental services in south London to examine whether electronic questionnaires are completed more readily than paper-based questionnaires over a 3-month period. Follow up process evaluation phone calls with a subset (n = 8) of caregivers explored system satisfaction and usability.<h4>Results</h4>MHE group assignment was significantly associated with an increased probability of completing an SDQ-P in the study period (adjusted hazard ratio (HR) 12.1, 95% CI 4.7-31.0; p = <.001). Of those caregivers' who received the MHE invitation (n = 68) 69.1% completed an SDQ using the platform compared to 8.8% in the control group (n = 68). The system was well received by caregivers, who cited numerous benefits of using MHE, for example, real-time feedback and ease of completion.<h4>Conclusions</h4>MHE holds promise for improving PROM completion rates. Research is needed to refine MHE, evaluate large-scale MHE implementation, cost effectiveness and explore factors associated with differences in electronic questionnaire uptake.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/camh.12571; doi:https://doi.org/10.1111/camh.12571; html:https://europepmc.org/articles/PMC10083915; pdf:https://europepmc.org/articles/PMC10083915?pdf=render
@@ -1109,10 +1109,10 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t
 33517835,https://doi.org/10.1080/17457300.2021.1876736,Identify the key characteristics of pedestrian collisions through in-depth interviews: a pilot study.,"Perkins M, Casalaz S, Mitra B, Gabbe B, Brown J, Oxley J, Cameron P, Beck B.",,International journal of injury control and safety promotion,2021,2021-01-31,N,Behaviour; Public Health; Pedestrian,,,"This study aimed to assess the feasibility of recruiting injured pedestrians from the emergency department of a major trauma centre, using an in-depth interview shortly post collision. Convenience sampling was used to prospectively recruit injured pedestrians from the Alfred Hospital Emergency and Trauma Centre. Of the 102 injured pedestrians, 39 met eligibility criteria and of these, 30 (77%) consented and completed the questionnaire. Over half of the collisions occurred at an intersection (57%), and of these the most common pre-impact vehicle manoeuvre was a vehicle turning into the street the pedestrian was crossing. In-depth interview during the early post-crash period was a feasible and effective method of collecting detailed data in an accessible sample. However, only 38% of patients met eligibility criteria. To enhance representativeness, supplementing interview data with police-reported crash data, recruiting from hospital wards and crash location assessment is recommended.",,pdf:https://figshare.com/articles/journal_contribution/Identify_the_key_characteristics_of_pedestrian_collisions_through_in-depth_interviews_a_pilot_study/13671482/1/files/26241158.pdf; doi:https://doi.org/10.1080/17457300.2021.1876736
 37408046,https://doi.org/10.1186/s40545-023-00590-9,Delivering the precision oncology paradigm: reduced R&D costs and greater return on investment through a companion diagnostic informed precision oncology medicines approach.,"Henderson RH, French D, Stewart E, Smart D, Idica A, Redmond S, Eckstein M, Clark J, Sullivan R, Keeling P, Lawler M.",,Journal of pharmaceutical policy and practice,2023,2023-07-05,Y,,,,"<h4>Background</h4>Precision oncology medicines represent a paradigm shift compared to non-precision oncology medicines in cancer therapy, in some situations delivering more clinical benefit, and potentially lowering healthcare costs. We determined whether employing a companion diagnostic (CDx) approach during oncology medicines development delivers effective therapies that are within the cost constraints of current health systems. R&D costs of developing a medicine are subject to debate, with average estimates ranging from $765 million (m) to $4.6 billion (b). Our aim was to determine whether precision oncology medicines are cheaper to bring from R&D to market; a secondary goal was to determine whether precision oncology medicines have a greater return on investment (ROI).<h4>Method</h4>Data on oncology medicines approved between 1997 and 2020 by the US Food and Drug Administration (FDA) were analysed from the Securities and Exchange Commission (SEC) filings. Data were compiled from 10-K, 10-Q, and 20-F financial performance filings on medicines' development costs through their R&D lifetime. Clinical trial data were split into clinical trial phases 1-3 and probability of success (POS) of trials was calculated, along with preclinical costs. Cost-of-capital (CoC) approach was applied and, if appropriate, a tax rebate was subtracted from the total.<h4>Results</h4>Data on 42 precision and 29 non-precision oncology medicines from 56 companies listed by the National Cancer Institute which had complete data available were analysed. Estimated mean cost to deliver a new oncology medicine was $4.4b (95% CI, $3.6-5.2b). Costs to bring a precision oncology medicine to market were $1.1b less ($3.5b; 95% CI, $2.7-4.5b) compared to non-precision oncology medicines ($4.6b; 95% CI, $3.5-6.1b). The key driver of costs was POS of clinical trials, accounting for a difference of $591.3 m. Additional data analysis illustrated that there was a 27% increase in return on investment (ROI) of precision oncology medicines over non-precision oncology medicines.<h4>Conclusion</h4>Our results provide an accurate estimate of the R&D spend required to bring an oncology medicine to market. Deployment of a CDx at the earliest stage substantially lowers the cost associated with oncology medicines development, potentially making them available to more patients, while staying within the cost constraints of cancer health systems.",,pdf:https://joppp.biomedcentral.com/counter/pdf/10.1186/s40545-023-00590-9; doi:https://doi.org/10.1186/s40545-023-00590-9; html:https://europepmc.org/articles/PMC10320864; pdf:https://europepmc.org/articles/PMC10320864?pdf=render
 35264566,https://doi.org/10.1038/s41467-022-28729-3,Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.,"Stacey D, Chen L, Stanczyk PJ, Howson JMM, Mason AM, Burgess S, MacDonald S, Langdown J, McKinney H, Downes K, Farahi N, Peters JE, Basu S, Pankow JS, Tang W, Pankratz N, Sabater-Lleal M, de Vries PS, Smith NL, CHARGE Hemostasis Working Group, Gelinas AD, Schneider DJ, Janjic N, Samani NJ, Ye S, Summers C, Chilvers ER, Danesh J, Paul DS.",,Nature communications,2022,2022-03-09,Y,,,,"Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, attenuating leukocyte-endothelial cell adhesion and vascular inflammation. We also associate PROCR-219Gly with an increased pro-thrombotic state via coagulation factor VII, a ligand of EPCR. Our study, which links PROCR-219Gly to CAD through anti-inflammatory mechanisms and to VTE through pro-thrombotic mechanisms, provides a framework to reveal the mechanisms underlying similar cross-phenotype associations.",,pdf:https://www.nature.com/articles/s41467-022-28729-3.pdf; doi:https://doi.org/10.1038/s41467-022-28729-3; html:https://europepmc.org/articles/PMC8907312; pdf:https://europepmc.org/articles/PMC8907312?pdf=render
-36729586,https://doi.org/10.2196/42965,Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.,"Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.",,JMIR research protocols,2023,2023-02-02,Y,Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot,,,"<h4>Background</h4>Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.<h4>Objective</h4>The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.<h4>Methods</h4>We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.<h4>Results</h4>This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.<h4>Conclusions</h4>This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/42965.",,pdf:https://www.researchprotocols.org/2023/1/e42965/PDF; doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366
 PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USING PRE-PANDEMIC RISK OF MORTALITY IN INDIVIDUALS WITH CHRONIC KIDNEY DISEASE,"Dashtban M, Mizani M, Gonazalez-Izquierdo A, Corbett R, Denaxas S, Quint J, Mamza J, Morris T, Hemingway H, Sudlow C, Banerjee A.",,Kidney international reports,2022,2022-02-01,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855010/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855010/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8855010; pdf:https://europepmc.org/articles/PMC8855010?pdf=render
-37813531,https://doi.org/10.1136/bmjopen-2023-073162,Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.,"Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMJ open,2023,2023-10-09,Y,Obstetrics; epidemiology; Maternal Medicine,,,"<h4>Introduction</h4>Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.<h4>Methods and analysis</h4>Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",,doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render
+36729586,https://doi.org/10.2196/42965,Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.,"Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.",,JMIR research protocols,2023,2023-02-02,Y,Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot,,,"<h4>Background</h4>Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.<h4>Objective</h4>The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.<h4>Methods</h4>We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.<h4>Results</h4>This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.<h4>Conclusions</h4>This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/42965.",,pdf:https://www.researchprotocols.org/2023/1/e42965/PDF; doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366
 33766511,https://doi.org/10.1016/j.jid.2021.02.744,Raising the Bar for Randomized Trials Involving Artificial Intelligence: The SPIRIT-Artificial Intelligence and CONSORT-Artificial Intelligence Guidelines.,"Taylor M, Liu X, Denniston A, Esteva A, Ko J, Daneshjou R, Chan AW, SPIRIT-AI and CONSORT-AI Working Group.",,The Journal of investigative dermatology,2021,2021-03-22,N,,,,"Artificial intelligence (AI)-based applications have the potential to improve the quality and efficiency of patient care in dermatology. Unique challenges in the development and validation of these technologies may limit their generalizability and real-world applicability. Before the widespread adoption of AI interventions, randomized trials should be conducted to evaluate their efficacy, safety, and cost effectiveness in clinical settings. The recent Standard Protocol Items: Recommendations for Interventional Trials-AI extension and Consolidated Standards of Reporting Trials-AI extension guidelines provide recommendations for reporting the methods and results of trials involving AI interventions. High-quality trials will provide gold standard evidence to support the adoption of AI for the benefit of patient care.",,doi:https://doi.org/10.1016/j.jid.2021.02.744
+37813531,https://doi.org/10.1136/bmjopen-2023-073162,Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.,"Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMJ open,2023,2023-10-09,Y,Obstetrics; epidemiology; Maternal Medicine,,,"<h4>Introduction</h4>Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.<h4>Methods and analysis</h4>Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",,doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render
 35487318,https://doi.org/10.1016/j.ijcard.2022.04.067,Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction (NIHR Health Informatics Collaborative: TROP-CABG study).,"Benedetto U, Sinha S, Mulla A, Glampson B, Davies J, Panoulas V, Gautama S, Papadimitriou D, Woods K, Elliott P, Hemingway H, Williams B, Asselbergs FW, Melikian N, Krasopoulos G, Sayeed R, Wendler O, Baig K, Chukwuemeka A, Angelini GD, Sterne JAC, Johnson T, Shah AM, Perera D, Patel RS, Kharbanda R, Channon KM, Mayet J, Kaura A.",,International journal of cardiology,2022,2022-04-27,N,Troponin; Myocardial infarction; Coronary Artery Bypass Grafting; Timing-to-surgery,,,"Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction(NIHR Health Informatics Collaborative:TROP-CABG study). Benedetto et al. BACKGROUND: The optimal timing of coronary artery bypass grafting (CABG) in patients with non-ST elevation myocardial infarction (NSTEMI) and the utility of pre-operative troponin levels in decision-making remains unclear. We investigated (a) the association between peak pre-operative troponin and survival post-CABG in a large cohort of NSTEMI patients and (b) the interaction between troponin and time-to-surgery. METHODS AND RESULTS: Our cohort consisted of 1746 patients (1684 NSTEMI; 62 unstable angina) (mean age 69 ± 11 years,21% female) with recorded troponins that had CABG at five United Kingdom centers between 2010 and 2017. Time-segmented Cox regression was used to investigate the interaction of peak troponin and time-to-surgery on early (within 30 days) and late (beyond 30 days) survival. Average interval from peak troponin to surgery was 9 ± 15 days, with 1466 (84.0%) patients having CABG during the same admission. Sixty patients died within 30-days and another 211 died after a mean follow-up of 4 ± 2 years (30-day survival 0.97 ± 0.004 and 5-year survival 0.83 ± 0.01). Peak troponin was a strong predictor of early survival (adjusted P = 0.002) with a significant interaction with time-to-surgery (P interaction = 0.007). For peak troponin levels <100 times the upper limit of normal, there was no improvement in early survival with longer time-to-surgery. However, in patients with higher troponins, early survival increased progressively with a longer time-to-surgery, till day 10. Peak troponin did not influence survival beyond 30 days (adjusted P = 0.64). CONCLUSIONS: Peak troponin in NSTEMI patients undergoing CABG was a significant predictor of early mortality, strongly influenced the time-to-surgery and may prove to be a clinically useful biomarker in the management of these patients.",,doi:https://doi.org/10.1016/j.ijcard.2022.04.067
 36289925,https://doi.org/10.3390/biomedicines10102662,"Temporal Evolution of Multiday, Epileptic Functional Networks Prior to Seizure Occurrence.","Laiou P, Biondi A, Bruno E, Viana PF, Winston JS, Rashid Z, Ranjan Y, Conde P, Stewart C, Sun S, Zhang Y, Folarin A, Dobson RJB, Schulze-Bonhage A, Dümpelmann M, Richardson MP, Radar-Cns Consortium.",,Biomedicines,2022,2022-10-21,Y,Epilepsy; EEG; Graph theory; ECG; Functional Network; Seizure Lateralization; Evolving Network,,,"Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify the properties of epileptic brain networks. In this study, we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of the variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed fromelectroencephalographic recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.",,pdf:https://www.mdpi.com/2227-9059/10/10/2662/pdf?version=1666684470; doi:https://doi.org/10.3390/biomedicines10102662; html:https://europepmc.org/articles/PMC9599905; pdf:https://europepmc.org/articles/PMC9599905?pdf=render
 35104366,https://doi.org/10.1111/bjd.21042,Vaccine hesitancy and access to psoriasis care during the COVID-19 pandemic: findings from a global patient-reported cross-sectional survey.,"Bechman K, Cook ES, Dand N, Yiu ZZN, Tsakok T, Meynell F, Coker B, Vincent A, Bachelez H, Barbosa I, Brown MA, Capon F, Contreras CR, De La Cruz C, Meglio PD, Gisondi P, Jullien D, Kelly J, Lambert J, Lancelot C, Langan SM, Mason KJ, McAteer H, Moorhead L, Naldi L, Norton S, Puig L, Spuls PI, Torres T, Urmston D, Vesty A, Warren RB, Waweru H, Weinman J, Griffiths CEM, Barker JN, Smith CH, Galloway JB, Mahil SK, PsoProtect study group.",,The British journal of dermatology,2022,2022-05-03,Y,,,,,,pdf:https://biblio.ugent.be/publication/8757812/file/8757816.pdf; doi:https://doi.org/10.1111/bjd.21042; html:https://europepmc.org/articles/PMC9545500; pdf:https://europepmc.org/articles/PMC9545500?pdf=render
@@ -1125,13 +1125,13 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 33789468,https://doi.org/10.1302/0301-620x.103b4.bjj-2020-1647.r1,Outcomes of severe lower limb injury with Mangled Extremity Severity Score ≥ 7.,"Hoogervorst LA, Hart MJ, Simpson PM, Kimmel LA, Oppy A, Edwards ER, Gabbe BJ.",,The bone & joint journal,2021,2021-04-01,N,Injury; Lower limb; Return To Work; Salvage; Functional Outcomes; Mess; Gos-e; Eq-5d-3l; Surgical Amputation; 2-Year,,,"<h4>Aims</h4>Complex fractures of the femur and tibia with associated severe soft tissue injury are often devastating for the individual. The aim of this study was to describe the two-year patient-reported outcomes of patients in a civilian population who sustained a complex fracture of the femur or tibia with a Mangled Extremity Severity Score (MESS) of ≥ 7, whereby the score ranges from 2 (lowest severity) to 11 (highest severity).<h4>Methods</h4>Patients aged ≥ 16 years with a fractured femur or tibia and a MESS of ≥ 7 were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (January 2007 to December 2018). Cases were grouped into surgical amputation or limb salvage. Descriptive analysis were used to examine return to work rates, three-level EuroQol five-dimension questionnaire (EQ-5D-3L), and Glasgow Outcome Scale-Extended (GOS-E) outcomes at 12 and 24 months post-injury.<h4>Results</h4>In all, 111 patients were included: 90 (81%) patients who underwent salvage and 21 (19%) patients with surgical amputation. The mean age of patients was 45.8 years (SD 15.8), 93 (84%) were male, 37 (33%) were involved in motor vehicle collisions, and the mean MESS score was 8.2 (SD 1.4). Two-year outcomes in the cohort were poor: six (7%) patients achieved a GOS-E good recovery, the mean EQ-5D-3L summary score was 0.52 (SD 0.27), and 17 (20%) patients had returned to work.<h4>Conclusion</h4>A small proportion of patients with severe lower limb injury (MESS ≥ 7) achieved a good level of function 24 months post-injury. Further follow-up is needed to better understand the long-term trajectory of these patients, including delayed amputation, hospital readmissions, and healthcare utilization. Cite this article: <i>Bone Joint J</i> 2021;103-B(4):769-774.",,doi:https://doi.org/10.1302/0301-620X.103B4.BJJ-2020-1647.R1
 35156082,https://doi.org/10.3389/fdgth.2022.833912,Artificial Intelligence and Statistics: Just the Old Wine in New Wineskins?,"Faes L, Sim DA, van Smeden M, Held U, Bossuyt PM, Bachmann LM.",,Frontiers in digital health,2022,2022-01-26,Y,Methodology; Statistics; Reporting Guideline; Machine Learning (Ml); Artificial Intelligence (Ai),,,,,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2022.833912/pdf; doi:https://doi.org/10.3389/fdgth.2022.833912; html:https://europepmc.org/articles/PMC8825497; pdf:https://europepmc.org/articles/PMC8825497?pdf=render
 33644414,https://doi.org/10.23889/ijpds.v5i3.1371,Public involvement & engagement in the work of a data safe haven: a case study of the SAIL Databank.,"Jones KH, Heys S, Thompson R, Cross L, Ford D.",,International journal of population data science,2020,2020-08-24,Y,Public Engagement; Data Safe Haven,,,"<h4>Background</h4>The SAIL Databank is a data safe haven established in 2007 at Swansea University (Wales). It was set up to create new opportunities for research using routinely-collected health and other public service datasets in linkable anonymised form. SAIL forms the bedrock of other Population Data Science initiatives made possible by the data and safe haven environment.<h4>Aim</h4>The aim of this paper is to provide an overview of public involvement & engagement in connection with the SAIL Databank and related Population Data Science initiatives.<h4>Approach</h4>We have a public involvement & engagement policy for SAIL in the context of Population Data Science. We established a Consumer Panel to provide advice on the work of SAIL and associated initiatives, including on proposed uses of SAIL data. We reviewed the topics discussed and provide examples of advice to researchers. We carried out a survey with members on their experiences of being on the Panel and their perceptions of the work of SAIL. We have a programme of wider public engagement and provide illustrations of this work.<h4>Discussion</h4>We summarise what this paper adds and some lessons learned. In the rapidly developing area of Population Data Science it is important that people feel welcome, that they are encouraged to ask questions and are provided with digestible information and adequate consideration time. Citizens have provided us with valuable anticipated and unanticipated opinions and novel viewpoints. We seek to take a pragmatic approach, prioritising the communication modes that allow maximum public input commensurate with the purpose of the activity.<h4>Conclusion</h4>This paper has set out our policy, rationale, scope and practical approaches to public involvement & engagement for SAIL and our related Population Data Science initiatives. Although there will be jurisdictional, cultural and organizational differences, we believe that the material covered in this paper will be of interest to other data focused enterprises across the world.",,pdf:https://ijpds.org/article/download/1371/2815; doi:https://doi.org/10.23889/ijpds.v5i3.1371; html:https://europepmc.org/articles/PMC7893854; pdf:https://europepmc.org/articles/PMC7893854?pdf=render
-37217302,https://doi.org/10.1136/emermed-2022-212827,External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.,"Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.",,Emergency medicine journal : EMJ,2023,2023-05-22,Y,risk management; Triage; Covid-19,,,"<h4>Background</h4>Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.<h4>Methods</h4>An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.<h4>Results</h4>Of the 446 084 patients, 15 397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.<h4>Conclusion</h4>No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.",,pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render
 32831176,https://doi.org/10.7554/elife.58699,The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship. ,"Emery JC, Russell TW, Liu Y, Hellewell J, Pearson CA, CMMID COVID-19 Working Group, Knight GM, Eggo RM, Kucharski AJ, Kucharski AJ, Funk S, Flasche S, Houben RM.",,eLife,2020,2020-08-24,Y,,,,"A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission.",,doi:https://doi.org/10.7554/elife.58699; doi:https://doi.org/10.7554/eLife.58699; html:https://europepmc.org/articles/PMC7527238; pdf:https://europepmc.org/articles/PMC7527238?pdf=render
+37217302,https://doi.org/10.1136/emermed-2022-212827,External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.,"Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.",,Emergency medicine journal : EMJ,2023,2023-05-22,Y,risk management; Triage; Covid-19,,,"<h4>Background</h4>Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.<h4>Methods</h4>An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.<h4>Results</h4>Of the 446 084 patients, 15 397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.<h4>Conclusion</h4>No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.",,pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render
 36285341,https://doi.org/10.1080/17434440.2022.2132147,Data-driven monitoring in patients on left ventricular assist device support.,"Numan L, Moazeni M, Oerlemans MIFJ, Aarts E, Van Der Kaaij NP, Asselbergs FW, Van Laake LW.",,Expert review of medical devices,2022,2022-09-01,N,Prediction; Circadian rhythm; Algorithms; Remote Monitoring; Left Ventricular Assist Device; Lvad,,,"<h4>Introduction</h4>Despite an increasing population of patients supported with a left ventricular assist device (LVAD), it remains a complex therapy, and patients are frequently admitted. Therefore, a strict follow-up including frequent hospital visits, patient self-management and telemonitoring is needed.<h4>Areas covered</h4>The current review describes the principles of LVADs, the possibilities of (tele)monitoring using noninvasive and invasive devices. Furthermore, possibilities, challenges, and future perspectives in this emerging field are discussed.<h4>Expert opinion</h4>Several studies described initial experiences on telemonitoring in LVAD patients, using mobile phone applications to collect clinical data and pump data. This may replace frequent hospital visits in near future. In addition, algorithms were developed aiming to early detect pump thrombosis or driveline infections. Since not all complications are reflected by pump parameters, data from different sources should be combined to detect a broader spectrum of complications in an early stage. We need to focus on the development of sophisticated but understandable algorithms and infrastructure combining different data sources, while addressing essential aspects such as data safety, privacy, and cost-effectiveness.",,doi:https://doi.org/10.1080/17434440.2022.2132147; doi:https://doi.org/10.1080/17434440.2022.2132147
 35440446,https://doi.org/10.1136/bmjopen-2021-052514,Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals.,"Blackstone J, Stirrup O, Mapp F, Panca M, Copas A, Flowers P, Hockey L, Price J, Partridge D, Peters C, de Silva T, Nebbia G, Snell LB, McComish R, COVID-19 Genomics UK (COG-UK) Consortium, Breuer J.",,BMJ open,2022,2022-04-19,Y,Molecular biology; Infection control; epidemiology; Covid-19,,,"<h4>Objectives</h4>Nosocomial transmission of SARS-CoV-2 has been a significant cause of mortality in National Health Service (NHS) hospitals during the COVID-19 pandemic. The COG-UK Consortium Hospital-Onset COVID-19 Infections (COG-UK HOCI) study aims to evaluate whether the use of rapid whole-genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, can inform infection prevention and control (IPC) practice within NHS hospital settings.<h4>Design</h4>Multicentre, prospective, interventional, superiority study.<h4>Setting</h4>14 participating NHS hospitals over winter-spring 2020/2021 in the UK.<h4>Participants</h4>Eligible patients must be admitted to hospital with first-confirmed SARS-CoV-2 PCR-positive test result >48 hour from time of admission, where COVID-19 diagnosis not suspected on admission. The projected sample size is 2380 patients.<h4>Intervention</h4>The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab processing) and within 5-10 days in a second phase (mimicking central lab), comparing the viral genome from an eligible study participant with others within and outside the hospital site.<h4>Primary and secondary outcome measures</h4>The primary outcomes are incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. Health economic analysis will be conducted to determine cost benefit of the intervention. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study.<h4>Trial registration number</h4>ISRCTN50212645. Pre-results stage. This manuscript is based on protocol V.6.0. 2 September 2021.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e052514.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052514; html:https://europepmc.org/articles/PMC9019828; pdf:https://europepmc.org/articles/PMC9019828?pdf=render
 35396183,https://doi.org/10.1016/s2589-7500(22)00003-6,The medical algorithmic audit.,"Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.",,The Lancet. Digital health,2022,2022-04-05,N,,,,"Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.",,pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6
-34244270,https://doi.org/10.1136/bmjopen-2020-048008,Protocol for development of a reporting guideline (TRIPOD-AI) and risk of bias tool (PROBAST-AI) for diagnostic and prognostic prediction model studies based on artificial intelligence.,"Collins GS, Dhiman P, Andaur Navarro CL, Ma J, Hooft L, Reitsma JB, Logullo P, Beam AL, Peng L, Van Calster B, van Smeden M, Riley RD, Moons KG.",,BMJ open,2021,2021-07-09,Y,epidemiology; Statistics & Research Methods; General Medicine (See Internal Medicine),,,"<h4>Introduction</h4>The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) were both published to improve the reporting and critical appraisal of prediction model studies for diagnosis and prognosis. This paper describes the processes and methods that will be used to develop an extension to the TRIPOD statement (TRIPOD-artificial intelligence, AI) and the PROBAST (PROBAST-AI) tool for prediction model studies that applied machine learning techniques.<h4>Methods and analysis</h4>TRIPOD-AI and PROBAST-AI will be developed following published guidance from the EQUATOR Network, and will comprise five stages. Stage 1 will comprise two systematic reviews (across all medical fields and specifically in oncology) to examine the quality of reporting in published machine-learning-based prediction model studies. In stage 2, we will consult a diverse group of key stakeholders using a Delphi process to identify items to be considered for inclusion in TRIPOD-AI and PROBAST-AI. Stage 3 will be virtual consensus meetings to consolidate and prioritise key items to be included in TRIPOD-AI and PROBAST-AI. Stage 4 will involve developing the TRIPOD-AI checklist and the PROBAST-AI tool, and writing the accompanying explanation and elaboration papers. In the final stage, stage 5, we will disseminate TRIPOD-AI and PROBAST-AI via journals, conferences, blogs, websites (including TRIPOD, PROBAST and EQUATOR Network) and social media. TRIPOD-AI will provide researchers working on prediction model studies based on machine learning with a reporting guideline that can help them report key details that readers need to evaluate the study quality and interpret its findings, potentially reducing research waste. We anticipate PROBAST-AI will help researchers, clinicians, systematic reviewers and policymakers critically appraise the design, conduct and analysis of machine learning based prediction model studies, with a robust standardised tool for bias evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been granted by the Central University Research Ethics Committee, University of Oxford on 10-December-2020 (R73034/RE001). Findings from this study will be disseminated through peer-review publications.<h4>Prospero registration number</h4>CRD42019140361 and CRD42019161764.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e048008.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048008; html:https://europepmc.org/articles/PMC8273461; pdf:https://europepmc.org/articles/PMC8273461?pdf=render
 30181555,https://doi.org/10.1038/s41398-018-0236-1,"Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression.","Strawbridge RJ, Ward J, Lyall LM, Tunbridge EM, Cullen B, Graham N, Ferguson A, Johnston KJA, Lyall DM, Mackay D, Cavanagh J, Howard DM, Adams MJ, Deary I, Escott-Price V, O'Donovan M, McIntosh AM, Bailey MES, Pell JP, Harrison PJ, Smith DJ.",,Translational psychiatry,2018,2018-09-04,Y,,Understanding the Causes of Disease,,"Risk-taking behaviour is an important component of several psychiatric disorders, including attention-deficit hyperactivity disorder, schizophrenia and bipolar disorder. Previously, two genetic loci have been associated with self-reported risk taking and significant genetic overlap with psychiatric disorders was identified within a subsample of UK Biobank. Using the white British participants of the full UK Biobank cohort (n = 83,677 risk takers versus 244,662 controls) for our primary analysis, we conducted a genome-wide association study of self-reported risk-taking behaviour. In secondary analyses, we assessed sex-specific effects, trans-ethnic heterogeneity and genetic overlap with psychiatric traits. We also investigated the impact of risk-taking-associated SNPs on both gene expression and structural brain imaging. We identified 10 independent loci for risk-taking behaviour, of which eight were novel and two replicated previous findings. In addition, we found two further sex-specific risk-taking loci. There were strong positive genetic correlations between risk-taking and attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia. Index genetic variants demonstrated effects generally consistent with the discovery analysis in individuals of non-British White, South Asian, African-Caribbean or mixed ethnicity. Polygenic risk scores comprising alleles associated with increased risk taking were associated with lower white matter integrity. Genotype-specific expression pattern analyses highlighted DPYSL5, CGREF1 and C15orf59 as plausible candidate genes. Overall, our findings substantially advance our understanding of the biology of risk-taking behaviour, including the possibility of sex-specific contributions, and reveal consistency across ethnicities. We further highlight several putative novel candidate genes, which may mediate these genetic effects.",,pdf:https://www.nature.com/articles/s41398-018-0236-1.pdf; doi:https://doi.org/10.1038/s41398-018-0236-1; html:https://europepmc.org/articles/PMC6123450; pdf:https://europepmc.org/articles/PMC6123450?pdf=render
+34244270,https://doi.org/10.1136/bmjopen-2020-048008,Protocol for development of a reporting guideline (TRIPOD-AI) and risk of bias tool (PROBAST-AI) for diagnostic and prognostic prediction model studies based on artificial intelligence.,"Collins GS, Dhiman P, Andaur Navarro CL, Ma J, Hooft L, Reitsma JB, Logullo P, Beam AL, Peng L, Van Calster B, van Smeden M, Riley RD, Moons KG.",,BMJ open,2021,2021-07-09,Y,epidemiology; Statistics & Research Methods; General Medicine (See Internal Medicine),,,"<h4>Introduction</h4>The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) were both published to improve the reporting and critical appraisal of prediction model studies for diagnosis and prognosis. This paper describes the processes and methods that will be used to develop an extension to the TRIPOD statement (TRIPOD-artificial intelligence, AI) and the PROBAST (PROBAST-AI) tool for prediction model studies that applied machine learning techniques.<h4>Methods and analysis</h4>TRIPOD-AI and PROBAST-AI will be developed following published guidance from the EQUATOR Network, and will comprise five stages. Stage 1 will comprise two systematic reviews (across all medical fields and specifically in oncology) to examine the quality of reporting in published machine-learning-based prediction model studies. In stage 2, we will consult a diverse group of key stakeholders using a Delphi process to identify items to be considered for inclusion in TRIPOD-AI and PROBAST-AI. Stage 3 will be virtual consensus meetings to consolidate and prioritise key items to be included in TRIPOD-AI and PROBAST-AI. Stage 4 will involve developing the TRIPOD-AI checklist and the PROBAST-AI tool, and writing the accompanying explanation and elaboration papers. In the final stage, stage 5, we will disseminate TRIPOD-AI and PROBAST-AI via journals, conferences, blogs, websites (including TRIPOD, PROBAST and EQUATOR Network) and social media. TRIPOD-AI will provide researchers working on prediction model studies based on machine learning with a reporting guideline that can help them report key details that readers need to evaluate the study quality and interpret its findings, potentially reducing research waste. We anticipate PROBAST-AI will help researchers, clinicians, systematic reviewers and policymakers critically appraise the design, conduct and analysis of machine learning based prediction model studies, with a robust standardised tool for bias evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been granted by the Central University Research Ethics Committee, University of Oxford on 10-December-2020 (R73034/RE001). Findings from this study will be disseminated through peer-review publications.<h4>Prospero registration number</h4>CRD42019140361 and CRD42019161764.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e048008.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048008; html:https://europepmc.org/articles/PMC8273461; pdf:https://europepmc.org/articles/PMC8273461?pdf=render
 32895316,https://doi.org/10.1136/thoraxjnl-2020-215566,We need a robust evidence base to unravel the relationship between sex hormones and asthma.,"Sheikh A, Mukherjee M.",,Thorax,2020,2020-09-07,N,Asthma,,,,,html:http://hdl.handle.net/20.500.11820/885f92d9-96bd-467c-893a-d5eb23d109e9; doi:https://doi.org/10.1136/thoraxjnl-2020-215566
 35022215,https://doi.org/10.1136/bmj-2021-067519,Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.,"Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.",,BMJ (Clinical research ed.),2022,2022-01-12,Y,,,,"<h4>Objective</h4>To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.<h4>Design</h4>Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.<h4>Setting</h4>Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.<h4>Population</h4>Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.<h4>Main outcome measures</h4>For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.<h4>Results</h4>After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.<h4>Conclusions</h4>During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.",,pdf:https://www.bmj.com/content/bmj/376/bmj-2021-067519.full.pdf; doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render
 37519214,https://doi.org/10.1177/09622802231188518,Multiple imputation approaches for epoch-level accelerometer data in trials.,"Tackney MS, Williamson E, Cook DG, Limb E, Harris T, Carpenter J.",,Statistical methods in medical research,2023,2023-07-31,Y,Missing Data; Accelerometer; Multiple Imputation; Wearables; Physical Activity Trial,,,"Clinical trials that investigate physical activity interventions often use accelerometers to measure step count at a very granular level, for example in 5-second epochs. Participants typically wear the accelerometer for a week-long period at baseline, and for one or more week-long follow-up periods after the intervention. The data is aggregated to provide daily or weekly step counts for the primary analysis. Missing data are common as participants may not wear the device as per protocol. Approaches to handling missing data in the literature have defined missingness on the day level using a threshold on daily weartime, which leads to loss of information on the time of day when data are missing. We propose an approach to identifying and classifying missingness at the finer epoch-level and present two approaches to handling missingness using multiple imputation. Firstly, we present a parametric approach which accounts for the number of missing epochs per day. Secondly, we describe a non-parametric approach where missing periods during the day are replaced by donor data from the same person where possible, or data from a different person who is matched on demographic and physical activity-related variables. Our simulation studies show that the non-parametric approach leads to estimates of the effect of treatment that are least biased while maintaining small standard errors. We illustrate the application of these different multiple imputation strategies to the analysis of the 2017 PACE-UP trial. The proposed framework is likely to be applicable to other digital health outcomes and to other wearable devices.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/09622802231188518; doi:https://doi.org/10.1177/09622802231188518; html:https://europepmc.org/articles/PMC10563375; pdf:https://europepmc.org/articles/PMC10563375?pdf=render
@@ -1144,14 +1144,14 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 36243582,https://doi.org/10.1016/j.injury.2022.09.052,Older trauma patients with isolated chest injuries have low rates of complications.,"Ferrah N, Beck B, Ibrahim J, Gabbe B, McLellan MS, Cameron P.",,Injury,2022,2022-10-07,N,Geriatric; Complication; Pneumonia; Chest Trauma; Older; Trauma Centre,,,"<h4>Introduction</h4>The number of older adults hospitalised for injury is growing rapidly. The population-adjusted incidence of isolated thoracic injuries in older adults is also growing. While some older adults are at high risk of post-traumatic complications, not all older adults will need treatment in a major trauma service (MTS). The aim of this study was to characterise older patients with isolated chest injuries, determine the rates of post-traumatic complications, including respiratory failure and pneumonia, and the factors associated with the risk of developing these complications.<h4>Patients and methods</h4>This was a retrospective review of patients aged 65 years and over with isolated chest trauma, from January 2007 to June 2017, using data from the Victorian State Trauma Registry. Patient characteristics and rates of complications were compared between patients with 1. isolated rib fractures, and 2. complex chest injury. Multivariable logistic regression was used to identify predictors of respiratory failure, and pneumonia.<h4>Results</h4>The study population comprised 5401 patients aged 65 years or more, with isolated chest injuries. Two-thirds (65%) of all patients had isolated rib fractures, and 58% of patients (n = 3156) were directly admitted to a non-major trauma centre. Complications were uncommon, with 5.45% of all patients (n = 295) having pneumonia and 3.2% (n = 175) having respiratory failure. Factors associated with increased risk of pneumonia and respiratory failure included advancing age, smoking, chronic obstructive pulmonary disease, congestive heart failure, and more severe and complex chest injury. The adjusted odds of complications were lowest amongst patients not classified as major trauma and receiving definitive treatment in non-MTS.<h4>Discussion</h4>Our findings suggest that rates of complications in older patients with isolated chest trauma in this study were low, and that there is a large group of patients with isolated, uncomplicated rib fractures, who may not need to be treated in a major trauma centre. Further work should be undertaken to appropriately risk stratify and manage older adults with isolated chest trauma.",,doi:https://doi.org/10.1016/j.injury.2022.09.052
 34000735,https://doi.org/10.1093/ije/dyab025,Commentary: Obstetric oxytocin exposure and risk of attention-deficit hyperactivity disorder and autism spectrum disorder in offspring-case closed.,"Morales DR, Nordeng HM.",,International journal of epidemiology,2021,2021-05-01,N,,,,,,pdf:https://academic.oup.com/ije/article-pdf/50/2/457/37947593/dyab025.pdf; doi:https://doi.org/10.1093/ije/dyab025
 34751629,https://doi.org/10.1080/09638288.2021.1998671,Long-term health and mobility of older adults following traumatic injury: a qualitative longitudinal study.,"Reeder S, Ameratunga S, Ponsford J, Fitzgerald M, Lyons R, Nunn A, Ekegren C, Cameron P, Gabbe B.",,Disability and rehabilitation,2022,2021-11-09,N,Ageing; Recovery; Qualitative; Disability; Older Adult; Traumatic Injury,,,"<h4>Purpose</h4>The aim of this study was to explore older adults' experiences of and approaches to managing their long-term health and mobility after traumatic injury.<h4>Methods</h4>A longitudinal qualitative study was undertaken with older adults following traumatic injury in Victoria, Australia. Fifteen participants (≥65 years) were interviewed at three years post-injury (<i>n</i> = 15), and re-interviewed at four (<i>n</i> = 14) and five years (<i>n</i> = 12) post-injury. Using a framework approach, a longitudinal thematic analysis was performed.<h4>Results</h4>Older age at the time of injury was identified by participants as a key factor influencing their recovery. Many participants reported actively attempting to regain their strength and fitness in the first five years following injury. However, their age, injury impacts, other health conditions, and weight gain made it difficult to achieve recovery goals. Many older adults reported a decline in their physical function over time. While these experiences and persistent disability constrained or changed the quality of social relationships, community participation, and independence, several participants described adapting to their functional limitations, and managing their secondary conditions over time.<h4>Conclusion</h4>In our cohort, the intertwined combination of ageing, injury, and comorbid conditions negatively affected health and mobility, reinforcing the need for preventative strategies.Implications for rehabilitationOlder adults recovering from traumatic injury may benefit from specialised care pathways that offer long-term and tailored therapies, with programs and services specific to their needs and goals.An integrated service approach by injury insurers, health care, primary care, disability, and aged care could more clearly identify and effectively address the individual needs and goals of older adults with complex conditions.Health and social services that work with people with injuries to develop personalised coping strategies can reduce anxiety related to uncertainty about the future, promote well-being, and support participation in valued activities.",,doi:https://doi.org/10.1080/09638288.2021.1998671
-37612010,https://doi.org/10.1016/j.jacc.2023.05.065,Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum.,"Kirkels FP, van Osta N, Rootwelt-Norberg C, Chivulescu M, van Loon T, Aabel EW, Castrini AI, Lie ØH, Asselbergs FW, Delhaas T, Cramer MJ, Teske AJ, Haugaa KH, Lumens J.",,Journal of the American College of Cardiology,2023,2023-08-01,N,Early Detection; Arvc; Family Screening; Arrhythmogenic Cardiomyopathy; Deformation Imaging; Digital Twin,,,"<h4>Background</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored.<h4>Objectives</h4>The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups.<h4>Methods</h4>We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and ≥50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework.<h4>Results</h4>We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up.<h4>Conclusions</h4>Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.",,doi:https://doi.org/10.1016/j.jacc.2023.05.065
 31353050,https://doi.org/10.1016/s0140-6736(19)31359-5,Eligibility and subsequent burden of cardiovascular disease of four strategies for blood pressure-lowering treatment: a retrospective cohort study.,"Herrett E, Gadd S, Jackson R, Bhaskaran K, Williamson E, van Staa T, Sofat R, Timmis A, Smeeth L.",,"Lancet (London, England)",2019,2019-07-25,Y,,Better Care,,"<h4>Background</h4>Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example.<h4>Methods</h4>We did a retrospective cohort study in primary care patients aged 30-79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality. We assessed and compared four different strategies to determine eligibility for treatment: using 2011 UK National Institute for Health and Care Excellence (NICE) guideline, or proposed 2019 NICE guideline, or blood pressure alone (threshold ≥140/90 mm Hg), or predicted 10-year cardiovascular risk alone (QRISK2 score ≥10%). Patients were followed up until the earliest occurrence of a cardiovascular disease diagnosis, death, or end of follow-up period (March 31, 2016). For each strategy, we estimated the proportion of patients eligible for treatment and number of cardiovascular events that could be prevented with treatment. We then estimated eligibility and number of events that would occur during 10 years in the UK general population.<h4>Findings</h4>Between Jan 1, 2011, and March 31, 2016, 1 222 670 patients in the cohort were followed up for a median of 4·3 years (IQR 2·5-5·2). 271 963 (22·2%) patients were eligible for treatment under the 2011 NICE guideline, 327 429 (26·8%) under the proposed 2019 NICE guideline, 481 859 (39·4%) on the basis of a blood pressure threshold of 140/90 mm Hg or higher, and 357 840 (29·3%) on the basis of a QRISK2 threshold of 10% or higher. During follow-up, 32 183 patients were diagnosed with cardiovascular disease (overall rate 7·1 per 1000 person-years, 95% CI 7·0-7·2). Cardiovascular event rates in patients eligible for each strategy were 15·2 per 1000 person-years (95% CI 15·0-15·5) under the 2011 NICE guideline, 14·9 (14·7-15·1) under the proposed 2019 NICE guideline, 11·4 (11·3-11·6) with blood pressure threshold alone, and 16·9 (16·7-17·1) with QRISK2 threshold alone. Scaled to the UK population, we estimated that 233 152 events would be avoided under the 2011 NICE guideline (28 patients needed to treat for 10 years to avoid one event), 270 233 under the 2019 NICE guideline (29 patients), 301 523 using a blood pressure threshold (38 patients), and 322 921 using QRISK2 threshold (27 patients).<h4>Interpretation</h4>A cardiovascular risk-based strategy (QRISK2 ≥10%) could prevent over a third more cardiovascular disease events than the 2011 NICE guideline and a fifth more than the 2019 NICE guideline, with similar efficiency regarding number treated per event avoided.<h4>Funding</h4>National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S0140673619313595/pdf; doi:https://doi.org/10.1016/S0140-6736(19)31359-5; html:https://europepmc.org/articles/PMC6717081
+37612010,https://doi.org/10.1016/j.jacc.2023.05.065,Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum.,"Kirkels FP, van Osta N, Rootwelt-Norberg C, Chivulescu M, van Loon T, Aabel EW, Castrini AI, Lie ØH, Asselbergs FW, Delhaas T, Cramer MJ, Teske AJ, Haugaa KH, Lumens J.",,Journal of the American College of Cardiology,2023,2023-08-01,N,Early Detection; Arvc; Family Screening; Arrhythmogenic Cardiomyopathy; Deformation Imaging; Digital Twin,,,"<h4>Background</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored.<h4>Objectives</h4>The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups.<h4>Methods</h4>We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and ≥50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework.<h4>Results</h4>We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up.<h4>Conclusions</h4>Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.",,doi:https://doi.org/10.1016/j.jacc.2023.05.065
 34356044,https://doi.org/10.3390/genes12071029,A Causal Web between Chronotype and Metabolic Health Traits. ,"Williams JA, Russ D, Bravo-Merodio L, Cardoso VR, Pendleton SC, Aziz F, Acharjee A, Gkoutos GV.",,Genes,2021,2021-07-01,Y,,,,"Observational and experimental evidence has linked chronotype to both psychological and cardiometabolic traits. Recent Mendelian randomization (MR) studies have investigated direct links between chronotype and several of these traits, often in isolation of outside potential mediating or moderating traits. We mined the EpiGraphDB MR database for calculated chronotype-trait associations (p-value < 5 × 10-8). We then re-analyzed those relevant to metabolic or mental health and investigated for statistical evidence of horizontal pleiotropy. Analyses passing multiple testing correction were then investigated for confounders, colliders, intermediates, and reverse intermediates using the EpiGraphDB database, creating multiple chronotype-trait interactions among each of the the traits studied. We revealed 10 significant chronotype-exposure associations (false discovery rate < 0.05) exposed to 111 potential previously known confounders, 52 intermediates, 18 reverse intermediates, and 31 colliders. Chronotype-lipid causal associations collided with treatment and diabetes effects; chronotype-bipolar associations were mediated by breast cancer; and chronotype-alcohol intake associations were impacted by confounders and intermediate variables including known zeitgebers and molecular traits. We have reported the influence of chronotype on several cardiometabolic and behavioural traits, and identified potential confounding variables not reported on in studies while discovering new associations to drugs and disease.",,pdf:https://www.mdpi.com/2073-4425/12/7/1029/pdf?version=1625724795; doi:https://doi.org/10.3390/genes12071029; html:https://europepmc.org/articles/PMC8303793; pdf:https://europepmc.org/articles/PMC8303793?pdf=render
 32485082,https://doi.org/10.1002/ejhf.1924,Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust.,"Bean DM, Kraljevic Z, Searle T, Bendayan R, Kevin O, Pickles A, Folarin A, Roguski L, Noor K, Shek A, Zakeri R, Shah AM, Teo JTH, Dobson RJB.",,European journal of heart failure,2020,2020-06-01,Y,Hypertension; Angiotensin-converting enzyme inhibitors; Disease Outcome; Covid-19,,,"<h4>Aims</h4>The SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID-19 infection.<h4>Methods and results</h4>We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID-19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01).<h4>Conclusions</h4>There was no evidence for increased severity of COVID-19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.","This study aimed to determine whether or not two specific types of medication (ACE inhibitors and angiotensin-2 blockers - ACEi/ARB) used for hypertension or diabetes are associated with increased risk of severe COVID-19 infection in a sample of 1,200 inpatients (one third of whom were taking the medications under investigation) in two London hospitals. The researchers used data from electonic medical notes and electronic health records. The patients who were taking the medication were, on average, older and had more underlying health conditions than patients who were not. After accounting for these differences in patient health the researchers found that the risk of severe COVID infection was not higher for patients taking ACEi/ARB. This finding is important for patients because it suggests that they should continue to take ACEi/ARB that have been presecribed to them.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.1924; doi:https://doi.org/10.1002/ejhf.1924; html:https://europepmc.org/articles/PMC7301045; pdf:https://europepmc.org/articles/PMC7301045?pdf=render
 33382071,https://doi.org/10.1093/schbul/sbaa176,Corrigendum to: Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.,,,Schizophrenia bulletin,2021,2021-03-01,N,,,,,,pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/575/36620724/sbaa176.pdf; doi:https://doi.org/10.1093/schbul/sbaa176; html:https://europepmc.org/articles/PMC7965055; pdf:https://europepmc.org/articles/PMC7965055?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa176
 34598995,https://doi.org/10.1136/bmjopen-2021-055219,"wEight chanGes, caRdio-mEtabolic risks and morTality in patients with hyperthyroidism (EGRET): a protocol for a CPRD-HES linked cohort study.","Torlinska B, Hazlehurst JM, Nirantharakumar K, Thomas GN, Priestley JR, Finnikin SJ, Saunders P, Abrams KR, Boelaert K.",,BMJ open,2021,2021-10-01,Y,Thyroid disease; epidemiology; Cardiac Epidemiology,,,"<h4>Introduction</h4>Hyperthyroidism is a common condition affecting up to 3% of the UK population. Treatment improves symptoms and reduces the risk of atrial fibrillation and stroke that contribute to increased mortality. The most common symptom is weight loss, which is reversed during treatment. However, the weight regain may be excessive, contributing to increased risk of obesity. Current treatment options include antithyroid drugs, radioiodine and thyroidectomy. Whether there are differences in either weight change or the long-term cardiometabolic risk between the three treatments is unclear.<h4>Methods and analysis</h4>The study will establish the natural history of weight change in hyperthyroidism, investigate the risk of obesity and risks of cardiometabolic conditions and death relative to the treatment. The data on patients diagnosed with hyperthyroidism between 1 January 1996 and 31 December 2015 will come from Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office of National Statistics Death Registry. The weight changes will be modelled using a flexible joint modelling, accounting for mortality. Obesity prevalence in the general population will be sourced from Health Survey for England and compared with the post-treatment prevalence of obesity in patients with hyperthyroidism. The incidence and time-to-event of major adverse cardiovascular events, other cardiometabolic outcomes and mortality will be compared between the treatments using the inverse propensity weighting model. Incidence rate ratios of outcomes will be modelled with Poisson regression. Time to event will be analysed using Cox proportional hazards model. A competing risks approach will be adopted to estimate comparative incidences to allow for the impact of mortality.<h4>Ethics and dissemination</h4>The study will bring new knowledge on the risk of developing obesity, cardiometabolic morbidity and mortality following treatment for hyperthyroidism to inform clinical practice and public health policies. The results will be disseminated via open-access peer-reviewed publications and directly to the patients and public groups (Independent Scientific Advisory Committee protocol approval #20_000185).",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e055219.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055219; html:https://europepmc.org/articles/PMC8488707; pdf:https://europepmc.org/articles/PMC8488707?pdf=render
-35869974,https://doi.org/10.1093/ndt/gfac224,Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.,"Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2023,2023-05-01,Y,Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes,,,"<h4>Background</h4>No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.<h4>Methods</h4>This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30 mL/min/1.73 m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.<h4>Results</h4>There were 41 313, 51 190, 32 171 and 17 781 new presentations of AKI and eGFR thresholds <60, <45 and <30  mL/min/1.73 m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5 years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60 mL/min/1.73 m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30 mL/min/1.73 m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60 mL/min/1.73 m2, AKI, males and those <65 years of age.<h4>Conclusions</h4>Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.",,pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render
 35452565,https://doi.org/10.1002/cpz1.373,The COPILOT Raw Illumina Genotyping QC Protocol.,"Patel H, Lee SH, Breen G, Menzel S, Ojewunmi O, Dobson RJB.",,Current protocols,2022,2022-04-01,N,Genotyping; Gwas; Illumina; Docker; Qc Pipeline,,,"The Illumina genotyping microarrays generate data in image format, which is processed by the platform-specific software GenomeStudio, followed by an array of complex bioinformatics analyses that rely on various software, different programming languages, and numerous dependencies to be installed and configured correctly. The entire process can be time-consuming, can lead to reproducibility errors, and can be a daunting task for bioinformaticians. To address this, we introduce the COPILOT protocol, which has been successfully used to transform raw Illumina genotype intensity data into high-quality analysis-ready data on tens of thousands of human patient samples that have been genotyped on a variety of Illumina genotyping arrays. This includes processing both mainstream and custom content genotyping chips with over 4 million markers per sample. The COPILOT QC protocol consists of two distinct tandem procedures to process raw Illumina genotyping data. The first protocol is an up-to-date process to systematically QC raw Illumina microarray genotyping data using the Illumina-specific GenomeStudio software. The second protocol takes the output from the first protocol and further processes the data through the COPILOT (Containerised wOrkflow for Processing ILlumina genOtyping daTa) containerized QC pipeline, to automate an array of complex bioinformatics analyses to improve data quality through a secondary clustering algorithm and to automatically identify typical Genome-Wide Association Study (GWAS) data issues, including gender discrepancies, heterozygosity outliers, related individuals, and population outliers, through ancestry estimation. The data is returned to the user in analysis-ready PLINK binary format and is accompanied by a comprehensive and interactive HTML summary report file which quickly helps the user understand the data and guides the user for further data analyses. The COPILOT protocol and containerized pipeline are also available at https://khp-informatics.github.io/COPILOT/index.html. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Processing raw Illumina genotyping data using GenomeStudio Basic Protocol 2: COPILOT: A containerised workflow for processing Illumina genotyping data.",,pdf:https://discovery.ucl.ac.uk/10149151/1/Dobson_The%20COPILOT%20Raw%20Illumina%20Genotyping%20QC%20Protocol_VoR.pdf; doi:https://doi.org/10.1002/cpz1.373
+35869974,https://doi.org/10.1093/ndt/gfac224,Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.,"Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2023,2023-05-01,Y,Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes,,,"<h4>Background</h4>No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.<h4>Methods</h4>This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30 mL/min/1.73 m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.<h4>Results</h4>There were 41 313, 51 190, 32 171 and 17 781 new presentations of AKI and eGFR thresholds <60, <45 and <30  mL/min/1.73 m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5 years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60 mL/min/1.73 m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30 mL/min/1.73 m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60 mL/min/1.73 m2, AKI, males and those <65 years of age.<h4>Conclusions</h4>Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.",,pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render
 32717063,https://doi.org/10.1093/cvr/cvaa233,Gene expression profiling of hypertrophic cardiomyocytes identifies new players in pathological remodelling.,"Vigil-Garcia M, Demkes CJ, Eding JEC, Versteeg D, de Ruiter H, Perini I, Kooijman L, Gladka MM, Asselbergs FW, Vink A, Harakalova M, Bossu A, van Veen TAB, Boogerd CJ, van Rooij E.",,Cardiovascular research,2021,2021-05-01,Y,Cardiomyocyte; hypertrophy; Heart Failure; Rna Sequencing; Pfkp; Pathological Remodelling,,,"<h4>Aims</h4>Pathological cardiac remodelling is characterized by cardiomyocyte (CM) hypertrophy and fibroblast activation, which can ultimately lead to maladaptive hypertrophy and heart failure (HF). Genome-wide expression analysis on heart tissue has been instrumental for the identification of molecular mechanisms at play. However, these data were based on signals derived from all cardiac cell types. Here, we aimed for a more detailed view on molecular changes driving maladaptive CM hypertrophy to aid in the development of therapies to reverse pathological remodelling.<h4>Methods and results</h4>Utilizing CM-specific reporter mice exposed to pressure overload by transverse aortic banding and CM isolation by flow cytometry, we obtained gene expression profiles of hypertrophic CMs in the more immediate phase after stress, and CMs showing pathological hypertrophy. We identified subsets of genes differentially regulated and specific for either stage. Among the genes specifically up-regulated in the CMs during the maladaptive phase we found known stress markers, such as Nppb and Myh7, but additionally identified a set of genes with unknown roles in pathological hypertrophy, including the platelet isoform of phosphofructokinase (PFKP). Norepinephrine-angiotensin II treatment of cultured human CMs induced the secretion of N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and recapitulated the up-regulation of these genes, indicating conservation of the up-regulation in failing CMs. Moreover, several genes induced during pathological hypertrophy were also found to be increased in human HF, with their expression positively correlating to the known stress markers NPPB and MYH7. Mechanistically, suppression of Pfkp in primary CMs attenuated stress-induced gene expression and hypertrophy, indicating that Pfkp is an important novel player in pathological remodelling of CMs.<h4>Conclusion</h4>Using CM-specific transcriptomic analysis, we identified novel genes induced during pathological hypertrophy that are relevant for human HF, and we show that PFKP is a conserved failure-induced gene that can modulate the CM stress response.",,doi:https://doi.org/10.1093/cvr/cvaa233; doi:https://doi.org/10.1093/cvr/cvaa233; html:https://europepmc.org/articles/PMC8152696; pdf:https://europepmc.org/articles/PMC8152696?pdf=render
 37477360,https://doi.org/10.1097/ypg.0000000000000349,Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.,"Shamsutdinova D, Ajnakina O, Roberts A, Stahl D.",,Psychiatric genetics,2023,2023-07-04,Y,,,,"<h4>Objectives</h4>An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence.<h4>Methods</h4>Using a population-representative sample of adults aged ≥50 from English Longitudinal Study of Ageing ( n  = 5968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected.<h4>Results</h4>We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and 1.01, 95% CI 0.94-1.09).<h4>Conclusion</h4>Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.",,doi:https://doi.org/10.1097/YPG.0000000000000349; html:https://europepmc.org/articles/PMC10501355; pdf:https://europepmc.org/articles/PMC10501355?pdf=render
 34907415,https://doi.org/10.1093/ehjci/jeab266,Left atrial structure and function are associated with cardiovascular outcomes independent of left ventricular measures: a UK Biobank CMR study.,"Raisi-Estabragh Z, McCracken C, Condurache D, Aung N, Vargas JD, Naderi H, Munroe PB, Neubauer S, Harvey NC, Petersen SE.",,European heart journal. Cardiovascular Imaging,2022,2022-08-01,Y,Mortality; Atrial fibrillation; Stroke; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Left ventricle; Vascular Risk Factors; Cardiovascular Outcomes; Lef; T Atrium,,,"<h4>Aims</h4>We evaluated the associations of left atrial (LA) structure and function with prevalent and incident cardiovascular disease (CVD), independent of left ventricular (LV) metrics, in 25 896 UK Biobank participants.<h4>Methods and results</h4>We estimated the association of cardiovascular magnetic resonance (CMR) metrics [LA maximum volume (LAV), LA ejection fraction (LAEF), LV mass : LV end-diastolic volume ratio (LVM : LVEDV), global longitudinal strain, and LV global function index (LVGFI)] with vascular risk factors (hypertension, diabetes, high cholesterol, and smoking), prevalent and incident CVDs [atrial fibrillation (AF), stroke, ischaemic heart disease (IHD), myocardial infarction], all-cause mortality, and CVD mortality. We created uncorrelated CMR variables using orthogonal principal component analysis rotation. All five CMR metrics were simultaneously entered into multivariable regression models adjusted for sex, age, ethnicity, deprivation, education, body size, and physical activity. Lower LAEF was associated with diabetes, smoking, and all the prevalent and incident CVDs. Diabetes, smoking, and high cholesterol were associated with smaller LAV. Hypertension, IHD, AF (incident and prevalent), incident stroke, and CVD mortality were associated with larger LAV. LV and LA metrics were both independently informative in associations with prevalent disease, however LAEF showed the most consistent associations with incident CVDs. Lower LVGFI was associated with greater all-cause and CVD mortality. In secondary analyses, compared with LVGFI, LV ejection fraction showed similar but less consistent disease associations.<h4>Conclusion</h4>LA structure and function measures (LAEF and LAV) demonstrate significant associations with key prevalent and incident cardiovascular outcomes, independent of LV metrics. These measures have potential clinical utility for disease discrimination and outcome prediction.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab266/41764801/jeab266.pdf; doi:https://doi.org/10.1093/ehjci/jeab266; html:https://europepmc.org/articles/PMC9365306; pdf:https://europepmc.org/articles/PMC9365306?pdf=render
@@ -1177,12 +1177,12 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 35048949,https://doi.org/10.1093/eurjpc/zwac008,Light to moderate coffee consumption is associated with lower risk of death: a UK Biobank study.,"Simon J, Fung K, Raisi-Estabragh Z, Aung N, Khanji MY, Kolossváry M, Merkely B, Munroe PB, Harvey NC, Piechnik SK, Neubauer S, Petersen SE, Maurovich-Horvat P.",,European journal of preventive cardiology,2022,2022-05-01,N,Cardiac Magnetic Resonance; Cardiovascular Health; Coffee Consumption,,,"<h4>Aims</h4>To study the association of daily coffee consumption with all-cause and cardiovascular (CV) mortality and major CV outcomes. In a subgroup of participants who underwent cardiovascular magnetic resonance (CMR) imaging, we evaluated the association between regular coffee intake and cardiac structure and function.<h4>Methods and results</h4>UK Biobank participants without clinically manifested heart disease at the time of recruitment were included. Regular coffee intake was categorized into three groups: zero, light-to-moderate (0.5-3 cups/day), and high (>3 cups/day). In the multivariate analysis, we adjusted for the main CV risk factors. We included 468 629 individuals (56.2 ± 8.1 years, 44.2% male), of whom 22.1% did not consume coffee regularly, 58.4% had 0.5-3 cups per day, and 19.5% had >3 cups per day. Compared to non-coffee drinkers, light-to-moderate (0.5-3 cups per day) coffee drinking was associated with lower risk of all-cause mortality [multivariate hazard ratio (HR) = 0.88, 95% confidence interval (CI): 0.83-0.92; P < 0.001] and CV mortality (multivariate HR = 0.83, 95% CI: 0.74-0.94; P = 0.006), and incident stroke (multivariate HR = 0.79, 95% CI: 0.63-0.99 P = 0.037) after a median follow-up of 11 years. CMR data were available in 30 650 participants. Both light-to-moderate and high coffee consuming categories were associated with dose-dependent increased left and right ventricular end-diastolic, end-systolic and stroke volumes, and greater left ventricular mass.<h4>Conclusion</h4>Coffee consumption of up to three cups per day was associated with favourable CV outcomes. Regular coffee consumption was also associated with a likely healthy pattern of CMR metrics in keeping with the reverse of age-related cardiac alterations.",,pdf:https://academic.oup.com/eurjpc/article-pdf/29/6/982/43589594/zwac008.pdf; doi:https://doi.org/10.1093/eurjpc/zwac008
 29944675,https://doi.org/10.1371/journal.pone.0199026,"The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England.","Pujades-Rodriguez M, Assi V, Gonzalez-Izquierdo A, Wilkinson T, Schnier C, Sudlow C, Hemingway H, Whiteley WN.",,PloS one,2018,2018-06-26,Y,,The Human Phenome,,"<h4>Objectives</h4>Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR.<h4>Methods and findings</h4>A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer's disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer's disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20-1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24-12.75), falls (cOR = 2.36;95%CI:2.31-2.41), depression (cOR = 2.03; 95%CI:1.98-2.09) or anxiety (cOR = 1.27; 95%CI:1.23-1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54-1.58).<h4>Conclusions</h4>Most people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199026&type=printable; doi:https://doi.org/10.1371/journal.pone.0199026; html:https://europepmc.org/articles/PMC6019102; pdf:https://europepmc.org/articles/PMC6019102?pdf=render
 32282926,https://doi.org/10.1111/bjd.19122,"Partner bereavement and risk of chronic urticaria, alopecia areata and vitiligo: cohort studies in the UK and Denmark.","Wong AYS, Kjaersgaard A, Frøslev T, Forbes HJ, Mansfield KE, Silverwood RJ, Sørensen HT, Smeeth L, Schmidt SAJ, Langan SM.",,The British journal of dermatology,2020,2020-06-10,N,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19122; doi:https://doi.org/10.1111/bjd.19122
-35435219,https://doi.org/10.1093/ehjqcco/qcac016,Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.,"Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2022,2022-12-01,Y,Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology,,,"<h4>Aims</h4>We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.<h4>Methods and results</h4>We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).<h4>Conclusion</h4>We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render
 31827124,https://doi.org/10.1038/s41598-019-54849-w,Improving the odds of drug development success through human genomics: modelling study.,"Hingorani AD, Kuan V, Finan C, Kruger FA, Gaulton A, Chopade S, Sofat R, MacAllister RJ, Overington JP, Hemingway H, Denaxas S, Prieto D, Casas JP.",,Scientific reports,2019,2019-12-11,Y,,,,"Lack of efficacy in the intended disease indication is the major cause of clinical phase drug development failure. Explanations could include the poor external validity of pre-clinical (cell, tissue, and animal) models of human disease and the high false discovery rate (FDR) in preclinical science. FDR is related to the proportion of true relationships available for discovery (γ), and the type 1 (false-positive) and type 2 (false negative) error rates of the experiments designed to uncover them. We estimated the FDR in preclinical science, its effect on drug development success rates, and improvements expected from use of human genomics rather than preclinical studies as the primary source of evidence for drug target identification. Calculations were based on a sample space defined by all human diseases - the 'disease-ome' - represented as columns; and all protein coding genes - 'the protein-coding genome'- represented as rows, producing a matrix of unique gene- (or protein-) disease pairings. We parameterised the space based on 10,000 diseases, 20,000 protein-coding genes, 100 causal genes per disease and 4000 genes encoding druggable targets, examining the effect of varying the parameters and a range of underlying assumptions, on the inferences drawn. We estimated γ, defined mathematical relationships between preclinical FDR and drug development success rates, and estimated improvements in success rates based on human genomics (rather than orthodox preclinical studies). Around one in every 200 protein-disease pairings was estimated to be causal (γ = 0.005) giving an FDR in preclinical research of 92.6%, which likely makes a major contribution to the reported drug development failure rate of 96%. Observed success rate was only slightly greater than expected for a random pick from the sample space. Values for γ back-calculated from reported preclinical and clinical drug development success rates were also close to the a priori estimates. Substituting genome wide (or druggable genome wide) association studies for preclinical studies as the major information source for drug target identification was estimated to reverse the probability of late stage failure because of the more stringent type 1 error rate employed and the ability to interrogate every potential druggable target in the same experiment. Genetic studies conducted at much larger scale, with greater resolution of disease end-points, e.g. by connecting genomics and electronic health record data within healthcare systems has the potential to produce radical improvement in drug development success rate.","This study investigates the unreliability of target identification leading to low development sucess rates, inefficiency and escalating costs to healthcare users. The more targeted use of genomics couldimprove improved efficency.",pdf:https://www.nature.com/articles/s41598-019-54849-w.pdf; doi:https://doi.org/10.1038/s41598-019-54849-w; html:https://europepmc.org/articles/PMC6906499; pdf:https://europepmc.org/articles/PMC6906499?pdf=render
+35435219,https://doi.org/10.1093/ehjqcco/qcac016,Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.,"Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2022,2022-12-01,Y,Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology,,,"<h4>Aims</h4>We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.<h4>Methods and results</h4>We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).<h4>Conclusion</h4>We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render
 35765237,https://doi.org/10.1111/1747-0080.12746,An investigation of early enteral nutrition provision in major burn patients in Australia and New Zealand.,"Kurmis R, Nicholls C, Singer Y, Edgar DW, Wood FM, Gabbe BJ, Tracy LM.",,Nutrition & dietetics: the journal of the Dietitians Association of Australia,2022,2022-06-28,Y,Burns; Parenteral nutrition; enteral nutrition,,,"<h4>Aims</h4>Early enteral nutrition (provided within 24 h of admission) is the optimal form of nutritional support for major burn injuries. The aim of this study was to (i) audit early enteral nutrition practices, (ii) identify characteristics of patients who received early enteral nutrition, and (iii) investigate whether early enteral nutrition was associated with in-hospital outcomes.<h4>Methods</h4>An analysis of prospectively collected data from the Burns Registry of Australia and New Zealand was conducted. Specifically, this study focused on major burns patients (defined as burns affecting more than 20% and 15% total body surface area for adult paediatric patients, respectively) admitted to a specialist burn service between 1 July 2016 and 30 June 2019.<h4>Results</h4>Data from 474 major burns patients (88 paediatric patients) revealed 69% received early enteral nutrition. Paediatric patients who received early enteral nutrition were younger than their counterparts who did not receive the same support (p = 0.04). Adult patients who received early enteral nutrition sustained larger burns (p < 0.001). Early enteral nutrition was not associated with in-hospital mortality following major burn injury in adult patients in either unadjusted (p = 0.77) or confounder-adjusted (p = 0.69) analyses.<h4>Conclusions</h4>Approximately two-thirds of patients with major burn injuries received early enteral nutrition. Early enteral nutrition was not associated with in-hospital mortality following major burn injury. Further research should focus on modifiable reasons why major burns patients do not receive enteral nutrition within 24 h of admission.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796319; doi:https://doi.org/10.1111/1747-0080.12746; html:https://europepmc.org/articles/PMC9796319; pdf:https://europepmc.org/articles/PMC9796319?pdf=render
 36798028,https://doi.org/10.1002/ehf2.14308,Identifying patients at risk: multi-centre comparison of HeartMate 3 and HeartWare left ventricular assist devices.,"Numan L, Zimpfer D, Zadok OIB, Aarts E, Morshuis M, Guenther SPW, Riebandt J, Wiedemann D, Ramjankhan FZ, Oppelaar AM, Ben-Gal T, Ben-Avraham B, Asselbergs FW, Schramm R, Van Laake LW.",,ESC heart failure,2023,2023-02-16,Y,Mechanical Circulatory Support; Left Ventricular Assist Device; End-stage Heart Failure; Lvad; Centrifugal Continuous Flow Pump,,,"<h4>Aims</h4>Since the withdrawal of HeartWare (HVAD) from the global market, there is an ongoing discussion if and which patients require prophylactically exchange for a HeartMate 3 (HM3). Therefore, it is important to study outcome differences between HVAD and HM3 patients. Because centres differ in patient selection and standard of care, we performed a propensity score (PS)-based study including centres that implanted both devices and aimed to identify which HVAD patients are at highest risk.<h4>Methods and results</h4>We performed an international multi-centre study (n = 1021) including centres that implanted HVAD and HM3. PS-matching was performed using clinical variables and the implanting centre. Survival and complications were compared. As a sensitivity analysis, PS-adjusted Cox regression was performed. Landmark analysis with conditional survival >2 years was conducted to evaluate long-term survival differences. To identify which HVAD patients may benefit from a HM3 upgrade, Cox regression using pre-operative variables and their interaction with device type was performed. Survival was significantly better for HM3 patients (P < 0.01) in 458 matched patients, with a median follow-up of 23 months. Within the matched cohort, HM3 patients had a median age of 58 years, and 83% were male, 80% of the HVAD patients were male, with a median age of 59 years. PS-adjusted Cox regression confirmed a significantly better survival for HM3 patients when compared with HVAD, with a HR of 1.46 (95% confidence interval 1.14-1.85, P < 0.01). Pump thrombosis (P < 0.01) and ischaemic stroke (P < 0.01) occurred less in HM3 patients. No difference was found for haemorrhagic stroke, right heart failure, driveline infection, and major bleeding. Landmark-analysis confirmed a significant difference in conditional survival >2 years after implantation (P = 0.03). None of the pre-operative variable interactions in the Cox regression were significant.<h4>Conclusions</h4>HM3 patients have a significantly better survival and a lower incidence of ischaemic strokes and pump thrombosis than HVAD patients. This survival difference persisted after 2 years of implantation. Additional research using post-operative variables is warranted to identify which HVAD patients need an upgrade to HM3 or expedited transplantation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14308; doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render
-35477524,https://doi.org/10.1136/bmj-2022-070230,Development and validation of the symptom burden questionnaire for long covid (SBQ-LC): Rasch analysis.,"Hughes SE, Haroon S, Subramanian A, McMullan C, Aiyegbusi OL, Turner GM, Jackson L, Davies EH, Frost C, McNamara G, Price G, Matthews K, Camaradou J, Ormerod J, Walker A, Calvert MJ.",,BMJ (Clinical research ed.),2022,2022-04-27,Y,,,,"<h4>Objective</h4>To describe the development and validation of a novel patient reported outcome measure for symptom burden from long covid, the symptom burden questionnaire for long covid (SBQ-LC).<h4>Design</h4>Multiphase, prospective mixed methods study.<h4>Setting</h4>Remote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021.<h4>Participants</h4>13 adults (aged ≥18 years) with self-reported long covid and 10 clinicians evaluated content validity. 274 adults with long covid field tested the draft questionnaire.<h4>Main outcome measures</h4>Published systematic reviews informed development of SBQ-LC's conceptual framework and initial item pool. Thematic analysis of transcripts from cognitive debriefing interviews and online clinician surveys established content validity. Consensus discussions with the patient and public involvement group of the Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient reported outcomes and immunology to targeted therapies (TLC Study) confirmed face validity. Rasch analysis of field test data guided item and scale refinement and provided initial evidence of the SBQ-LC's measurement properties.<h4>Results</h4>SBQ-LC (version 1.0) is a modular instrument measuring patient reported outcomes and is composed of 17 independent scales with promising psychometric properties. Respondents rate their symptom burden during the past seven days using a dichotomous response or 4 point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that can be transformed to a linear (0-100) score. Higher scores represent higher symptom burden. After rating scale refinement and item reduction, all scales satisfied the Rasch model requirements for unidimensionality (principal component analysis of residuals: first residual contrast values <2.00 eigenvalue units) and item fit (outfit mean square values within 0.5 -1.5 logits). Rating scale categories were ordered with acceptable category fit statistics (outfit mean square values <2.0 logits). 14 item pairs had evidence of local dependency (residual correlation values >0.4). Across the 17 scales, person reliability ranged from 0.34 to 0.87, person separation ranged from 0.71 to 2.56, item separation ranged from 1.34 to 13.86, and internal consistency reliability (Cronbach's alpha) ranged from 0.56 to 0.91.<h4>Conclusions</h4>SBQ-LC (version 1.0) is a comprehensive patient reported outcome instrument developed using modern psychometric methods. It measures symptoms of long covid important to people with lived experience of the condition and may be used to evaluate the impact of interventions and inform best practice in clinical management.",,pdf:https://www.bmj.com/content/bmj/377/bmj-2022-070230.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070230; html:https://europepmc.org/articles/PMC9043395; pdf:https://europepmc.org/articles/PMC9043395?pdf=render
 31349307,https://doi.org/10.3233/shti190058,Phenotyping UK Electronic Health Records from 15 Million Individuals for Precision Medicine: The CALIBER Resource.,"Denaxas S, Gonzalez-Izquierdo A, Fitzpatrick N, Direk K, Hemingway H.",,Studies in health technology and informatics,2019,2019-07-01,N,Prognosis; Phenotyping; Data Linkage; Electronic Health Records; Biomedical Informatics,,,"Electronic health records (EHR) are increasingly being used for observational research at scale. In the UK, we have established the CALIBER research resource which utilizes national primary and hospital EHR data sources and enables researchers to create and validate longitudinal disease phenotypes at scale. In this work, we will describe the core components of the resource and provide results from three exemplar research studies on high-resolution epidemiology, disease risk prediction and subtype discovery which demonstrate both the opportunities and challenges of using EHR for research.",,doi:https://doi.org/10.3233/SHTI190058
+35477524,https://doi.org/10.1136/bmj-2022-070230,Development and validation of the symptom burden questionnaire for long covid (SBQ-LC): Rasch analysis.,"Hughes SE, Haroon S, Subramanian A, McMullan C, Aiyegbusi OL, Turner GM, Jackson L, Davies EH, Frost C, McNamara G, Price G, Matthews K, Camaradou J, Ormerod J, Walker A, Calvert MJ.",,BMJ (Clinical research ed.),2022,2022-04-27,Y,,,,"<h4>Objective</h4>To describe the development and validation of a novel patient reported outcome measure for symptom burden from long covid, the symptom burden questionnaire for long covid (SBQ-LC).<h4>Design</h4>Multiphase, prospective mixed methods study.<h4>Setting</h4>Remote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021.<h4>Participants</h4>13 adults (aged ≥18 years) with self-reported long covid and 10 clinicians evaluated content validity. 274 adults with long covid field tested the draft questionnaire.<h4>Main outcome measures</h4>Published systematic reviews informed development of SBQ-LC's conceptual framework and initial item pool. Thematic analysis of transcripts from cognitive debriefing interviews and online clinician surveys established content validity. Consensus discussions with the patient and public involvement group of the Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient reported outcomes and immunology to targeted therapies (TLC Study) confirmed face validity. Rasch analysis of field test data guided item and scale refinement and provided initial evidence of the SBQ-LC's measurement properties.<h4>Results</h4>SBQ-LC (version 1.0) is a modular instrument measuring patient reported outcomes and is composed of 17 independent scales with promising psychometric properties. Respondents rate their symptom burden during the past seven days using a dichotomous response or 4 point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that can be transformed to a linear (0-100) score. Higher scores represent higher symptom burden. After rating scale refinement and item reduction, all scales satisfied the Rasch model requirements for unidimensionality (principal component analysis of residuals: first residual contrast values <2.00 eigenvalue units) and item fit (outfit mean square values within 0.5 -1.5 logits). Rating scale categories were ordered with acceptable category fit statistics (outfit mean square values <2.0 logits). 14 item pairs had evidence of local dependency (residual correlation values >0.4). Across the 17 scales, person reliability ranged from 0.34 to 0.87, person separation ranged from 0.71 to 2.56, item separation ranged from 1.34 to 13.86, and internal consistency reliability (Cronbach's alpha) ranged from 0.56 to 0.91.<h4>Conclusions</h4>SBQ-LC (version 1.0) is a comprehensive patient reported outcome instrument developed using modern psychometric methods. It measures symptoms of long covid important to people with lived experience of the condition and may be used to evaluate the impact of interventions and inform best practice in clinical management.",,pdf:https://www.bmj.com/content/bmj/377/bmj-2022-070230.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070230; html:https://europepmc.org/articles/PMC9043395; pdf:https://europepmc.org/articles/PMC9043395?pdf=render
 31446406,https://doi.org/10.1136/bmjopen-2018-027577,Global health competencies in UK postgraduate medical training: a scoping review and curricular content analysis.,"Al-Shakarchi N, Obolensky L, Walpole S, Hemingway H, Banerjee A.",,BMJ open,2019,2019-08-24,Y,Global Health; Competencies; Postgraduate Medical Training,,,"<h4>Objective</h4>To assess global health (GH) training in all postgraduate medical education in the UK.<h4>Design</h4>Mixed methodology: scoping review and curricular content analysis using two GH competency frameworks.<h4>Setting and participants</h4>A scoping review (until December 2017) was used to develop a framework of GH competencies for doctors. National postgraduate medical training curricula were analysed against this and a prior framework for GH competencies. The number of core competencies addressed and/or appearing in each programme was recorded.<h4>Outcomes</h4>The scoping review identified eight relevant publications. A 16-competency framework was developed and, with a prior 5-competency framework, used to analyse each of 71 postgraduate medical curricula. Curricula were examined by a team of researchers and relevant learning outcomes were coded as one of the 5 or 16 core competencies. The number of core competencies in each programme was recorded.<h4>Results</h4>Using the 5-competency and 16-competency frameworks, 23 and 20, respectively, out of 71 programmes contained no global health competencies, most notably the Foundation Programme (equivalent to internship), a compulsory programme for UK medical graduates. Of a possible 16 competencies, the mean number across all 71 programmes was 1.73 (95% CI 1.42 to 2.04) and the highest number were in paediatrics and infectious diseases, each with five competencies. Of the 16 core competencies, global burden of disease and socioeconomic determinants of health were the two most cited with 47 and 35 citations, respectively. 8/16 competencies were not cited in any curriculum.<h4>Conclusions</h4>Equity of care and the challenges of practising in an increasingly globalised world necessitate GH competencies for all doctors. Across the whole of postgraduate training, the majority of UK doctors are receiving minimal or no training in GH. Our GH competency framework can be used to map and plan integration across postgraduate programmes.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e027577.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-027577; html:https://europepmc.org/articles/PMC6720244; pdf:https://europepmc.org/articles/PMC6720244?pdf=render
 37419925,https://doi.org/10.1038/s41467-023-38930-7,Optimal strategies for learning multi-ancestry polygenic scores vary across traits.,"Lehmann B, Mackintosh M, McVean G, Holmes C.",,Nature communications,2023,2023-07-07,Y,,,,"Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.",,pdf:https://www.nature.com/articles/s41467-023-38930-7.pdf; doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render
 32861307,https://doi.org/10.1016/s0140-6736(20)30930-2,Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data.,"Kaura A, Sterne JAC, Trickey A, Abbott S, Mulla A, Glampson B, Panoulas V, Davies J, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Johnson T, Francis DP, Shah AM, Perera D, Kharbanda R, Patel RS, Mayet J.",,"Lancet (London, England)",2020,2020-08-01,Y,,,,"<h4>Background</h4>Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI.<h4>Methods</h4>Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure.<h4>Findings</h4>Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82-89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2-4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55-0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48-0·93).<h4>Interpretation</h4>The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.<h4>Funding</h4>NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.",,pdf:http://www.thelancet.com/article/S0140673620309302/pdf; doi:https://doi.org/10.1016/S0140-6736(20)30930-2; html:https://europepmc.org/articles/PMC7456783; pdf:https://europepmc.org/articles/PMC7456783?pdf=render
@@ -1193,20 +1193,20 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 31558464,https://doi.org/10.1136/bmjopen-2019-033013,Long-term impact of giving antibiotics before skin incision versus after cord clamping on children born by caesarean section: protocol for a longitudinal study based on UK electronic health records.,"Šumilo D, Nirantharakumar K, Willis BH, Rudge G, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",,BMJ open,2019,2019-09-26,Y,Child; Asthma; Caesarean section; Eczema; Antibiotic Prophylaxis; Immune System Diseases,,,"<h4>Introduction</h4>In the UK, about a quarter of women give birth by caesarean section (CS) and are offered prophylactic broad-spectrum antibiotics to reduce the risk of maternal postpartum infection. In 2011, national guidance was changed from recommending antibiotics after the umbilical cord was cut to giving antibiotics prior to skin incision based on evidence that earlier administration reduces maternal infectious morbidity. Although antibiotics cross the placenta, there are no known short-term harms to the baby. This study aims to address the research gap on longer term impact of these antibiotics on child health.<h4>Methods and analysis</h4>A controlled interrupted time series study will use anonymised mother-baby linked routine electronic health records for children born during 2006-2018 recorded in UK primary care (The Health Improvement Network, THIN and Clinical Practice Research Datalink, CPRD) and secondary care (Hospital Episode Statistics, HES) databases. The primary outcomes of interest are asthma and eczema, two common allergy-related diseases in childhood. In-utero exposure to antibiotics immediately prior to CS will be compared with no exposure when given after cord clamping. The risk of outcomes in children delivered by CS will also be compared with a control cohort delivered vaginally to account for time effects. We will use all available data from THIN, CPRD and HES with estimated power of 80% and 90% to detect relative increase in risk of asthma of 16% and 18%, respectively at the 5% significance level.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the University of Birmingham Ethical Review Committee with scientific approvals obtained from the independent scientific advisory committees from the Medicines and Healthcare products Regulatory Agency for CPRD and the data provider, IQVIA for THIN. The results will be published in peer-reviewed journals, presented at national and international conferences and disseminated to stakeholders.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/9/e033013.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033013; html:https://europepmc.org/articles/PMC6773283; pdf:https://europepmc.org/articles/PMC6773283?pdf=render
 36692937,https://doi.org/10.2196/42866,The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.,"de Angel V, Adeleye F, Zhang Y, Cummins N, Munir S, Lewis S, Laporta Puyal E, Matcham F, Sun S, Folarin AA, Ranjan Y, Conde P, Rashid Z, Dobson R, Hotopf M.",,JMIR mental health,2023,2023-01-24,Y,Depression; Mobile phone; Anxiety; Smartphone; Mhealth; Mobile Health; Wearable Devices; Digital Health; Digital Phenotyping; Passive Sensing,,,"<h4>Background</h4>Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment.<h4>Objective</h4>A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement.<h4>Methods</h4>A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device.<h4>Results</h4>The overall retention rate was 60%. Higher-intensity treatment (χ<sup>2</sup><sub>1</sub>=4.6; P=.03) and higher baseline anxiety (t<sub>56.28</sub>=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t<sub>50.4</sub>=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list.<h4>Conclusions</h4>Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.",,pdf:https://mental.jmir.org/2023/1/e42866/PDF; doi:https://doi.org/10.2196/42866; html:https://europepmc.org/articles/PMC9906314
 34145643,https://doi.org/10.1111/jdv.17450,Describing the burden of the COVID-19 pandemic in people with psoriasis: findings from a global cross-sectional study.,"Mahil SK, Yates M, Yiu ZZN, Langan SM, Tsakok T, Dand N, Mason KJ, McAteer H, Meynell F, Coker B, Vincent A, Urmston D, Vesty A, Kelly J, Lancelot C, Moorhead L, Bachelez H, Capon F, Contreras CR, De La Cruz C, Di Meglio P, Gisondi P, Jullien D, Lambert J, Naldi L, Norton S, Puig L, Spuls P, Torres T, Warren RB, Waweru H, Weinman J, Brown MA, Galloway JB, Griffiths CM, Barker JN, Smith CH, PsoProtect study group.",,Journal of the European Academy of Dermatology and Venereology : JEADV,2021,2021-08-19,Y,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.17450; doi:https://doi.org/10.1111/jdv.17450; html:https://europepmc.org/articles/PMC8447018; pdf:https://europepmc.org/articles/PMC8447018?pdf=render
-37393610,https://doi.org/10.1016/j.xpro.2023.102392,Protocol for the automatic extraction of epidemiological information via a pre-trained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.",,STAR protocols,2023,2023-07-01,Y,Health Sciences; Clinical Protocol; Computer Sciences,,,"The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.<sup>1</sup> We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et al.<sup>2</sup>.",,doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?pdf=render
 32991065,https://doi.org/10.1111/dom.14203,Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study.,"Sainsbury C, Wang J, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, Chandan JS, Anand A, Cooper J, Okoth K, Subramanian A, Bangash MN, Taverner T, Hanif W, Ghosh S, Narendran P, Cheng KK, Marshall T, Gkoutos G, Toulis K, Thomas N, Tahrani A, Adderley NJ, Haroon S, Nirantharakumar K.",,"Diabetes, obesity & metabolism",2021,2020-10-19,Y,Type 2 diabetes; Dpp-4 Inhibitor; Pharmaco-epidemiology; Sglt2 Inhibitor; Antidiabetic Drug,,,"Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dom.14203; doi:https://doi.org/10.1111/dom.14203; html:https://europepmc.org/articles/PMC7537530; pdf:https://europepmc.org/articles/PMC7537530?pdf=render
-35144240,https://doi.org/10.2196/32543,Artificial Intelligence-Enabled Social Media Analysis for Pharmacovigilance of COVID-19 Vaccinations in the United Kingdom: Observational Study.,"Hussain Z, Sheikh Z, Tahir A, Dashtipour K, Gogate M, Sheikh A, Hussain A.",,JMIR public health and surveillance,2022,2022-05-27,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19,,,"<h4>Background</h4>The rollout of vaccines for COVID-19 in the United Kingdom started in December 2020. Uptake has been high, and there has been a subsequent reduction in infections, hospitalizations, and deaths among vaccinated individuals. However, vaccine hesitancy remains a concern, in particular relating to adverse effects following immunization (AEFIs). Social media analysis has the potential to inform policy makers about AEFIs being discussed by the public as well as public attitudes toward the national immunization campaign.<h4>Objective</h4>We sought to assess the frequency and nature of AEFI-related mentions on social media in the United Kingdom and to provide insights on public sentiments toward COVID-19 vaccines.<h4>Methods</h4>We extracted and analyzed over 121,406 relevant Twitter and Facebook posts, from December 8, 2020, to April 30, 2021. These were thematically filtered using a 2-step approach, initially using COVID-19-related keywords and then using vaccine- and manufacturer-related keywords. We identified AEFI-related keywords and modeled their word frequency to monitor their trends over 2-week periods. We also adapted and utilized our recently developed hybrid ensemble model, which combines state-of-the-art lexicon rule-based and deep learning-based approaches, to analyze sentiment trends relating to the main vaccines available in the United Kingdom.<h4>Results</h4>Our COVID-19 AEFI search strategy identified 46,762 unique Facebook posts by 14,346 users and 74,644 tweets (excluding retweets) by 36,446 users over the 4-month period. We identified an increasing trend in the number of mentions for each AEFI on social media over the study period. The most frequent AEFI mentions were found to be symptoms related to appetite (n=79,132, 14%), allergy (n=53,924, 9%), injection site (n=56,152, 10%), and clots (n=43,907, 8%). We also found some rarely reported AEFIs such as Bell palsy (n=11,909, 2%) and Guillain-Barre syndrome (n=9576, 2%) being discussed as frequently as more well-known side effects like headache (n=10,641, 2%), fever (n=12,707, 2%), and diarrhea (n=16,559, 3%). Overall, we found public sentiment toward vaccines and their manufacturers to be largely positive (58%), with a near equal split between negative (22%) and neutral (19%) sentiments. The sentiment trend was relatively steady over time and had minor variations, likely based on political and regulatory announcements and debates.<h4>Conclusions</h4>The most frequently discussed COVID-19 AEFIs on social media were found to be broadly consistent with those reported in the literature and by government pharmacovigilance. We also detected potential safety signals from our analysis that have been detected elsewhere and are currently being investigated. As such, we believe our findings support the use of social media analysis to provide a complementary data source to conventional knowledge sources being used for pharmacovigilance purposes.",,pdf:https://publichealth.jmir.org/2022/5/e32543/PDF; doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729
+37393610,https://doi.org/10.1016/j.xpro.2023.102392,Protocol for the automatic extraction of epidemiological information via a pre-trained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.",,STAR protocols,2023,2023-07-01,Y,Health Sciences; Clinical Protocol; Computer Sciences,,,"The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.<sup>1</sup> We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et al.<sup>2</sup>.",,doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?pdf=render
 33328048,https://doi.org/10.1016/s2589-7500(20)30218-1,Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension.,"Liu X, Cruz Rivera S, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",,The Lancet. Digital health,2020,2020-09-09,N,,,,"The CONSORT 2010 statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders), and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,pdf:http://www.thelancet.com/article/S2589750020302181/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30218-1; html:https://europepmc.org/articles/PMC8183333; pdf:https://europepmc.org/articles/PMC8183333?pdf=render; doi:https://doi.org/10.1016/s2589-7500(20)30218-1
-35748342,https://doi.org/10.1093/ije/dyac130,Linkage of multiple electronic health record datasets using a 'spine linkage' approach compared with all 'pairwise linkages'.,"Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K.",,International journal of epidemiology,2023,2023-02-01,Y,Electronic Health Records; Record Linkage; Pairwise Linkage; Spine Linkage Approach,,,"<h4>Background</h4>Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all 'pairwise linkages'-linking each dataset to every other dataset-is the most inclusive, but resource-intensive, approach. The 'spine' approach links each dataset to a designated 'spine dataset', reducing the number of linkages, but potentially reducing linkage quality.<h4>Methods</h4>We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31 October 2013 and 30 April 2018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery.<h4>Results</h4>The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15 826 patients, equating to 98.3% of the 16 100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14 509 patients (90.0% compared with pairwise linkage).<h4>Conclusion</h4>Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac130/44245961/dyac130.pdf; doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render
+35144240,https://doi.org/10.2196/32543,Artificial Intelligence-Enabled Social Media Analysis for Pharmacovigilance of COVID-19 Vaccinations in the United Kingdom: Observational Study.,"Hussain Z, Sheikh Z, Tahir A, Dashtipour K, Gogate M, Sheikh A, Hussain A.",,JMIR public health and surveillance,2022,2022-05-27,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19,,,"<h4>Background</h4>The rollout of vaccines for COVID-19 in the United Kingdom started in December 2020. Uptake has been high, and there has been a subsequent reduction in infections, hospitalizations, and deaths among vaccinated individuals. However, vaccine hesitancy remains a concern, in particular relating to adverse effects following immunization (AEFIs). Social media analysis has the potential to inform policy makers about AEFIs being discussed by the public as well as public attitudes toward the national immunization campaign.<h4>Objective</h4>We sought to assess the frequency and nature of AEFI-related mentions on social media in the United Kingdom and to provide insights on public sentiments toward COVID-19 vaccines.<h4>Methods</h4>We extracted and analyzed over 121,406 relevant Twitter and Facebook posts, from December 8, 2020, to April 30, 2021. These were thematically filtered using a 2-step approach, initially using COVID-19-related keywords and then using vaccine- and manufacturer-related keywords. We identified AEFI-related keywords and modeled their word frequency to monitor their trends over 2-week periods. We also adapted and utilized our recently developed hybrid ensemble model, which combines state-of-the-art lexicon rule-based and deep learning-based approaches, to analyze sentiment trends relating to the main vaccines available in the United Kingdom.<h4>Results</h4>Our COVID-19 AEFI search strategy identified 46,762 unique Facebook posts by 14,346 users and 74,644 tweets (excluding retweets) by 36,446 users over the 4-month period. We identified an increasing trend in the number of mentions for each AEFI on social media over the study period. The most frequent AEFI mentions were found to be symptoms related to appetite (n=79,132, 14%), allergy (n=53,924, 9%), injection site (n=56,152, 10%), and clots (n=43,907, 8%). We also found some rarely reported AEFIs such as Bell palsy (n=11,909, 2%) and Guillain-Barre syndrome (n=9576, 2%) being discussed as frequently as more well-known side effects like headache (n=10,641, 2%), fever (n=12,707, 2%), and diarrhea (n=16,559, 3%). Overall, we found public sentiment toward vaccines and their manufacturers to be largely positive (58%), with a near equal split between negative (22%) and neutral (19%) sentiments. The sentiment trend was relatively steady over time and had minor variations, likely based on political and regulatory announcements and debates.<h4>Conclusions</h4>The most frequently discussed COVID-19 AEFIs on social media were found to be broadly consistent with those reported in the literature and by government pharmacovigilance. We also detected potential safety signals from our analysis that have been detected elsewhere and are currently being investigated. As such, we believe our findings support the use of social media analysis to provide a complementary data source to conventional knowledge sources being used for pharmacovigilance purposes.",,pdf:https://publichealth.jmir.org/2022/5/e32543/PDF; doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729
 32929109,https://doi.org/10.1038/s41598-020-72060-0,A data-driven typology of asthma medication adherence using cluster analysis.,"Tibble H, Chan A, Mitchell EA, Horne E, Doudesis D, Horne R, Mizani MA, Sheikh A, Tsanas A.",,Scientific reports,2020,2020-09-14,Y,,,,"Asthma preventer medication non-adherence is strongly associated with poor asthma control. One-dimensional measures of adherence may ignore clinically important patterns of medication-taking behavior. We sought to construct a data-driven multi-dimensional typology of medication non-adherence in children with asthma. We analyzed data from an intervention study of electronic inhaler monitoring devices, comprising 211 patients yielding 35,161 person-days of data. Five adherence measures were extracted: the percentage of doses taken, the percentage of days on which zero doses were taken, the percentage of days on which both doses were taken, the number of treatment intermissions per 100 study days, and the duration of treatment intermissions per 100 study days. We applied principal component analysis on the measures and subsequently applied k-means to determine cluster membership. Decision trees identified the measure that could predict cluster assignment with the highest accuracy, increasing interpretability and increasing clinical utility. We demonstrate the use of adherence measures towards a three-group categorization of medication non-adherence, which succinctly describes the diversity of patient medication taking patterns in asthma. The percentage of prescribed doses taken during the study contributed to the prediction of cluster assignment most accurately (84% in out-of-sample data).",,pdf:https://www.nature.com/articles/s41598-020-72060-0.pdf; doi:https://doi.org/10.1038/s41598-020-72060-0; html:https://europepmc.org/articles/PMC7490405; pdf:https://europepmc.org/articles/PMC7490405?pdf=render
+35748342,https://doi.org/10.1093/ije/dyac130,Linkage of multiple electronic health record datasets using a 'spine linkage' approach compared with all 'pairwise linkages'.,"Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K.",,International journal of epidemiology,2023,2023-02-01,Y,Electronic Health Records; Record Linkage; Pairwise Linkage; Spine Linkage Approach,,,"<h4>Background</h4>Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all 'pairwise linkages'-linking each dataset to every other dataset-is the most inclusive, but resource-intensive, approach. The 'spine' approach links each dataset to a designated 'spine dataset', reducing the number of linkages, but potentially reducing linkage quality.<h4>Methods</h4>We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31 October 2013 and 30 April 2018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery.<h4>Results</h4>The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15 826 patients, equating to 98.3% of the 16 100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14 509 patients (90.0% compared with pairwise linkage).<h4>Conclusion</h4>Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac130/44245961/dyac130.pdf; doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render
 35028631,https://doi.org/10.1016/s2666-7568(21)00281-6,The importance of blood pressure thresholds versus predicted cardiovascular risk on subsequent rates of cardiovascular disease: a cohort study in English primary care.,"Herrett E, Strongman H, Gadd S, Tomlinson L, Nitsch D, Bhaskaran K, Williamson E, van Staa T, Sofat R, Timmis A, Wells S, Smeeth L, Jackson R.",,The lancet. Healthy longevity,2022,2022-01-01,Y,,,,"<h4>Background</h4>For five decades, blood pressure lowering treatment has been recommended for patients with hypertension (currently defined as blood pressure of ≥140/90 mm Hg). In the past 20 years, guidelines for treatment began incorporating predicted absolute cardiovascular disease risk (predicted risk) and reducing blood pressure thresholds. The blood pressure threshold at which to start treatment has become a secondary consideration in some countries. We aimed to provide descriptive data to assess the relative importance of blood pressure thresholds versus predicted risk on the subsequent rate of cardiovascular disease to inform treatment decisions.<h4>Methods</h4>In this English population-based cohort study, we used linked data from the Clinical Practice Research Datalink (CPRD) GOLD, Hospital Episode Statistics Admitted Patient Care, and the Office for National Statistics mortality data, and area-based deprivation indices (Townsend scores). Eligible patients were aged 30-79 years on Jan 1, 2011 (cohort entry date) and could be linked to hospital, mortality, and deprivation data. Patients were followed up until death, end of CPRD follow-up, or Nov 31, 2018. We examined three outcomes: cardiovascular disease, markers of potential target organ damage, and incident dementia without a known cause. The rate of each outcome was estimated and stratified by systolic blood pressure and predicted 10-year risk of cardiovascular disease (QRISK2 algorithm).<h4>Findings</h4>Between Jan 1, 2011, and Nov 31, 2018, 1 098 991 patients were included in the cohort and followed up for a median of 4·3 years (IQR 2·6-6·0; total follow-up of 4·6 million person-years). Median age at entry was 52 years (IQR 42-62) and 629 711 (57·3%) patients were female. There were 51 996 cardiovascular disease events and the overall rate of cardiovascular disease was 11·2 per 1000 person-years (95% CI 11·1-11·3). Median QRISK2 10-year predicted risk was 4·6% (IQR 1·4-12·0) and mean systolic blood pressure before cohort entry was 129·1 mm Hg (SD 15·7). Within strata of predicted risk, the effect of increasing systolic blood pressure on outcomes was small. For example, in the group with 10·0-19·9% predicted risk, rates of all cardiovascular disease rose from 20·1 to 23·6 per 1000 person-years between systolic blood pressures less than 110 mm Hg and 180 and higher mm Hg. But among patients with systolic blood pressure 140·0-149·9 mm Hg, rates rose from 6·9 to 52·3 per 1000 person-years between those with less than 10·0% risk and those with 30·0% or higher predicted risk.<h4>Interpretation</h4>For a wide range of blood pressures, the rate of cardiovascular disease and effectiveness of blood pressure drug treatment was mainly determined by predicted risk, with blood pressure thresholds 140/90 mm Hg or 160/100 mm Hg-ubiquitous in most countries-adding little useful information. When medium-term predicted risk is low, there is no urgency to initiate drug treatment, allowing time to attempt non-pharmacological blood pressure reduction.<h4>Funding</h4>National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2666756821002816/pdf; doi:https://doi.org/10.1016/S2666-7568(21)00281-6; html:https://europepmc.org/articles/PMC8732286
-37563195,https://doi.org/10.1038/s41598-023-38880-6,Locational memory of macrovessel vascular cells is transcriptionally imprinted.,"Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.",,Scientific reports,2023,2023-08-10,Y,,,,"Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.",,pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render
 36344532,https://doi.org/10.1038/s41598-022-21663-w,Atrial fibrillation prediction by combining ECG markers and CMR radiomics.,"Pujadas ER, Raisi-Estabragh Z, Szabo L, Morcillo CI, Campello VM, Martin-Isla C, Vago H, Merkely B, Harvey NC, Petersen SE, Lekadir K.",,Scientific reports,2022,2022-11-07,Y,,,,"Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with a higher risk of important adverse health outcomes such as stroke and death. AF is linked to distinct electro-anatomic alterations. The main tool for AF diagnosis is the Electrocardiogram (ECG). However, an ECG recorded at a single time point may not detect individuals with paroxysmal AF. In this study, we developed machine learning models for discrimination of prevalent AF using a combination of image-derived radiomics phenotypes and ECG features. Thus, we characterize the phenotypes of prevalent AF in terms of ECG and imaging alterations. Moreover, we explore sex-differential remodelling by building sex-specific models. Our integrative model including radiomics and ECG together resulted in a better performance than ECG alone, particularly in women. ECG had a lower performance in women than men (AUC: 0.77 vs 0.88, p < 0.05) but adding radiomics features, the accuracy of the model was able to improve significantly. The sensitivity also increased considerably in women by adding the radiomics (0.68 vs 0.79, p < 0.05) having a higher detection of AF events. Our findings provide novel insights into AF-related electro-anatomic remodelling and its variations by sex. The integrative radiomics-ECG model also presents a potential novel approach for earlier detection of AF.",,pdf:https://www.nature.com/articles/s41598-022-21663-w.pdf; doi:https://doi.org/10.1038/s41598-022-21663-w; html:https://europepmc.org/articles/PMC9640662; pdf:https://europepmc.org/articles/PMC9640662?pdf=render
+37563195,https://doi.org/10.1038/s41598-023-38880-6,Locational memory of macrovessel vascular cells is transcriptionally imprinted.,"Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.",,Scientific reports,2023,2023-08-10,Y,,,,"Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.",,pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render
 36576811,https://doi.org/10.1001/jamacardio.2022.4466,Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.,"Marston NA, Pirruccello JP, Melloni GEM, Koyama S, Kamanu FK, Weng LC, Roselli C, Kamatani Y, Komuro I, Aragam KG, Butterworth AS, Ito K, Lubitz SA, Ellinor PT, Sabatine MS, Ruff CT.",,JAMA cardiology,2023,2023-02-01,N,,,,"<h4>Importance</h4>The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.<h4>Objective</h4>To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.<h4>Design, setting, and participants</h4>This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022.<h4>Exposures</h4>Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), or high risk (≥20%).<h4>Main outcomes and measures</h4>Myocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death).<h4>Results</h4>A total of 330 201 patients (median [IQR] age, 57 [40-74] years; 189 107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; 95% CI, 1.56-1.89; age 50-60 years: HR, 1.46; 95% CI, 1.38-1.53; age >60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy.<h4>Conclusions and relevance</h4>Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.",,doi:https://doi.org/10.1001/jamacardio.2022.4466
 34849869,https://doi.org/10.1093/gigascience/giab076,An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.,"Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, NCCID Collaborative.",,GigaScience,2021,2021-11-01,Y,Medical imaging; Machine Learning; Thoracic Imaging; Covid-19; Sars-cov2,,,"<h4>Background</h4>The National COVID-19 Chest Imaging Database (NCCID) is a centralized database containing mainly chest X-rays and computed tomography scans from patients across the UK. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and the development of machine learning technologies that will improve care for patients hospitalized with a severe COVID-19 infection. This article introduces the training dataset, including a snapshot analysis covering the completeness of clinical data, and availability of image data for the various use-cases (diagnosis, prognosis, longitudinal risk). An additional cohort analysis measures how well the NCCID represents the wider COVID-19-affected UK population in terms of geographic, demographic, and temporal coverage.<h4>Findings</h4>The NCCID offers high-quality DICOM images acquired across a variety of imaging machinery; multiple time points including historical images are available for a subset of patients. This volume and variety make the database well suited to development of diagnostic/prognostic models for COVID-associated respiratory conditions. Historical images and clinical data may aid long-term risk stratification, particularly as availability of comorbidity data increases through linkage to other resources. The cohort analysis revealed good alignment to general UK COVID-19 statistics for some categories, e.g., sex, whilst identifying areas for improvements to data collection methods, particularly geographic coverage.<h4>Conclusion</h4>The NCCID is a growing resource that provides researchers with a large, high-quality database that can be leveraged both to support the response to the COVID-19 pandemic and as a test bed for building clinically viable medical imaging models.",,pdf:https://academic.oup.com/gigascience/article-pdf/10/11/giab076/41395024/giab076.pdf; doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render
-36701266,https://doi.org/10.1371/journal.pmed.1004036,"Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.","Vinther JL, Cadman T, Avraam D, Ekstrøm CT, Sørensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, Iñiguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fernández-Barrés S, Turvey S, Santos S, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.",,PLoS medicine,2023,2023-01-26,Y,,,,"<h4>Background</h4>Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.<h4>Methods and findings</h4>We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.<h4>Conclusions</h4>This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render
 34306597,https://doi.org/10.1155/2021/6663884,Automatic Prediction of Recurrence of Major Cardiovascular Events: A Text Mining Study Using Chest X-Ray Reports.,"Bagheri A, Groenhof TKJ, Asselbergs FW, Haitjema S, Bots ML, Veldhuis WB, de Jong PA, Oberski DL.",,Journal of healthcare engineering,2021,2021-07-09,Y,,,,"<h4>Methods</h4>We used EHR data of patients included in the Second Manifestations of ARTerial disease (SMART) study. We propose a deep learning-based multimodal architecture for our text mining pipeline that integrates neural text representation with preprocessed clinical predictors for the prediction of recurrence of major cardiovascular events in cardiovascular patients. Text preprocessing, including cleaning and stemming, was first applied to filter out the unwanted texts from X-ray radiology reports. Thereafter, text representation methods were used to numerically represent unstructured radiology reports with vectors. Subsequently, these text representation methods were added to prediction models to assess their clinical relevance. In this step, we applied logistic regression, support vector machine (SVM), multilayer perceptron neural network, convolutional neural network, long short-term memory (LSTM), and bidirectional LSTM deep neural network (BiLSTM).<h4>Results</h4>We performed various experiments to evaluate the added value of the text in the prediction of major cardiovascular events. The two main scenarios were the integration of radiology reports (1) with classical clinical predictors and (2) with only age and sex in the case of unavailable clinical predictors. In total, data of 5603 patients were used with 5-fold cross-validation to train the models. In the first scenario, the multimodal BiLSTM (MI-BiLSTM) model achieved an area under the curve (AUC) of 84.7%, misclassification rate of 14.3%, and F1 score of 83.8%. In this scenario, the SVM model, trained on clinical variables and bag-of-words representation, achieved the lowest misclassification rate of 12.2%. In the case of unavailable clinical predictors, the MI-BiLSTM model trained on radiology reports and demographic (age and sex) variables reached an AUC, F1 score, and misclassification rate of 74.5%, 70.8%, and 20.4%, respectively.<h4>Conclusions</h4>Using the case study of routine care chest X-ray radiology reports, we demonstrated the clinical relevance of integrating text features and classical predictors in our text mining pipeline for cardiovascular risk prediction. The MI-BiLSTM model with word embedding representation appeared to have a desirable performance when trained on text data integrated with the clinical variables from the SMART study. Our results mined from chest X-ray reports showed that models using text data in addition to laboratory values outperform those using only known clinical predictors.",,pdf:https://downloads.hindawi.com/journals/jhe/2021/6663884.pdf; doi:https://doi.org/10.1155/2021/6663884; html:https://europepmc.org/articles/PMC8285182; pdf:https://europepmc.org/articles/PMC8285182?pdf=render
 30183734,https://doi.org/10.1371/journal.pone.0202359,Time spent at blood pressure target and the risk of death and cardiovascular diseases.,"Chung SC, Pujades-Rodriguez M, Duyx B, Denaxas SC, Pasea L, Hingorani A, Timmis A, Williams B, Hemingway H.",,PloS one,2018,2018-09-05,Y,,The Human Phenome,,"<h4>Background</h4>The time a patient spends with blood pressure at target level is an intuitive measure of successful BP management, but population studies on its effectiveness are as yet unavailable.<h4>Method</h4>We identified a population-based cohort of 169,082 individuals with newly identified high blood pressure who were free of cardiovascular disease from January 1997 to March 2010. We used 1.64 million clinical blood pressure readings to calculate the TIme at TaRgEt (TITRE) based on current target blood pressure levels.<h4>Result</h4>The median (Inter-quartile range) TITRE among all patients was 2.8 (0.3, 5.6) months per year, only 1077 (0.6%) patients had a TITRE ≥11 months. Compared to people with a 0% TITRE, patients with a TITRE of 3-5.9 months, and 6-8.9 months had 75% and 78% lower odds of the composite of cardiovascular death, myocardial infarction and stroke (adjusted odds ratios, 0.25 (95% confidence interval: 0.21, 0.31) and 0.22 (0.17, 0.27), respectively). These associations were consistent for heart failure and any cardiovascular disease and death (comparing a 3-5.9 month to 0% TITRE, 63% and 60% lower in odds, respectively), among people who did or did not have blood pressure 'controlled' on a single occasion during the first year of follow-up, and across groups defined by number of follow-up BP measure categories.<h4>Conclusion</h4>Based on the current frequency of measurement of blood pressure this study suggests that few newly hypertensive patients sustained a complete, year-round on target blood pressure over time. The inverse associations between a higher TITRE and lower risk of incident cardiovascular diseases were independent of widely-used blood pressure 'control' indicators. Randomized trials are required to evaluate interventions to increase a person's time spent at blood pressure target.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202359&type=printable; doi:https://doi.org/10.1371/journal.pone.0202359; html:https://europepmc.org/articles/PMC6124703; pdf:https://europepmc.org/articles/PMC6124703?pdf=render
+36701266,https://doi.org/10.1371/journal.pmed.1004036,"Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.","Vinther JL, Cadman T, Avraam D, Ekstrøm CT, Sørensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, Iñiguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fernández-Barrés S, Turvey S, Santos S, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.",,PLoS medicine,2023,2023-01-26,Y,,,,"<h4>Background</h4>Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.<h4>Methods and findings</h4>We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.<h4>Conclusions</h4>This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render
 35536740,https://doi.org/10.1136/bmjopen-2021-052884,Gaps in antihypertensive and statin treatments and benefits of optimisation: a modelling study in a 1 million ethnically diverse urban population in UK.,"Wu R, Rison SCG, Raisi-Estabragh Z, Dostal I, Carvalho C, Robson J, Mihaylova B.",,BMJ open,2021,2021-12-30,Y,Hypertension; Preventive Medicine; Ischaemic Heart Disease; Primary Care; Health Policy; Quality In Health Care,,,"<h4>Objectives</h4>To characterise gaps in antihypertensive treatment in people with hypertension and statin treatment in people with cardiovascular diseases (CVD) in a large urban population and quantify the health and economic impacts of their optimisation.<h4>Design</h4>A cross-sectional population study and a long-term CVD decision model.<h4>Setting</h4>Primary care, UK.<h4>Participants</h4>All adults with diagnosed hypertension or CVD in a population of about 1 million people, served by 123 primary care practices in London, UK in 2019.<h4>Interventions</h4>Following UK clinical guidelines, all adults with diagnosed hypertension were categorised into optimal, suboptimal and untreated groups with respect to their antihypertensive treatment, and all adults with diagnosed CVD were categorised in the same manner with respect to their statin treatment.<h4>Outcomes</h4>Proportion of patients suboptimally treated or untreated. Projected cardiovascular events avoided, years and quality-adjusted life years (QALYs) gained and healthcare costs saved with optimised treatments.<h4>Results</h4>21 954 of the 91 828 adults with hypertension (24%; mean age 59 years; 49% women) and 9062 of the 23 723 adults with CVD (38%; mean age 69 years; 43% women) were not optimally treated with antihypertensive or statin treatment, respectively. Per 1000 additional patients optimised over 5 years, hypertension treatment is projected to prevent 25 (95% CI 16 to 32) major vascular events (MVEs) and 7 (3 to 10) vascular deaths, statin treatment, 28 (22 to 33) MVEs and 6 (4 to 7) vascular deaths. Over their lifespan, a patient with uncontrolled hypertension aged 60-69 years is projected to gain 0.64 (95% CI 0.36 to 0.87) QALYs with optimised hypertension treatment, and a similarly aged patient with previous CVD not optimally treated with statin is projected to gain 0.3 (0.24 to 0.37) QALYs with optimised statin treatment. In both cases, the hospital cost savings minus extra medication costs were about £1100 per person over remaining lifespan.<h4>Conclusions</h4>Optimising cardiovascular treatments can cost-effectively reduce cardiovascular risk and improve life expectancy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/12/e052884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052884; html:https://europepmc.org/articles/PMC8719215; pdf:https://europepmc.org/articles/PMC8719215?pdf=render
 35796550,https://doi.org/10.1093/hmg/ddac153,The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.,"Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,Human molecular genetics,2022,2022-11-01,N,,,,"Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.",,pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153
 35579056,https://doi.org/10.1111/eci.13814,Lifestyle changes and kidney function: A 10-year follow-up study in patients with manifest cardiovascular disease.,"Østergaard HB, Demirhan I, Westerink J, Verhaar MC, Asselbergs FW, de Borst GJ, Kappelle LJ, Visseren FLJ, van der Leeuw J, UCC-SMART studygroup.",,European journal of clinical investigation,2022,2022-05-27,Y,Cardiovascular disease; Lifestyle Factors; Kidney Function Decline,,,"<h4>Background</h4>Patients with cardiovascular disease (CVD) are at higher risk of kidney function decline. The current study aimed to examine the association of lifestyle changes with kidney function decline in patients with manifest CVD.<h4>Methods</h4>A total of 2260 patients from the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease cohort with manifest CVD who returned for a follow-up visit after a median of 9.9 years were included. The relation between change in lifestyle factors (smoking, alcohol consumption, physical activity and obesity) and change in kidney function (eGFR and uACR) was assessed using linear regression models.<h4>Results</h4>An increase in body mass index (β -2.81; 95% CI -3.98; -1.63 per 5 kg/m<sup>2</sup> ) and for men also an increase in waist circumference (β -0.87; 95% CI -1.28; -0.47 per 5 cm) were significantly associated with a steeper decline in eGFR over 10 years. Continuing smoking (β -2.44, 95% CI -4.43; -0.45) and recent smoking cessation during follow-up (β -3.27; 95% CI -5.20; -1.34) were both associated with a steeper eGFR decline compared to patients who remained as non- or previous smokers from baseline. No significant association was observed between physical exercise or alcohol consumption and kidney function decline. No significant relation between any lifestyle factor and change in uACR was observed.<h4>Conclusions</h4>In patients with CVD, continuing smoking, recent smoking cessation and an increase in obesity markers were related to a steeper kidney function decline. Although no definite conclusions from this study can be drawn, the results support the importance of encouraging weight loss and smoking cessation in high-risk patients as a means of slowing down kidney function decline.",,pdf:https://discovery.ucl.ac.uk/10151289/1/Asselbergs_Lifestyle%20changes%20and%20kidney%20function_AOP.pdf; doi:https://doi.org/10.1111/eci.13814; html:https://europepmc.org/articles/PMC9540114; pdf:https://europepmc.org/articles/PMC9540114?pdf=render
@@ -1219,13 +1219,13 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI
 35804579,https://doi.org/10.3390/ani12131679,Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model.,"Gaar-Humphreys KR, Spanjersberg TCF, Santarelli G, Grinwis GCM, Szatmári V, Roelen BAJ, Vink A, van Tintelen JP, Asselbergs FW, Fieten H, Harakalova M, van Steenbeek FG.",,Animals : an open access journal from MDPI,2022,2022-06-29,Y,cardiovascular; Human Induced Pluripotent Stem Cells; Fibrofatty Infiltration; Attenuated Wavy Fibers; Canine Induced Pluripotent Stem Cells,,,"Cardiac disease is a leading cause of death for both humans and dogs. Genetic cardiomyopathies, including dilated cardiomyopathy (DCM), account for a proportion of these cases in both species. Patients may suffer from ventricular enlargement and systolic dysfunction resulting in congestive heart failure and ventricular arrhythmias with high risk for sudden cardiac death. Although canine DCM has similar disease progression and subtypes as in humans, only a few candidate genes have been found to be associated with DCM while the genetic background of human DCM has been more thoroughly studied. Additionally, experimental disease models using induced pluripotent stem cells have been widely adopted in the study of human genetic cardiomyopathy but have not yet been fully adapted for the in-depth study of canine genetic cardiomyopathies. The clinical presentation of DCM is extremely heterogeneous for both species with differences occurring based on sex predisposition, age of onset, and the rate of disease progression. Both genetic predisposition and environmental factors play a role in disease development which are identical in dogs and humans in contrast to other experimental animals. Interestingly, different dog breeds have been shown to develop distinct DCM phenotypes, and this presents a unique opportunity for modeling as there are multiple breed-specific models for DCM with less genetic variance than human DCM. A better understanding of DCM in dogs has the potential for improved selection for breeding and could lead to better overall care and treatment for human and canine DCM patients. At the same time, progress in research made for human DCM can have a positive impact on the care given to dogs affected by DCM. Therefore, this review will analyze the feasibility of canines as a naturally occurring bidirectional disease model for DCM in both species. The histopathology of the myocardium in canine DCM will be evaluated in three different breeds compared to control tissue, and the known genetics that contributes to both canine and human DCM will be summarized. Lastly, the prospect of canine iPSCs as a novel method to uncover the contributions of genetic variants to the pathogenesis of canine DCM will be introduced along with the applications for disease modeling and treatment.",,pdf:https://www.mdpi.com/2076-2615/12/13/1679/pdf?version=1656561768; doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?pdf=render
 37670953,https://doi.org/10.23889/ijpds.v8i1.2113,Lessons learned from using linked administrative data to evaluate the Family Nurse Partnership in England and Scotland.,"Cavallaro FL, Cannings-John R, Lugg-Widger F, Gilbert R, Kennedy E, Kendall S, Robling M, Harron KL.",,International journal of population data science,2023,2023-05-11,Y,Evaluation; Early Years; Administrative Data; Adolescent Motherhood; Cross-Sectoral Linkage,,,"<h4>Introduction</h4>""Big data"" - including linked administrative data - can be exploited to evaluate interventions for maternal and child health, providing time- and cost-effective alternatives to randomised controlled trials. However, using these data to evaluate population-level interventions can be challenging.<h4>Objectives</h4>We aimed to inform future evaluations of complex interventions by describing sources of bias, lessons learned, and suggestions for improvements, based on two observational studies using linked administrative data from health, education and social care sectors to evaluate the Family Nurse Partnership (FNP) in England and Scotland.<h4>Methods</h4>We first considered how different sources of potential bias within the administrative data could affect results of the evaluations. We explored how each study design addressed these sources of bias using maternal confounders captured in the data. We then determined what additional information could be captured at each step of the complex intervention to enable analysts to minimise bias and maximise comparability between intervention and usual care groups, so that any observed differences can be attributed to the intervention.<h4>Results</h4>Lessons learned include the need for i) detailed data on intervention activity (dates/geography) and usual care; ii) improved information on data linkage quality to accurately characterise control groups; iii) more efficient provision of linked data to ensure timeliness of results; iv) better measurement of confounding characteristics affecting who is eligible, approached and enrolled.<h4>Conclusions</h4>Linked administrative data are a valuable resource for evaluations of the FNP national programme and other complex population-level interventions. However, information on local programme delivery and usual care are required to account for biases that characterise those who receive the intervention, and to inform understanding of mechanisms of effect. National, ongoing, robust evaluations of complex public health evaluations would be more achievable if programme implementation was integrated with improved national and local data collection, and robust quasi-experimental designs.",,doi:https://doi.org/10.23889/ijpds.v8i1.2113; html:https://europepmc.org/articles/PMC10476150; pdf:https://europepmc.org/articles/PMC10476150?pdf=render
 PMC10630987,https://doi.org/,A qualitative study exploring healthcare workers’ lived experiences of the impacts of COVID-19 policies and guidelines on maternal and reproductive healthcare services in the United Kingdom,"Chaloner J, Qureshi I, Gogoi M, Ekezie W, Al-Oraibi A, Wobi F, Agbonmwandolor J, Nellums L, Pareek M.",,European journal of midwifery,2023,2023-01-01,Y,Healthcare Workers; Vaccine Hesitancy; Redeployment; Infection Controls; Covid-19; Policies And Guidelines,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630987/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630987/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10630987; pdf:https://europepmc.org/articles/PMC10630987?pdf=render
-34409990,https://doi.org/10.1093/dote/doab058,Demographic and lifestyle risk factors for gastroesophageal reflux disease and Barrett's esophagus in Australia. ,"Wang SE, Kendall BJ, Hodge AM, Dixon-Suen SC, Dashti SG, Makalic E, Williamson EM, Thomas RJS, Giles GG, English DR.",,Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus,2022,2022-01-01,N,,,,"We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n = 1,318) for daily, 7.5% (n = 1,333) for 2-6 days/week, and 4.3% (n = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.",,pdf:https://academic.oup.com/dote/article-pdf/35/1/doab058/42098674/doab058.pdf; doi:https://doi.org/10.1093/dote/doab058
 32352158,https://doi.org/10.1002/bjs.11580,Author response to: Comment on: Impact of bariatric surgery on cardiovascular outcomes and mortality: a population-based cohort study.,"Adderley N, Singh P, Tahrani AA, Nirantharakumar K.",,The British journal of surgery,2020,2020-04-30,N,,,,,,pdf:https://academic.oup.com/bjs/article-pdf/107/7/e220/35705126/bjs11580.pdf; doi:https://doi.org/10.1002/bjs.11580
+34409990,https://doi.org/10.1093/dote/doab058,Demographic and lifestyle risk factors for gastroesophageal reflux disease and Barrett's esophagus in Australia. ,"Wang SE, Kendall BJ, Hodge AM, Dixon-Suen SC, Dashti SG, Makalic E, Williamson EM, Thomas RJS, Giles GG, English DR.",,Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus,2022,2022-01-01,N,,,,"We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n = 1,318) for daily, 7.5% (n = 1,333) for 2-6 days/week, and 4.3% (n = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.",,pdf:https://academic.oup.com/dote/article-pdf/35/1/doab058/42098674/doab058.pdf; doi:https://doi.org/10.1093/dote/doab058
 37321240,https://doi.org/10.1016/s2215-0366(23)00113-x,Mental health in Europe during the COVID-19 pandemic: a systematic review.,"Ahmed N, Barnett P, Greenburgh A, Pemovska T, Stefanidou T, Lyons N, Ikhtabi S, Talwar S, Francis ER, Harris SM, Shah P, Machin K, Jeffreys S, Mitchell L, Lynch C, Foye U, Schlief M, Appleton R, Saunders KRK, Baldwin H, Allan SM, Sheridan-Rains L, Kharboutly O, Kular A, Goldblatt P, Stewart R, Kirkbride JB, Lloyd-Evans B, Johnson S.",,The lancet. Psychiatry,2023,2023-06-12,Y,,,,"The COVID-19 pandemic caused immediate and far-reaching disruption to society, the economy, and health-care services. We synthesised evidence on the effect of the pandemic on mental health and mental health care in high-income European countries. We included 177 longitudinal and repeated cross-sectional studies comparing prevalence or incidence of mental health problems, mental health symptom severity in people with pre-existing mental health conditions, or mental health service use before versus during the pandemic, or between different timepoints of the pandemic. We found that epidemiological studies reported higher prevalence of some mental health problems during the pandemic compared with before it, but that in most cases this increase reduced over time. Conversely, studies of health records showed reduced incidence of new diagnoses at the start of the pandemic, which further declined during 2020. Mental health service use also declined at the onset of the pandemic but increased later in 2020 and through 2021, although rates of use did not return to pre-pandemic levels for some services. We found mixed patterns of effects of the pandemic on mental health and social outcome for adults already living with mental health conditions.",,pdf:http://www.thelancet.com/article/S221503662300113X/pdf; doi:https://doi.org/10.1016/S2215-0366(23)00113-X; html:https://europepmc.org/articles/PMC10259832; pdf:https://europepmc.org/articles/PMC10259832?pdf=render
 34378227,https://doi.org/10.1111/tri.14010,"Health-related quality of life, uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic.","McKay SC, Lembach H, Hann A, Okoth K, Anderton J, Nirantharakumar K, Magill L, Torlinska B, Armstrong M, Mascaro J, Inston N, Pinkney T, Ranasinghe A, Borrows R, Ferguson J, Isaac J, Calvert M, Perera MTPR, Hartog H.",,Transplant international : official journal of the European Society for Organ Transplantation,2021,2021-09-16,Y,Isolation; Transplant; Mental health; Health-related Quality Of Life; Shielding; Covid-19,,,"Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420473; doi:https://doi.org/10.1111/tri.14010; html:https://europepmc.org/articles/PMC8420473; pdf:https://europepmc.org/articles/PMC8420473?pdf=render
+31302040,https://doi.org/10.1016/j.jchf.2019.03.009,Risk for Heart Failure: The Opportunity for Prevention With the American Heart Association's Life's Simple 7.,"Uijl A, Koudstaal S, Vaartjes I, Boer JMA, Verschuren WMM, van der Schouw YT, Asselbergs FW, Hoes AW, Sluijs I.",,JACC. Heart failure,2019,2019-07-10,N,Heart Failure; Cardiovascular Disease Risk Factors; Healthy Lifestyle; Life’s Simple 7,,,"<h4>Objectives</h4>The aim of this study is to determine whether combinations of specific Life's Simple 7 (LS7) components are associated with reduced risk for heart failure (HF).<h4>Background</h4>The American Heart Association recommends the concept of LS7: healthy behaviors that have been shown to reduce cardiovascular disease.<h4>Methods</h4>A total of 37,803 participants from the EPIC-NL (European Prospective Investigation Into Cancer and Nutrition-Netherlands) cohort were included (mean age: 49.4 ± 11.9 years, 74.7% women). The LS7 score ranged from 0 to 14 and was calculated by assigning 0, 1, or 2 points for smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. An overall ideal score (11 to 14 points) was present in 23.2% of participants, an intermediate score (9 or 10 points) in 35.3%, and an inadequate score (0 to 8 points) in 41.5%.<h4>Results</h4>Over a median follow-up period of 15.2 years (interquartile range: 14.1 to 16.5 years), 690 participants (1.8%) developed HF. In Cox proportional hazards models, ideal and intermediate LS7 scores were associated with reduced risk for HF compared with the inadequate category (hazard ratio: 0.45 [95% confidence interval (CI): 0.34 to 0.60] and hazard ratio: 0.53 [95% CI: 0.44 to 0.64], respectively). Our analyses show that combinations with specific LS7 components, notably glucose, body mass index, smoking, and blood pressure, are associated with a lower incidence of HF.<h4>Conclusions</h4>A healthy lifestyle, as reflected in an ideal LS7 score, was associated with a 55% lower risk for HF compared with an inadequate LS7 score. Preventive strategies that target combinations of specific LS7 components could have a significant impact on decreasing incident HF in the population at large.",,doi:https://doi.org/10.1016/j.jchf.2019.03.009
 36469091,https://doi.org/10.1093/ageing/afac252,Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.",,Age and ageing,2022,2022-12-01,N,Prevalence; Atrial fibrillation; Stroke; Older People; Care Homes; Health Outcomes,,,"<h4>Objective</h4>To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents.<h4>Methods</h4>Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality.<h4>Results</h4>There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P < 0.001).<h4>Conclusions</h4>Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy.",,pdf:https://academic.oup.com/ageing/article-pdf/51/12/afac252/47589319/afac252.pdf; doi:https://doi.org/10.1093/ageing/afac252
 34734970,https://doi.org/10.1001/jamaophthalmol.2021.4601,"Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration: A Mendelian Randomization Study.","Kuan V, Warwick A, Hingorani A, Tufail A, Cipriani V, Burgess S, Sofat R, International AMD Genomics Consortium (IAMDGC).",,JAMA ophthalmology,2021,2021-12-01,Y,,,,"<h4>Importance</h4>Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.<h4>Objective</h4>To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.<h4>Design, setting, participants</h4>This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16 144 individuals with AMD and 17 832 control individuals. Data were analyzed from July 2020 to September 2021.<h4>Exposures</h4>Smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin.<h4>Main outcomes and measures</h4>Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.<h4>Results</h4>A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P < .001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P = .003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P = .004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P = .001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.<h4>Conclusions and relevance</h4>This study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.",,pdf:https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2785704/jamaophthalmology_kuan_2021_oi_210068_1639510445.31311.pdf; doi:https://doi.org/10.1001/jamaophthalmol.2021.4601; html:https://europepmc.org/articles/PMC8569599
-31302040,https://doi.org/10.1016/j.jchf.2019.03.009,Risk for Heart Failure: The Opportunity for Prevention With the American Heart Association's Life's Simple 7.,"Uijl A, Koudstaal S, Vaartjes I, Boer JMA, Verschuren WMM, van der Schouw YT, Asselbergs FW, Hoes AW, Sluijs I.",,JACC. Heart failure,2019,2019-07-10,N,Heart Failure; Cardiovascular Disease Risk Factors; Healthy Lifestyle; Life’s Simple 7,,,"<h4>Objectives</h4>The aim of this study is to determine whether combinations of specific Life's Simple 7 (LS7) components are associated with reduced risk for heart failure (HF).<h4>Background</h4>The American Heart Association recommends the concept of LS7: healthy behaviors that have been shown to reduce cardiovascular disease.<h4>Methods</h4>A total of 37,803 participants from the EPIC-NL (European Prospective Investigation Into Cancer and Nutrition-Netherlands) cohort were included (mean age: 49.4 ± 11.9 years, 74.7% women). The LS7 score ranged from 0 to 14 and was calculated by assigning 0, 1, or 2 points for smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. An overall ideal score (11 to 14 points) was present in 23.2% of participants, an intermediate score (9 or 10 points) in 35.3%, and an inadequate score (0 to 8 points) in 41.5%.<h4>Results</h4>Over a median follow-up period of 15.2 years (interquartile range: 14.1 to 16.5 years), 690 participants (1.8%) developed HF. In Cox proportional hazards models, ideal and intermediate LS7 scores were associated with reduced risk for HF compared with the inadequate category (hazard ratio: 0.45 [95% confidence interval (CI): 0.34 to 0.60] and hazard ratio: 0.53 [95% CI: 0.44 to 0.64], respectively). Our analyses show that combinations with specific LS7 components, notably glucose, body mass index, smoking, and blood pressure, are associated with a lower incidence of HF.<h4>Conclusions</h4>A healthy lifestyle, as reflected in an ideal LS7 score, was associated with a 55% lower risk for HF compared with an inadequate LS7 score. Preventive strategies that target combinations of specific LS7 components could have a significant impact on decreasing incident HF in the population at large.",,doi:https://doi.org/10.1016/j.jchf.2019.03.009
 34038519,https://doi.org/10.1093/ageing/afab084,Developing a UK sarcopenia registry: recruitment and baseline characteristics of the SarcNet pilot.,"Witham MD, Heslop P, Dodds RM, Clegg AP, Hope SV, McDonald C, Smithard D, Storey B, Tan AL, Thornhill A, Sayer AA.",,Age and ageing,2021,2021-09-01,Y,Recruitment; Older People; Registry; Sarcopenia,,,"<h4>Background</h4>sarcopenia registries are a potential method to meet the challenge of recruitment to sarcopenia trials. We tested the feasibility of setting up a UK sarcopenia registry, the feasibility of recruitment methods and sought to characterise the pilot registry population.<h4>Methods</h4>six diverse UK sites took part, with potential participants aged 65 and over approached via mailshots from local primary care practices. Telephone pre-screening using the SARC-F score was followed by in-person screening and baseline visit. Co-morbidities, medications, grip strength, Short Physical Performance Battery, bioimpedance analysis, Geriatric Depression Score, Montreal Cognitive Assessment, Sarcopenia Quality of Life score were performed and permission sought for future recontact. Descriptive statistics for recruitment rates and baseline measures were generated; an embedded randomised trial examined the effect of a University logo on the primary care mailshot on recruitment rates.<h4>Results</h4>sixteen practices contributed a total of 3,508 letters. In total, 428 replies were received (12% response rate); 380 underwent telephone pre-screening of whom 215 (57%) were eligible to attend a screening visit; 150 participants were recruited (40% of those pre-screened) with 147 contributing baseline data. No significant difference was seen in response rates between mailshots with and without the logo (between-group difference 1.1% [95% confidence interval -1.0% to 3.4%], P = 0.31). The mean age of enrollees was 78 years; 72 (49%) were women. In total, 138/147 (94%) had probable sarcopenia on European Working Group on Sarcopenia 2019 criteria and 145/147 (98%) agreed to be recontacted about future studies.<h4>Conclusion</h4>recruitment to a multisite UK sarcopenia registry is feasible, with high levels of consent for recontact.",,pdf:https://academic.oup.com/ageing/article-pdf/50/5/1762/40349116/afab084.pdf; doi:https://doi.org/10.1093/ageing/afab084; html:https://europepmc.org/articles/PMC8437066; pdf:https://europepmc.org/articles/PMC8437066?pdf=render
 32426117,https://doi.org/10.7189/jogh.10.010348,Novel approaches to estimate compliance with lockdown measures in the COVID-19 pandemic.,"Sheikh A, Sheikh Z, Sheikh A.",,Journal of global health,2020,2020-06-01,Y,,,,,This is a summary of new methods for estimating phyiscal distancing and compliance with lockdown. I haven't scored the content because it isn't primary research.,doi:https://doi.org/10.7189/jogh.10.010348; doi:https://doi.org/10.7189/jogh.10.010348; html:https://europepmc.org/articles/PMC7211415; pdf:https://europepmc.org/articles/PMC7211415?pdf=render
 33830993,https://doi.org/10.1371/journal.pgen.1009428,Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank.,"Johnston KJA, Ward J, Ray PR, Adams MJ, McIntosh AM, Smith BH, Strawbridge RJ, Price TJ, Smith DJ, Nicholl BI, Bailey MES.",,PLoS genetics,2021,2021-04-08,Y,,,,"Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009428&type=printable; doi:https://doi.org/10.1371/journal.pgen.1009428; html:https://europepmc.org/articles/PMC8031124; pdf:https://europepmc.org/articles/PMC8031124?pdf=render
@@ -1237,8 +1237,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 32355555,https://doi.org/10.7189/jogh.10.010104,COVID-19 must catalyse key global natural experiments.,"Been JV, Sheikh A.",,Journal of global health,2020,2020-06-01,Y,,,,,"""Been and Sheikh’s editorial about COVID-19, outlines the importance of two natural experiments: a- how different countries responded to the pandemic and its effects and b- impact of improvements in air quality on human and planetary health.""",doi:https://doi.org/10.7189/jogh.10.010104; doi:https://doi.org/10.7189/jogh.10.010104; html:https://europepmc.org/articles/PMC7179980; pdf:https://europepmc.org/articles/PMC7179980?pdf=render
 33531486,https://doi.org/10.1038/s41467-021-21370-6,Author Correction: Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2021,2021-02-02,Y,,,,,,pdf:https://www.nature.com/articles/s41467-021-21370-6.pdf; doi:https://doi.org/10.1038/s41467-021-21370-6; html:https://europepmc.org/articles/PMC7854714; pdf:https://europepmc.org/articles/PMC7854714?pdf=render
 32379357,https://doi.org/10.1002/sim.8563,A Bayesian hierarchical approach for multiple outcomes in routinely collected healthcare data.,"Carragher R, Mueller T, Bennie M, Robertson C.",,Statistics in medicine,2020,2020-05-07,N,Observational Study; Multiple Outcomes; Direct Oral Anticoagulants; Safety Outcomes; Bayesian Hierarchy,,,"Clinical trials are the standard approach for evaluating new treatments, but may lack the power to assess rare outcomes. Trial results are also necessarily restricted to the population considered in the study. The availability of routinely collected healthcare data provides a source of information on the performance of treatments beyond that offered by clinical trials, but the analysis of this type of data presents a number of challenges. Hierarchical methods, which take advantage of known relationships between clinical outcomes, while accounting for bias, may be a suitable statistical approach for the analysis of this data. A study of direct oral anticoagulants in Scotland is discussed and used to motivate a modeling approach. A Bayesian hierarchical model, which allows a stratification of the population into clusters with similar characteristics, is proposed and applied to the direct oral anticoagulant study data. A simulation study is used to assess its performance in terms of outcome detection and error rates.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8563; doi:https://doi.org/10.1002/sim.8563
-36828609,https://doi.org/10.1016/s2589-7500(22)00252-7,Embedding patient-reported outcomes at the heart of artificial intelligence health-care technologies.,"Cruz Rivera S, Liu X, Hughes SE, Dunster H, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"Integration of patient-reported outcome measures (PROMs) in artificial intelligence (AI) studies is a critical part of the humanisation of AI for health. It allows AI technologies to incorporate patients' own views of their symptoms and predict outcomes, reflecting a more holistic picture of health and wellbeing and ultimately helping patients and clinicians to make the best health-care decisions together. By positioning patient-reported outcomes (PROs) as a model input or output we propose a framework to embed PROMs within the function and evaluation of AI health care. However, the integration of PROs in AI systems presents several challenges. These challenges include (1) fragmentation of PRO data collection; (2) validation of AI systems trained and validated against clinician performance, rather than outcome data; (3) scarcity of large-scale PRO datasets; (4) inadequate selection of PROMs for the target population and inadequate infrastructure for collecting PROs; and (5) clinicians might not recognise the value of PROs and therefore not prioritise their adoption; and (6) studies involving PRO or AI frequently present suboptimal design. Notwithstanding these challenges, we propose considerations for the inclusion of PROs in AI health-care technologies to avoid promoting survival at the expense of wellbeing.",,doi:https://doi.org/10.1016/s2589-7500(22)00252-7; doi:https://doi.org/10.1016/S2589-7500(22)00252-7
 34095541,https://doi.org/10.23889/ijpds.v4i2.1134,A Profile of the SAIL Databank on the UK Secure Research Platform.,"Jones KH, Ford DV, Thompson S, Lyons RA.",,International journal of population data science,2019,2019-11-20,Y,,,,"<h4>Background</h4>The Secure Anonymised Information Linkage (SAIL) Databank is a national data safe haven of de identified datasets principally about the population of Wales, made available in anonymised form to researchers across the world. It was established to enable the vast arrays of data collected about individuals in the course of health and other public service delivery to be made available to answer important questions that could not otherwise be addressed without prohibitive effort. The SAIL Databank is the bedrock of other funded centres relying on the data for research.<h4>Approach</h4>SAIL is a data repository surrounded by a suite of physical, technical and procedural control measures embodying a proportionate privacy-by-design governance model, informed by public engagement, to safeguard the data and facilitate data utility. SAIL operates on the UK Secure Research Platform (SeRP), which is a customisable technology and analysis platform. Researchers access anonymised data via this secure research environment, from which results can be released following scrutiny for disclosure risk. SAIL data are being used in multiple research areas to evaluate the impact of health and social exposures and policy interventions.<h4>Discussion</h4>Lessons learned and their applications include: managing evolving legislative and regulatory requirements; employing multiple, tiered security mechanisms; working hard to increase analytical capacity efficiency; and developing a multi-faceted programme of public engagement. Further work includes: incorporating new data types; enabling alternative means of data access; and developing further efficiencies across our operations.<h4>Conclusion</h4>SAIL represents an ongoing programme of work to develop and maintain an extensive, whole population data resource for research. Its privacy-by-design model and UK SeRP technology have received international acclaim, and we continually endeavour to demonstrate trustworthiness to support data provider assurance and public acceptability in data use. We strive for further improvement and continue a mutual learning process with our contemporaries in this rapidly developing field.",,pdf:https://ijpds.org/article/download/1134/2643; doi:https://doi.org/10.23889/ijpds.v4i2.1134; html:https://europepmc.org/articles/PMC8142954; pdf:https://europepmc.org/articles/PMC8142954?pdf=render
+36828609,https://doi.org/10.1016/s2589-7500(22)00252-7,Embedding patient-reported outcomes at the heart of artificial intelligence health-care technologies.,"Cruz Rivera S, Liu X, Hughes SE, Dunster H, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"Integration of patient-reported outcome measures (PROMs) in artificial intelligence (AI) studies is a critical part of the humanisation of AI for health. It allows AI technologies to incorporate patients' own views of their symptoms and predict outcomes, reflecting a more holistic picture of health and wellbeing and ultimately helping patients and clinicians to make the best health-care decisions together. By positioning patient-reported outcomes (PROs) as a model input or output we propose a framework to embed PROMs within the function and evaluation of AI health care. However, the integration of PROs in AI systems presents several challenges. These challenges include (1) fragmentation of PRO data collection; (2) validation of AI systems trained and validated against clinician performance, rather than outcome data; (3) scarcity of large-scale PRO datasets; (4) inadequate selection of PROMs for the target population and inadequate infrastructure for collecting PROs; and (5) clinicians might not recognise the value of PROs and therefore not prioritise their adoption; and (6) studies involving PRO or AI frequently present suboptimal design. Notwithstanding these challenges, we propose considerations for the inclusion of PROs in AI health-care technologies to avoid promoting survival at the expense of wellbeing.",,doi:https://doi.org/10.1016/s2589-7500(22)00252-7; doi:https://doi.org/10.1016/S2589-7500(22)00252-7
 34761838,https://doi.org/10.1002/biof.1801,Neutrophil to lymphocyte ratio is not related to carotid atherosclerosis progression and cardiovascular events in the primary prevention of cardiovascular disease: Results from the IMPROVE study.,"Mannarino MR, Bianconi V, Gigante B, Strawbridge RJ, Savonen K, Kurl S, Giral P, Smit A, Eriksson P, Tremoli E, Veglia F, Baldassarre D, Pirro M, IMPROVE study group.",,"BioFactors (Oxford, England)",2022,2021-11-11,Y,Lymphocyte; neutrophil; cardiovascular; Carotid; Prospective; Imt; Nlr,,,"Inflammation is a component of the pathogenesis of atherosclerosis and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). The neutrophil to lymphocyte ratio (NLR) is a possible inflammation metric for the detection of ASCVD risk, although results of prospective studies are highly inconsistent on this topic. We investigated the cross-sectional relationship between NLR and carotid intima-media thickness (cIMT) in subjects at moderate-to-high ASCVD risk. The prospective association between NLR, cIMT progression, and incident vascular events (VEs) was also explored. In 3341 subjects from the IMT-Progression as Predictors of VEs (IMPROVE) study, we analyzed the association between NLR, cIMT, and its 15-month progression. The association between NLR and incident VEs was also investigated. NLR was positively associated with cross-sectional measures of cIMT, but not with cIMT progression. The association between NLR and cross-sectional cIMT measures was abolished when adjusted for confounders. No association was found between NRL and incident VEs. Similarly, there were no significant differences in the hazard ratios (HRs) of VEs across NLR quartiles. NLR was neither associated with the presence and progression of carotid atherosclerosis, nor with the risk of VEs. Our findings do not support the role of NLR as a predictor of the risk of atherosclerosis progression and ASCVD events in subjects at moderate-to-high ASCVD risk, in primary prevention. However, the usefulness of NLR for patients at a different level of ASCVD risk cannot be inferred from this study.",,pdf:https://air.unimi.it/bitstream/2434/890337/2/0127%20IMPROVE%20mannarino%20Neutrophil%20to%20lymphocyte%20e%20suppl%20.pdf; doi:https://doi.org/10.1002/biof.1801; html:https://europepmc.org/articles/PMC9299016; pdf:https://europepmc.org/articles/PMC9299016?pdf=render
 37198662,https://doi.org/10.1186/s13293-023-00516-9,Sex-based differences in cardiovascular proteomic profiles and their associations with adverse outcomes in patients with chronic heart failure.,"de Bakker M, Petersen TB, Akkerhuis KM, Harakalova M, Umans VA, Germans T, Caliskan K, Katsikis PD, van der Spek PJ, Suthahar N, de Boer RA, Rizopoulos D, Asselbergs FW, Boersma E, Kardys I.",,Biology of sex differences,2023,2023-05-17,Y,Proteomics; Sex differences; Heart Failure; Hfref,,,"<h4>Background</h4>Studies focusing on sex differences in circulating proteins in patients with heart failure with reduced ejection fraction (HFrEF) are scarce. Insight into sex-specific cardiovascular protein profiles and their associations with the risk of adverse outcomes may contribute to a better understanding of the pathophysiological processes involved in HFrEF. Moreover, it could provide a basis for the use of circulating protein measurements for prognostication in women and men, wherein the most relevant protein measurements are applied in each of the sexes.<h4>Methods</h4>In 382 patients with HFrEF, we performed tri-monthly blood sampling (median follow-up: 25 [13-31] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or censoring. We then applied an aptamer-based multiplex proteomic assay identifying 1105 proteins previously associated with cardiovascular disease. We used linear regression models and gene-enrichment analysis to study sex-based differences in baseline levels. We used time-dependent Cox models to study differences in the prognostic value of serially measured proteins. All models were adjusted for the MAGGIC HF mortality risk score and p-values for multiple testing.<h4>Results</h4>In 104 women and 278 men (mean age 62 and 64 years, respectively) cumulative PEP incidence at 30 months was 25% and 35%, respectively. At baseline, 55 (5%) out of the 1105 proteins were significantly different between women and men. The female protein profile was most strongly associated with extracellular matrix organization, while the male profile was dominated by regulation of cell death. The association of endothelin-1 (P<sub>interaction</sub> < 0.001) and somatostatin (P<sub>interaction</sub> = 0.040) with the PEP was modified by sex, independent of clinical characteristics. Endothelin-1 was more strongly associated with the PEP in men (HR 2.62 [95%CI, 1.98, 3.46], p < 0.001) compared to women (1.14 [1.01, 1.29], p = 0.036). Somatostatin was positively associated with the PEP in men (1.23 [1.10, 1.38], p < 0.001), but inversely associated in women (0.33 [0.12, 0.93], p = 0.036).<h4>Conclusion</h4>Baseline cardiovascular protein levels differ between women and men. However, the predictive value of repeatedly measured circulating proteins does not seem to differ except for endothelin-1 and somatostatin.",,pdf:https://bsd.biomedcentral.com/counter/pdf/10.1186/s13293-023-00516-9; doi:https://doi.org/10.1186/s13293-023-00516-9; html:https://europepmc.org/articles/PMC10193800; pdf:https://europepmc.org/articles/PMC10193800?pdf=render
 34772649,https://doi.org/10.1016/s2589-7500(21)00252-1,Characteristics of publicly available skin cancer image datasets: a systematic review.,"Wen D, Khan SM, Ji Xu A, Ibrahim H, Smith L, Caballero J, Zepeda L, de Blas Perez C, Denniston AK, Liu X, Matin RN.",,The Lancet. Digital health,2022,2021-11-09,N,,,,"Publicly available skin image datasets are increasingly used to develop machine learning algorithms for skin cancer diagnosis. However, the total number of datasets and their respective content is currently unclear. This systematic review aimed to identify and evaluate all publicly available skin image datasets used for skin cancer diagnosis by exploring their characteristics, data access requirements, and associated image metadata. A combined MEDLINE, Google, and Google Dataset search identified 21 open access datasets containing 106 950 skin lesion images, 17 open access atlases, eight regulated access datasets, and three regulated access atlases. Images and accompanying data from open access datasets were evaluated by two independent reviewers. Among the 14 datasets that reported country of origin, most (11 [79%]) originated from Europe, North America, and Oceania exclusively. Most datasets (19 [91%]) contained dermoscopic images or macroscopic photographs only. Clinical information was available regarding age for 81 662 images (76·4%), sex for 82 848 (77·5%), and body site for 79 561 (74·4%). Subject ethnicity data were available for 1415 images (1·3%), and Fitzpatrick skin type data for 2236 (2·1%). There was limited and variable reporting of characteristics and metadata among datasets, with substantial under-representation of darker skin types. This is the first systematic review to characterise publicly available skin image datasets, highlighting limited applicability to real-life clinical settings and restricted population representation, precluding generalisability. Quality standards for characteristics and metadata reporting for skin image datasets are needed.",,pdf:http://www.thelancet.com/article/S2589750021002521/pdf; doi:https://doi.org/10.1016/S2589-7500(21)00252-1
@@ -1250,9 +1250,9 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 37422075,https://doi.org/10.1016/j.jval.2023.06.019,Perspectives on Patient-Reported Outcome Data After Treatment Discontinuation in Cancer Clinical Trials.,"King-Kallimanis BL, Calvert M, Cella D, Cocks K, Coens C, Fairclough D, Howie L, Jonsson P, Mahendraratnam N, Maues J, Sarac S, Shaw J, Stigger N, Trask P, Wieseler B.",,Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research,2023,2023-07-06,N,Oncology; Clinical Trials; Patient-reported Outcomes; Multistakeholder Perspective,,,"<h4>Objectives</h4>Patient-reported outcome (PRO) data are critical in understanding treatments from the patient perspective in cancer clinical trials. The potential benefits and methodological approaches to the collection of PRO data after treatment discontinuation (eg, because of progressive disease or unacceptable drug toxicity) are less clear. The purpose of this article is to describe the Food and Drug Administration's Oncology Center of Excellence and the Critical Path Institute cosponsored 2-hour virtual roundtable, held in 2020, to discuss this specific issue.<h4>Methods</h4>We summarize key points from this discussion with 16 stakeholders representing academia, clinical practice, patients, international regulatory agencies, health technology assessment bodies/payers, industry, and PRO instrument development.<h4>Results</h4>Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.<h4>Conclusions</h4>Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical.",,doi:https://doi.org/10.1016/j.jval.2023.06.019
 33500288,https://doi.org/10.1136/bmjopen-2020-042945,Hospital bed capacity and usage across secondary healthcare providers in England during the first wave of the COVID-19 pandemic: a descriptive analysis.,"Mateen BA, Wilde H, Dennis JM, Duncan A, Thomas N, McGovern A, Denaxas S, Keeling M, Vollmer S.",,BMJ open,2021,2021-01-26,Y,Public Health; Health Policy; Intensive & Critical Care; Covid-19,,,"<h4>Objective</h4>In this study, we describe the pattern of bed occupancy across England during the peak of the first wave of the COVID-19 pandemic.<h4>Design</h4>Descriptive survey.<h4>Setting</h4>All non-specialist secondary care providers in England from 27 March27to 5 June 2020.<h4>Participants</h4>Acute (non-specialist) trusts with a type 1 (ie, 24 hours/day, consultant-led) accident and emergency department (n=125), Nightingale (field) hospitals (n=7) and independent sector secondary care providers (n=195).<h4>Main outcome measures</h4>Two thresholds for 'safe occupancy' were used: 85% as per the Royal College of Emergency Medicine and 92% as per NHS Improvement.<h4>Results</h4>At peak availability, there were 2711 additional beds compatible with mechanical ventilation across England, reflecting a 53% increase in capacity, and occupancy never exceeded 62%. A consequence of the repurposing of beds meant that at the trough there were 8.7% (8508) fewer general and acute beds across England, but occupancy never exceeded 72%. The closest to full occupancy of general and acute bed (surge) capacity that any trust in England reached was 99.8% . For beds compatible with mechanical ventilation there were 326 trust-days (3.7%) spent above 85% of surge capacity and 154 trust-days (1.8%) spent above 92%. 23 trusts spent a cumulative 81 days at 100% saturation of their surge ventilator bed capacity (median number of days per trust=1, range: 1-17). However, only three sustainability and transformation partnerships (aggregates of geographically co-located trusts) reached 100% saturation of their mechanical ventilation beds.<h4>Conclusions</h4>Throughout the first wave of the pandemic, an adequate supply of all bed types existed at a national level. However, due to an unequal distribution of bed utilisation, many trusts spent a significant period operating above 'safe-occupancy' thresholds despite substantial capacity in geographically co-located trusts, a key operational issue to address in preparing for future waves.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e042945.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042945; html:https://europepmc.org/articles/PMC7843315; pdf:https://europepmc.org/articles/PMC7843315?pdf=render
 35587337,https://doi.org/10.1093/ije/dyac105,"Gestational age at birth, chronic conditions and school outcomes: a population-based data linkage study of children born in England. ","Libuy N, Gilbert R, Mc Grath-Lone L, Blackburn R, Etoori D, Harron K.",,International journal of epidemiology,2023,2023-02-01,Y,,,,"We aimed to generate evidence about child development measured through school attainment and provision of special educational needs (SEN) across the spectrum of gestational age, including for children born early term and >41 weeks of gestation, with and without chronic health conditions. We used a national linked dataset of hospital and education records of children born in England between 1 September 2004 and 31 August 2005. We evaluated school attainment at Key Stage 1 (KS1; age 7) and Key Stage 2 (KS2; age 11) and any SEN by age 11. We stratified analyses by chronic health conditions up to age 2, and size-for-gestation, and calculated population attributable fractions (PAF). Of 306 717 children, 5.8% were born <37 weeks gestation and 7.0% had a chronic condition. The percentage of children not achieving the expected level at KS1 increased from 7.6% at 41 weeks, to 50.0% at 24 weeks of gestation. A similar pattern was seen at KS2. SEN ranged from 29.0% at 41 weeks to 82.6% at 24 weeks. Children born early term (37-38 weeks of gestation) had poorer outcomes than those born at 40 weeks; 3.2% of children with SEN were attributable to having a chronic condition compared with 2.0% attributable to preterm birth. Children born with early identified chronic conditions contribute more to the burden of poor school outcomes than preterm birth. Evaluation is needed of how early health characteristics can be used to improve preparation for education, before and at entry to school.",,pdf:https://academic.oup.com/ije/article-pdf/52/1/132/49127281/dyac105.pdf; doi:https://doi.org/10.1093/ije/dyac105; html:https://europepmc.org/articles/PMC9908051; pdf:https://europepmc.org/articles/PMC9908051?pdf=render
-37046260,https://doi.org/10.1186/s12913-023-09363-1,Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.,"Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar Á, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.",,BMC health services research,2023,2023-04-12,Y,Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions,,,"<h4>Background</h4>Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear. In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.<h4>Methods</h4>Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15 months pre-COVID (January 2019-March 2020). We used the Oxford COVID-19 Government Response Tracker (OxCGRT) index and multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.<h4>Findings</h4>Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.<h4>Conclusions</h4>Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render
 33749694,https://doi.org/,The evidence for assessing frailty and sarcopenia in an acute medical unit: a systematic review.,"Kamwa V, Seccombe A, Sapey E.",,Acute medicine,2021,2021-01-01,N,,,,"<h4>Background/objectives</h4>A systematic review was conducted to assess if frailty and sarcopenia were associated with poorer outcomes in older adults admitted to an acute medical unit (AMU).<h4>Methods</h4>Eligible studies included older adults with an unplanned admission to an AMU and included a measure of frailty or sarcopenia, completed within 72 hours of admission. Risk of bias was assessed.<h4>Results</h4>Of 1659 identified articles, 16 were included (4 on sarcopenia and 12 on frailty). There was significant study heterogeneity. Overall, frailty and sarcopenia were associated with worse outcomes. Targeted interventions appeared to improve outcomes.<h4>Conclusion</h4>Current evidence suggests some benefit in screening older adults admitted to an AMU for frailty and sarcopenia. However, further studies are required before clinical adoption.",,
 33632741,https://doi.org/10.2337/db20-0895,"Relationship Between Glycemia and Cognitive Function, Structural Brain Outcomes, and Dementia: A Mendelian Randomization Study in the UK Biobank.","Garfield V, Farmaki AE, Fatemifar G, Eastwood SV, Mathur R, Rentsch CT, Denaxas S, Bhaskaran K, Smeeth L, Chaturvedi N.",,Diabetes,2021,2021-02-25,N,,,,"We investigated the relationship between glycemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomization (MR). Data were from the UK Biobank (<i>n</i> = ∼500,000). Our exposures were genetic instruments for type 2 diabetes (157 variants) and HbA<sub>1c</sub> (51 variants) and our outcomes were reaction time (RT), visual memory, hippocampal volume (HV), white matter hyperintensity volume (WMHV), and Alzheimer dementia (AD). We also investigated associations between genetic variants for RT (43 variants) and diabetes and HbA<sub>1c</sub> We used conventional inverse-variance-weighted (IVW) MR alongside MR sensitivity analyses. Using IVW, genetic liability to type 2 diabetes was not associated with RT (exponentiated β [expβ] = 1.00 [95% CI 1.00; 1.00]), visual memory (expβ = 1.00 [95% CI 0.99; 1.00]), WMHV (expβ = 0.99 [95% CI 0.97; 1.01]), HV (β-coefficient mm<sup>3</sup> = -2.30 [95% CI -12.39; 7.78]) or AD (odds ratio [OR] 1.15 [95% CI 0.87; 1.52]). HbA<sub>1c</sub> was not associated with RT (expβ = 1.00 [95% CI 0.99; 1.02]), visual memory (expβ = 0.99 [95% CI 0.96; 1.02]), WMHV (expβ = 1.03 [95% CI 0.88; 1.22]), HV (β = -21.31 [95% CI -82.96; 40.34]), or risk of AD (OR 1.09 [95% CI 0.42; 2.83]). IVW showed that reaction time was not associated with diabetes risk (OR 0.94 [95% CI 0.54; 1.65]), or with HbA<sub>1c</sub> (β-coefficient mmol/mol = -0.88 [95% CI = -1.88; 0.13]) after exclusion of a pleiotropic variant. Overall, we observed little evidence of causal association between genetic instruments for type 2 diabetes or peripheral glycemia and some measures of cognition and brain structure in midlife.",,pdf:https://diabetesjournals.org/diabetes/article-pdf/70/10/2313/628539/db200895.pdf; doi:https://doi.org/10.2337/db20-0895
+37046260,https://doi.org/10.1186/s12913-023-09363-1,Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.,"Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar Á, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.",,BMC health services research,2023,2023-04-12,Y,Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions,,,"<h4>Background</h4>Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear. In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.<h4>Methods</h4>Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15 months pre-COVID (January 2019-March 2020). We used the Oxford COVID-19 Government Response Tracker (OxCGRT) index and multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.<h4>Findings</h4>Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.<h4>Conclusions</h4>Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render
 34390586,https://doi.org/10.1111/ejn.15423,Spectral clustering based on structural magnetic resonance imaging and its relationship with major depressive disorder and cognitive ability.,"Yeung HW, Shen X, Stolicyn A, de Nooij L, Harris MA, Romaniuk L, Buchanan CR, Waiter GD, Sandu AL, McNeil CJ, Murray A, Steele JD, Campbell A, Porteous D, Lawrie SM, McIntosh AM, Cox SR, Smith KM, Whalley HC.",,The European journal of neuroscience,2021,2021-09-02,N,Cognition; Clustering; Machine Learning; Major Depressive Disorder; Structural Neuroimaging; Markov Stability,,,"There is increasing interest in using data-driven unsupervised methods to identify structural underpinnings of common mental illnesses, including major depressive disorder (MDD) and associated traits such as cognition. However, studies are often limited to severe clinical cases with small sample sizes and most do not include replication. Here, we examine two relatively large samples with structural magnetic resonance imaging (MRI), measures of lifetime MDD and cognitive variables: Generation Scotland (GS subsample, N = 980) and UK Biobank (UKB, N = 8,900), for discovery and replication, using an exploratory approach. Regional measures of FreeSurfer derived cortical thickness (CT), cortical surface area (CSA), cortical volume (CV) and subcortical volume (subCV) were input into a clustering process, controlling for common covariates. The main analysis steps involved constructing participant K-nearest neighbour graphs and graph partitioning with Markov stability to determine optimal clustering of participants. Resultant clusters were (1) checked whether they were replicated in an independent cohort and (2) tested for associations with depression status and cognitive measures. Participants separated into two clusters based on structural brain measurements in GS subsample, with large Cohen's d effect sizes between clusters in higher order cortical regions, commonly associated with executive function and decision making. Clustering was replicated in the UKB sample, with high correlations of cluster effect sizes for CT, CSA, CV and subCV between cohorts across regions. The identified clusters were not significantly different with respect to MDD case-control status in either cohort (GS subsample: p<sub>FDR</sub>  = .2239-.6585; UKB: p<sub>FDR</sub>  = .2003-.7690). Significant differences in general cognitive ability were, however, found between the clusters for both datasets, for CSA, CV and subCV (GS subsample: d = 0.2529-.3490, p<sub>FDR</sub>  < .005; UKB: d = 0.0868-0.1070, p<sub>FDR</sub>  < .005). Our results suggest that there are replicable natural groupings of participants based on cortical and subcortical brain measures, which may be related to differences in cognitive performance, but not to the MDD case-control status.",,pdf:https://aura.abdn.ac.uk/bitstream/2164/19062/1/Yeung_etal_EJN_Spectral_Clustering_Based_AAM.pdf; doi:https://doi.org/10.1111/ejn.15423
 33536532,https://doi.org/10.1038/s41598-021-82459-y,Data-driven identification of ageing-related diseases from electronic health records.,"Kuan V, Fraser HC, Hingorani M, Denaxas S, Gonzalez-Izquierdo A, Direk K, Nitsch D, Mathur R, Parisinos CA, Lumbers RT, Sofat R, Wong ICK, Casas JP, Thornton JM, Hemingway H, Partridge L, Hingorani AD.",,Scientific reports,2021,2021-02-03,Y,,,,"Reducing the burden of late-life morbidity requires an understanding of the mechanisms of ageing-related diseases (ARDs), defined as diseases that accumulate with increasing age. This has been hampered by the lack of formal criteria to identify ARDs. Here, we present a framework to identify ARDs using two complementary methods consisting of unsupervised machine learning and actuarial techniques, which we applied to electronic health records (EHRs) from 3,009,048 individuals in England using primary care data from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics admitted patient care dataset between 1 April 2010 and 31 March 2015 (mean age 49.7 years (s.d. 18.6), 51% female, 70% white ethnicity). We grouped 278 high-burden diseases into nine main clusters according to their patterns of disease onset, using a hierarchical agglomerative clustering algorithm. Four of these clusters, encompassing 207 diseases spanning diverse organ systems and clinical specialties, had rates of disease onset that clearly increased with chronological age. However, the ages of onset for these four clusters were strikingly different, with median age of onset 82 years (IQR 82-83) for Cluster 1, 77 years (IQR 75-77) for Cluster 2, 69 years (IQR 66-71) for Cluster 3 and 57 years (IQR 54-59) for Cluster 4. Fitting to ageing-related actuarial models confirmed that the vast majority of these 207 diseases had a high probability of being ageing-related. Cardiovascular diseases and cancers were highly represented, while benign neoplastic, skin and psychiatric conditions were largely absent from the four ageing-related clusters. Our framework identifies and clusters ARDs and can form the basis for fundamental and translational research into ageing pathways.",,pdf:https://www.nature.com/articles/s41598-021-82459-y.pdf; doi:https://doi.org/10.1038/s41598-021-82459-y; html:https://europepmc.org/articles/PMC7859412; pdf:https://europepmc.org/articles/PMC7859412?pdf=render
 36273236,https://doi.org/10.1038/s41746-022-00705-7,"Automated clinical coding: what, why, and where we are?","Dong H, Falis M, Whiteley W, Alex B, Matterson J, Ji S, Chen J, Wu H.",,NPJ digital medicine,2022,2022-10-22,Y,,,,"Clinical coding is the task of transforming medical information in a patient's health records into structured codes so that they can be used for statistical analysis. This is a cognitive and time-consuming task that follows a standard process in order to achieve a high level of consistency. Clinical coding could potentially be supported by an automated system to improve the efficiency and accuracy of the process. We introduce the idea of automated clinical coding and summarise its challenges from the perspective of Artificial Intelligence (AI) and Natural Language Processing (NLP), based on the literature, our project experience over the past two and half years (late 2019-early 2022), and discussions with clinical coding experts in Scotland and the UK. Our research reveals the gaps between the current deep learning-based approach applied to clinical coding and the need for explainability and consistency in real-world practice. Knowledge-based methods that represent and reason the standard, explainable process of a task may need to be incorporated into deep learning-based methods for clinical coding. Automated clinical coding is a promising task for AI, despite the technical and organisational challenges. Coders are needed to be involved in the development process. There is much to achieve to develop and deploy an AI-based automated system to support coding in the next five years and beyond.",,pdf:https://www.nature.com/articles/s41746-022-00705-7.pdf; doi:https://doi.org/10.1038/s41746-022-00705-7; html:https://europepmc.org/articles/PMC9588058; pdf:https://europepmc.org/articles/PMC9588058?pdf=render
@@ -1261,31 +1261,31 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 37777287,https://doi.org/10.1016/s2468-2667(23)00178-0,"All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration.","Rein SM, Lampe FC, Ingle SM, Sterne JAC, Trickey A, Gill MJ, Papastamopoulos V, Wittkop L, van der Valk M, Kitchen M, Guest JL, Satre DD, Wandeler G, Galindo P, Castilho J, Crane HM, Smith CJ.",,The Lancet. Public health,2023,2023-10-01,N,,,,"<h4>Background</h4>Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning.<h4>Methods</h4>Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year.<h4>Findings</h4>Among 23 594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals.<h4>Interpretation</h4>Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support.<h4>Funding</h4>Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.",,doi:https://doi.org/10.1016/S2468-2667(23)00178-0
 37264679,https://doi.org/10.1093/eurjpc/zwad187,Improving 10-year cardiovascular risk prediction in apparently healthy people: flexible addition of risk modifiers on top of SCORE2.,"Hageman SHJ, Petitjaen C, Pennells L, Kaptoge S, Pajouheshnia R, Tillmann T, Blaha MJ, McClelland RL, Matsushita K, Nambi V, Klungel OH, Souverein PC, van der Schouw YT, Verschuren WMM, Lehmann N, Erbel R, Jöckel KH, Di Angelantonio E, Visseren FLJ, Dorresteijn JAN.",,European journal of preventive cardiology,2023,2023-10-01,Y,Biomarkers; Risk stratification; Risk Prediction; cardiovascular; Coronary Calcium Score; Score2,,,"<h4>Aims</h4>In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium (CAC) are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics.<h4>Methods and results</h4>Individuals without previous CVD or DM were included from the UK Biobank; Atherosclerosis Risk in Communities (ARIC); Multi-Ethnic Study of Atherosclerosis (MESA); European Prospective Investigation into Cancer, The Netherlands (EPIC-NL); and Heinz Nixdorf Recall (HNR) studies (n = 409 757) in whom 16 166 CVD events and 19 149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant predictor. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 [95% confidence interval (CI) 0.0115; 0.0281] and hs-Troponin-T with 0.0100 (95% CI 0.0063; 0.0137). External validation was performed in the Clinical Practice Research Datalink (CPRD) cohort (UK, n = 518 015, 12 675 CVD events). Adjustment of SCORE2-predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination [0.740 (95% CI 0.736-0.745) vs. unimproved SCORE2 risk C-index 0.737 (95% CI 0.732-0.741)].<h4>Conclusion</h4>The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers.",,pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad187/50506335/zwad187.pdf; doi:https://doi.org/10.1093/eurjpc/zwad187; html:https://europepmc.org/articles/PMC10600319; pdf:https://europepmc.org/articles/PMC10600319?pdf=render
 35297548,https://doi.org/10.1002/humu.24369,"Beacon v2 and Beacon networks: A ""lingua franca"" for federated data discovery in biomedical genomics, and beyond.","Rambla J, Baudis M, Ariosa R, Beck T, Fromont LA, Navarro A, Paloots R, Rueda M, Saunders G, Singh B, Spalding JD, Törnroos J, Vasallo C, Veal CD, Brookes AJ.",,Human mutation,2022,2022-04-08,Y,data sharing; Clinical Genomics; Beacon; Data Discovery; Rest Api; Ga4gh,,,"Beacon is a basic data discovery protocol issued by the Global Alliance for Genomics and Health (GA4GH). The main goal addressed by version 1 of the Beacon protocol was to test the feasibility of broadly sharing human genomic data, through providing simple ""yes"" or ""no"" responses to queries about the presence of a given variant in datasets hosted by Beacon providers. The popularity of this concept has fostered the design of a version 2, that better serves real-world requirements and addresses the needs of clinical genomics research and healthcare, as assessed by several contributing projects and organizations. Particularly, rare disease genetics and cancer research will benefit from new case level and genomic variant level requests and the enabling of richer phenotype and clinical queries as well as support for fuzzy searches. Beacon is designed as a ""lingua franca"" to bridge data collections hosted in software solutions with different and rich interfaces. Beacon version 2 works alongside popular standards like Phenopackets, OMOP, or FHIR, allowing implementing consortia to return matches in beacon responses and provide a handover to their preferred data exchange format. The protocol is being explored by other research domains and is being tested in several international projects.",,pdf:http://repositori.upf.edu/bitstream/10230/53310/1/Rambla_2022.pdf; doi:https://doi.org/10.1002/humu.24369; html:https://europepmc.org/articles/PMC9322265; pdf:https://europepmc.org/articles/PMC9322265?pdf=render
-34275648,https://doi.org/10.1016/j.injury.2021.06.037,Patterns and predictors of personal responsibility attributions after major trauma.,"Lau G, Gabbe BJ, Giummarra MJ.",,Injury,2021,2021-07-06,N,"wounds and injuries; Insurance, Accident; Violence; Guilt; Accidental Injuries; Liability, Legal",,,"<h4>Background</h4>External responsibility attributions after injury are associated with worse recovery. However, there remains limited understanding of who accepts personal responsibilityfor their injury and whether or how responsibility attributions change over time.<h4>Methods</h4>This prospective cohort study included patients who received care from recovery co-ordinators following serious injury and admission to a major trauma centre in Victoria, Australia (n=850). Self-reported personal responsibility attributions (totally, partially, not responsible, or did not know) were collected at three timepoints (admission, discharge, and six months post-injury) and linked to demographic, injury and clinical characteristics from the Victorian State Trauma Registry.<h4>Results</h4>Mixed effects multinomial analyses revealed that female sex (adjusted relative risk ratio, aRRR=3.11-4.66) and compensable injury (aRRR=7.83-15.27) were associated with reporting lower personal responsibility relative to total responsibility. Falls and motorcyclists had decreased risk of reporting lower personal responsibility than non-drivers (motor vehicle/motorcycle passengers, cyclists and pedestrians) (aRRR=0.11-0.19). More than one-third of participants changed their personal responsibility attribution within six months post-injury. Kappa analyses revealed fair to moderate agreement between the three timepoints (kappa=0.38-0.59), and Stuart-Maxwell tests showed unidirectional bias towards reporting lower levels of personal responsibility between admission and discharge (p<0.001). No demographic, health or injury characteristics predicted a change in responsibility attributions in logistic regression analyses.<h4>Conclusions</h4>Personal responsibility attributions often change over time. Therefore, responsibility attributions should not be considered static, and attributions made at different times post-injury should not be used interchangeably in research or clinical settings. Given that external responsibility attributions are associated with worse post-injury outcomes, potential interventions to optimise recovery should be prioritised for patients who predominantly report lower levels of personal responsibility, especially women and people with compensable injuries. Meanwhile, factors associated with high levels of personal responsibility highlight opportunities to implement targeted injury prevention strategies.",,doi:https://doi.org/10.1016/j.injury.2021.06.037
 32119825,https://doi.org/10.1016/s2214-109x(20)30074-7,Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts.,"Hellewell J, Abbott S, Gimma A, Bosse NI, Jarvis CI, Russell TW, Munday JD, Kucharski AJ, Edmunds WJ, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Funk S, Eggo RM.",,The Lancet. Global health,2020,2020-02-28,Y,,Improving Public Health,COVID-19,"<h4>Background</h4>Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19.<h4>Methods</h4>We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R<sub>0</sub>), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort.<h4>Findings</h4>Simulated outbreaks starting with five initial cases, an R<sub>0</sub> of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R<sub>0</sub> was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R<sub>0</sub> of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R<sub>0</sub> of 2·5 more than 70% of contacts had to be traced, and for an R<sub>0</sub> of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R<sub>0</sub> was 1·5. For R<sub>0</sub> values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset.<h4>Interpretation</h4>In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts.<h4>Funding</h4>Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2214109X20300747/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30074-7; html:https://europepmc.org/articles/PMC7097845; pdf:https://europepmc.org/articles/PMC7097845?pdf=render
+34275648,https://doi.org/10.1016/j.injury.2021.06.037,Patterns and predictors of personal responsibility attributions after major trauma.,"Lau G, Gabbe BJ, Giummarra MJ.",,Injury,2021,2021-07-06,N,"wounds and injuries; Insurance, Accident; Violence; Guilt; Accidental Injuries; Liability, Legal",,,"<h4>Background</h4>External responsibility attributions after injury are associated with worse recovery. However, there remains limited understanding of who accepts personal responsibilityfor their injury and whether or how responsibility attributions change over time.<h4>Methods</h4>This prospective cohort study included patients who received care from recovery co-ordinators following serious injury and admission to a major trauma centre in Victoria, Australia (n=850). Self-reported personal responsibility attributions (totally, partially, not responsible, or did not know) were collected at three timepoints (admission, discharge, and six months post-injury) and linked to demographic, injury and clinical characteristics from the Victorian State Trauma Registry.<h4>Results</h4>Mixed effects multinomial analyses revealed that female sex (adjusted relative risk ratio, aRRR=3.11-4.66) and compensable injury (aRRR=7.83-15.27) were associated with reporting lower personal responsibility relative to total responsibility. Falls and motorcyclists had decreased risk of reporting lower personal responsibility than non-drivers (motor vehicle/motorcycle passengers, cyclists and pedestrians) (aRRR=0.11-0.19). More than one-third of participants changed their personal responsibility attribution within six months post-injury. Kappa analyses revealed fair to moderate agreement between the three timepoints (kappa=0.38-0.59), and Stuart-Maxwell tests showed unidirectional bias towards reporting lower levels of personal responsibility between admission and discharge (p<0.001). No demographic, health or injury characteristics predicted a change in responsibility attributions in logistic regression analyses.<h4>Conclusions</h4>Personal responsibility attributions often change over time. Therefore, responsibility attributions should not be considered static, and attributions made at different times post-injury should not be used interchangeably in research or clinical settings. Given that external responsibility attributions are associated with worse post-injury outcomes, potential interventions to optimise recovery should be prioritised for patients who predominantly report lower levels of personal responsibility, especially women and people with compensable injuries. Meanwhile, factors associated with high levels of personal responsibility highlight opportunities to implement targeted injury prevention strategies.",,doi:https://doi.org/10.1016/j.injury.2021.06.037
 36722341,https://doi.org/10.1093/cei/uxad008,Practical challenges for functional validation of STAT1 gain of function genetic variants.,"Albuquerque AS, Maimaris J, McKenna AJ, Lambourne J, Moreira F, Workman S, Megy K, Simeoni I, Lango Allen H, NIHR BioResource-Rare Disease Consortium, Morris EC, Burns SO.",,Clinical and experimental immunology,2023,2023-04-01,Y,Flow cytometry; STAT1; Primary Immunodeficiency; Gain Of Function; Chronic Mucocutaneous Candidiasis; Variants Of Unknown Significance,,,,,pdf:https://academic.oup.com/cei/advance-article-pdf/doi/10.1093/cei/uxad008/49549101/uxad008.pdf; doi:https://doi.org/10.1093/cei/uxad008; html:https://europepmc.org/articles/PMC10128160; pdf:https://europepmc.org/articles/PMC10128160?pdf=render
 35842920,https://doi.org/10.1002/ehf2.14073,Blood-based biomarkers for the prediction of hypertrophic cardiomyopathy prognosis: a systematic review and meta-analysis. ,"Jansen M, Algül S, Bosman LP, Michels M, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,ESC heart failure,2022,2022-07-17,Y,,,,"Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease. HCM is an important cause of sudden cardiac death and may also lead to outflow tract obstruction and heart failure. Disease severity is highly variable and risk stratification remains limited. Therefore, we aimed to review current knowledge of prognostic blood-based biomarkers in HCM. A systematic literature search was performed on PubMed, Embase, and the Cochrane library to identify studies assessing plasma or serum biomarkers for outcomes involving malignant ventricular arrhythmia, outflow tract obstruction, and heart failure. Risk of bias was assessed using the QUIPS tool. Meta-analyses were performed using the random effects method. A total of 26 unique cohort studies assessing 42 biomarkers were identified. Overall risk of bias was moderate. Thirty-two biomarkers were significantly associated to an HCM outcome in at least one study (nine biomarkers in at least two studies). In pooled analyses, cardiovascular mortality was predicted by N-terminal prohormone of brain natriuretic peptide (hazard ratio [HR] 5.38 per log[pg/mL], 95% confidence interval [CI] 2.07-14.03, P < 0.001, I2  = 0%) and high-sensitivity C-reactive protein (HR 1.30 per μg/mL, 95% CI 1.00-1.68, P = 0.05, I2  = 78%), all-cause mortality by low-density lipoprotein cholesterol (HR 0.63 per μmol/mL, 95% CI 0.49-0.80, P < 0.001, I2  = 0%), and a combined congestive heart failure, malignant ventricular arrhythmia, and stroke outcome by high-sensitivity cardiac troponin T (pooled HR 4.19 for ≥0.014 ng/mL, 95% CI 2.22-7.88, P < 0.001, I2  = 0%). Quality of evidence was low-moderate. Several blood-based biomarkers were identified as predictors of HCM outcomes. Additional studies are required to validate their prognostic utility within current risk stratification models.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14073; doi:https://doi.org/10.1002/ehf2.14073; html:https://europepmc.org/articles/PMC9715795; pdf:https://europepmc.org/articles/PMC9715795?pdf=render
 34873059,https://doi.org/10.1073/pnas.2108395118,How immunity from and interaction with seasonal coronaviruses can shape SARS-CoV-2 epidemiology.,"Waterlow NR, van Leeuwen E, Davies NG, CMMID COVID-19 Working Group, Flasche S, Eggo RM.",,Proceedings of the National Academy of Sciences of the United States of America,2021,2021-12-01,Y,Immunity; Coronaviruses; Cross-protection; Covid-19; Sars-cov-2,,,"We hypothesized that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, including generating reduced susceptibility in children. To determine what the prepandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 y of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.8 y (95% CI 6.3 to 8.1) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission.",,doi:https://doi.org/10.1073/pnas.2108395118; doi:https://doi.org/10.1073/pnas.2108395118; html:https://europepmc.org/articles/PMC8670441; pdf:https://europepmc.org/articles/PMC8670441?pdf=render
 35004880,https://doi.org/10.3389/fcvm.2021.763361,"Cardiac Magnetic Resonance Radiomics Reveal Differential Impact of Sex, Age, and Vascular Risk Factors on Cardiac Structure and Myocardial Tissue.","Raisi-Estabragh Z, Jaggi A, Gkontra P, McCracken C, Aung N, Munroe PB, Neubauer S, Harvey NC, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2021-12-22,Y,Hypertension; Diabetes; Smoking; Sex differences; High cholesterol; Cardiovascular Magnetic Resonance; Healthy Individuals; Radiomics,,,"<b>Background:</b> Cardiovascular magnetic resonance (CMR) radiomics analysis provides multiple quantifiers of ventricular shape and myocardial texture, which may be used for detailed cardiovascular phenotyping. <b>Objectives:</b> We studied variation in CMR radiomics phenotypes by age and sex in healthy UK Biobank participants. Then, we examined independent associations of classical vascular risk factors (VRFs: smoking, diabetes, hypertension, high cholesterol) with CMR radiomics features, considering potential sex and age differential relationships. <b>Design:</b> Image acquisition was with 1.5 Tesla scanners (MAGNETOM Aera, Siemens). Three regions of interest were segmented from short axis stack images using an automated pipeline: right ventricle, left ventricle, myocardium. We extracted 237 radiomics features from each study using Pyradiomics. In a healthy subset of participants (<i>n</i> = 14,902) without cardiovascular disease or VRFs, we estimated independent associations of age and sex with each radiomics feature using linear regression models adjusted for body size. We then created a sample comprising individuals with at least one VRF matched to an equal number of healthy participants (<i>n</i> = 27,400). We linearly modelled each radiomics feature against age, sex, body size, and all the VRFs. Bonferroni adjustment for multiple testing was applied to all <i>p</i>-values. To aid interpretation, we organised the results into six feature clusters. <b>Results:</b> Amongst the healthy subset, men had larger ventricles with dimmer and less texturally complex myocardium than women. Increasing age was associated with smaller ventricles and greater variation in myocardial intensities. Broadly, all the VRFs were associated with dimmer, less varied signal intensities, greater uniformity of local intensity levels, and greater relative presence of low signal intensity areas within the myocardium. Diabetes and high cholesterol were also associated with smaller ventricular size, this association was of greater magnitude in men than women. The pattern of alteration of radiomics features with the VRFs was broadly consistent in men and women. However, the associations between intensity based radiomics features with both diabetes and hypertension were more prominent in women than men. <b>Conclusions:</b> We demonstrate novel independent associations of sex, age, and major VRFs with CMR radiomics phenotypes. Further studies into the nature and clinical significance of these phenotypes are needed.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.763361/pdf; doi:https://doi.org/10.3389/fcvm.2021.763361; html:https://europepmc.org/articles/PMC8727756; pdf:https://europepmc.org/articles/PMC8727756?pdf=render
 33127858,https://doi.org/10.1681/asn.2020050679,Conventional and Genetic Evidence on the Association between Adiposity and CKD.,"Zhu P, Herrington WG, Haynes R, Emberson J, Landray MJ, Sudlow CLM, Woodward M, Baigent C, Lewington S, Staplin N.",,Journal of the American Society of Nephrology : JASN,2021,2020-10-30,N,Obesity; body mass index; Chronic Kidney Disease; Mendelian Randomization; Central Adiposity; Epidemiology And Outcomes,,,"<h4>Background</h4>The size of any causal contribution of central and general adiposity to CKD risk and the underlying mechanism of mediation are unknown.<h4>Methods</h4>Data from 281,228 UK Biobank participants were used to estimate the relevance of waist-to-hip ratio and body mass index (BMI) to CKD prevalence. Conventional approaches used logistic regression. Genetic analyses used Mendelian randomization (MR) and data from 394 waist-to-hip ratio and 773 BMI-associated loci. Models assessed the role of known mediators (diabetes mellitus and BP) by adjusting for measured values (conventional analyses) or genetic associations of the selected loci (multivariable MR).<h4>Results</h4>Evidence of CKD was found in 18,034 (6.4%) participants. Each 0.06 higher measured waist-to-hip ratio and each 5-kg/m<sup>2</sup> increase in BMI were associated with 69% (odds ratio, 1.69; 95% CI, 1.64 to 1.74) and 58% (1.58; 1.55 to 1.62) higher odds of CKD, respectively. In analogous MR analyses, each 0.06-genetically-predicted higher waist-to-hip ratio was associated with a 29% (1.29; 1.20 to 1.38) increased odds of CKD, and each 5-kg/m<sup>2</sup> genetically-predicted higher BMI was associated with a 49% (1.49; 1.39 to 1.59) increased odds. After adjusting for diabetes and measured BP, chi-squared values for associations for waist-to-hip ratio and BMI fell by 56%. In contrast, mediator adjustment using multivariable MR found 83% and 69% reductions in chi-squared values for genetically-predicted waist-to-hip ratio and BMI models, respectively.<h4>Conclusions</h4>Genetic analyses suggest that conventional associations between central and general adiposity with CKD are largely causal. However, conventional approaches underestimate mediating roles of diabetes, BP, and their correlates. Genetic approaches suggest these mediators explain most of adiposity-CKD-associated risk.",,pdf:https://jasn.asnjournals.org/content/jnephrol/32/1/127.full.pdf; doi:https://doi.org/10.1681/ASN.2020050679; html:https://europepmc.org/articles/PMC7894659; doi:https://doi.org/10.1681/asn.2020050679
-37722858,https://doi.org/10.3399/bjgp.2023.0077,Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.,"Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-10-26,Y,Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities,,,"<h4>Background</h4>Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.<h4>Aim</h4>To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.<h4>Design and setting</h4>A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.<h4>Method</h4>Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.<h4>Results</h4>In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged ≥50 years) were more likely to have controlled hypertension than younger patients.<h4>Conclusion</h4>Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.",,doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render
 32571619,https://doi.org/10.1016/j.schres.2020.05.007,Real-world implementation of precision psychiatry: Transdiagnostic risk calculator for the automatic detection of individuals at-risk of psychosis.,"Oliver D, Spada G, Colling C, Broadbent M, Baldwin H, Patel R, Stewart R, Stahl D, Dobson R, McGuire P, Fusar-Poli P.",,Schizophrenia research,2021,2020-06-19,Y,Feasibility; Implementation; Risk Calculator; Precision Psychiatry; Psychosis;transdiagnostic,,,"<h4>Background</h4>Risk estimation models integrated into Electronic Health Records (EHRs) can deliver innovative approaches in psychiatry, but clinicians' endorsement and their real-world usability are unknown. This study aimed to investigate the real-world feasibility of implementing an individualised, transdiagnostic risk calculator to automatically screen EHRs and detect individuals at-risk for psychosis.<h4>Methods</h4>Feasibility implementation study encompassing an in-vitro phase (March 2018 to May 2018) and in-vivo phase (May 2018 to April 2019). The in-vitro phase addressed implementation barriers and embedded the risk calculator (predictors: age, gender, ethnicity, index cluster diagnosis, age*gender) into the local EHR. The in-vivo phase investigated the real-world feasibility of screening individuals accessing secondary mental healthcare at the South London and Maudsley NHS Trust. The primary outcome was adherence of clinicians to automatic EHR screening, defined by the proportion of clinicians who responded to alerts from the risk calculator, over those contacted.<h4>Results</h4>In-vitro phase: implementation barriers were identified/overcome with clinician and service user engagement, and the calculator was successfully integrated into the local EHR through the CogStack platform. In-vivo phase: 3722 individuals were automatically screened and 115 were detected. Clinician adherence was 74% without outreach and 85% with outreach. One-third of clinicians responded to the first email (37.1%) or phone calls (33.7%). Among those detected, cumulative risk of developing psychosis was 12% at six-month follow-up.<h4>Conclusion</h4>This is the first implementation study suggesting that combining precision psychiatry and EHR methods to improve detection of individuals with emerging psychosis is feasible. Future psychiatric implementation research is urgently needed.",,doi:https://doi.org/10.1016/j.schres.2020.05.007; doi:https://doi.org/10.1016/j.schres.2020.05.007; html:https://europepmc.org/articles/PMC7875179
+37722858,https://doi.org/10.3399/bjgp.2023.0077,Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.,"Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-10-26,Y,Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities,,,"<h4>Background</h4>Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.<h4>Aim</h4>To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.<h4>Design and setting</h4>A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.<h4>Method</h4>Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.<h4>Results</h4>In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged ≥50 years) were more likely to have controlled hypertension than younger patients.<h4>Conclusion</h4>Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.",,doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render
 33144367,https://doi.org/10.3399/bjgpopen20x101109,Evaluating a cardiovascular disease risk management care continuum within a learning healthcare system: a prospective cohort study. ,"Groenhof TKJ, Lely AT, Haitjema S, Nathoe HM, Kortekaas MF, Asselbergs FW, Bots ML, Hollander M, UCC CVRM study group.",,BJGP open,2020,2020-12-15,Y,,,,"Many patients now present with multimorbidity and chronicity of disease. This means that multidisciplinary management in a care continuum, integrating primary care and hospital care services, is needed to ensure high quality care. To evaluate cardiovascular risk management (CVRM) via linkage of health data sources, as an example of a multidisciplinary continuum within a learning healthcare system (LHS). In this prospective cohort study, data were linked from the Utrecht Cardiovascular Cohort (UCC) to the Julius General Practitioners' Network (JGPN) database. UCC offers structured CVRM at referral to the University Medical Centre (UMC) Utrecht. JGPN consists of electronic health record (EHR) data from referring GPs. The cardiovascular risk factors were extracted for each patient 13 months before referral (JGPN), at UCC inclusion, and during 12 months follow-up (JGPN). The following areas were assessed: registration of risk factors; detection of risk factor(s) requiring treatment at UCC; communication of risk factors and actionable suggestions from the specialist to the GP; and change of management during follow-up. In 52% of patients, ≥1 risk factors were registered (that is, extractable from structured fields within routine care health records) before UCC. In 12%-72% of patients, risk factor(s) existed that required (change or start of) treatment at UCC inclusion. Specialist communication included the complete risk profile in 67% of letters, but lacked actionable suggestions in 86%. In 29% of patients, at least one risk factor was registered after UCC. Change in management in GP records was seen in 21%-58% of them. Evaluation of a multidisciplinary LHS is possible via linkage of health data sources. Efforts have to be made to improve registration in primary care, as well as communication on findings and actionable suggestions for follow-up to bridge the gap in the CVRM continuum.",,pdf:https://bjgpopen.org/content/bjgpoa/4/5/bjgpopen20X101109.full.pdf; doi:https://doi.org/10.3399/bjgpopen20X101109; html:https://europepmc.org/articles/PMC7880177; pdf:https://europepmc.org/articles/PMC7880177?pdf=render
 31361079,https://doi.org/10.1111/1742-6723.13361,"Animal-vehicle collisions in Victoria, Australia: An under-recognised cause of road traffic crashes.","Ang JY, Gabbe B, Cameron P, Beck B.",,Emergency medicine Australasia : EMA,2019,2019-07-30,N,Injury; Prevention; Traffic; Motor Vehicle,,,"<h4>Objective</h4>Non-fatal injuries sustained from animal-vehicle collisions are a globally under-recognised road safety issue, with limited data on these crash types. The present study aimed to quantify the number and causes of major trauma events resulting from animal-vehicle collisions.<h4>Methods</h4>The study was a retrospective analysis of major trauma cases occurring in Victoria, Australia, between 2007 and 2016, using data from the population-based Victorian State Trauma Registry. To identify animal-vehicle collisions, Victorian State Trauma Registry injury codes were combined with text-mining of the text description of the injury event.<h4>Results</h4>Over the 10 year period, there were 152 major trauma patients who were admitted to Victorian trauma-receiving hospitals due to vehicle collisions with animals. The crude population-based incidence rate for animal-vehicle collisions increased by 6.7% per year (incidence rate ratio 1.07; 95% confidence interval 1.01-1.13; P = 0.02).<h4>Conclusion</h4>Development of systematic recording methods of animal-vehicle collisions will improve reporting of these crash types to assist future studies in implementing effective countermeasures.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.13361; doi:https://doi.org/10.1111/1742-6723.13361
 36298714,https://doi.org/10.3390/v14102159,Production and Characterisation of Stabilised PV-3 Virus-like Particles Using <i>Pichia pastoris</i>.,"Sherry L, Grehan K, Swanson JJ, Bahar MW, Porta C, Fry EE, Stuart DI, Rowlands DJ, Stonehouse NJ.",,Viruses,2022,2022-09-30,Y,Poliovirus; Vaccine; virus-like particle; Pichia pastoris,,,"Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using <i>Pichia pastoris</i>, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using <i>Pichia pastoris</i>. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.",,pdf:https://www.mdpi.com/1999-4915/14/10/2159/pdf?version=1665465973; doi:https://doi.org/10.3390/v14102159; html:https://europepmc.org/articles/PMC9611624; pdf:https://europepmc.org/articles/PMC9611624?pdf=render
 35259281,https://doi.org/10.1111/acel.13524,Biological mechanisms of aging predict age-related disease co-occurrence in patients.,"Fraser HC, Kuan V, Johnen R, Zwierzyna M, Hingorani AD, Beyer A, Partridge L.",,Aging cell,2022,2022-03-08,Y,Aging; Genetics; Age-related Disease; Multimorbidity; Aging Hallmarks,,,"Genetic, environmental, and pharmacological interventions into the aging process can confer resistance to multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that individual mechanisms of aging might contribute to the co-occurrence of age-related diseases in humans and could be targeted to prevent these conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation and found strong, non-random associations between age-related diseases and aging mechanisms in humans, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signaling pathway and activity of the ERK1/2 pathway were associated with multiple aging mechanisms and diverse age-related diseases. Mechanisms of aging hence contribute both together and individually to age-related disease co-occurrence in humans and could potentially be targeted accordingly to prevent multimorbidity.",,pdf:https://discovery.ucl.ac.uk/10145565/1/Hignorani_Biological%20mechanisms%20of%20aging%20predict%20age-related%20disease%20co-occurrence%20in%20patients_AOP.pdf; doi:https://doi.org/10.1111/acel.13524; html:https://europepmc.org/articles/PMC9009120; pdf:https://europepmc.org/articles/PMC9009120?pdf=render
+32838035,https://doi.org/10.1002/lrh2.10236,Rapid translation of clinical guidelines into executable knowledge: A case study of COVID-19 and online demonstration.,"Fox J, Khan O, Curtis H, Wright A, Pal C, Cockburn N, Cooper J, Chandan JS, Nirantharakumar K.",,Learning health systems,2021,2020-07-14,Y,Artificial intelligence; Covid‐19; Rapid Learning Systems,,,"<h4>Introduction</h4>We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID-19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020.<h4>Methods</h4>The <i>PROforma</i> guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID-19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice.<h4>Results</h4><i>PROforma</i> and OpenClinical.net proved to be an effective combination for rapidly creating the COVID-19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746.<h4>Conclusions</h4>This is believed to be the first use of AI/knowledge engineering methods for disseminating best-practice in COVID-19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10236; doi:https://doi.org/10.1002/lrh2.10236; html:https://europepmc.org/articles/PMC7323421; pdf:https://europepmc.org/articles/PMC7323421?pdf=render
 36331190,https://doi.org/10.1056/nejmoa2204233,Empagliflozin in Patients with Chronic Kidney Disease.,"The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R.",,The New England journal of medicine,2023,2022-11-04,Y,,,,"<h4>Background</h4>The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients.<h4>Methods</h4>We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m<sup>2</sup> of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m<sup>2</sup> with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m<sup>2</sup>, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes.<h4>Results</h4>A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups.<h4>Conclusions</h4>Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).",,pdf:https://ora.ox.ac.uk/objects/uuid:f91f9722-f207-4d97-aa64-58636b323acc/files/r6969z144v; doi:https://doi.org/10.1056/NEJMoa2204233; html:https://europepmc.org/articles/PMC7614055; pdf:https://europepmc.org/articles/PMC7614055?pdf=render
 33866023,https://doi.org/10.1016/j.oret.2021.04.001,Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade.,"Schwartz R, Warwick A, Olvera-Barrios A, Pikoula M, Lee AY, Denaxas S, Taylor P, Egan C, Chakravarthy U, Lip PL, Tufail A, of the UK EMR Users Group.",,Ophthalmology. Retina,2021,2021-04-16,N,AMD; Ranibizumab; Anti-vegf; Aflibercept; Electronic Health Records; Etdrs; Early Treatment Diabetic Retinopathy Study,,,"<h4>Purpose</h4>Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and medications. This study describes the treatment patterns and visual outcomes over 10 years in a large cohort of patients.<h4>Design</h4>Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare providers in the UK.<h4>Participants</h4>Treatment-naïve patients receiving at least 3 intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first 6 months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 years were excluded.<h4>Methods</h4>Eyes with at least 3 years of follow-up were grouped by years of treatment initiation, and 3-year outcomes were compared between the groups. Data were generated during routine clinical care between September 2008 and December 2018.<h4>Main outcome measures</h4>Visual acuity (VA), number of injections, and number of visits.<h4>Results</h4>A total of 15 810 eyes of 13 705 patients receiving 195 104 injections were included. Visual acuity improved from baseline during the first year, but decreased thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting VA over the decade. The number of injections decreased substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at 3 years.<h4>Conclusions</h4>Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165682; doi:https://doi.org/10.1016/j.oret.2021.04.001; html:https://europepmc.org/articles/PMC9165682; pdf:https://europepmc.org/articles/PMC9165682?pdf=render; doi:https://doi.org/10.1016/j.oret.2021.04.001
-32838035,https://doi.org/10.1002/lrh2.10236,Rapid translation of clinical guidelines into executable knowledge: A case study of COVID-19 and online demonstration.,"Fox J, Khan O, Curtis H, Wright A, Pal C, Cockburn N, Cooper J, Chandan JS, Nirantharakumar K.",,Learning health systems,2021,2020-07-14,Y,Artificial intelligence; Covid‐19; Rapid Learning Systems,,,"<h4>Introduction</h4>We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID-19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020.<h4>Methods</h4>The <i>PROforma</i> guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID-19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice.<h4>Results</h4><i>PROforma</i> and OpenClinical.net proved to be an effective combination for rapidly creating the COVID-19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746.<h4>Conclusions</h4>This is believed to be the first use of AI/knowledge engineering methods for disseminating best-practice in COVID-19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10236; doi:https://doi.org/10.1002/lrh2.10236; html:https://europepmc.org/articles/PMC7323421; pdf:https://europepmc.org/articles/PMC7323421?pdf=render
 31757515,https://doi.org/10.1016/j.jaci.2019.09.015,Atopic eczema and fracture risk in adults: A population-based cohort study.,"Lowe KE, Mansfield KE, Delmestri A, Smeeth L, Roberts A, Abuabara K, Prieto-Alhambra D, Langan SM.",,The Journal of allergy and clinical immunology,2020,2019-11-19,Y,Osteoporosis; Fracture; Atopic Eczema; Severity; Population Based,Understanding the Causes of Disease,,"<h4>Background</h4>Limited evidence suggests increased fracture risk in people with atopic eczema. Any link could have substantial effect; atopic eczema is common, and fractures have associated morbidity and mortality.<h4>Objective</h4>We sought to examine whether atopic eczema is associated with fracture and whether fracture risk varies with eczema severity.<h4>Methods</h4>We performed a matched cohort study set in primary care (Clinical Practice Research Datalink GOLD 1998-2016) and linked hospital admissions data (Hospital Episode Statistics), including adults (≥18 years old) with atopic eczema matched (by age, sex, general practice, and cohort entry date) with up to 5 individuals without eczema. We estimated hazard ratios (HRs) from stratified Cox regression comparing risk of major osteoporotic (hip, pelvis, spine, wrist, and proximal humerus) fractures individually and any fracture in those with and without atopic eczema.<h4>Results</h4>We identified 526,808 people with atopic eczema and 2,569,030 people without atopic eczema. Those with eczema had increased risk of hip (HR, 1.10; 99% CI, 1.06-1.14), pelvic (HR, 1.10; 99% CI, 1.02-1.19), spinal (HR, 1.18; 99% CI, 1.10-1.27), and wrist (HR, 1.07; 99% CI, 1.03,-1.11) fractures. We found no evidence of increased proximal humeral (HR, 1.06; 99% CI, 0.97-1.15) fracture risk. Fracture risk increased with increasing eczema severity, with the strongest associations in people with severe eczema (compared with those without) for spinal (HR, 2.09; 99% CI, 1.66-2.65), pelvic (HR, 1.66; 99% CI, 1.26-2.20), and hip (HR, 1.50; 99% CI, 1.30-1.74) fractures. Associations persisted after oral glucocorticoid adjustment.<h4>Conclusions</h4>People with atopic eczema have increased fracture risk, particularly major osteoporotic fractures.",This population-wide study used datalinkage methods to create a matched cohort study between 1998-2016. The study estimated hazard ratios and compared the risk of major fractures and any fracture in people with and without atopic eczema. Findings suggest that people with atopic eczema have an increased fracture risk.,pdf:http://www.jacionline.org/article/S0091674919312515/pdf; doi:https://doi.org/10.1016/j.jaci.2019.09.015; html:https://europepmc.org/articles/PMC7014587; pdf:https://europepmc.org/articles/PMC7014587?pdf=render
 31345952,https://doi.org/10.1136/heartjnl-2018-313855,Do beta-blockers and inhibitors of the renin-angiotensin aldosterone system improve outcomes in patients with heart failure and left ventricular ejection fraction >40%?,"Lumbers RT, Martin N, Manoharan K, Thomas J, Davies LC.",,Heart (British Cardiac Society),2019,2019-07-25,N,Pharmacology; Meta-analysis; epidemiology; Heart Failure With Preserved Ejection Fraction; Systemic Review,,,,,doi:https://doi.org/10.1136/heartjnl-2018-313855
 35953815,https://doi.org/10.1186/s12931-022-02130-6,Dynamic early warning scores for predicting clinical deterioration in patients with respiratory disease.,"Gonem S, Taylor A, Figueredo G, Forster S, Quinlan P, Garibaldi JM, McKeever TM, Shaw D.",,Respiratory research,2022,2022-08-11,Y,Risk Prediction; Clinical Deterioration; Early Warning Score,,,"<h4>Background</h4>The National Early Warning Score-2 (NEWS-2) is used to detect patient deterioration in UK hospitals but fails to take account of the detailed granularity or temporal trends in clinical observations. We used data-driven methods to develop dynamic early warning scores (DEWS) to address these deficiencies, and tested their accuracy in patients with respiratory disease for predicting (1) death or intensive care unit admission, occurring within 24 h (D/ICU), and (2) clinically significant deterioration requiring urgent intervention, occurring within 4 h (CSD).<h4>Methods</h4>Clinical observations data were extracted from electronic records for 31,590 respiratory in-patient episodes from April 2015 to December 2020 at a large acute NHS Trust. The timing of D/ICU was extracted for all episodes. 1100 in-patient episodes were annotated manually to record the timing of CSD, defined as a specific event requiring a change in treatment. Time series features were entered into logistic regression models to derive DEWS for each of the clinical outcomes. Area under the receiver operating characteristic curve (AUROC) was the primary measure of model accuracy.<h4>Results</h4>AUROC (95% confidence interval) for predicting D/ICU was 0.857 (0.852-0.862) for NEWS-2 and 0.906 (0.899-0.914) for DEWS in the validation data. AUROC for predicting CSD was 0.829 (0.817-0.842) for NEWS-2 and 0.877 (0.862-0.892) for DEWS. NEWS-2 ≥ 5 had sensitivity of 88.2% and specificity of 54.2% for predicting CSD, while DEWS ≥ 0.021 had higher sensitivity of 93.6% and approximately the same specificity of 54.3% for the same outcome. Using these cut-offs, 315 out of 347 (90.8%) CSD events were detected by both NEWS-2 and DEWS, at the time of the event or within the previous 4 h; 12 (3.5%) were detected by DEWS but not by NEWS-2, while 4 (1.2%) were detected by NEWS-2 but not by DEWS; 16 (4.6%) were not detected by either scoring system.<h4>Conclusion</h4>We have developed DEWS that display greater accuracy than NEWS-2 for predicting clinical deterioration events in patients with respiratory disease. Prospective validation studies are required to assess whether DEWS can be used to reduce missed deteriorations and false alarms in real-life clinical settings.",,pdf:https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-022-02130-6; doi:https://doi.org/10.1186/s12931-022-02130-6; html:https://europepmc.org/articles/PMC9367123; pdf:https://europepmc.org/articles/PMC9367123?pdf=render
 30972781,https://doi.org/10.1111/apt.15232,Early and late mortality following unscheduled admissions for severe liver disease across England and Wales.,"Roberts SE, John A, Brown J, Napier DJ, Lyons RA, Williams JG.",,Alimentary pharmacology & therapeutics,2019,2019-04-11,Y,,,,"<h4>Background</h4>There is a known shortfall in hepatology service resources across England and Wales.<h4>Aim</h4>To investigate early and late mortality following unscheduled admissions for severe liver disease, overall and by cause of death, and to determine how mortality is related to admissions to transplant centres, transplant surgery, hospital size, consultant specialty, patient socio-demographics, seasonal and geographical factors.<h4>Methods</h4>Cohorts of people with a first unscheduled admission for severe liver disease across England and Wales from 2004, based on record linkage of national inpatient and mortality data.<h4>Findings</h4>Mortality for alcoholic liver disease and hepatic failure was 23.4% and 35.4% respectively at 60 days and 61.8% and 57.1% at 5 years. Standardised mortality ratios (SMRs) were extremely high at 60 days (184 and 117 respectively) and remained highly increased at 5 years (16.7 and 6.3). Mortality at 5 years was most elevated from liver disease, viral hepatitis and varices. The 60-day mortality was significantly lower for patients seen by consultant hepatologists and gastroenterologists. Both early and late mortality were significantly reduced for patients admitted to transplant centres or larger hospitals, who received a liver transplant, or were resident in London. Early mortality was significantly higher for patients admitted in winter and autumn, while elevated mortality among the most vs least deprived quintile increased with longer follow-up.<h4>Conclusions</h4>The study shows a very poor prognosis for people with unscheduled hospitalisation for severe liver disease. The findings suggest that access to specialist expertise and services improves survival, both in the short and long term.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.15232; doi:https://doi.org/10.1111/apt.15232; html:https://europepmc.org/articles/PMC6519290; pdf:https://europepmc.org/articles/PMC6519290?pdf=render
 36240828,https://doi.org/10.1016/s2214-109x(22)00358-8,Prediction of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study.,"Ali ST, Lau YC, Shan S, Ryu S, Du Z, Wang L, Xu XK, Chen D, Xiong J, Tae J, Tsang TK, Wu P, Lau EHY, Cowling BJ.",,The Lancet. Global health,2022,2022-11-01,Y,,,,"<h4>Background</h4>The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics.<h4>Methods</h4>For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect.<h4>Findings</h4>We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes.<h4>Interpretation</h4>Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community.<h4>Funding</h4>Health and Medical Research Fund, Hong Kong.",,pdf:https://www.repository.cam.ac.uk/bitstreams/bb5465bd-c08f-4c3d-ab0e-87fee39fc92b/download; doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849
 36689332,https://doi.org/10.1093/neuonc/noad021,GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.,"Ajaib S, Lodha D, Pollock S, Hemmings G, Finetti MA, Gusnanto A, Chakrabarty A, Ismail A, Wilson E, Varn FS, Hunter B, Filby A, Brockman AA, McDonald D, Verhaak RGW, Ihrie RA, Stead LF.",,Neuro-oncology,2023,2023-07-01,Y,Immune; Deconvolution; Glioblastoma; Neoplastic; Transcriptomics,,,"<h4>Background</h4>Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data.<h4>Methods</h4>We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumors, to determine which deconvolution approach performed best.<h4>Results</h4>Marker-based deconvolution using GBM-tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis.<h4>Conclusions</h4>GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.",,pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?pdf=render
-37278928,https://doi.org/10.1007/s12265-023-10398-2,Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers.,"Jansen M, Schmidt AF, Jans JJM, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Lekanne Deprez RH, Wilde AAM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,Journal of cardiovascular translational research,2023,2023-06-06,N,Metabolism; Biomarker; hypertrophic cardiomyopathy; Acylcarnitine; Mybpc3,,,"Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G + P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G + P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G + P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p = 0.005 and coefficient 0.803, p = 0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p = 0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.",,pdf:https://link.springer.com/content/pdf/10.1007/s12265-023-10398-2.pdf; doi:https://doi.org/10.1007/s12265-023-10398-2
 34426417,https://doi.org/10.1136/bmjhci-2021-100385,Review of study reporting guidelines for clinical studies using artificial intelligence in healthcare. ,"Shelmerdine SC, Arthurs OJ, Denniston A, Sebire NJ.",,BMJ health & care informatics,2021,2021-08-01,Y,,,,"High-quality research is essential in guiding evidence-based care, and should be reported in a way that is reproducible, transparent and where appropriate, provide sufficient detail for inclusion in future meta-analyses. Reporting guidelines for various study designs have been widely used for clinical (and preclinical) studies, consisting of checklists with a minimum set of points for inclusion. With the recent rise in volume of research using artificial intelligence (AI), additional factors need to be evaluated, which do not neatly conform to traditional reporting guidelines (eg, details relating to technical algorithm development). In this review, reporting guidelines are highlighted to promote awareness of essential content required for studies evaluating AI interventions in healthcare. These include published and in progress extensions to well-known reporting guidelines such as Standard Protocol Items: Recommendations for Interventional Trials-AI (study protocols), Consolidated Standards of Reporting Trials-AI (randomised controlled trials), Standards for Reporting of Diagnostic Accuracy Studies-AI (diagnostic accuracy studies) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis-AI (prediction model studies). Additionally there are a number of guidelines that consider AI for health interventions more generally (eg, Checklist for Artificial Intelligence in Medical Imaging (CLAIM), minimum information (MI)-CLAIM, MI for Medical AI Reporting) or address a specific element such as the 'learning curve' (Developmental and Exploratory Clinical Investigation of Decision-AI) . Economic evaluation of AI health interventions is not currently addressed, and may benefit from extension to an existing guideline. In the face of a rapid influx of studies of AI health interventions, reporting guidelines help ensure that investigators and those appraising studies consider both the well-recognised elements of good study design and reporting, while also adequately addressing new challenges posed by AI-specific elements.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100385.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100385; html:https://europepmc.org/articles/PMC8383863; pdf:https://europepmc.org/articles/PMC8383863?pdf=render
 35504525,https://doi.org/10.1016/j.jclinepi.2022.04.025,How traditional informed consent impairs inclusivity in a learning healthcare system: lessons learned from the Utrecht Cardiovascular Cohort.,"Groenhof TKJ, Mostert M, Lea NC, Haitjema S, de Vries MC, van Dijk WB, Grobbee DE, Asselbergs FW, Bots ML, van der Graaf R.",,Journal of clinical epidemiology,2022,2022-04-30,N,,,,,,doi:https://doi.org/10.1016/j.jclinepi.2022.04.025
+37278928,https://doi.org/10.1007/s12265-023-10398-2,Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers.,"Jansen M, Schmidt AF, Jans JJM, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Lekanne Deprez RH, Wilde AAM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,Journal of cardiovascular translational research,2023,2023-06-06,N,Metabolism; Biomarker; hypertrophic cardiomyopathy; Acylcarnitine; Mybpc3,,,"Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G + P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G + P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G + P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p = 0.005 and coefficient 0.803, p = 0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p = 0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.",,pdf:https://link.springer.com/content/pdf/10.1007/s12265-023-10398-2.pdf; doi:https://doi.org/10.1007/s12265-023-10398-2
 36819459,https://doi.org/10.1210/jendso/bvad020,"Polygenic Risk of Prediabetes, Undiagnosed Diabetes, and Incident Type 2 Diabetes Stratified by Diabetes Risk Factors.","Liu X, Collister JA, Clifton L, Hunter DJ, Littlejohns TJ.",,Journal of the Endocrine Society,2023,2023-01-30,Y,BMI; Family History; Polygenic Risk And Diabetes,,,"<h4>Context</h4>Early diagnosis of type 2 diabetes is crucial to reduce severe comorbidities and complications. Current screening recommendations for type 2 diabetes include traditional risk factors, primarily body mass index (BMI) and family history, however genetics also plays a key role in type 2 diabetes risk. It is important to understand whether genetic predisposition to type 2 diabetes modifies the effect of these traditional factors on type 2 diabetes risk.<h4>Objective</h4>This work aimed to investigate whether genetic risk of type 2 diabetes modifies associations between BMI and first-degree family history of diabetes with 1) prevalent prediabetes or undiagnosed diabetes; and 2) incident confirmed type 2 diabetes.<h4>Methods</h4>We included 431 658 individuals aged 40 to 69 years at baseline of multiethnic ancestry from the UK Biobank. We used a multiethnic polygenic risk score for type 2 diabetes (PRS<sub>T2D</sub>) developed by Genomics PLC. Prediabetes or undiagnosed diabetes was defined as baseline glycated hemoglobin greater than or equal to 42 mmol/mol (6.0%), and incident type 2 diabetes was derived from medical records.<h4>Results</h4>At baseline, 43 472 participants had prediabetes or undiagnosed diabetes, and 17 259 developed type 2 diabetes over 15 years follow-up. Dose-response associations were observed for PRS<sub>T2D</sub> with each outcome in each category of BMI or first-degree family history of diabetes. Those in the highest quintile of PRS<sub>T2D</sub> with a normal BMI were at a similar risk as those in the middle quintile who were overweight. Participants who were in the highest quintile of PRS<sub>T2D</sub> and did not have a first-degree family history of diabetes were at a similar risk as those with a family history who were in the middle category of PRS<sub>T2D</sub>.<h4>Conclusion</h4>Genetic risk of type 2 diabetes remains strongly associated with risk of prediabetes, undiagnosed diabetes, and future type 2 diabetes within categories of nongenetic risk factors. This could have important implications for identifying individuals at risk of type 2 diabetes for prevention and early diagnosis programs.",,pdf:https://academic.oup.com/jes/article-pdf/7/4/bvad020/49229172/bvad020.pdf; doi:https://doi.org/10.1210/jendso/bvad020; html:https://europepmc.org/articles/PMC9933896; pdf:https://europepmc.org/articles/PMC9933896?pdf=render
 31822919,https://doi.org/10.1093/pubmed/fdz172,"Unmet needs of women with GDM: a health needs assessment in Sandwell, West Midlands.","Plant N, Šumilo D, Chapman R, Webber J, Saravanan P, Nirantharakumar K.",,"Journal of public health (Oxford, England)",2020,2020-11-01,N,United Kingdom; Needs Assessment; Gestational Diabetes,,,"<h4>Background</h4>Gestational diabetes mellitus (GDM) affects over 4% of pregnancies in England. We investigated GDM epidemiology within ethnically diverse population and the current offer of services to women with previous GDM to reduce their type 2 diabetes mellitus (T2DM) risk.<h4>Methods</h4>(i) Analysis of routinely collected maternity data examining GDM incidence and risk factors; (ii) local authority self-assessment questionnaire on public health interventions targeting women with previous GDM and (iii) service development discussions regarding the current pathway and areas for improvement.<h4>Results</h4>Of 9390 births between 2014 and 2018, 6.8% had a record of GDM. High body mass index (BMI), maternal age, and ethnicity (South Asian and some mixed ethnic backgrounds) were independent predictors of GDM. There were no public health commissioned services specifically targeting women with previous GDM. Weaknesses in transition from secondary to primary care and areas for improvement when screening for GDM were identified.<h4>Conclusions</h4>GDM burden in this population was high. Awareness should be raised on the importance of regular glucose testing and lifestyle modification to delay or prevent progression to T2DM, particularly within high risk groups. The potential for health visitors to contribute to this should be explored. Commissioners should review evidence to develop a flexible lifestyle services model to meet the specific needs of these women.",,pdf:https://academic.oup.com/jpubhealth/article-pdf/42/4/e516/34469316/fdz172.pdf; doi:https://doi.org/10.1093/pubmed/fdz172
 37751444,https://doi.org/10.1371/journal.pone.0290583,Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,PloS one,2023,2023-09-26,Y,,,,"<h4>Background</h4>Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.<h4>Aims</h4>To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.<h4>Methods</h4>We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.<h4>Results</h4>We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.<h4>Conclusions</h4>Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render
@@ -1293,39 +1293,39 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 35692035,https://doi.org/10.1186/s12916-022-02399-w,"Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.","Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,BMC medicine,2022,2022-06-13,Y,Fatty acids; Cardiovascular diseases; Mendelian Randomization,,,"<h4>Background</h4>Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization.<h4>Methods</h4>We conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis).<h4>Results</h4>GWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8-7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol.<h4>Conclusions</h4>We have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02399-w; doi:https://doi.org/10.1186/s12916-022-02399-w; html:https://europepmc.org/articles/PMC9190170; pdf:https://europepmc.org/articles/PMC9190170?pdf=render
 35351727,https://doi.org/10.1136/bmjopen-2021-057909,Impact of chronic kidney disease on case ascertainment for hospitalised acute myocardial infarction: an English cohort study.,"Bidulka P, Scott J, Taylor DM, Udayaraj U, Caskey F, Teece L, Sweeting M, Deanfield J, de Belder M, Denaxas S, Weston C, Adlam D, Nitsch D.",,BMJ open,2022,2022-03-28,Y,Myocardial infarction; Cardiology; Nephrology; Audit; Statistics & Research Methods,,,"<h4>Objectives</h4>Acute myocardial infarction (AMI) case ascertainment improves for the UK general population using linked health data sets. Because care pathways for people with chronic kidney disease (CKD) change based on disease severity, AMI case ascertainment for these people may differ compared with the general population. We aimed to determine the association between CKD severity and AMI case ascertainment in two secondary care data sets, and the agreement in estimated glomerular filtration rate (eGFR) between the same data sets.<h4>Methods</h4>We used a cohort study design. Primary care records for people with CKD or risk factors for CKD, identified using the National CKD Audit (2015-2017), were linked to the Myocardial Ischaemia National Audit Project (MINAP, 2007-2017) and Hospital Episode Statistics (HES, 2007-2017) secondary care registries. People with an AMI recorded in either MINAP, HES or both were included in the study cohort. CKD status was defined using eGFR, derived from the most recent serum creatinine value recorded in primary care. Moderate-severe CKD was defined as eGFR <60 mL/min/1.73 m<sup>2</sup>, and mild CKD or at risk of CKD was defined as eGFR ≥60 mL/min/1.73 m<sup>2</sup> or eGFR missing. CKD stages were grouped as (1) At risk of CKD and Stages 1-2 (eGFR missing or ≥60 mL/min/1.73 m<sup>2</sup>), (2) Stage 3a (eGFR 45-59 mL/min/1.73 m<sup>2</sup>), (3) Stage 3b (eGFR 30-44 mL/min/1.73 m<sup>2</sup>) and (4) Stages 4-5 (eGFR <30 mL/min/1.73 m<sup>2</sup>).<h4>Results</h4>We identified 6748 AMIs: 23% were recorded in both MINAP and HES, 66% in HES only and 11% in MINAP only. Compared with people at risk of CKD or with mild CKD, AMIs in people with moderate-severe CKD were more likely to be recorded in both MINAP and HES (42% vs 11%, respectively), or MINAP only (22% vs 5%), and less likely to be recorded in HES only (36% vs 84%). People with AMIs recorded in HES only or MINAP only had increased odds of death during hospitalisation compared with those recorded in both (adjusted OR 1.61, 95% CI 1.32 to 1.96 and OR 1.60, 95% CI 1.26 to 2.04, respectively). Agreement between eGFR at AMI admission (MINAP) and in primary care was poor (kappa (K) 0.42, SE 0.012).<h4>Conclusions</h4>AMI case ascertainment is incomplete in both MINAP and HES, and is associated with CKD severity.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/3/e057909.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057909; html:https://europepmc.org/articles/PMC8961119; pdf:https://europepmc.org/articles/PMC8961119?pdf=render
 35177264,https://doi.org/10.1016/j.injury.2022.02.027,Chronic physical health conditions up to five years after serious orthopaedic injury.,"Gelaw AY, Gabbe BJ, Ekegren CL.",,Injury,2022,2022-02-09,N,Chronic Conditions; Cvd; Major Trauma; Orthopaedic Trauma; Physical Health Conditions; Orthopaedic Injury,,,"<h4>Background</h4>Information about the prevalence of chronic physical health conditions following serious orthopaedic injury is currently lacking in the general population and is essential for quantifying the burden of injury and improving outcomes.<h4>Objectives</h4>To determine the prevalence of chronic physical health conditions recorded within hospitalisations and emergency department presentations and associated factors five years following serious orthopaedic injury.<h4>Methods</h4>We conducted a registry-based cohort study using data from the Victorian State Trauma Registry (2007-2016) linked with hospital admissions and ED presentations for 16,249 adults with serious orthopaedic injuries. We considered that people who were admitted to hospital or presented to an emergency department with a chronic physical health condition one to five years post-injury had ""new-onset"" conditions. We applied Kaplan-Meier failure curves and Cox proportional hazard regression models to determine factors associated with new-onset conditions.<h4>Results</h4>There were 1420 people (11.0%) with at least one new-onset condition. Cancer (6.1%), cardiovascular disease (5.1%) and hypertension (6.2%) were the three most common ""new-onset"" chronic physical health conditions. Older adults, women, smokers, and people with mental health and alcohol and drug-related conditions had a higher risk of hospitalisation or emergency department presentation with new-onset conditions post-injury.<h4>Conclusion</h4>People with serious orthopaedic injuries experienced a significant additional burden of chronic physical health conditions up to five years after serious orthopaedic injury, posing a new challenge to post-trauma care. Early preventive interventions may be required in people with serious orthopaedic injuries to minimise modifiable risk factors such as smoking, excessive consumption of alcohol or drug use.",,doi:https://doi.org/10.1016/j.injury.2022.02.027
-35916366,https://doi.org/10.7554/elife.76272,Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans.,"Lemmelä S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T, Wollert KC, Blankenberg S, Zeller T, Peters JE, Salomaa V, Fritsch M, March R, Palotie A, Daly M, Butterworth AS, Kinnunen M, Paul DS, Matakidou A.",,eLife,2022,2022-08-02,Y,Human; Genetics; Obesity; Genomics; BMI; epidemiology; Causality; Global Health; Gdf15; Mendelian Randomisation,,,"Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in <i>GDF15</i>, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW p<sub>FDR</sub> = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.",,doi:https://doi.org/10.7554/elife.76272; doi:https://doi.org/10.7554/eLife.76272; html:https://europepmc.org/articles/PMC9391041; pdf:https://europepmc.org/articles/PMC9391041?pdf=render
 34018481,https://doi.org/10.2807/1560-7917.es.2021.26.20.2100428,The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant.,"Hodgson D, Flasche S, Jit M, Kucharski AJ, CMMID COVID-19 Working Group, Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-05-01,Y,Vaccination; Herd immunity; Seroprevalence; Sars-cov-2,,,"We assess the feasibility of reaching the herd immunity threshold against SARS-CoV-2 through vaccination, considering vaccine effectiveness (VE), transmissibility of the virus and the level of pre-existing immunity in populations, as well as their age structure. If highly transmissible variants of concern become dominant in areas with low levels of naturally-acquired immunity and/or in populations with large proportions of < 15 year-olds, control of infection without non-pharmaceutical interventions may only be possible with a VE ≥ 80%, and coverage extended to children.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/20/eurosurv-26-20-1.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.20.2100428&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428; html:https://europepmc.org/articles/PMC8138959; pdf:https://europepmc.org/articles/PMC8138959?pdf=render
+35916366,https://doi.org/10.7554/elife.76272,Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans.,"Lemmelä S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T, Wollert KC, Blankenberg S, Zeller T, Peters JE, Salomaa V, Fritsch M, March R, Palotie A, Daly M, Butterworth AS, Kinnunen M, Paul DS, Matakidou A.",,eLife,2022,2022-08-02,Y,Human; Genetics; Obesity; Genomics; BMI; epidemiology; Causality; Global Health; Gdf15; Mendelian Randomisation,,,"Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in <i>GDF15</i>, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW p<sub>FDR</sub> = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.",,doi:https://doi.org/10.7554/elife.76272; doi:https://doi.org/10.7554/eLife.76272; html:https://europepmc.org/articles/PMC9391041; pdf:https://europepmc.org/articles/PMC9391041?pdf=render
 32524641,https://doi.org/10.1002/sim.8556,Selective recruitment designs for improving observational studies using electronic health records.,"Barrett JE, Cakiroglu A, Bunce C, Shah A, Denaxas S.",,Statistics in medicine,2020,2020-06-10,Y,Electronic Health Records; Observational Study; Optimal Experimental Design; Selective Recruitment,,,"Large-scale electronic health records (EHRs) present an opportunity to quickly identify suitable individuals in order to directly invite them to participate in an observational study. EHRs can contain data from millions of individuals, raising the question of how to optimally select a cohort of size n from a larger pool of size N. In this article, we propose a simple selective recruitment protocol that selects a cohort in which covariates of interest tend to have a uniform distribution. We show that selectively recruited cohorts potentially offer greater statistical power and more accurate parameter estimates than randomly selected cohorts. Our protocol can be applied to studies with multiple categorical and continuous covariates. We apply our protocol to a numerically simulated prospective observational study using an EHR database of stable acute coronary disease patients from 82 089 individuals in the U.K. Selective recruitment designs require a smaller sample size, leading to more efficient and cost-effective studies.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8556; doi:https://doi.org/10.1002/sim.8556; html:https://europepmc.org/articles/PMC8432147; pdf:https://europepmc.org/articles/PMC8432147?pdf=render
 34095527,https://doi.org/10.23889/ijpds.v4i1.581,Electronic Longitudinal Alcohol Study in Communities (ELAStiC) Wales - protocol for platform development.,"Trefan L, Akbari A, Paranjothy S, Farewell DM, Gartner A, Fone D, Greene J, Evans A, Smith A, Adekanmbi V, Kennedy J, Lyons RA, Moore SC.",,International journal of population data science,2019,2019-05-20,Y,,,,"<h4>Introduction</h4>Excessive alcohol consumption has adverse effects on health and there is a recognised need for the longitudinal analysis of population data to improve our understanding of the patterns of alcohol use, harms to consumers and those in their immediate environment. The UK has a number of linkable, longitudinal databases that if assembled properly could support valuable research on this topic.<h4>Aims and objectives</h4>This paper describes the development of a broad set of cross-linked cohorts, e-cohorts, surveys and linked electronic healthcare records (EHRs) to construct an alcohol-specific analytical platform in the United Kingdom using datasets on the population of Wales.The objective of this paper is to provide a description of existing key datasets integrated with existing, routinely collected electronic health data on a secure platform, and relevant derived variables to enable population-based research on alcohol-related harm in Wales. We illustrate our use of these data with some exemplar research questions that are currently under investigation.<h4>Methods</h4>Record-linkage of routine and observational datasets. Routine data includes hospital admissions, general practice, and cohorts specific to children. Two observational studies were included. Routine socioeconomic descriptors and mortality data were also linked.<h4>Conclusion</h4>We described a record-linked, population-based research protocol for alcohol related harm on a secure platform. As the datasets used here are available in many countries, ELAStiC provides a template for setting up similar initiatives in other countries. We have also defined a number of alcohol specific variables using routinely-collected available data that can be used in other epidemiological studies into alcohol related outcomes. With over 10 years of longitudinal data, it will help to understand alcohol-related disease and health trajectories across the lifespan.",,pdf:https://ijpds.org/article/download/581/2923; doi:https://doi.org/10.23889/ijpds.v4i1.581; html:https://europepmc.org/articles/PMC8142962; pdf:https://europepmc.org/articles/PMC8142962?pdf=render
 32142356,https://doi.org/10.1164/rccm.201902-0286oc,"Prenatal, Early-Life, and Childhood Exposure to Air Pollution and Lung Function: The ALSPAC Cohort.","Cai Y, Hansell AL, Granell R, Blangiardo M, Zottoli M, Fecht D, Gulliver J, Henderson AJ, Elliott P.",,American journal of respiratory and critical care medicine,2020,2020-07-01,N,Air pollution; Children; Traffic; Alspac; Respiratory Health,,,"<b>Rationale</b>: Exposure to air pollution during intrauterine development and through childhood may have lasting effects on respiratory health.<b>Objectives</b>: To investigate lung function at ages 8 and 15 years in relation to air pollution exposures during pregnancy, infancy, and childhood in a UK population-based birth cohort.<b>Methods</b>: Individual exposures to source-specific particulate matter ≤10 μm in aerodynamic diameter (PM<sub>10</sub>) during each trimester, 0-6 months, 7-12 months (1990-1993), and up to age 15 years (1991-2008) were examined in relation to FEV<sub>1</sub>% predicted and FVC% predicted at ages 8 (<i>n</i> = 5,276) and 15 (<i>n</i> = 3,446) years using linear regression models adjusted for potential confounders. A profile regression model was used to identify sensitive time periods.<b>Measurements and Main Results</b>: We did not find clear evidence of a sensitive exposure period for PM<sub>10</sub> from road traffic. At age 8 years, 1 μg/m<sup>3</sup> higher exposure during the first trimester was associated with lower FEV<sub>1</sub>% predicted (-0.826; 95% confidence interval [CI], -1.357 to -0.296) and FVC% predicted (-0.817; 95% CI, -1.357 to -0.276), but similar associations were seen for exposures for other trimesters, 0-6 months, 7-12 months, and 0-7 years. Associations were stronger among boys, as well as children whose mother had a lower education level or smoked during pregnancy. For PM<sub>10</sub> from all sources, the third trimester was associated with lower FVC% predicted (-1.312; 95% CI, -2.100 to -0.525). At age 15 years, no adverse associations with lung function were seen.<b>Conclusions</b>: Exposure to road-traffic PM<sub>10</sub> during pregnancy may result in small but significant reductions in lung function at age 8 years.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328307; doi:https://doi.org/10.1164/rccm.201902-0286OC; html:https://europepmc.org/articles/PMC7328307; pdf:https://europepmc.org/articles/PMC7328307?pdf=render; doi:https://doi.org/10.1164/rccm.201902-0286oc
 32651323,https://doi.org/10.3233/jad-200338,"Alzheimer's Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769).","Ferguson AC, Tank R, Lyall LM, Ward J, Celis-Morales C, Strawbridge R, Ho F, Whelan CD, Gill J, Welsh P, Anderson JJ, Mark PB, Mackay DF, Smith DJ, Pell JP, Cavanagh J, Sattar N, Lyall DM.",,Journal of Alzheimer's disease : JAD,2020,2020-01-01,N,Cholesterol; apoE; Alzheimer’s disease; Dementia; Uk Biobank,,,"<h4>Background</h4>Alzheimer's disease (AD) is a neurodegenerative condition where the underlying etiology is still unclear. Investigating the potential influence of apolipoprotein E (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk.<h4>Objective</h4>Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank.<h4>Methods</h4>After quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers.<h4>Results</h4>Several biomarkers significantly associated with APOEɛ4 'risk' and ɛ2 'protective' genotypes (versus neutral ɛ3/ɛ3). Most associations supported previous data: for example, ɛ4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p < 0.001) and ɛ2 with lower LDL (b = -0.456 SDs, p < 0.001). There were however instances of associations found in unexpected directions: e.g., ɛ4 and increased insulin-like growth factor (IGF-1) (b = 0.017, p < 0.001) where lower levels have been previously suggested as an AD risk factor.<h4>Conclusion</h4>These findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence herein supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.",,pdf:https://eprints.gla.ac.uk/217500/1/217500.pdf; doi:https://doi.org/10.3233/JAD-200338
 35802687,https://doi.org/10.1371/journal.pone.0270668,"Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.","Godolphin PJ, Fisher DJ, Berry LR, Derde LPG, Diaz JV, Gordon AC, Lorenzi E, Marshall JC, Murthy S, Shankar-Hari M, Sterne JAC, Tierney JF, Vale CL.",,PloS one,2022,2022-07-08,Y,,,,"<h4>Background</h4>A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence.<h4>Methods</h4>Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence.<h4>Findings</h4>One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71-0·95, p = 0·008]] and sarilumab [0·80 [0·61-1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81-1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28.<h4>Conclusions</h4>Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable; doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render
-37814896,https://doi.org/10.1161/circgen.123.004181,Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.,"Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Thomas Lumbers R, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.",,Circulation. Genomic and precision medicine,2023,2023-10-10,N,Phenotype; Myocardial infarction; Biomarker; Cardiovascular disease; epigenomics,,,,,doi:https://doi.org/10.1161/CIRCGEN.123.004181
 33719753,https://doi.org/10.1080/13607863.2021.1893270,Cognition in informal caregivers: evidence from an English population study.,"García-Castro FJ, Bendayan R, Dobson RJB, Blanca MJ.",,Aging & mental health,2022,2021-03-14,N,Older Adults; Executive Function; Verbal Memory; Caregiving Duration,,,"<h4>Background and objectives</h4>The relationship between caregiving and cognition remains unclear. We investigate this association comparing four cognitive tasks and exploring the role of potential explanatory pathways such as healthy behaviours (healthy caregiver hypothesis) and depression (stress process model).<h4>Research design and methods</h4>Respondents were from English Longitudinal Study of Ageing (ELSA) (<i>N</i> = 8910). Cognitive tasks included immediate and delayed word recall, verbal fluency and serial 7 subtraction. Series of hierarchical linear regressions were performed. Adjustments included socio-demographics, health related variables, health behaviours and depression.<h4>Results</h4>Being a caregiver was positively associated with immediate and delayed recall, verbal fluency but not with serial 7. For immediate and delayed recall, these associations were partially attenuated when adjusting for health behaviours, and depression. For verbal fluency, associations were partially attenuated when adjusting for depression but fully attenuated when adjusting for health behaviours. No associations were found for serial 7.<h4>Discussion and implications</h4>Our findings show that caregivers have higher level of memory and executive function compared to non-caregivers. For memory, we found that although health behaviours and depression can have a role in this association, they do not fully explain it. However, health behaviours seem to have a clear role in the association with executive function. Public health and policy do not need to target specifically cognitive function but other areas as the promotion of healthy behaviours and psychological adjustment such as preventing depression and promoting physical activity in caregivers.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/13607863.2021.1893270?needAccess=true; doi:https://doi.org/10.1080/13607863.2021.1893270
-37270201,https://doi.org/10.1136/heartjnl-2023-322616,Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data.,"Harper C, Mafham M, Herrington W, Staplin N, Stevens W, Wallendszus K, Haynes R, Landray MJ, Parish S, Bowman L, Armitage J.",,Heart (British Cardiac Society),2023,2023-09-13,Y,"Atherosclerosis; Research Design; Electronic Health Records; Outcome Assessment, Health Care",,,"<h4>Objective</h4>To assess how reliable UK routine data are for ascertaining major bleeding events compared with adjudicated follow-up.<h4>Methods</h4>The ASCEND (A Study of Cardiovascular Events iN Diabetes) primary prevention trial randomised 15 480 UK people with diabetes to aspirin versus matching placebo. The primary safety outcome was major bleeding (including intracranial haemorrhage, sight-threatening eye bleeding, serious gastrointestinal bleeding and other major bleeding (epistaxis, haemoptysis, haematuria, vaginal and other bleeding)) ascertained by direct-participant mail-based follow-up, with >90% of outcomes undergoing adjudication. Nearly all participants were linked to routinely collected hospitalisation and death data (ie, routine data). An algorithm categorised bleeding events from routine data as major/minor. Kappa statistics were used to assess agreement between data sources, and randomised comparisons were re-run using routine data.<h4>Results</h4>When adjudicated follow-up and routine data were compared, there was agreement for 318 major bleeding events, with routine data identifying 281 additional-potential events, and not identifying 241 participant-reported events (kappa 0.53, 95% CI 0.49 to 0.57). Repeating ASCEND's randomised comparisons using routine data only found estimated relative and absolute effects of allocation to aspirin versus placebo on major bleeding similar to adjudicated follow-up (adjudicated follow-up: aspirin 314 (4.1%) vs placebo 245 (3.2%); rate ratio (RR) 1.29, 95% CI 1.09 to 1.52; absolute excess +6.3/5000 person-years (mean SE±2.1); vs routine data: 327 (4.2%) vs 272 (3.5%); RR 1.21, 95% CI 1.03 to 1.41; absolute excess +5.0/5000 (±2.2)).<h4>Conclusions</h4>Analyses of the ASCEND randomised trial found that major bleeding events ascertained via UK routine data sources provided relative and absolute treatment effects similar to adjudicated follow-up.<h4>Trial registration number</h4>ISRCTN60635500; NCT00135226.",,pdf:https://heart.bmj.com/content/heartjnl/early/2023/06/02/heartjnl-2023-322616.full.pdf; doi:https://doi.org/10.1136/heartjnl-2023-322616; html:https://europepmc.org/articles/PMC10511984; pdf:https://europepmc.org/articles/PMC10511984?pdf=render
+37814896,https://doi.org/10.1161/circgen.123.004181,Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.,"Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Thomas Lumbers R, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.",,Circulation. Genomic and precision medicine,2023,2023-10-10,N,Phenotype; Myocardial infarction; Biomarker; Cardiovascular disease; epigenomics,,,,,doi:https://doi.org/10.1161/CIRCGEN.123.004181
 36752447,https://doi.org/10.1016/j.jcmg.2022.11.012,Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis.,"Wang J, Zhang J, Hosadurg N, Iwanaga Y, Chen Y, Liu W, Wan K, Patel AR, Wicks EC, Gkoutos GV, Han Y, Chen Y.",,JACC. Cardiovascular imaging,2023,2023-01-11,N,Right Ventricle; Sudden Cardiac Death; Cardiac Sarcoidosis; Cardiac Magnetic Resonance; Late Gadolinium Enhancement,,,"<h4>Background</h4>Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.<h4>Objectives</h4>This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.<h4>Methods</h4>This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95% CIs were weighted and summarized.<h4>Results</h4>Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 ± 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95% CI: 1.7-5.5; P < 0.01) for composite events and 3.0 (95% CI: 1.3-7.0; P < 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95% CI: 2.4-9.6]; P < 0.01) and a higher risk for SCD (RR: 9.5 [95% CI: 4.4-20.5]; P < 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95% CI: 0.8-0.9), 69% (95% CI: 50%-84%), and 90% (95% CI: 70%-97%), respectively.<h4>Conclusions</h4>In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.",,doi:https://doi.org/10.1016/j.jcmg.2022.11.012
+37270201,https://doi.org/10.1136/heartjnl-2023-322616,Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data.,"Harper C, Mafham M, Herrington W, Staplin N, Stevens W, Wallendszus K, Haynes R, Landray MJ, Parish S, Bowman L, Armitage J.",,Heart (British Cardiac Society),2023,2023-09-13,Y,"Atherosclerosis; Research Design; Electronic Health Records; Outcome Assessment, Health Care",,,"<h4>Objective</h4>To assess how reliable UK routine data are for ascertaining major bleeding events compared with adjudicated follow-up.<h4>Methods</h4>The ASCEND (A Study of Cardiovascular Events iN Diabetes) primary prevention trial randomised 15 480 UK people with diabetes to aspirin versus matching placebo. The primary safety outcome was major bleeding (including intracranial haemorrhage, sight-threatening eye bleeding, serious gastrointestinal bleeding and other major bleeding (epistaxis, haemoptysis, haematuria, vaginal and other bleeding)) ascertained by direct-participant mail-based follow-up, with >90% of outcomes undergoing adjudication. Nearly all participants were linked to routinely collected hospitalisation and death data (ie, routine data). An algorithm categorised bleeding events from routine data as major/minor. Kappa statistics were used to assess agreement between data sources, and randomised comparisons were re-run using routine data.<h4>Results</h4>When adjudicated follow-up and routine data were compared, there was agreement for 318 major bleeding events, with routine data identifying 281 additional-potential events, and not identifying 241 participant-reported events (kappa 0.53, 95% CI 0.49 to 0.57). Repeating ASCEND's randomised comparisons using routine data only found estimated relative and absolute effects of allocation to aspirin versus placebo on major bleeding similar to adjudicated follow-up (adjudicated follow-up: aspirin 314 (4.1%) vs placebo 245 (3.2%); rate ratio (RR) 1.29, 95% CI 1.09 to 1.52; absolute excess +6.3/5000 person-years (mean SE±2.1); vs routine data: 327 (4.2%) vs 272 (3.5%); RR 1.21, 95% CI 1.03 to 1.41; absolute excess +5.0/5000 (±2.2)).<h4>Conclusions</h4>Analyses of the ASCEND randomised trial found that major bleeding events ascertained via UK routine data sources provided relative and absolute treatment effects similar to adjudicated follow-up.<h4>Trial registration number</h4>ISRCTN60635500; NCT00135226.",,pdf:https://heart.bmj.com/content/heartjnl/early/2023/06/02/heartjnl-2023-322616.full.pdf; doi:https://doi.org/10.1136/heartjnl-2023-322616; html:https://europepmc.org/articles/PMC10511984; pdf:https://europepmc.org/articles/PMC10511984?pdf=render
 34769922,https://doi.org/10.3390/ijerph182111380,"Driver, Collision and Meteorological Characteristics of Motor Vehicle Collisions among Road Trauma Survivors. ","Giummarra MJ, Xu R, Guo Y, Dipnall JF, Ponsford J, Cameron PA, Ameratunga S, Gabbe BJ.",,International journal of environmental research and public health,2021,2021-10-29,Y,,,,"Road trauma remains a significant public health problem. We aimed to identify sub-groups of motor vehicle collisions in Victoria, Australia, and the association between collision characteristics and outcomes up to 24 months post-injury. Data were extracted from the Victorian State Trauma Registry for injured drivers aged ≥16 years, from 2010 to 2016, with a compensation claim who survived ≥12 months post-injury. People with intentional or severe head injury were excluded, resulting in 2735 cases. Latent class analysis was used to identify collision classes for driver fault and blood alcohol concentration (BAC), day and time of collision, weather conditions, single vs. multi-vehicle and regional vs. metropolitan injury location. Five classes were identified: (1) daytime multi-vehicle collisions, no other at fault; (2) daytime single-vehicle predominantly weekday collisions; (3) evening single-vehicle collisions, no other at fault, 36% with BAC ≥ 0.05; (4) sunrise or sunset weekday collisions; and (5) dusk and evening multi-vehicle in metropolitan areas with BAC < 0.05. Mixed linear and logistic regression analyses examined associations between collision class and return to work, health (EQ-5D-3L summary score) and independent function Glasgow Outcome Scale - Extended at 6, 12 and 24 months. After adjusting for demographic, health and injury characteristics, collision class was not associated with outcomes. Rather, risk of poor outcomes was associated with age, sex and socioeconomic disadvantage, education, pre-injury health and injury severity. People at risk of poor recovery may be identified from factors available during the hospital admission and may benefit from clinical assessment and targeted referrals and treatments.",,pdf:https://www.mdpi.com/1660-4601/18/21/11380/pdf?version=1635513758; doi:https://doi.org/10.3390/ijerph182111380; html:https://europepmc.org/articles/PMC8583338; pdf:https://europepmc.org/articles/PMC8583338?pdf=render
 35089054,https://doi.org/10.1161/circep.121.010221,Integrating Exercise Into Personalized Ventricular Arrhythmia Risk Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy.,"Bosman LP, Wang W, Lie ØH, van Lint FHM, Rootwelt-Norberg C, Murray B, Tichnell C, Cadrin-Tourigny J, van Tintelen JP, Asselbergs FW, Calkins H, Te Riele ASJM, Haugaa KH, James CA.",,Circulation. Arrhythmia and electrophysiology,2022,2022-01-28,N,Prognosis; Exercise; Arrhythmogenic right ventricular dysplasia,,,"<h4>Background</h4>Exercise is associated with sustained ventricular arrhythmias (VA) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) but is not included in the ARVC risk calculator (arvcrisk.com). The objective of this study is to quantify the influence of exercise at diagnosis on incident VA risk and evaluate whether the risk calculator needs adjustment for exercise.<h4>Methods</h4>We interviewed ARVC patients without sustained VA at diagnosis about their exercise history. The relationship between exercise dose 3 years preceding diagnosis (average METh/wk) and incident VA during follow-up was analyzed with time-to-event analysis. The incremental prognostic value of exercise to the risk calculator was evaluated by Cox models.<h4>Results</h4>We included 176 patients (male, 43.2%; age, 37.6±16.1 years) from 3 ARVC centers, of whom 53 (30.1%) developed sustained VA during 5.4 (2.7-9.7) years of follow-up. Exercise at diagnosis showed a dose-dependent nonlinear relationship with VA, with no significant risk increase <15 to 30 METh/wk. Athlete status, using 3 definitions from literature (>18, >24, and >36 METh/wk), was significantly associated with VA (hazard ratios, 2.53-2.91) but was also correlated with risk factors currently in the risk calculator model. Thus, adding athlete status to the model did not change the C index of 0.77 (0.71-0.84) and showed no significant improvement (Akaike information criterion change, <2).<h4>Conclusions</h4>Exercise at diagnosis was dose dependently associated with risk of sustained VA in ARVC patients but only above 15 to 30 METh/wk. Exercise does not appear to have incremental prognostic value over the risk calculator. The ARVC risk calculator can be used accurately in athletic patients without modification.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.121.010221; doi:https://doi.org/10.1161/CIRCEP.121.010221
 30648344,https://doi.org/10.1002/cnm.3180,A semi-active human digital twin model for detecting severity of carotid stenoses from head vibration-A coupled computational mechanics and computer vision method.,"Chakshu NK, Carson J, Sazonov I, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-02-20,Y,Computer vision; Blood flow; Systemic Circulation; Carotid Stenoses; Digital Twin; Biomechanical Vibrations; Face Video,Applied Analytics,,"In this work, we propose a methodology to detect the severity of carotid stenosis from a video of a human face with the help of a coupled blood flow and head vibration model. This semi-active digital twin model is an attempt to link noninvasive video of a patient face to the percentage of carotid occlusion. The pulsatile nature of blood flow through the carotid arteries induces a subtle head vibration. This vibration is a potential indicator of carotid stenosis severity, and it is exploited in the present study. A head vibration model has been proposed in the present work that is linked to the forces generated by blood flow with or without occlusion. The model is used to generate a large number of virtual head vibration data for different degrees of occlusion. In order to determine the in vivo head vibration, a computer vision algorithm is adopted to use human face videos. The in vivo vibrations are compared against the virtual vibration data generated from the coupled computational blood flow/vibration model. A comparison of the in vivo vibration is made against the virtual data to find the best fit between in vivo and virtual data. The preliminary results on healthy subjects and a patient clearly indicate that the model is accurate and it possesses the potential for detecting approximate severity of carotid artery stenoses.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3180; doi:https://doi.org/10.1002/cnm.3180; html:https://europepmc.org/articles/PMC6593817; pdf:https://europepmc.org/articles/PMC6593817?pdf=render
 33824583,https://doi.org/10.2147/copd.s298585,There is No Fast Track to Identify Fast Decliners in Alpha-1 Antitrypsin Deficiency by Spirometry: A Longitudinal Study of Repeated Measurements.,"Stockley JA, Stockley RA, Sapey E.",,International journal of chronic obstructive pulmonary disease,2021,2021-03-29,Y,Lung function; decline; Alpha-1 Antitrypsin Deficiency; Obstructive Airways Disease,,,"<h4>Background</h4>It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease.<h4>Methods</h4>Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex- or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years.<h4>Results</h4>Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months' data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%.<h4>Conclusion</h4>This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.",,pdf:https://www.dovepress.com/getfile.php?fileID=68078; doi:https://doi.org/10.2147/COPD.S298585; html:https://europepmc.org/articles/PMC8018552; pdf:https://europepmc.org/articles/PMC8018552?pdf=render
 33735069,https://doi.org/10.1016/s2589-7500(20)30240-5,"A global review of publicly available datasets for ophthalmological imaging: barriers to access, usability, and generalisability.","Khan SM, Liu X, Nath S, Korot E, Faes L, Wagner SK, Keane PA, Sebire NJ, Burton MJ, Denniston AK.",,The Lancet. Digital health,2021,2020-10-01,N,,,,"Health data that are publicly available are valuable resources for digital health research. Several public datasets containing ophthalmological imaging have been frequently used in machine learning research; however, the total number of datasets containing ophthalmological health information and their respective content is unclear. This Review aimed to identify all publicly available ophthalmological imaging datasets, detail their accessibility, describe which diseases and populations are represented, and report on the completeness of the associated metadata. With the use of MEDLINE, Google's search engine, and Google Dataset Search, we identified 94 open access datasets containing 507 724 images and 125 videos from 122 364 patients. Most datasets originated from Asia, North America, and Europe. Disease populations were unevenly represented, with glaucoma, diabetic retinopathy, and age-related macular degeneration disproportionately overrepresented in comparison with other eye diseases. The reporting of basic demographic characteristics such as age, sex, and ethnicity was poor, even at the aggregate level. This Review provides greater visibility for ophthalmological datasets that are publicly available as powerful resources for research. Our paper also exposes an increasing divide in the representation of different population and disease groups in health data repositories. The improved reporting of metadata would enable researchers to access the most appropriate datasets for their needs and maximise the potential of such resources.",,pdf:http://www.thelancet.com/article/S2589750020302405/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30240-5
-35355205,https://doi.org/10.1007/s11897-022-00544-3,LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.,"Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",,Current heart failure reports,2022,2022-03-30,Y,Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan,,,"<h4>Purpose of review</h4>The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.<h4>Recent findings</h4>In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render
 33328453,https://doi.org/10.1038/s41467-020-19996-z,Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2020,2020-12-16,Y,,,,"Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).",,pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render
+35355205,https://doi.org/10.1007/s11897-022-00544-3,LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.,"Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",,Current heart failure reports,2022,2022-03-30,Y,Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan,,,"<h4>Purpose of review</h4>The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.<h4>Recent findings</h4>In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render
 35072885,https://doi.org/10.1007/s10439-022-02905-4,Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation.,"Boonstra MJ, Roudijk RW, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, Loh P, van Dam PM.",,Annals of biomedical engineering,2022,2022-01-24,Y,Electrophysiology; Electrocardiography; Cardiovascular Imaging; Electrocardiographic Imaging; Electro-anatomical Mapping; Inverse Electrocardiography; Equivalent Dipole Layer; His-purkinje System; Non-invasive Cardiac Activation Mapping,,,"Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.",,pdf:https://link.springer.com/content/pdf/10.1007/s10439-022-02905-4.pdf; doi:https://doi.org/10.1007/s10439-022-02905-4; html:https://europepmc.org/articles/PMC8847268; pdf:https://europepmc.org/articles/PMC8847268?pdf=render
 35275087,https://doi.org/10.2196/34898,Longitudinal Relationships Between Depressive Symptom Severity and Phone-Measured Mobility: Dynamic Structural Equation Modeling Study.,"Zhang Y, Folarin AA, Sun S, Cummins N, Vairavan S, Bendayan R, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Sankesara H, Matcham F, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Vilella E, Simblett S, Rintala A, Bruce S, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BW, Narayan VA, Annas P, Hotopf M, Dobson RJ, RADAR-CNS consortium.",,JMIR mental health,2022,2022-03-11,Y,Modeling; Mobility; Depression; Mental health; Medical Informatics; Mhealth; Mobile Health; Dynamic Structural Equation Modeling; Location Data,,,"<h4>Background</h4>The mobility of an individual measured by phone-collected location data has been found to be associated with depression; however, the longitudinal relationships (the temporal direction of relationships) between depressive symptom severity and phone-measured mobility have yet to be fully explored.<h4>Objective</h4>We aimed to explore the relationships and the direction of the relationships between depressive symptom severity and phone-measured mobility over time.<h4>Methods</h4>Data used in this paper came from a major EU program, called the Remote Assessment of Disease and Relapse-Major Depressive Disorder, which was conducted in 3 European countries. Depressive symptom severity was measured with the 8-item Patient Health Questionnaire (PHQ-8) through mobile phones every 2 weeks. Participants' location data were recorded by GPS and network sensors in mobile phones every 10 minutes, and 11 mobility features were extracted from location data for the 2 weeks prior to the PHQ-8 assessment. Dynamic structural equation modeling was used to explore the longitudinal relationships between depressive symptom severity and phone-measured mobility.<h4>Results</h4>This study included 2341 PHQ-8 records and corresponding phone-collected location data from 290 participants (age: median 50.0 IQR 34.0, 59.0) years; of whom 215 (74.1%) were female, and 149 (51.4%) were employed. Significant negative correlations were found between depressive symptom severity and phone-measured mobility, and these correlations were more significant at the within-individual level than the between-individual level. For the direction of relationships over time, Homestay (time at home) (φ=0.09, P=.01), Location Entropy (time distribution on different locations) (φ=-0.04, P=.02), and Residential Location Count (reflecting traveling) (φ=0.05, P=.02) were significantly correlated with the subsequent changes in the PHQ-8 score, while changes in the PHQ-8 score significantly affected (φ=-0.07, P<.001) the subsequent periodicity of mobility.<h4>Conclusions</h4>Several phone-derived mobility features have the potential to predict future depression, which may provide support for future clinical applications, relapse prevention, and remote mental health monitoring practices in real-world settings.",,pdf:https://mental.jmir.org/2022/3/e34898/PDF; doi:https://doi.org/10.2196/34898; html:https://europepmc.org/articles/PMC8957008
 34364665,https://doi.org/10.1016/j.cardfail.2021.05.012,Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial.,"Savarese G, Uijl A, Lund LH, Anker SD, Asselbergs F, Fitchett D, Inzucchi SE, Koudstaal S, Ofstad AP, Schrage B, Vedin O, Wanner C, Zannad F, Zwiener I, Butler J.",,Journal of cardiac failure,2021,2021-08-01,N,Type 2 diabetes mellitus; Heart Failure With Preserved Ejection Fraction; Heart Failure With Reduced Ejection Fraction; Empagliflozin; Empa-reg Outcome; Heart Failure With Mid-range Ejection Fraction; Heart Failure With Mildly Reduced Ejection Fraction,,,"<h4>Background</h4>In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF.<h4>Methods and results</h4>We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin's treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31-1.17], 0.79 [0.51-1.23], and 0.63 [0.50-0.78], respectively; P interaction = 0.62).<h4>Conclusions</h4>In EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/HFrEF.",,pdf:https://hal.univ-lorraine.fr/hal-03320880/file/1-s2.0-S1071916421002025-main.pdf; doi:https://doi.org/10.1016/j.cardfail.2021.05.012
 34429368,https://doi.org/10.1136/heartjnl-2021-319566,Sex disparity in subsequent outcomes in survivors of coronary heart disease.,"Akyea RK, Kontopantelis E, Kai J, Weng SF, Patel RS, Asselbergs FW, Qureshi N.",,Heart (British Cardiac Society),2022,2021-08-24,N,Sex difference; Coronary Heart Disease; Secondary Prevention; Competing Risks; Major Adverse Cardiovascular Events,,,"<h4>Objective</h4>Evidence on sex differences in outcomes after developing coronary heart disease (CHD) has focused on recurrent CHD, all-cause mortality or revascularisation. We assessed sex disparities in subsequent major adverse cardiovascular events (MACE) in adults surviving their first-time CHD.<h4>Methods</h4>Using a population-based cohort obtained from the Clinical Practice Research Datalink (CPRD GOLD) linked to hospitalisation and death records in the UK, we identified 143 702 adults (aged ≥18 years) between 1 January 1998 and 31 December 2017 with no prior history of MACE. MACE outcome was a composite of recurrent CHD, stroke, peripheral vascular disease, heart failure and cardiovascular-related mortality. Multivariable models (Cox and competing risks regressions) were used to assess differences between sexes.<h4>Results</h4>There were 143 702 adults with any incident CHD (either angina, myocardial infarction or coronary revascularisation). Women (n=63 078, 43.9%) were older than men (median age, 73 vs 66 years). First subsequent MACE outcome was observed in 91 706 (63.8%). Women had a significantly lower risk of MACE (hazard ratio (HR), 0.68 (95% CI 0.67 to 0.69); sub-hazard ratio (HRsd), 0.71 (0.70 to 0.72), respectively) and recurrent CHD (n=66 543, 46.3%) (HR, 0.60 (0.59 to 0.61); HRsd, 0.62 (0.61 to 0.63)) when compared with men after incident CHD. However, women had a significantly higher risk of stroke (n=5740, 4.0%) (HR, 1.26 (1.19 to 1.33); HRsd, 1.32 (1.25 to 1.39)), heart failure (n=7905, 5.5%) (HR, 1.09 (1.04 to 1.15); HRsd, 1.13 (1.07 to 1.18)) and all-cause mortality (n=29 503, 20.5%) (HR, 1.05 (1.02 to 1.07); HRsd, 1.11 (1.08 to 1.13)).<h4>Conclusions</h4>After incident CHD, women have lower risk of composite MACE and recurrent CHD outcomes but higher risk of stroke, heart failure, and all-cause mortality compared with men.",,pdf:https://heart.bmj.com/content/heartjnl/108/1/37.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-319566
-36224602,https://doi.org/10.1186/s12916-022-02544-5,Early onset of immune-mediated diseases in minority ethnic groups in the UK. ,"Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM.",,BMC medicine,2022,2022-10-13,Y,,,,"The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis. This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB). After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size. Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?pdf=render
 30745170,https://doi.org/10.1016/j.ebiom.2019.02.005,"Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.","Strawbridge RJ, Ward J, Ferguson A, Graham N, Shaw RJ, Cullen B, Pearsall R, Lyall LM, Johnston KJA, Niedzwiedz CL, Pell JP, Mackay D, Martin JL, Lyall DM, Bailey MES, Smith DJ.",,EBioMedicine,2019,2019-02-08,Y,,Understanding the Causes of Disease,,"<h4>Background</h4>Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic.<h4>Methods</h4>Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: 'no suicidality' controls (N = 83,557); 'thoughts that life was not worth living' (N = 21,063); 'ever contemplated self-harm' (N = 13,038); 'act of deliberate self-harm in the past' (N = 2498); and 'previous suicide attempt' (N = 2666).<h4>Outcomes</h4>We identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (r<sub>g</sub> 0·81).<h4>Interpretation</h4>These findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level. FUND: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217). MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/1). MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh. UKRI Innovation Fellowship (MR/R024774/1).",,pdf:http://www.thelancet.com/article/S2352396419300775/pdf; doi:https://doi.org/10.1016/j.ebiom.2019.02.005; html:https://europepmc.org/articles/PMC6442001; pdf:https://europepmc.org/articles/PMC6442001?pdf=render
-37206266,https://doi.org/10.1002/jha2.698,Biallelic deleterious germline <i>SH2B3</i> variants cause a novel syndrome of myeloproliferation and multi-organ autoimmunity.,"Blombery P, Pazhakh V, Albuquerque AS, Maimaris J, Tu L, Briones Miranda B, Evans F, Thompson ER, Carpenter B, Proctor I, Curtin JA, Lambert J, Burns SO, Lieschke GJ.",,EJHaem,2023,2023-04-30,Y,Genetics; Molecular diagnosis; Myeloid Function And Development,,,"<i>SH2B3</i> is a negative regulator of multiple cytokine receptor signalling pathways in haematopoietic tissue. To date, a single kindred has been described with germline biallelic loss-of-function <i>SH2B3</i> variants characterized by early onset developmental delay, hepatosplenomegaly and autoimmune thyroiditis/hepatitis. Herein, we described two further unrelated kindreds with germline biallelic loss-of-function <i>SH2B3</i> variants that show striking phenotypic similarity to each other as well as to the previous kindred of myeloproliferation and multi-organ autoimmunity. One proband also suffered severe thrombotic complications. CRISPR-Cas9 gene editing of zebrafish <i>sh2b3</i> created assorted deleterious variants in F0 crispants, which manifest significantly increased number of macrophages and thrombocytes, partially replicating the human phenotype. Treatment of the <i>sh2b3</i> crispant fish with ruxolitinib intercepted this myeloproliferative phenotype. Skin-derived fibroblasts from one patient demonstrated increased phosphorylation of JAK2 and STAT5 after stimulation with IL-3, GH, GM-CSF and EPO compared to healthy controls. In conclusion, these additional probands and functional data in combination with the previous kindred provide sufficient evidence for biallelic homozygous deleterious variants in <i>SH2B3</i> to be considered a valid gene-disease association for a clinical syndrome of bone marrow myeloproliferation and multi-organ autoimmune manifestations.",,doi:https://doi.org/10.1002/jha2.698; doi:https://doi.org/10.1002/jha2.698; html:https://europepmc.org/articles/PMC10188477; pdf:https://europepmc.org/articles/PMC10188477?pdf=render
+36224602,https://doi.org/10.1186/s12916-022-02544-5,Early onset of immune-mediated diseases in minority ethnic groups in the UK. ,"Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM.",,BMC medicine,2022,2022-10-13,Y,,,,"The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis. This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB). After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size. Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?pdf=render
 36228971,https://doi.org/10.1016/j.jclinepi.2022.10.011,"In simulated data and health records, latent class analysis was the optimum multimorbidity clustering algorithm.","Nichols L, Taverner T, Crowe F, Richardson S, Yau C, Kiddle S, Kirk P, Barrett J, Nirantharakumar K, Griffin S, Edwards D, Marshall T.",,Journal of clinical epidemiology,2022,2022-10-11,Y,Hierarchical cluster analysis; Clustering Methods; Latent Class Analysis; Electronic Medical Records; Multimorbidity; K-means; Multiple Correspondence Analysis,,,"<h4>Background and objectives</h4>To investigate the reproducibility and validity of latent class analysis (LCA) and hierarchical cluster analysis (HCA), multiple correspondence analysis followed by k-means (MCA-kmeans) and k-means (kmeans) for multimorbidity clustering.<h4>Methods</h4>We first investigated clustering algorithms in simulated datasets with 26 diseases of varying prevalence in predetermined clusters, comparing the derived clusters to known clusters using the adjusted Rand Index (aRI). We then them investigated the medical records of male patients, aged 65 to 84 years from 50 UK general practices, with 49 long-term health conditions. We compared within cluster morbidity profiles using the Pearson correlation coefficient and assessed cluster stability using in 400 bootstrap samples.<h4>Results</h4>In the simulated datasets, the closest agreement (largest aRI) to known clusters was with LCA and then MCA-kmeans algorithms. In the medical records dataset, all four algorithms identified one cluster of 20-25% of the dataset with about 82% of the same patients across all four algorithms. LCA and MCA-kmeans both found a second cluster of 7% of the dataset. Other clusters were found by only one algorithm. LCA and MCA-kmeans clustering gave the most similar partitioning (aRI 0.54).<h4>Conclusion</h4>LCA achieved higher aRI than other clustering algorithms.",,doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; html:https://europepmc.org/articles/PMC7613854; pdf:https://europepmc.org/articles/PMC7613854?pdf=render
+37206266,https://doi.org/10.1002/jha2.698,Biallelic deleterious germline <i>SH2B3</i> variants cause a novel syndrome of myeloproliferation and multi-organ autoimmunity.,"Blombery P, Pazhakh V, Albuquerque AS, Maimaris J, Tu L, Briones Miranda B, Evans F, Thompson ER, Carpenter B, Proctor I, Curtin JA, Lambert J, Burns SO, Lieschke GJ.",,EJHaem,2023,2023-04-30,Y,Genetics; Molecular diagnosis; Myeloid Function And Development,,,"<i>SH2B3</i> is a negative regulator of multiple cytokine receptor signalling pathways in haematopoietic tissue. To date, a single kindred has been described with germline biallelic loss-of-function <i>SH2B3</i> variants characterized by early onset developmental delay, hepatosplenomegaly and autoimmune thyroiditis/hepatitis. Herein, we described two further unrelated kindreds with germline biallelic loss-of-function <i>SH2B3</i> variants that show striking phenotypic similarity to each other as well as to the previous kindred of myeloproliferation and multi-organ autoimmunity. One proband also suffered severe thrombotic complications. CRISPR-Cas9 gene editing of zebrafish <i>sh2b3</i> created assorted deleterious variants in F0 crispants, which manifest significantly increased number of macrophages and thrombocytes, partially replicating the human phenotype. Treatment of the <i>sh2b3</i> crispant fish with ruxolitinib intercepted this myeloproliferative phenotype. Skin-derived fibroblasts from one patient demonstrated increased phosphorylation of JAK2 and STAT5 after stimulation with IL-3, GH, GM-CSF and EPO compared to healthy controls. In conclusion, these additional probands and functional data in combination with the previous kindred provide sufficient evidence for biallelic homozygous deleterious variants in <i>SH2B3</i> to be considered a valid gene-disease association for a clinical syndrome of bone marrow myeloproliferation and multi-organ autoimmune manifestations.",,doi:https://doi.org/10.1002/jha2.698; doi:https://doi.org/10.1002/jha2.698; html:https://europepmc.org/articles/PMC10188477; pdf:https://europepmc.org/articles/PMC10188477?pdf=render
 32579178,https://doi.org/10.1001/jamadermatol.2020.1948,Association Between Atopic Eczema and Cancer in England and Denmark.,"Mansfield KE, Schmidt SAJ, Darvalics B, Mulick A, Abuabara K, Wong AYS, Sørensen HT, Smeeth L, Bhaskaran K, Dos Santos Silva I, Silverwood RJ, Langan SM.",,JAMA dermatology,2020,2020-10-01,Y,,,,"<h4>Importance</h4>Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk.<h4>Objective</h4>To investigate whether atopic eczema is associated with cancer.<h4>Design, setting, and participants</h4>Matched cohort studies were conducted from January 2, 1998, to March 31, 2016, in England and from January 1, 1982, to June 30, 2016, in Denmark. We conducted our analyses between July 2018 and July 2019. The setting was English primary care and nationwide Danish data. Participants with atopic eczema (adults only in England and any age in Denmark) were matched on age, sex, and calendar period (as well as primary care practice in England only) to those without atopic eczema.<h4>Exposure</h4>Atopic eczema.<h4>Main outcomes and measures</h4>Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema.<h4>Results</h4>In England, matched cohorts included 471 970 individuals with atopic eczema (median [IQR] age, 41.1 [24.9-60.7] years; 276 510 [58.6%] female) and 2 239 775 individuals without atopic eczema (median [IQR] age, 39.8 [25.9-58.4] years; 1 301 074 [58.1%] female). In Denmark, matched cohorts included 44 945 individuals with atopic eczema (median [IQR] age, 13.7 [1.7-21.1] years; 22 826 [50.8%] female) and 445 673 individuals without atopic eczema (median [IQR] age, 13.5 [1.7-20.8] years; 226 323 [50.8%] female). Little evidence was found of associations between atopic eczema and overall cancer (adjusted hazard ratio [HR], 1.04; 99% CI, 1.02-1.06 in England and 1.05; 99% CI, 0.95-1.16 in Denmark) or for most specific cancers. However, noncutaneous lymphoma risk was increased in people with atopic eczema in England (adjusted HR, 1.19; 99% CI, 1.07-1.34 for non-Hodgkin lymphoma [NHL] and 1.48; 99% CI, 1.07-2.04 for Hodgkin lymphoma). Lymphoma risk was increased in people with greater eczema severity vs those without atopic eczema (NHL adjusted HR, 1.06; 99% CI, 0.90-1.25 for mild eczema; 1.24; 99% CI, 1.04-1.48 for moderate eczema; and 2.08; 99% CI, 1.42-3.04 for severe eczema). Danish point estimates also showed increased lymphoma risk in people with moderate to severe eczema compared with those without atopic eczema (minimally adjusted HR, 1.31; 99% CI, 0.76-2.26 for NHL and 1.35; 99% CI, 0.65-2.82 for Hodgkin lymphoma), but the 99% CIs were wide.<h4>Conclusions and relevance</h4>The findings from 2 large population-based studies performed in different settings do not support associations between atopic eczema and most cancers. However, an association was observed between atopic eczema and lymphoma, particularly NHL, that increased with eczema severity. This finding warrants further study as new immunomodulatory systemic therapeutics are brought to market that may alter cancer risk.",,pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2767601/jamadermatology_mansfield_2020_oi_200037_1602515656.45058.pdf; doi:https://doi.org/10.1001/jamadermatol.2020.1948; html:https://europepmc.org/articles/PMC7315391
 35477354,https://doi.org/10.1186/s12877-022-03077-5,Performance of the SarQoL quality of life tool in a UK population of older people with probable sarcopenia and implications for use in clinical trials: findings from the SarcNet registry.,"Witham MD, Heslop P, Dodds RM, Clegg AP, Hope SV, McDonald C, Smithard D, Storey B, Tan AL, Thornhill A, Sayer AA.",,BMC geriatrics,2022,2022-04-27,Y,Quality of life; Validity; Sarcopenia; Responsiveness; Minimum Clinical Important Difference,,,"<h4>Background</h4>The Sarcopenia Quality of Life (SarQoL) questionnaire is a disease-specific sarcopenia quality of life tool. We aimed to independently assess SarQoL with a particular focus on its suitability as a clinical trial outcome measure.<h4>Methods</h4>We analysed data from the UK Sarcopenia Network and Registry. Measures of physical performance and lean mass were collected at baseline. SarQoL and the Strength, Assistance, Rise, Climb - Falls (SARC-F) questionnaire (to assess functional ability) were collected at both baseline and six-month follow-up. Global changes in fitness and quality of life at 6 months were elicited on seven-point Likert scales. Internal consistency was assessed using Cronbach's alpha. Responsiveness (Cohen's d and Guyatt coefficients) and minimum clinically important differences were calculated for participants reporting slight improvement or worsening in their global scores. Concurrent validity was assessed by correlating baseline SarQoL scores with measures of physical performance and functional ability.<h4>Results</h4>We analysed data from 147 participants, 125 of whom underwent follow up assessment; mean age 78 years; 72 (49%) were women. Internal consistency was good; Cronbach's alpha was 0.944 at baseline and 0.732 at telephone follow-up. Correlation between baseline and follow-up SarQoL was weak (r = 0.27; p = 0.03). The minimum clinically important improvement ranged from 5 to 21 points giving trial sample size estimates of 25-100 participants. SarQoL scores were moderately correlated with handgrip (r = 0.37; p < 0.001), SARC-F (r = - 0.45; p < 0.001), short physical performance battery (r = 0.48; p < 0.001) and 4-m walk speed (r = 0.48; p < 0.001).<h4>Conclusions</h4>SarQoL has acceptable performance in older UK participants with probable sarcopenia and is sufficiently responsive for use in clinical trials for sarcopenia.",,pdf:https://bmcgeriatr.biomedcentral.com/track/pdf/10.1186/s12877-022-03077-5; doi:https://doi.org/10.1186/s12877-022-03077-5; html:https://europepmc.org/articles/PMC9043890; pdf:https://europepmc.org/articles/PMC9043890?pdf=render
-35922433,https://doi.org/10.1038/s41467-022-32219-x,Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities.,"Francis CM, Futschik ME, Huang J, Bai W, Sargurupremraj M, Teumer A, Breteler MMB, Petretto E, Ho ASR, Amouyel P, Engelter ST, Bülow R, Völker U, Völzke H, Dörr M, Imtiaz MA, Aziz NA, Lohner V, Ware JS, Debette S, Elliott P, Dehghan A, Matthews PM.",,Nature communications,2022,2022-08-03,Y,,,,"Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-β, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.",,pdf:https://www.nature.com/articles/s41467-022-32219-x.pdf; doi:https://doi.org/10.1038/s41467-022-32219-x; html:https://europepmc.org/articles/PMC9349177; pdf:https://europepmc.org/articles/PMC9349177?pdf=render
 31714636,https://doi.org/10.1002/ana.25642,Lipid lowering and Alzheimer disease risk: A mendelian randomization study.,"Williams DM, Finan C, Schmidt AF, Burgess S, Hingorani AD.",,Annals of neurology,2020,2020-01-01,Y,,,,"<h4>Objective</h4>To examine whether genetic variation affecting the expression or function of lipid-lowering drug targets is associated with Alzheimer disease (AD) risk, to evaluate the potential impact of long-term exposure to corresponding therapeutics.<h4>Methods</h4>We conducted Mendelian randomization analyses using variants in genes that encode the protein targets of several approved lipid-lowering drug classes: HMGCR (encoding the target for statins), PCSK9 (encoding the target for PCSK9 inhibitors, eg, evolocumab and alirocumab), NPC1L1 (encoding the target for ezetimibe), and APOB (encoding the target of mipomersen). Variants were weighted by associations with low-density lipoprotein cholesterol (LDL-C) using data from lipid genetics consortia (n up to 295,826). We meta-analyzed Mendelian randomization estimates for regional variants weighted by LDL-C on AD risk from 2 large samples (total n = 24,718 cases, 56,685 controls).<h4>Results</h4>Models for HMGCR, APOB, and NPC1L1 did not suggest that the use of related lipid-lowering drug classes would affect AD risk. In contrast, genetically instrumented exposure to PCSK9 inhibitors was predicted to increase AD risk in both of the AD samples (combined odds ratio per standard deviation lower LDL-C inducible by the drug target = 1.45, 95% confidence interval = 1.23-1.69). This risk increase was opposite to, although more modest than, the degree of protection from coronary artery disease predicted by these same methods for PCSK9 inhibition.<h4>Interpretation</h4>We did not identify genetic support for the repurposing of statins, ezetimibe, or mipomersen for AD prevention. Notwithstanding caveats to this genetic evidence, pharmacovigilance for AD risk among users of PCSK9 inhibitors may be warranted. ANN NEUROL 2020;87:30-39.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.25642; doi:https://doi.org/10.1002/ana.25642; html:https://europepmc.org/articles/PMC6944510; pdf:https://europepmc.org/articles/PMC6944510?pdf=render
+35922433,https://doi.org/10.1038/s41467-022-32219-x,Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities.,"Francis CM, Futschik ME, Huang J, Bai W, Sargurupremraj M, Teumer A, Breteler MMB, Petretto E, Ho ASR, Amouyel P, Engelter ST, Bülow R, Völker U, Völzke H, Dörr M, Imtiaz MA, Aziz NA, Lohner V, Ware JS, Debette S, Elliott P, Dehghan A, Matthews PM.",,Nature communications,2022,2022-08-03,Y,,,,"Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-β, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.",,pdf:https://www.nature.com/articles/s41467-022-32219-x.pdf; doi:https://doi.org/10.1038/s41467-022-32219-x; html:https://europepmc.org/articles/PMC9349177; pdf:https://europepmc.org/articles/PMC9349177?pdf=render
 34870256,https://doi.org/10.1016/j.lanepe.2021.100267,Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region: a mathematical modelling study.,"Liu Y, Sandmann FG, Barnard RC, Pearson CAB, Pastore R, Pebody R, Flasche S, Jit M.",,The Lancet regional health. Europe,2022,2021-11-30,Y,Europe; Health Economics; Mathematical Modelling; Policy Evaluation; Vaccine Policy; Multicountry Analysis; Covid-19,,,"<h4>Background</h4>Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine supply conditions. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region.<h4>Methods</h4>We fitted age-specific compartmental models to the reported daily COVID-19 mortality in 2020 to inform the immunity level before vaccine roll-out. Models capture country-specific differences in population structures, contact patterns, epidemic history, life expectancy, and GDP per capita.We examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incrementally younger age groups. We explored four roll-out scenarios (R1-4) - the slowest scenario (R1) reached 30% coverage by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy, comorbidity- and quality-adjusted life years, and human capital. Six vaccine profiles were tested - the highest performing vaccine has 95% efficacy against both infection and disease, and the lowest 50% against diseases and 0% against infection.<h4>Findings</h4>Of the 20 decision-making metrics and roll-out scenario combinations, the same optimal strategy applied to all countries in only one combination; V60 was more or similarly desirable than V75 in 19 combinations. Of the 38 countries with fitted models, 11-37 countries had variable optimal strategies by decision-making metrics or roll-out scenarios. There are greater benefits in prioritising older adults when roll-out is slow and when vaccine profiles are less favourable.<h4>Interpretation</h4>The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults.<h4>Funding</h4>World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust.",,doi:https://doi.org/10.1016/j.lanepe.2021.100267; doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?pdf=render
-36828655,https://doi.org/10.1136/bmjopen-2022-068718,Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.,"Lee SI, Hope H, O'Reilly D, Kent L, Santorelli G, Subramanian A, Moss N, Azcoaga-Lorenzo A, Fagbamigbe AF, Nelson-Piercy C, Yau C, McCowan C, Kennedy JI, Phillips K, Singh M, Mhereeg M, Cockburn N, Brocklehurst P, Plachcinski R, Riley RD, Thangaratinam S, Brophy S, Hemali Sudasinghe SPB, Agrawal U, Vowles Z, Abel KM, Nirantharakumar K, Black M, Eastwood KA, MuM-PreDiCT.",,BMJ open,2023,2023-02-24,Y,Obstetrics; epidemiology; Maternal Medicine,,,"<h4>Introduction</h4>One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).<h4>Methods and analysis</h4>Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.<h4>Ethics and dissemination</h4>Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e068718.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068718; html:https://europepmc.org/articles/PMC9972454; pdf:https://europepmc.org/articles/PMC9972454?pdf=render
 33053479,https://doi.org/10.1016/j.chiabu.2020.104760,Characterizing newborn and older infant entries into care in England between 2006 and 2014.,"Pearson RJ, Jay MA, O'Donnell M, Wijlaars L, Gilbert R.",,Child abuse & neglect,2020,2020-10-11,Y,Longitudinal data; Infancy; Latent Class Analysis; Entry Into Care; Out-of-court Arrangements,,,"<h4>Background</h4>The risk of entry to state care during infancy is increasing, both here in England and abroad, with most entering within a week of birth ('newborns'). However, little is known about these infants or of their pathways through care over early childhood.<h4>Objective</h4>To characterize infant entries to care in England.<h4>Participants and setting</h4>All children in England who first entered care during infancy, between April 2006 and March 2014 (n = 42,000).<h4>Methods</h4>We compared sociodemographic and care characteristics for infants entering care over the study period by age at first entry (newborn: <1wks, older infant 1-51wks). Among those who entered before April 2010, we further characterized care over follow-up (i.e. 4 years from first entry) and employed latent class analysis to uncover any common pathways through care.<h4>Results</h4>Almost 40 % of infants first entered care as a newborn. Most infants first entered care under s 20 arrangements (i.e. out-of-court, 60 % of newborns vs 47 % of older infants). Among infants entering before April 2010, most were adopted over follow-up (60 % vs 37 %), though many were restored to parental care (20 % vs 32 %) or exited care to live with extended family (13 % vs 19 %). One in six infants (17.7 %) had particularly unstable care trajectories over early childhood, typified by three or more placements or failed reunification.<h4>Conclusions</h4>Evidence-based strengthening of pre-birth social work support is needed to improve preventive interventions before birth, to more effectively target infant placement into care. Linkages between child protection records and information on parents are needed to inform preventive strategies.",,doi:https://doi.org/10.1016/j.chiabu.2020.104760; doi:https://doi.org/10.1016/j.chiabu.2020.104760; html:https://europepmc.org/articles/PMC7718112
+36828655,https://doi.org/10.1136/bmjopen-2022-068718,Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.,"Lee SI, Hope H, O'Reilly D, Kent L, Santorelli G, Subramanian A, Moss N, Azcoaga-Lorenzo A, Fagbamigbe AF, Nelson-Piercy C, Yau C, McCowan C, Kennedy JI, Phillips K, Singh M, Mhereeg M, Cockburn N, Brocklehurst P, Plachcinski R, Riley RD, Thangaratinam S, Brophy S, Hemali Sudasinghe SPB, Agrawal U, Vowles Z, Abel KM, Nirantharakumar K, Black M, Eastwood KA, MuM-PreDiCT.",,BMJ open,2023,2023-02-24,Y,Obstetrics; epidemiology; Maternal Medicine,,,"<h4>Introduction</h4>One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).<h4>Methods and analysis</h4>Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.<h4>Ethics and dissemination</h4>Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e068718.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068718; html:https://europepmc.org/articles/PMC9972454; pdf:https://europepmc.org/articles/PMC9972454?pdf=render
 36054463,https://doi.org/10.1111/ans.17985,Examining the patient profile and variance of management and in-hospital outcomes for Australian adult burns patients.,"Tracy LM, Darton A, Gabbe BJ, Heath K, Kurmis R, Lisec C, Lo C, Singer Y, Wood FM, Cleland HJ.",,ANZ journal of surgery,2022,2022-08-22,Y,Adult; Variation; Australia; Burn; Registry,,,"<h4>Background</h4>Burn injuries are a common subtype of trauma. Variation in models of care impacts clinical measures of interest, but a nation-wide examination of these measures has not been undertaken. Using data from the Burns Registry of Australia and New Zealand (BRANZ), we explored variation between Australian adult burn services with respect to treatment and clinical measures of interest.<h4>Methods</h4>Data for admissions July 2016 to June 2020 were extracted. Clinical measures of interest included intensive care admission, skin grafting, in-hospital death, unplanned readmissions, and length of stay (LOS). Estimated probabilities, means, and corresponding 95% confidence intervals (CI) were calculated for each service.<h4>Results</h4>The BRANZ recorded 8365 admissions during the study period. Variation between specialist burn services in admissions, demographics, management, and clinical measures of interest were observed. This variation remained after accounting for covariates. Specifically, the adjusted proportion (95% CI) of in-hospital mortality ranged from 0.15% (0.10-0.21%) to 1.22% (0.9-1.5%). The adjusted mean LOS ranged from 3.8 (3.3-4.3) to 8.2 (6.7-9.7) days.<h4>Conclusions</h4>A decade after its launch, BRANZ data displays variation between Australian specialist burn services. We suspect differences in models of care between services contributes to this variation. Ongoing research has begun to explore reasons underlying how this variation influences clinical measures of interest. Further engagement with services about models of care will enhance understanding of this variation and develop evidence-based guidelines for burn care in Australia.",,doi:https://doi.org/10.1111/ans.17985; doi:https://doi.org/10.1111/ans.17985; html:https://europepmc.org/articles/PMC9804322; pdf:https://europepmc.org/articles/PMC9804322?pdf=render
 35585575,https://doi.org/10.1186/s12889-022-13219-4,The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.,"McCarthy CV, O'Mara O, van Leeuwen E, CMMID COVID-19 Working Group, Jit M, Sandmann F.",,BMC public health,2022,2022-05-18,Y,Vaccination; mathematical model; Public Health; Prisons; Covid-19,,,"<h4>Background</h4>High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community.<h4>Methods</h4>We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals who are incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths.<h4>Results</h4>Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50 years old averted one death for every 104 vaccination courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points.<h4>Conclusions</h4>The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render
 32611631,https://doi.org/10.1212/wnl.0000000000009814,"Genetically determined blood pressure, antihypertensive drug classes, and risk of stroke subtypes.","Georgakis MK, Gill D, Webb AJS, Evangelou E, Elliott P, Sudlow CLM, Dehghan A, Malik R, Tzoulaki I, Dichgans M.",,Neurology,2020,2020-07-01,Y,,,,"<h4>Objective</h4>We employed Mendelian randomization to explore whether the effects of blood pressure (BP) and BP-lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology.<h4>Methods</h4>We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from genome-wide association studies (GWAS) on 757,601 individuals. Applying 2-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of white matter hyperintensities (WMH).<h4>Results</h4>Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not β-blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for calcium channel blockers showed particularly strong associations with small vessel stroke and the related radiologic phenotype of WMH.<h4>Conclusions</h4>This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP-lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.",,pdf:https://n.neurology.org/content/neurology/95/4/e353.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009814; html:https://europepmc.org/articles/PMC7455321; pdf:https://europepmc.org/articles/PMC7455321?pdf=render
@@ -1335,18 +1335,18 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit
 34688720,https://doi.org/10.1016/j.ijcard.2021.10.029,Methodological issues in meta-analyses of real-world clinical data to infer causality.,"Uijl A, Lund LH, Asselbergs FW, Savarese G.",,International journal of cardiology,2021,2021-10-22,N,Meta-analysis; Causality; Observational; Sacubitril/valsartan,,,,,doi:https://doi.org/10.1016/j.ijcard.2021.10.029
 31711543,https://doi.org/10.1186/s13326-019-0214-4,Natural language processing for disease phenotyping in UK primary care records for research: a pilot study in myocardial infarction and death.,"Shah AD, Bailey E, Williams T, Denaxas S, Dobson R, Hemingway H.",,Journal of biomedical semantics,2019,2019-11-12,Y,Myocardial infarction; Chest pain; Primary Care; Natural Language Processing; Free Text,Applied Analytics,,"<h4>Background</h4>Free text in electronic health records (EHR) may contain additional phenotypic information beyond structured (coded) information. For major health events - heart attack and death - there is a lack of studies evaluating the extent to which free text in the primary care record might add information. Our objectives were to describe the contribution of free text in primary care to the recording of information about myocardial infarction (MI), including subtype, left ventricular function, laboratory results and symptoms; and recording of cause of death. We used the CALIBER EHR research platform which contains primary care data from the Clinical Practice Research Datalink (CPRD) linked to hospital admission data, the MINAP registry of acute coronary syndromes and the death registry. In CALIBER we randomly selected 2000 patients with MI and 1800 deaths. We implemented a rule-based natural language engine, the Freetext Matching Algorithm, on site at CPRD to analyse free text in the primary care record without raw data being released to researchers. We analysed text recorded within 90 days before or 90 days after the MI, and on or after the date of death.<h4>Results</h4>We extracted 10,927 diagnoses, 3658 test results, 3313 statements of negation, and 850 suspected diagnoses from the myocardial infarction patients. Inclusion of free text increased the recorded proportion of patients with chest pain in the week prior to MI from 19 to 27%, and differentiated between MI subtypes in a quarter more patients than structured data alone. Cause of death was incompletely recorded in primary care; in 36% the cause was in coded data and in 21% it was in free text. Only 47% of patients had exactly the same cause of death in primary care and the death registry, but this did not differ between coded and free text causes of death.<h4>Conclusions</h4>Among patients who suffer MI or die, unstructured free text in primary care records contains much information that is potentially useful for research such as symptoms, investigation results and specific diagnoses. Access to large scale unstructured data in electronic health records (millions of patients) might yield important insights.", NLP methods were used to analyse free text from hospital records for people with MI. They analysed text recorded within 90 days bfore or 90 days after the MI and found that free text in hospital records contains unformation useful for diagnoses,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0214-4; doi:https://doi.org/10.1186/s13326-019-0214-4; html:https://europepmc.org/articles/PMC6849160; pdf:https://europepmc.org/articles/PMC6849160?pdf=render
 35087703,https://doi.org/10.5334/aogh.3465,Household Air Pollution and Respiratory Symptoms a Month Before and During the Stringent COVID-19 Lockdown Levels 5 and 4 in South Africa.,"Wright CY, Kapwata T, Abdelatif N, Batini C, Wernecke B, Kunene Z, Millar DA, Mathee A, Street R, Panchal R, Hansell A, Cordell R, Hey JV.",,Annals of global health,2022,2022-01-10,Y,,,,"<h4>Background</h4>Household air pollution (HAP) is associated with adverse human health impacts. During COVID-19 Lockdown Levels 5 and 4 (the most stringent levels), South Africans remained at home, potentially increasing their exposure to HAP.<h4>Objectives</h4>To investigate changes in fuel use behaviours/patterns of use affecting HAP exposure and associated HAP-related respiratory health outcomes during COVID-19 Lockdown Levels 5 and 4.<h4>Methods</h4>This was a cross-sectional online and telephonic survey of participants from an existing database. Logistic regression and McNemar's test were used to analyse household-level data.<h4>Results</h4>Among 2 505 participants, while electricity was the main energy source for cooking and heating the month before and during Lockdown Levels 5 and 4, some households used less electricity during Lockdown Levels 5 and 4 or switched to ""dirty fuels."" One third of participants reported presence of environmental tobacco smoke in the home, a source of HAP associated with respiratory illnesses. Prevalence of HAP-related respiratory health outcomes were <10% (except dry cough). Majority of households reported cooking more, cleaning more and spending more time indoors during Lockdown Levels 5 and 4 - potentially exposed to HAP.<h4>Conclusion</h4>Should South Africa return to Lockdown Levels 5 or 4, awareness raising about the risks associated with HAP as well as messaging information for prevention of exposure to HAP, including environmental tobacco smoke, and associated adverse health impacts will be necessary.",,pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?pdf=render
-35410933,https://doi.org/10.1136/bmjopen-2021-057885,"Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.","Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.",,BMJ open,2022,2022-04-11,Y,Infectious diseases; Rehabilitation Medicine; Covid-19,,,"<h4>Introduction</h4>Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.<h4>Aims</h4>This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.<h4>Methods and analysis</h4>Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.<h4>Ethics and dissemination</h4>This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.<h4>Prospero registration number</h4>The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render
 30928915,https://doi.org/10.1136/injuryprev-2018-043085,Comparison of revised Functional Capacity Index scores with Abbreviated Injury Scale 2008 scores in predicting 12-month severe trauma outcomes.,"Palmer CS, Cameron PA, Gabbe BJ.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2020,2019-03-30,N,Trauma Registry; Trauma Scoring; Functional Outcomes; Prediction Models; Abbreviated Injury Scale; Major Trauma; Functional Capacity Index; 12-Month Outcomes,,,"<h4>Introduction</h4>Anatomical injury as measured by the AIS often accounts for only a small proportion of variability in outcomes after injury. The predictive Functional Capacity Index (FCI) appended to the 2008 AIS claims to provide a widely available method of predicting 12-month function following injury.<h4>Objectives</h4>To determine the extent to which AIS-based and FCI-based scoring is able to add to a simple predictive model of 12-month function following severe injury.<h4>Methods</h4>Adult trauma patients were drawn from the population-based Victorian State Trauma Registry. Major trauma and severely injured orthopaedic trauma patients were followed up via telephone interview including Glasgow Outcome Scale-Extended, the EQ-5D-3L and return to work status. A battery of AIS-based and FCI-based scores, and a simple count of AIS-coded injuries were added in turn to a base model using age and gender.<h4>Results</h4>A total of 20 813 patients survived to 12 months and had at least one functional outcome recorded, representing 85% follow-up. Predictions using the base model varied substantially across outcome measures. Irrespective of the method used to classify the severity of injury, adding injury severity to the model significantly, but only slightly improved model fit. Across the outcomes evaluated, no method of injury severity assessment consistently outperformed any other.<h4>Conclusions</h4>Anatomical injury is a predictor of trauma outcome. However, injury severity as described by the FCI does not consistently improve discrimination, or even provide the best discrimination compared with AIS-based severity scores or a simple injury count.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa50163/Download/0050163-25062019060819.pdf; doi:https://doi.org/10.1136/injuryprev-2018-043085
+35410933,https://doi.org/10.1136/bmjopen-2021-057885,"Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.","Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.",,BMJ open,2022,2022-04-11,Y,Infectious diseases; Rehabilitation Medicine; Covid-19,,,"<h4>Introduction</h4>Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.<h4>Aims</h4>This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.<h4>Methods and analysis</h4>Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.<h4>Ethics and dissemination</h4>This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.<h4>Prospero registration number</h4>The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render
 33939952,https://doi.org/10.1016/s0140-6736(21)00949-1,COVID-19 and disparities affecting ethnic minorities.,"Morales DR, Ali SN.",,"Lancet (London, England)",2021,2021-04-30,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755653; doi:https://doi.org/10.1016/S0140-6736(21)00949-1; html:https://europepmc.org/articles/PMC9755653; pdf:https://europepmc.org/articles/PMC9755653?pdf=render
 36960327,https://doi.org/10.2147/clep.s384605,Severe Mental Illness Among Adults with Atopic Eczema or Psoriasis: Population-Based Matched Cohort Studies within UK Primary Care.,"Adesanya EI, Henderson AD, Matthewman J, Bhate K, Hayes JF, Mulick A, Mathur R, Smith C, Carreira H, Rathod SD, Langan SM, Mansfield KE.",,Clinical epidemiology,2023,2023-03-17,Y,Psychology; epidemiology; Dermatology,,,"<h4>Background</h4>Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI - ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults.<h4>Methods</h4>We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis.<h4>Results</h4>We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12-1.22; psoriasis: HR=1.26,95% CI=1.18-1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93-1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05-1.23).<h4>Conclusion</h4>Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis.",,pdf:https://www.dovepress.com/getfile.php?fileID=88236; doi:https://doi.org/10.2147/CLEP.S384605; html:https://europepmc.org/articles/PMC10030004; pdf:https://europepmc.org/articles/PMC10030004?pdf=render
 35381001,https://doi.org/10.1371/journal.pgen.1010093,Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index.,"Gurtan A, Dominy J, Khalid S, Vong L, Caplan S, Currie T, Richards S, Lamarche L, Denning D, Shpektor D, Gurinovich A, Rasheed A, Hameed S, Saeed S, Saleem I, Jalal A, Abbas S, Sultana R, Rasheed SZ, Memon FU, Shah N, Ishaq M, Khera AV, Danesh J, Frossard P, Saleheen D.",,PLoS genetics,2022,2022-04-05,Y,,,,"Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010093&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render
-37407123,https://doi.org/10.1016/j.jcmg.2023.01.016,Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging.,"Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",,JACC. Cardiovascular imaging,2023,2023-04-12,Y,brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health,,,"<h4>Background</h4>Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.<h4>Objectives</h4>The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.<h4>Methods</h4>Brain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).<h4>Results</h4>Prevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.<h4>Conclusions</h4>Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",,doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render
 35866236,https://doi.org/10.7189/jogh.12.05033,The road to recovery: an interrupted time series analysis of policy intervention to restore essential health services in Mexico during the COVID-19 pandemic.,"Doubova SV, Arsenault C, Contreras-Sánchez SE, Borrayo-Sánchez G, Leslie HH.",,Journal of global health,2022,2022-07-23,Y,,,,"<h4>Background</h4>Recovery of health services disrupted by the COVID-19 pandemic represents a significant challenge in low- and middle-income countries. In April 2021, the Mexican Institute of Social Security (IMSS), which provides health care to 68.5 million people, launched the National Strategy for Health Services Recovery (Recovery policy). The study objective was to evaluate whether the Recovery policy addressed COVID-related declines in maternal, child health, and non-communicable diseases (NCDs) services.<h4>Methods</h4>We analysed the data of 35 IMSS delegations from January 2019 to November 2021 on contraceptive visits, antenatal care consultations, deliveries, caesarean sections, sick children's consultations, child vaccination, breast and cervical cancer screening, diabetes and hypertension consultations, and control. We focused on the period before (April 2020 - March 2021) and during (April 2021 - November 2021) the Recovery policy and used an interrupted time series design and Poisson Generalized Estimating Equation models to estimate the association of this policy with service use and outcomes and change in their trends.<h4>Results</h4>Despite the third wave of the pandemic in 2021, service utilization increased in the Recovery period, reaching (at minimum) 49% of pre-pandemic levels for sick children's consultations and (at maximum) 106% of pre-pandemic levels for breast cancer screenings. Evidence for the Recovery policy role was mixed: the policy was associated with increased facility deliveries (IRR = 1.15, 95%CI = 1.11-1.19) with a growing trend over time (IRR = 1.04, 95%CI = 1.03-1.05); antenatal care and child health services saw strong level effects but decrease over time. Additionally, the Recovery policy was associated with diabetes and hypertension control. Services recovery varied across delegations.<h4>Conclusions</h4>Health service utilization and NCDs control demonstrated important gains in 2021, but evidence suggests the policy had inconsistent effects across services and decreasing impact over time. Further efforts to strengthen essential health services and ensure consistent recovery across delegations are warranted.",,pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render
-36253349,https://doi.org/10.1038/s41467-022-33675-1,Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke.,"Chen L, Peters JE, Prins B, Persyn E, Traylor M, Surendran P, Karthikeyan S, Yonova-Doing E, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Danesh J, Lewis CM, Bronson PG, Markus HS, Burgess S, Butterworth AS, Howson JMM.",,Nature communications,2022,2022-10-17,Y,,,,"Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P ≤ 1.62 × 10<sup>-4</sup>). The genetic associations with stroke colocalize (Posterior Probability >0.7) with the genetic associations of four proteins (TFPI, TMPRSS5, CD6, CD40). Mendelian randomization supports atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes as stroke risk factors (P ≤ 0.0071). Body mass index, white matter hyperintensity and atrial fibrillation appear to mediate the TFPI, IL6RA, TMPRSS5 associations with stroke. Furthermore, thirty-six proteins are associated with one or more of these risk factors using Mendelian randomization. Our results highlight causal pathways and potential therapeutic targets for stroke.",,pdf:https://www.nature.com/articles/s41467-022-33675-1.pdf; doi:https://doi.org/10.1038/s41467-022-33675-1; html:https://europepmc.org/articles/PMC9576777; pdf:https://europepmc.org/articles/PMC9576777?pdf=render
+37407123,https://doi.org/10.1016/j.jcmg.2023.01.016,Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging.,"Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",,JACC. Cardiovascular imaging,2023,2023-04-12,Y,brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health,,,"<h4>Background</h4>Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.<h4>Objectives</h4>The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.<h4>Methods</h4>Brain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).<h4>Results</h4>Prevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.<h4>Conclusions</h4>Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",,doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render
 36711167,https://doi.org/10.1093/ehjdh/ztaa016,Real-time imputation of missing predictor values in clinical practice.,"Nijman SWJ, Hoogland J, Groenhof TKJ, Brandjes M, Jacobs JJL, Bots ML, Asselbergs FW, Moons KGM, Debray TPA.",,European heart journal. Digital health,2021,2020-12-19,Y,Prediction; Missing Data; Electronic Health Records; Computerized Decision Support System; Real-time Imputation; Joint Modelling Imputation,,,"<h4>Aims</h4>Use of prediction models is widely recommended by clinical guidelines, but usually requires complete information on all predictors, which is not always available in daily practice. We aim to describe two methods for real-time handling of missing predictor values when using prediction models in practice.<h4>Methods and results</h4>We compare the widely used method of mean imputation (M-imp) to a method that personalizes the imputations by taking advantage of the observed patient characteristics. These characteristics may include both prediction model variables and other characteristics (auxiliary variables). The method was implemented using imputation from a joint multivariate normal model of the patient characteristics (joint modelling imputation; JMI). Data from two different cardiovascular cohorts with cardiovascular predictors and outcome were used to evaluate the real-time imputation methods. We quantified the prediction model's overall performance [mean squared error (MSE) of linear predictor], discrimination (c-index), calibration (intercept and slope), and net benefit (decision curve analysis). When compared with mean imputation, JMI substantially improved the MSE (0.10 vs. 0.13), c-index (0.70 vs. 0.68), and calibration (calibration-in-the-large: 0.04 vs. 0.06; calibration slope: 1.01 vs. 0.92), especially when incorporating auxiliary variables. When the imputation method was based on an external cohort, calibration deteriorated, but discrimination remained similar.<h4>Conclusions</h4>We recommend JMI with auxiliary variables for real-time imputation of missing values, and to update imputation models when implementing them in new settings or (sub)populations.",,pdf:https://academic.oup.com/ehjdh/article-pdf/2/1/154/37807088/ztaa016.pdf; doi:https://doi.org/10.1093/ehjdh/ztaa016; html:https://europepmc.org/articles/PMC9707891; pdf:https://europepmc.org/articles/PMC9707891?pdf=render
+36253349,https://doi.org/10.1038/s41467-022-33675-1,Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke.,"Chen L, Peters JE, Prins B, Persyn E, Traylor M, Surendran P, Karthikeyan S, Yonova-Doing E, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Danesh J, Lewis CM, Bronson PG, Markus HS, Burgess S, Butterworth AS, Howson JMM.",,Nature communications,2022,2022-10-17,Y,,,,"Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P ≤ 1.62 × 10<sup>-4</sup>). The genetic associations with stroke colocalize (Posterior Probability >0.7) with the genetic associations of four proteins (TFPI, TMPRSS5, CD6, CD40). Mendelian randomization supports atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes as stroke risk factors (P ≤ 0.0071). Body mass index, white matter hyperintensity and atrial fibrillation appear to mediate the TFPI, IL6RA, TMPRSS5 associations with stroke. Furthermore, thirty-six proteins are associated with one or more of these risk factors using Mendelian randomization. Our results highlight causal pathways and potential therapeutic targets for stroke.",,pdf:https://www.nature.com/articles/s41467-022-33675-1.pdf; doi:https://doi.org/10.1038/s41467-022-33675-1; html:https://europepmc.org/articles/PMC9576777; pdf:https://europepmc.org/articles/PMC9576777?pdf=render
 32738956,https://doi.org/10.1016/s0140-6736(20)31286-1,Atopic dermatitis.,"Langan SM, Irvine AD, Weidinger S.",,"Lancet (London, England)",2020,2020-08-01,N,,,,"Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. The disorder affects people of all ages and ethnicities, has a substantial psychosocial impact on patients and relatives, and is the leading cause of the global burden from skin disease. Atopic dermatitis is associated with increased risk of multiple comorbidities, including food allergy, asthma, allergic rhinitis, and mental health disorders. The pathophysiology is complex and involves a strong genetic predisposition, epidermal dysfunction, and T-cell driven inflammation. Although type-2 mechanisms are dominant, there is increasing evidence that the disorder involves multiple immune pathways. Currently, there is no cure, but increasing numbers of innovative and targeted therapies hold promise for achieving disease control, including in patients with recalcitrant disease. We summarise and discuss advances in our understanding of the disease and their implications for prevention, management, and future research.",,doi:https://doi.org/10.1016/S0140-6736(20)31286-1
-34606520,https://doi.org/10.1371/journal.pmed.1003815,"COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.","Pearson CAB, Bozzani F, Procter SR, Davies NG, Huda M, Jensen HT, Keogh-Brown M, Khalid M, Sweeney S, Torres-Rueda S, CHiL COVID-19 Working Group, CMMID COVID-19 Working Group, Eggo RM, Vassall A, Jit M.",,PLoS medicine,2021,2021-10-04,Y,,,,"<h4>Background</h4>Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).<h4>Methods and findings</h4>We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.<h4>Conclusions</h4>COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003815&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render
 32817390,https://doi.org/10.1212/wnl.0000000000010463,"Sleep, major depressive disorder, and Alzheimer disease: A Mendelian randomization study.","Huang J, Zuber V, Matthews PM, Elliott P, Tzoulaki J, Dehghan A.",,Neurology,2020,2020-08-19,Y,,,,"<h4>Objective</h4>To explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer disease (AD).<h4>Methods</h4>We conducted bidirectional 2-sample Mendelian randomization analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (n = 446,118), Psychiatric Genomics Consortium (n = 18,759), and International Genomics of Alzheimer's Project (n = 63,926). We used the inverse variance-weighted Mendelian randomization method to estimate causal effects and weighted median and Mendelian randomization-Egger for sensitivity analyses to test for pleiotropic effects.<h4>Results</h4>We found that higher risk of AD was significantly associated with being a ""morning person"" (odds ratio [OR] 1.01, <i>p</i> = 0.001), shorter sleep duration (self-reported: β = -0.006, <i>p</i> = 1.9 × 10<sup>-4</sup>; accelerometer based: β = -0.015, <i>p</i> = 6.9 × 10<sup>-5</sup>), less likely to report long sleep (β = -0.003, <i>p</i> = 7.3 × 10<sup>-7</sup>), earlier timing of the least active 5 hours (β = -0.024, <i>p</i> = 1.7 × 10<sup>-13</sup>), and a smaller number of sleep episodes (β = -0.025, <i>p</i> = 5.7 × 10<sup>-14</sup>) after adjustment for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR 0.99, <i>p</i> = 7 × 10<sup>-13</sup>). However, we did not find evidence that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD.<h4>Conclusion</h4>We found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.",,pdf:https://n.neurology.org/content/neurology/95/14/e1963.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000010463; html:https://europepmc.org/articles/PMC7682841; pdf:https://europepmc.org/articles/PMC7682841?pdf=render
+34606520,https://doi.org/10.1371/journal.pmed.1003815,"COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.","Pearson CAB, Bozzani F, Procter SR, Davies NG, Huda M, Jensen HT, Keogh-Brown M, Khalid M, Sweeney S, Torres-Rueda S, CHiL COVID-19 Working Group, CMMID COVID-19 Working Group, Eggo RM, Vassall A, Jit M.",,PLoS medicine,2021,2021-10-04,Y,,,,"<h4>Background</h4>Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).<h4>Methods and findings</h4>We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.<h4>Conclusions</h4>COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003815&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render
 33372069,https://doi.org/10.1136/bmjopen-2020-038360,Cardiovascular risk prediction using physical performance measures in COPD: results from a multicentre observational study.,"Fermont JM, Fisk M, Bolton CE, MacNee W, Cockcroft JR, Fuld J, Cheriyan J, Mohan D, Mäki-Petäjä KM, Al-Hadithi AB, Tal-Singer R, Müllerova H, Polkey MI, Wood AM, McEniery CM, Wilkinson IB, ERICA consortium.",,BMJ open,2020,2020-12-28,Y,epidemiology; Primary Care; Cardiac Epidemiology; Chronic Airways Disease; Respiratory Medicine (See Thoracic Medicine),,,"<h4>Objectives</h4>Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD. Traditional CV risk scores have been tested in different populations but not uniquely in COPD. The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown. We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors.<h4>Design</h4>Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV COPD were used. Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up.<h4>Setting</h4>Five UK centres interested in COPD.<h4>Participants</h4>Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks.<h4>Interventions</h4>Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima-media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test.<h4>Primary and secondary outcome measures</h4>New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality.<h4>Results</h4>Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD. The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction. CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all). However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728).<h4>Conclusion</h4>Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD.<h4>Trial registration number</h4>ID 11101.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038360.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038360; html:https://europepmc.org/articles/PMC7772292; pdf:https://europepmc.org/articles/PMC7772292?pdf=render
 36958365,https://doi.org/10.1016/s2352-3018(23)00028-0,Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.,"Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.",,The lancet. HIV,2023,2023-03-20,N,,,,"<h4>Background</h4>The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.<h4>Methods</h4>We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.<h4>Findings</h4>Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2-36·4) of life left if they started ART before 2015, and 39·0 years (38·5-39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8-35·2) and 37·0 (36·5-37·6). Women with CD4 counts of fewer than 49 cells per μL at the start of follow-up had an estimated 19·4 years (18·2-20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9-25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1-19·4) and 23·7 years (22·7-24·8). Women with CD4 counts of at least 500 cells per μL at the start of follow-up had an estimated 40·2 years (39·7-40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7-42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5-38·5) and 39·2 years (38·7-39·7).<h4>Interpretation</h4>For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.<h4>Funding</h4>US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.",,doi:https://doi.org/10.1016/s2352-3018(23)00028-0; doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0
 35152298,https://doi.org/10.1093/ehjci/jeac030,Prognostic value of strain by feature-tracking cardiac magnetic resonance in arrhythmogenic right ventricular cardiomyopathy.,"Bourfiss M, Prakken NHJ, James CA, Planken RN, Boekholdt SM, Ahmetagic D, van den Berg MP, Tichnell C, Van der Heijden JF, Loh P, Murray B, Tandri H, Kamel I, Calkins H, Asselbergs FW, Zimmerman SL, Velthuis BK, Te Riele ASJM.",,European heart journal. Cardiovascular Imaging,2022,2022-12-01,Y,Strain; Arrhythmias; Cardiac Magnetic Resonance Imaging; Arrhythmogenic Right Ventricular Cardiomyopathy; Feature Tracking,,,"<h4>Aims</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients.<h4>Methods and results</h4>CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0-7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03-1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18).<h4>Conclusion</h4>Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac030/42506545/jeac030.pdf; doi:https://doi.org/10.1093/ehjci/jeac030; html:https://europepmc.org/articles/PMC9762936; pdf:https://europepmc.org/articles/PMC9762936?pdf=render
@@ -1356,8 +1356,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33033797,https://doi.org/10.1016/j.eclinm.2020.100560,Investigating the effects of comprehensive smoke-free legislation on neonatal and infant mortality in Thailand using the synthetic control method.,"Radó MK, van Lenthe FJ, Sheikh A, Been JV.",,EClinicalMedicine,2020,2020-10-02,Y,Thailand; Infant Mortality; Child Health; Smoke-free Legislation; Synthetic Control Method,,,"<h4>Background</h4>Almost all of the evidence on the benefits of smoke-free legislation on child health comes from evaluations in high-income countries. We investigated the effects of Thailand's 2010 comprehensive smoke-free legislation on neonatal and infant mortality.<h4>Methods</h4>To overcome some of the methodological issues inherent to traditional quasi-experimental methods, we applied the novel synthetic control approach. Using 2001-2017 country-level panel data from the World Bank and Penn World datasets, we estimated the effects of smoke-free legislation as the difference between the outcome trends in Thailand versus those in a synthetic control country. The synthetic control country was composed of 'control' middle-income countries without comprehensive smoke-free legislation to recreate trends in Thailand in the 2001-2009 pre-legislation outcomes and covariates. We compared the legislation effects to 'placebo effects' obtained for each control country by fictitiously assuming that comprehensive smoke-free legislation was introduced there in 2010, similar to Thailand.<h4>Findings</h4>Neonatal and infant mortality decreased by 2.9% and 2.8%/year respectively following smoke-free legislation, with an estimated 7463 infant deaths (including 4623 neonatal deaths) having been averted over eight years. The results were robust to different specifications of the control countries. Comparison with placebo effects indicated that the findings were unlikely to be attributable to factors other than the smoke-free legislation.<h4>Interpretation</h4>Expanding comprehensive smoke-free policies to middle-income countries can support national efforts to achieve Sustainable Development Goal 3.2 for reducing preventable early-life deaths.<h4>Funding</h4>Netherlands Lung Foundation, HDRUK, Asthma UK center for Applied Research and NIHR Global Respiratory Health Unit (RESPIRE).",,pdf:http://www.thelancet.com/article/S2589537020303047/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100560; html:https://europepmc.org/articles/PMC7533363; pdf:https://europepmc.org/articles/PMC7533363?pdf=render
 35983770,https://doi.org/10.2807/1560-7917.es.2022.27.33.2100885,"Recording of 'COVID-19 vaccine declined': a cohort study on 57.9 million National Health Service patients' records in situ using OpenSAFELY, England, 8 December 2020 to 25 May 2021.","Curtis HJ, Inglesby P, MacKenna B, Croker R, Hulme WJ, Rentsch CT, Bhaskaran K, Mathur R, Morton CE, Bacon SC, Smith RM, Evans D, Mehrkar A, Tomlinson L, Walker AJ, Bates C, Hickman G, Ward T, Morley J, Cockburn J, Davy S, Williamson EJ, Eggo RM, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Evans SJ, Douglas IJ, Smeeth L, Goldacre B.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2022,2022-08-01,Y,Vaccination; Vaccine Hesitancy; Nhs England; Covid-19; Sars-cov-2,,,"BackgroundPriority patients in England were offered COVID-19 vaccination by mid-April 2021. Codes in clinical record systems can denote the vaccine being declined.AimWe describe records of COVID-19 vaccines being declined, according to clinical and demographic factors.MethodsWith the approval of NHS England, we conducted a retrospective cohort study between 8 December 2020 and 25 May 2021 with primary care records for 57.9 million patients using OpenSAFELY, a secure health analytics platform. COVID-19 vaccination priority patients were those aged ≥ 50 years or ≥ 16 years clinically extremely vulnerable (CEV) or 'at risk'. We describe the proportion recorded as declining vaccination for each group and stratified by clinical and demographic subgroups, subsequent vaccination and distribution of clinical code usage across general practices.ResultsOf 24.5 million priority patients, 663,033 (2.7%) had a decline recorded, while 2,155,076 (8.8%) had neither a vaccine nor decline recorded. Those recorded as declining, who were subsequently vaccinated (n = 125,587; 18.9%) were overrepresented in the South Asian population (32.3% vs 22.8% for other ethnicities aged ≥ 65 years). The proportion of declining unvaccinated patients was highest in CEV (3.3%), varied strongly with ethnicity (black 15.3%, South Asian 5.6%, white 1.5% for ≥ 80 years) and correlated positively with increasing deprivation.ConclusionsClinical codes indicative of COVID-19 vaccinations being declined are commonly used in England, but substantially more common among black and South Asian people, and in more deprived areas. Qualitative research is needed to determine typical reasons for recorded declines, including to what extent they reflect patients actively declining.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/27/33/eurosurv-27-33-5.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2022.27.33.2100885&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2022.27.33.2100885; html:https://europepmc.org/articles/PMC9389857
 34753797,https://doi.org/10.2337/db21-0320,An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript.,"Riveros-Mckay F, Roberts D, Di Angelantonio E, Yu B, Soranzo N, Danesh J, Selvin E, Butterworth AS, Barroso I.",,Diabetes,2022,2022-02-01,N,,,,"Fructosamine is a measure of short-term glycemic control, which has been suggested as a useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of diabetes. To date, a single genome-wide association study (GWAS) including 8,951 U.S. White and 2,712 U.S. Black individuals without a diabetes diagnosis has been published. Results in Whites and Blacks yielded different association loci, near RCN3 and CNTN5, respectively. In this study, we performed a GWAS on 20,731 European-ancestry blood donors and meta-analyzed our results with previous data from U.S. White participants from the Atherosclerosis Risk in Communities (ARIC) study (Nmeta = 29,685). We identified a novel association near GCK (rs3757840, βmeta = 0.0062; minor allele frequency [MAF] = 0.49; Pmeta = 3.66 × 10-8) and confirmed the association near RCN3 (rs113886122, βmeta = 0.0134; MAF = 0.17; Pmeta = 5.71 × 10-18). Colocalization analysis with whole-blood expression quantitative trait loci data suggested FCGRT as the effector transcript at the RCN3 locus. We further showed that fructosamine has low heritability (h2 = 7.7%), has no significant genetic correlation with HbA1c and other glycemic traits in individuals without a diabetes diagnosis (P > 0.05), but has evidence of shared genetic etiology with some anthropometric traits (Bonferroni-corrected P < 0.0012). Our results broaden knowledge of the genetic architecture of fructosamine and prioritize FCGRT for downstream functional studies at the established RCN3 locus.",,pdf:https://diabetesjournals.org/diabetes/article-pdf/71/2/359/640867/db210320.pdf; doi:https://doi.org/10.2337/db21-0320; html:https://europepmc.org/articles/PMC8914280; pdf:https://europepmc.org/articles/PMC8914280?pdf=render; doi:https://doi.org/10.2337/db21-0320
-36609282,https://doi.org/10.1186/s13063-022-06967-6,A comparison of covariate adjustment approaches under model misspecification in individually randomized trials.,"Tackney MS, Morris T, White I, Leyrat C, Diaz-Ordaz K, Williamson E.",,Trials,2023,2023-01-06,Y,Randomized controlled trials; Iptw; G-computation; Tmle; Covariate Adjustment; Ancova; Misspecification; Aiptw,,,"Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the covariate and outcome is misspecified when taking an adjusted approach. Using a simulation study focusing on individually randomized trials with small sample sizes, we explore whether a range of adjustment methods are robust to misspecification, either in the covariate-outcome relationship or through an omitted covariate-treatment interaction. Specifically, we aim to identify potential settings where G-computation, inverse probability of treatment weighting (IPTW), augmented inverse probability of treatment weighting (AIPTW) and targeted maximum likelihood estimation (TMLE) offer improvement over the commonly used analysis of covariance (ANCOVA). Our simulations show that all adjustment methods are generally robust to model misspecification if adjusting for a few covariates, sample size is 100 or larger, and there are no covariate-treatment interactions. When there is a non-linear interaction of treatment with a skewed covariate and sample size is small, all adjustment methods can suffer from bias; however, methods that allow for interactions (such as G-computation with interaction and IPTW) show improved results compared to ANCOVA. When there are a high number of covariates to adjust for, ANCOVA retains good properties while other methods suffer from under- or over-coverage. An outstanding issue for G-computation, IPTW and AIPTW in small samples is that standard errors are underestimated; they should be used with caution without the availability of small-sample corrections, development of which is needed. These findings are relevant for covariate adjustment in interim analyses of larger trials.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06967-6; doi:https://doi.org/10.1186/s13063-022-06967-6; html:https://europepmc.org/articles/PMC9817411; pdf:https://europepmc.org/articles/PMC9817411?pdf=render
 33905476,https://doi.org/10.1093/cid/ciab192,Model-Based Geostatistical Methods Enable Efficient Design and Analysis of Prevalence Surveys for Soil-Transmitted Helminth Infection and Other Neglected Tropical Diseases.,"Johnson O, Fronterre C, Amoah B, Montresor A, Giorgi E, Midzi N, Mutsaka-Makuvaza MJ, Kargbo-Labor I, Hodges MH, Zhang Y, Okoyo C, Mwandawiro C, Minnery M, Diggle PJ.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2021,2021-06-01,Y,Geospatial Analysis; Prevalence Survey; Soil-transmitted Helminth Infection; Model-based Geostatistics; Control Of Neglected Tropical Diseases; Impact Survey,,,"Maps of the geographical variation in prevalence play an important role in large-scale programs for the control of neglected tropical diseases. Precontrol mapping is needed to establish the appropriate control intervention in each area of the country in question. Mapping is also needed postintervention to measure the success of control efforts. In the absence of comprehensive disease registries, mapping efforts can be informed by 2 kinds of data: empirical estimates of local prevalence obtained by testing individuals from a sample of communities within the geographical region of interest, and digital images of environmental factors that are predictive of local prevalence. In this article, we focus on the design and analysis of impact surveys, that is, prevalence surveys that are conducted postintervention with the aim of informing decisions on what further intervention, if any, is needed to achieve elimination of the disease as a public health problem. We show that geospatial statistical methods enable prevalence surveys to be designed and analyzed as efficiently as possible so as to make best use of hard-won field data. We use 3 case studies based on data from soil-transmitted helminth impact surveys in Kenya, Sierra Leone, and Zimbabwe to compare the predictive performance of model-based geostatistics with methods described in current World Health Organization (WHO) guidelines. In all 3 cases, we find that model-based geostatistics substantially outperforms the current WHO guidelines, delivering improved precision for reduced field-sampling effort. We argue from experience that similar improvements will hold for prevalence mapping of other neglected tropical diseases.",,pdf:https://academic.oup.com/cid/article-pdf/72/Supplement_3/S172/38618862/ciab192.pdf; doi:https://doi.org/10.1093/cid/ciab192; html:https://europepmc.org/articles/PMC8201574; pdf:https://europepmc.org/articles/PMC8201574?pdf=render
+36609282,https://doi.org/10.1186/s13063-022-06967-6,A comparison of covariate adjustment approaches under model misspecification in individually randomized trials.,"Tackney MS, Morris T, White I, Leyrat C, Diaz-Ordaz K, Williamson E.",,Trials,2023,2023-01-06,Y,Randomized controlled trials; Iptw; G-computation; Tmle; Covariate Adjustment; Ancova; Misspecification; Aiptw,,,"Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the covariate and outcome is misspecified when taking an adjusted approach. Using a simulation study focusing on individually randomized trials with small sample sizes, we explore whether a range of adjustment methods are robust to misspecification, either in the covariate-outcome relationship or through an omitted covariate-treatment interaction. Specifically, we aim to identify potential settings where G-computation, inverse probability of treatment weighting (IPTW), augmented inverse probability of treatment weighting (AIPTW) and targeted maximum likelihood estimation (TMLE) offer improvement over the commonly used analysis of covariance (ANCOVA). Our simulations show that all adjustment methods are generally robust to model misspecification if adjusting for a few covariates, sample size is 100 or larger, and there are no covariate-treatment interactions. When there is a non-linear interaction of treatment with a skewed covariate and sample size is small, all adjustment methods can suffer from bias; however, methods that allow for interactions (such as G-computation with interaction and IPTW) show improved results compared to ANCOVA. When there are a high number of covariates to adjust for, ANCOVA retains good properties while other methods suffer from under- or over-coverage. An outstanding issue for G-computation, IPTW and AIPTW in small samples is that standard errors are underestimated; they should be used with caution without the availability of small-sample corrections, development of which is needed. These findings are relevant for covariate adjustment in interim analyses of larger trials.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06967-6; doi:https://doi.org/10.1186/s13063-022-06967-6; html:https://europepmc.org/articles/PMC9817411; pdf:https://europepmc.org/articles/PMC9817411?pdf=render
 33206055,https://doi.org/10.2196/19650,Mobile Clinical Decision Support System for the Management of Diabetic Patients With Kidney Complications in UK Primary Care Settings: Mixed Methods Feasibility Study.,"Alhodaib HI, Antza C, Chandan JS, Hanif W, Sankaranarayanan S, Paul S, Sutcliffe P, Nirantharakumar K.",,JMIR diabetes,2020,2020-11-18,Y,Diabetes mellitus; Chronic Kidney Disease; Feasibility Study; Ehealth; Clinical Decision Support Application,,,"<h4>Background</h4>Attempts to utilize eHealth in diabetes mellitus (DM) management have shown promising outcomes, mostly targeted at patients; however, few solutions have been designed for health care providers.<h4>Objective</h4>The purpose of this study was to conduct a feasibility project developing and evaluating a mobile clinical decision support system (CDSS) tool exclusively for health care providers to manage chronic kidney disease (CKD) in patients with DM.<h4>Methods</h4>The design process was based on the 3 key stages of the user-centered design framework. First, an exploratory qualitative study collected the experiences and views of DM specialist nurses regarding the use of mobile apps in clinical practice. Second, a CDSS tool was developed for the management of patients with DM and CKD. Finally, a randomized controlled trial examined the acceptability and impact of the tool.<h4>Results</h4>We interviewed 15 DM specialist nurses. DM specialist nurses were not currently using eHealth solutions in their clinical practice, while most nurses were not even aware of existing medical apps. However, they appreciated the potential benefits that apps may bring to their clinical practice. Taking into consideration the needs and preferences of end users, a new mobile CDSS app, ""Diabetes & CKD,"" was developed based on guidelines. We recruited 39 junior foundation year 1 doctors (44% male) to evaluate the app. Of them, 44% (17/39) were allocated to the intervention group, and 56% (22/39) were allocated to the control group. There was no significant difference in scores (maximum score=13) assessing the management decisions between the app and paper-based version of the app's algorithm (intervention group: mean 7.24 points, SD 2.46 points; control group: mean 7.39, SD 2.56; t<sub>37</sub>=-0.19, P=.85). However, 82% (14/17) of the participants were satisfied with using the app.<h4>Conclusions</h4>The findings will guide the design of future CDSS apps for the management of DM, aiming to help health care providers with a personalized approach depending on patients' comorbidities, specifically CKD, in accordance with guidelines.",,pdf:https://diabetes.jmir.org/2020/4/e19650/PDF; doi:https://doi.org/10.2196/19650; html:https://europepmc.org/articles/PMC7710444; pdf:https://europepmc.org/articles/PMC7710444?pdf=render
 36732776,https://doi.org/10.1186/s13040-023-00321-5,LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.,"Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.",,BioData mining,2023,2023-02-02,Y,Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes,,,"<h4>Background</h4>Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.<h4>Results</h4>We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.<h4>Conclusions</h4>LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .",,pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render
 32345651,https://doi.org/10.2337/dc19-2116,"Obstructive Sleep Apnea, a Risk Factor for Cardiovascular and Microvascular Disease in Patients With Type 2 Diabetes: Findings From a Population-Based Cohort Study.","Adderley NJ, Subramanian A, Toulis K, Gokhale K, Taverner T, Hanif W, Haroon S, Thomas GN, Sainsbury C, Tahrani AA, Nirantharakumar K.",,Diabetes care,2020,2020-04-28,N,,,,"<h4>Objective</h4>To determine the risk of cardiovascular disease (CVD), microvascular complications, and mortality in patients with type 2 diabetes who subsequently develop obstructive sleep apnea (OSA) compared with patients with type 2 diabetes without a diagnosis of OSA.<h4>Research design and methods</h4>This age-, sex-, BMI-, and diabetes duration-matched cohort study used data from a U.K. primary care database from 1 January 2005 to 17 January 2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischemic heart disease [IHD], stroke/transient ischemic attack [TIA], heart failure [HF]), peripheral vascular disease (PVD), atrial fibrillation (AF), peripheral neuropathy (PN), diabetes-related foot disease (DFD), referable retinopathy, chronic kidney disease (CKD), and all-cause mortality. The same outcomes were explored in patients with preexisting OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA.<h4>Results</h4>A total of 3,667 exposed participants and 10,450 matched control participants were included. Adjusted hazard ratios for the outcomes were as follows: composite CVD 1.54 (95% CI 1.32, 1.79), IHD 1.55 (1.26, 1.90), HF 1.67 (1.35, 2.06), stroke/TIA 1.57 (1.27, 1.94), PVD 1.10 (0.91, 1.32), AF 1.53 (1.28, 1.83), PN 1.32 (1.14, 1.51), DFD 1.42 (1.16, 1.74), referable retinopathy 0.99 (0.82, 1.21), CKD (stage 3-5) 1.18 (1.02, 1.36), albuminuria 1.11 (1.01, 1.22), and all-cause mortality 1.24 (1.10, 1.40). In the prevalent OSA cohort, the results were similar, but some associations were not observed.<h4>Conclusions</h4>Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared with patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population, and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.",,pdf:https://care.diabetesjournals.org/content/diacare/43/8/1868.full.pdf; doi:https://doi.org/10.2337/dc19-2116
@@ -1365,18 +1365,18 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34535484,https://doi.org/10.1136/bmjopen-2021-050647,The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): protocol for a prospective longitudinal cohort study of healthcare and ancillary workers in UK healthcare settings.,"Woolf K, Melbourne C, Bryant L, Guyatt AL, McManus IC, Gupta A, Free RC, Nellums L, Carr S, John C, Martin CA, Wain LV, Gray LJ, Garwood C, Modhwadia V, Abrams KR, Tobin MD, Khunti K, Pareek M, UK-REACH Study Collaborative Group+.",,BMJ open,2021,2021-09-17,Y,Mental health; Public Health; Covid-19,,,"<h4>Introduction</h4>The COVID-19 pandemic has resulted in significant morbidity and mortality and devastated economies globally. Among groups at increased risk are healthcare workers (HCWs) and ethnic minority groups. Emerging evidence suggests that HCWs from ethnic minority groups are at increased risk of adverse COVID-19-related outcomes. To date, there has been no large-scale analysis of these risks in UK HCWs or ancillary workers in healthcare settings, stratified by ethnicity or occupation, and adjusted for confounders. This paper reports the protocol for a prospective longitudinal questionnaire study of UK HCWs, as part of the UK-REACH programme (The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers).<h4>Methods and analysis</h4>A baseline questionnaire will be administered to a national cohort of UK HCWs and ancillary workers in healthcare settings, and those registered with UK healthcare regulators, with follow-up questionnaires administered at 4 and 8 months. With consent, questionnaire data will be linked to health records with 25-year follow-up. Univariate associations between ethnicity and clinical COVID-19 outcomes, physical and mental health, and key confounders/explanatory variables will be tested. Multivariable analyses will test for associations between ethnicity and key outcomes adjusted for the confounder/explanatory variables. We will model changes over time by ethnic group, facilitating understanding of absolute and relative risks in different ethnic groups, and generalisability of findings.<h4>Ethics and dissemination</h4>The study is approved by Health Research Authority (reference 20/HRA/4718), and carries minimal risk. We aim to manage the small risk of participant distress about questions on sensitive topics by clearly participant information that the questionnaire covers sensitive topics and there is no obligation to answer these or any other questions, and by providing support organisation links. Results will be disseminated with reports to Government and papers submitted to pre-print servers and peer reviewed journals.<h4>Trial registration number</h4>ISRCTN11811602; Pre-results.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/9/e050647.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050647; html:https://europepmc.org/articles/PMC8450967; pdf:https://europepmc.org/articles/PMC8450967?pdf=render
 35115689,https://doi.org/10.1038/s41588-021-00991-z,Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort.,"Qin Y, Havulinna AS, Liu Y, Jousilahti P, Ritchie SC, Tokolyi A, Sanders JG, Valsta L, Brożyńska M, Zhu Q, Tripathi A, Vázquez-Baeza Y, Loomba R, Cheng S, Jain M, Niiranen T, Lahti L, Knight R, Salomaa V, Inouye M, Méric G.",,Nature genetics,2022,2022-02-03,N,,,,"Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.",,pdf:https://www.nature.com/articles/s41588-021-00991-z.pdf; doi:https://doi.org/10.1038/s41588-021-00991-z; html:https://europepmc.org/articles/PMC9883041; pdf:https://europepmc.org/articles/PMC9883041?pdf=render; doi:https://doi.org/10.1038/s41588-021-00991-z
 36814324,https://doi.org/10.1186/s13195-023-01184-y,"Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease.","Green RE, Lord J, Scelsi MA, Xu J, Wong A, Naomi-James S, Handy A, Gilchrist L, Williams DM, Parker TD, Lane CA, Malone IB, Cash DM, Sudre CH, Coath W, Thomas DL, Keuss S, Dobson R, Legido-Quigley C, Fox NC, Schott JM, Richards M, Proitsi P, Insight 46 study team.",,Alzheimer's research & therapy,2023,2023-02-22,Y,Metabolites; Ageing; Brain imaging; Alzheimer’s disease; Dementia; Birth Cohort; Polygenic Scores; Weighted-gene Coexpression Network Analysis,,,"<h4>Background</h4>Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD).<h4>Methods</h4>Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (p<sub>FDR</sub> < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (p<sub>FDR</sub> < 0.05) with an imaging outcome (N = 1638).<h4>Results</h4>In the fully adjusted model, three lipid modules were associated with a brain volume measure (p<sub>FDR</sub> < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß =  - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß =  - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (p<sub>FDR</sub> < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.<h4>Conclusions</h4>Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.",,pdf:https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-023-01184-y; doi:https://doi.org/10.1186/s13195-023-01184-y; html:https://europepmc.org/articles/PMC9945600; pdf:https://europepmc.org/articles/PMC9945600?pdf=render
-36944376,https://doi.org/10.1098/rsob.220373,"The lipid linked oligosaccharide polymerase Wzy and its regulating co-polymerase, Wzz, from enterobacterial common antigen biosynthesis form a complex.","Weckener M, Woodward LS, Clarke BR, Liu H, Ward PN, Le Bas A, Bhella D, Whitfield C, Naismith JH.",,Open biology,2023,2023-03-22,Y,Oligosaccharides; Lipid; Regulating; Polymerase; Wzy,,,"The enterobacterial common antigen (ECA) is a carbohydrate polymer that is associated with the cell envelope in the <i>Enterobacteriaceae</i>. ECA contains a repeating trisaccharide which is polymerized by WzyE, a member of the Wzy membrane protein polymerase superfamily. WzyE activity is regulated by a membrane protein polysaccharide co-polymerase, WzzE. Förster resonance energy transfer experiments demonstrate that WzyE and WzzE from <i>Pectobacterium atrosepticum</i> form a complex <i>in vivo</i>, and immunoblotting and cryo-electron microscopy (cryo-EM) analysis confirm a defined stoichiometry of approximately eight WzzE to one WzyE. Low-resolution cryo-EM reconstructions of the complex, aided by an antibody recognizing the C-terminus of WzyE, reveals WzyE sits in the central membrane lumen formed by the octameric arrangement of the transmembrane helices of WzzE. The pairing of Wzy and Wzz is found in polymerization systems for other bacterial polymers, including lipopolysaccharide O-antigens and capsular polysaccharides. The data provide new structural insight into a conserved mechanism for regulating polysaccharide chain length in bacteria.",,doi:https://doi.org/10.1098/rsob.220373; doi:https://doi.org/10.1098/rsob.220373; html:https://europepmc.org/articles/PMC10030265; pdf:https://europepmc.org/articles/PMC10030265?pdf=render
 36029662,https://doi.org/10.1016/j.bios.2022.114623,Triazole-derivatized near-infrared cyanine dyes enable local functional fluorescent imaging of ocular inflammation.,"Thomas CN, Alfahad N, Capewell N, Cowley J, Hickman E, Fernandez A, Harrison N, Qureshi OS, Bennett N, Barnes NM, Dick AD, Chu CJ, Liu X, Denniston AK, Vendrell M, Hill LJ.",,Biosensors & bioelectronics,2022,2022-08-13,N,Leukocytes; Uveitis; Cyanine; Near-infrared; optical coherence tomography; Fluorophores,,,"Near-infrared (NIR) chemical fluorophores are promising tools for in-vivo imaging in real time but often succumb to rapid photodegradation. Indocyanine green (ICG) is the only NIR dye with regulatory approval for ocular imaging in humans; however, ICG, when employed for applications such as labelling immune cells, has limited sensitivity and does not allow precise detection of specific inflammatory events, for example leukocyte recruitment during uveitic flare-ups. We investigated the potential use of photostable novel triazole NIR cyanine (TNC) dyes for detecting and characterising activated T-cell activity within the eye. Three TNC dyes were evaluated for ocular cytotoxicity in-vitro using a MTT assay and optimised concentrations for intraocular detection within ex-vivo porcine eyes after topical application or intracameral injections of the dyes. TNC labelled T-cell tracking experiments and mechanistic studies were also performed in-vitro. TNC-1 and TNC-2 dyes exhibited greater fluorescence intensity than ICG at 10 μM, whereas TNC-3 was only detectable at 100 μM within the porcine eye. TNC dyes did not demonstrate any ocular cell toxicity at working concentrations of 10 μM. CD4<sup>+</sup>T-cells labelled with TNC-1 or TNC-2 were detected within the porcine eye, with TNC-1 being brighter than TNC-2. Detection of TNC-1 and TNC-2 into CD4<sup>+</sup>T-cells was prevented by prior incubation with dynole 34-2 (50 μM), suggesting active uptake of these dyes via dynamin-dependent processes. The present study provides evidence that TNC dyes are suitable to detect activated CD4<sup>+</sup>T-cells within the eye with potential as a diagnostic marker for ocular inflammatory diseases.",,pdf:https://research-information.bris.ac.uk/files/338519213/1_s2.0_S0956566322006637_main.pdf; doi:https://doi.org/10.1016/j.bios.2022.114623
-37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"<h4>Background</h4>During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.<h4>Methods</h4>A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.<h4>Results</h4>Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.<h4>Conclusion</h4>e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render
-36774358,https://doi.org/10.1038/s41467-023-36439-7,Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer. ,"Malagoli Tagliazucchi G, Wiecek AJ, Withnell E, Secrier M.",,Nature communications,2023,2023-02-11,Y,,,,"The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.",,pdf:https://www.nature.com/articles/s41467-023-36439-7.pdf; doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?pdf=render
+36944376,https://doi.org/10.1098/rsob.220373,"The lipid linked oligosaccharide polymerase Wzy and its regulating co-polymerase, Wzz, from enterobacterial common antigen biosynthesis form a complex.","Weckener M, Woodward LS, Clarke BR, Liu H, Ward PN, Le Bas A, Bhella D, Whitfield C, Naismith JH.",,Open biology,2023,2023-03-22,Y,Oligosaccharides; Lipid; Regulating; Polymerase; Wzy,,,"The enterobacterial common antigen (ECA) is a carbohydrate polymer that is associated with the cell envelope in the <i>Enterobacteriaceae</i>. ECA contains a repeating trisaccharide which is polymerized by WzyE, a member of the Wzy membrane protein polymerase superfamily. WzyE activity is regulated by a membrane protein polysaccharide co-polymerase, WzzE. Förster resonance energy transfer experiments demonstrate that WzyE and WzzE from <i>Pectobacterium atrosepticum</i> form a complex <i>in vivo</i>, and immunoblotting and cryo-electron microscopy (cryo-EM) analysis confirm a defined stoichiometry of approximately eight WzzE to one WzyE. Low-resolution cryo-EM reconstructions of the complex, aided by an antibody recognizing the C-terminus of WzyE, reveals WzyE sits in the central membrane lumen formed by the octameric arrangement of the transmembrane helices of WzzE. The pairing of Wzy and Wzz is found in polymerization systems for other bacterial polymers, including lipopolysaccharide O-antigens and capsular polysaccharides. The data provide new structural insight into a conserved mechanism for regulating polysaccharide chain length in bacteria.",,doi:https://doi.org/10.1098/rsob.220373; doi:https://doi.org/10.1098/rsob.220373; html:https://europepmc.org/articles/PMC10030265; pdf:https://europepmc.org/articles/PMC10030265?pdf=render
 36456017,https://doi.org/10.1136/bmjopen-2022-066288,"Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.","Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",,BMJ open,2022,2022-12-01,Y,Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19,,,"<h4>Objectives</h4>To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.<h4>Design</h4>Longitudinal study using primary care electronic health records.<h4>Setting</h4>285 general practices in North East London.<h4>Participants</h4>Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).<h4>Main outcome measure</h4>Receipt of timely MMR vaccination between 12 and 18 months of age.<h4>Methods</h4>We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.<h4>Results</h4>Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (<i>n</i>=33 226; 51.3% boys) and pandemic (<i>n</i>=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.<h4>Conclusions</h4>The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render
+36774358,https://doi.org/10.1038/s41467-023-36439-7,Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer. ,"Malagoli Tagliazucchi G, Wiecek AJ, Withnell E, Secrier M.",,Nature communications,2023,2023-02-11,Y,,,,"The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.",,pdf:https://www.nature.com/articles/s41467-023-36439-7.pdf; doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?pdf=render
+37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"<h4>Background</h4>During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.<h4>Methods</h4>A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.<h4>Results</h4>Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.<h4>Conclusion</h4>e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render
 32017129,https://doi.org/10.5694/mja2.50485,Discharge destination and patient-reported outcomes after inpatient treatment for isolated lower limb fractures.,"Kimmel LA, Simpson PM, Holland AE, Edwards ER, Cameron PA, de Steiger RS, Page RS, Hau R, Bucknill A, Kasza J, Gabbe BJ.",,The Medical journal of Australia,2020,2020-02-04,N,"Rehabilitation; Treatment outcome; Orthopedic Procedures; Fractures, Bone; Trauma Surgery",,,"<h4>Objectives</h4>To examine the association between discharge destination (home or inpatient rehabilitation) for adult patients treated in hospital for isolated lower limb fractures and patient-reported outcomes.<h4>Design</h4>Review of prospectively collected Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) data.<h4>Setting, participants</h4>Adults (18-64 years old) treated for isolated lower limb fractures at four Melbourne trauma hospitals that contribute data to the VOTOR, 1 March 2007 - 31 March 2016.<h4>Main outcome measures</h4>Return to work and functional recovery (assessed with the extended Glasgow Outcomes Scale, GOS-E); propensity score analysis of association between discharge destination and outcome.<h4>Results</h4>Of 7961 eligible patients, 1432 (18%) were discharged to inpatient rehabilitation, and 6775 (85%) were followed up 12 months after their injuries. After propensity score adjustment, the odds of better functional recovery were 56% lower for patients discharged to inpatient rehabilitation than for those discharged directly home (odds ratio, 0.44; 95% CI, 0.37-0.51); for the 5057 people working before their accident, the odds of return to work were reduced by 66% (odds ratio, 0.34; 95% CI, 0.26-0.46). Propensity score analysis improved matching of the discharge destination groups, but imbalances in funding source remained for both outcome analyses, and for also for site and cause of injury in the GOS-E analysis (standardised differences, 10-16%).<h4>Conclusions</h4>Discharge to inpatient rehabilitation after treatment for isolated lower limb fractures was associated with poorer outcomes than discharge home. Factors that remained unbalanced after propensity score analysis could be assessed in controlled trials.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50485; doi:https://doi.org/10.5694/mja2.50485
-36457326,https://doi.org/10.3389/fpubh.2022.1017337,Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.,"Cerbino-Neto J, Peres IT, Varela MC, Brandão LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.",,Frontiers in public health,2022,2022-11-14,Y,Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19,,,"<h4>Background</h4>A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.<h4>Objective</h4>We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.<h4>Methods</h4>We performed a seroepidemiologic survey in all residents of Paquetá Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.<h4>Results</h4>We included in the study 3,016 residents of Paquetá (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).<h4>Conclusions</h4>Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render
 33148619,https://doi.org/10.1136/bmj.m3919,Consistency of variety of machine learning and statistical models in predicting clinical risks of individual patients: longitudinal cohort study using cardiovascular disease as exemplar.,"Li Y, Li Y, Sperrin M, Ashcroft DM, van Staa TP.",,BMJ (Clinical research ed.),2020,2020-11-04,Y,,,,"<h4>Objective</h4>To assess the consistency of machine learning and statistical techniques in predicting individual level and population level risks of cardiovascular disease and the effects of censoring on risk predictions.<h4>Design</h4>Longitudinal cohort study from 1 January 1998 to 31 December 2018.<h4>Setting and participants</h4>3.6 million patients from the Clinical Practice Research Datalink registered at 391 general practices in England with linked hospital admission and mortality records.<h4>Main outcome measures</h4>Model performance including discrimination, calibration, and consistency of individual risk prediction for the same patients among models with comparable model performance. 19 different prediction techniques were applied, including 12 families of machine learning models (grid searched for best models), three Cox proportional hazards models (local fitted, QRISK3, and Framingham), three parametric survival models, and one logistic model.<h4>Results</h4>The various models had similar population level performance (C statistics of about 0.87 and similar calibration). However, the predictions for individual risks of cardiovascular disease varied widely between and within different types of machine learning and statistical models, especially in patients with higher risks. A patient with a risk of 9.5-10.5% predicted by QRISK3 had a risk of 2.9-9.2% in a random forest and 2.4-7.2% in a neural network. The differences in predicted risks between QRISK3 and a neural network ranged between -23.2% and 0.1% (95% range). Models that ignored censoring (that is, assumed censored patients to be event free) substantially underestimated risk of cardiovascular disease. Of the 223 815 patients with a cardiovascular disease risk above 7.5% with QRISK3, 57.8% would be reclassified below 7.5% when using another model.<h4>Conclusions</h4>A variety of models predicted risks for the same patients very differently despite similar model performances. The logistic models and commonly used machine learning models should not be directly applied to the prediction of long term risks without considering censoring. Survival models that consider censoring and that are explainable, such as QRISK3, are preferable. The level of consistency within and between models should be routinely assessed before they are used for clinical decision making.",,pdf:https://www.bmj.com/content/bmj/371/bmj.m3919.full.pdf; doi:https://doi.org/10.1136/bmj.m3919; html:https://europepmc.org/articles/PMC7610202
+36457326,https://doi.org/10.3389/fpubh.2022.1017337,Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.,"Cerbino-Neto J, Peres IT, Varela MC, Brandão LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.",,Frontiers in public health,2022,2022-11-14,Y,Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19,,,"<h4>Background</h4>A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.<h4>Objective</h4>We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.<h4>Methods</h4>We performed a seroepidemiologic survey in all residents of Paquetá Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.<h4>Results</h4>We included in the study 3,016 residents of Paquetá (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).<h4>Conclusions</h4>Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render
 36060542,https://doi.org/10.3389/fdgth.2022.939292,Clinical deployment environments: Five pillars of translational machine learning for health.,"Harris S, Bonnici T, Keen T, Lilaonitkul W, White MJ, Swanepoel N.",,Frontiers in digital health,2022,2022-08-19,Y,Safety; Artificial intelligence; Machine Learning; Health Informatics; Translational Medicine; Ml-ops,,,"Machine Learning for Health (ML4H) has demonstrated efficacy in computer imaging and other self-contained digital workflows, but has failed to substantially impact routine clinical care. This is no longer because of poor adoption of Electronic Health Records Systems (EHRS), but because ML4H needs an infrastructure for development, deployment and evaluation within the healthcare institution. In this paper, we propose a design pattern called a Clinical Deployment Environment (CDE). We sketch the five pillars of the CDE: (1) real world development supported by live data where ML4H teams can iteratively build and test at the bedside (2) an ML-Ops platform that brings the rigour and standards of continuous deployment to ML4H (3) design and supervision by those with expertise in AI safety (4) the methods of implementation science that enable the algorithmic insights to influence the behaviour of clinicians and patients and (5) continuous evaluation that uses randomisation to avoid bias but in an agile manner. The CDE is intended to answer the same requirements that bio-medicine articulated in establishing the translational medicine domain. It envisions a transition from ""real-world"" data to ""real-world"" development.",,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2022.939292/pdf; doi:https://doi.org/10.3389/fdgth.2022.939292; html:https://europepmc.org/articles/PMC9437594; pdf:https://europepmc.org/articles/PMC9437594?pdf=render
 32709646,https://doi.org/10.1136/bmjopen-2019-036099,"Predicting the risk of asthma attacks in children, adolescents and adults: protocol for a machine learning algorithm derived from a primary care-based retrospective cohort.","Hussain Z, Shah SA, Mukherjee M, Sheikh A.",,BMJ open,2020,2020-07-23,Y,Asthma; epidemiology; Public Health; Health Informatics,,,"<h4>Introduction</h4>Most asthma attacks and subsequent deaths are potentially preventable. We aim to develop a prognostic tool for identifying patients at high risk of asthma attacks in primary care by leveraging advances in machine learning.<h4>Methods and analysis</h4>Current prognostic tools use logistic regression to develop a risk scoring model for asthma attacks. We propose to build on this by systematically applying various well-known machine learning techniques to a large longitudinal deidentified primary care database, the Optimum Patient Care Research Database, and comparatively evaluate their performance with the existing logistic regression model and against each other. Machine learning algorithms vary in their predictive abilities based on the dataset and the approach to analysis employed. We will undertake feature selection, classification (both one-class and two-class classifiers) and performance evaluation. Patients who have had actively treated clinician-diagnosed asthma, aged 8-80 years and with 3 years of continuous data, from 2016 to 2018, will be selected. Risk factors will be obtained from the first year, while the next 2 years will form the outcome period, in which the primary endpoint will be the occurrence of an asthma attack.<h4>Ethics and dissemination</h4>We have obtained approval from OPCRD's Anonymous Data Ethics Protocols and Transparency (ADEPT) Committee. We will seek ethics approval from The University of Edinburgh's Research Ethics Group (UREG). We aim to present our findings at scientific conferences and in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/7/e036099.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-036099; html:https://europepmc.org/articles/PMC7380838; pdf:https://europepmc.org/articles/PMC7380838?pdf=render
-32814581,https://doi.org/10.1186/s12916-020-01687-7,Seasonal influenza vaccination in Kenya: an economic evaluation using dynamic transmission modelling.,"Dawa J, Emukule GO, Barasa E, Widdowson MA, Anzala O, van Leeuwen E, Baguelin M, Chaves SS, Eggo RM.",,BMC medicine,2020,2020-08-20,Y,Economic evaluation; Influenza vaccine; Cost-effectiveness; Low- And Middle-income Countries; Dynamic Transmission Model; Vaccine Timing; Vaccine Target Group,,,"<h4>Background</h4>There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya.<h4>Methods</h4>We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23 months (strategy I), 2-5 years (strategy II) and 6-14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872).<h4>Results</h4>The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23 months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5 years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14 years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23 months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit.<h4>Conclusion</h4>Vaccinating children 6-23 months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01687-7; doi:https://doi.org/10.1186/s12916-020-01687-7; html:https://europepmc.org/articles/PMC7438179; pdf:https://europepmc.org/articles/PMC7438179?pdf=render
 31984563,https://doi.org/10.1111/jce.14368,Early recurrences of atrial tachyarrhythmias post pulmonary vein isolation.,"von Olshausen G, Uijl A, Jensen-Urstad M, Schwieler J, Drca N, Bastani H, Tapanainen J, Saluveer O, Bourke T, Kennebäck G, Insulander P, Deisenhofer I, Braunschweig F.",,Journal of cardiovascular electrophysiology,2020,2020-01-31,N,Atrial fibrillation; Catheter ablation; Late Recurrence; Early Recurrence; Blanking Period,,,"<h4>Aims</h4>To investigate the significance of early recurrence (ER) of atrial tachyarrhythmias after pulmonary vein isolation (PVI) on the development of late recurrence (LR) and to redefine the blanking period during which an ER is considered nonspecific.<h4>Methods</h4>Data of 713 patients undergoing their first PVI for paroxysmal or persistent atrial fibrillation between January 2012 and December 2017 were included. All patients were followed-up for 12 months according to clinical and outpatient routine and were screened for any atrial tachyarrhythmia lasting >30 seconds occurring during the first 3 months postablation (ER) and after the 3 months blanking period (LR).<h4>Results</h4>Patients with ER compared to those without ER had significantly more LR (74.5% vs 16.5% vs, P < .001). The occurrence of ER during the first, second and third months showed increasing LR rates of 35.2%, 67.9%, and 94.8%, respectively (P < .001). Receiver operator characteristic analysis revealed a blanking period of 46 days with the highest sensitivity (68.1%) and specificity (96.5%). Later timing and longer time span of ER were independent predictors for LR in multivariable analysis.<h4>Conclusion</h4>ER is a strong predictor for LR. Our study advocates a shortening of the post-PVI blanking period followed by a ""gray zone"" up to 3 months where individualized therapeutic decisions based on additional risk factors should be considered. We suggest that the ER time span might serve as such a predictor identifying patients at the highest risk for LR.",,doi:https://doi.org/10.1111/jce.14368
+32814581,https://doi.org/10.1186/s12916-020-01687-7,Seasonal influenza vaccination in Kenya: an economic evaluation using dynamic transmission modelling.,"Dawa J, Emukule GO, Barasa E, Widdowson MA, Anzala O, van Leeuwen E, Baguelin M, Chaves SS, Eggo RM.",,BMC medicine,2020,2020-08-20,Y,Economic evaluation; Influenza vaccine; Cost-effectiveness; Low- And Middle-income Countries; Dynamic Transmission Model; Vaccine Timing; Vaccine Target Group,,,"<h4>Background</h4>There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya.<h4>Methods</h4>We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23 months (strategy I), 2-5 years (strategy II) and 6-14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872).<h4>Results</h4>The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23 months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5 years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14 years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23 months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit.<h4>Conclusion</h4>Vaccinating children 6-23 months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01687-7; doi:https://doi.org/10.1186/s12916-020-01687-7; html:https://europepmc.org/articles/PMC7438179; pdf:https://europepmc.org/articles/PMC7438179?pdf=render
 33588321,https://doi.org/10.1016/j.retram.2021.103276,Biological responses to COVID-19: Insights from physiological and blood biomarker profiles.,"Zakeri R, Pickles A, Carr E, Bean DM, O'Gallagher K, Kraljewic Z, Searle T, Shek A, Galloway JB, Teo JTH, Shah AM, Dobson RJB, Bendayan R.",,Current research in translational medicine,2021,2021-02-03,Y,Inflammation; Biomarkers; Classes; Sars-cov-2,,,"<h4>Background</h4>Understanding the spectrum and course of biological responses to coronavirus disease 2019 (COVID-19) may have important therapeutic implications. We sought to characterise biological responses among patients hospitalised with severe COVID-19 based on serial, routinely collected, physiological and blood biomarker values.<h4>Methods and findings</h4>We performed a retrospective cohort study of 1335 patients hospitalised with laboratory-confirmed COVID-19 (median age 70 years, 56 % male), between 1st March and 30th April 2020. Latent profile analysis was performed on serial physiological and blood biomarkers. Patient characteristics, comorbidities and rates of death and admission to intensive care, were compared between the latent classes. A five class solution provided the best fit. Class 1 ""Typical response"" exhibited a moderately elevated and rising C-reactive protein (CRP), stable lymphopaenia, and the lowest rates of 14-day adverse outcomes. Class 2 ""Rapid hyperinflammatory response"" comprised older patients, with higher admission white cell and neutrophil counts, which declined over time, accompanied by a very high and rising CRP and platelet count, and exibited the highest mortality risk. Class 3 ""Progressive inflammatory response"" was similar to the typical response except for a higher and rising CRP, though similar mortality rate. Class 4 ""Inflammatory response with kidney injury"" had prominent lymphopaenia, moderately elevated (and rising) CRP, and severe renal failure. Class 5 ""Hyperinflammatory response with kidney injury"" comprised older patients, with a very high and rising CRP, and severe renal failure that attenuated over time. Physiological measures did not substantially vary between classes at baseline or early admission.<h4>Conclusions and relevance</h4>Our identification of five distinct classes of biomarker profiles provides empirical evidence for heterogeneous biological responses to COVID-19. Early hyperinflammatory responses and kidney injury may signify unique pathophysiology that requires targeted therapy.",,doi:https://doi.org/10.1016/j.retram.2021.103276; doi:https://doi.org/10.1016/j.retram.2021.103276; html:https://europepmc.org/articles/PMC7857048; pdf:https://europepmc.org/articles/PMC7857048?pdf=render
 32234121,https://doi.org/10.2807/1560-7917.es.2020.25.12.2000256,"Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020.","Russell TW, Hellewell J, Jarvis CI, van Zandvoort K, Abbott S, Ratnayake R, CMMID COVID-19 working group, Flasche S, Eggo RM, Edmunds WJ, Kucharski AJ.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-03-01,Y,Coronavirus; outbreak; Severity; Asymptomatic; Case Fatality Ratio; Cruise Ship; Covid-19; Infection Fatality Ratio,"COVID-19, Improving Public Health","COVID-19, infection","Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.12.2000256; html:https://europepmc.org/articles/PMC7118348; pdf:https://europepmc.org/articles/PMC7118348?pdf=render
 30863860,https://doi.org/10.1093/eurheartj/ehz089,Big data analytics in adult congenital heart disease: why coding matters.,"Asselbergs FW, Meijboom FJ.",,European heart journal,2019,2019-04-01,N,,,,,,pdf:https://discovery.ucl.ac.uk/10076628/1/Asselbergs_AAM_Big%20data%20analytics%20in%20adult%20congenital%20heart%20disease.pdf; doi:https://doi.org/10.1093/eurheartj/ehz089
@@ -1386,36 +1386,36 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33956386,https://doi.org/10.1111/ceo.13943,Reporting guidelines for artificial intelligence in healthcare research.,"Ibrahim H, Liu X, Denniston AK.",,Clinical & experimental ophthalmology,2021,2021-05-25,N,Artificial intelligence; Checklist; Research Report; Guidelines; Research Design; Machine Learning,,,"Reporting guidelines are structured tools developed using explicit methodology that specify the minimum information required by researchers when reporting a study. The use of artificial intelligence (AI) reporting guidelines that address potential sources of bias specific to studies involving AI interventions has the potential to improve the quality of AI studies, through improvements in their design and delivery, and the completeness and transparency of their reporting. With a number of guidance documents relating to AI studies emerging from different specialist societies, this Review article provides researchers with some key principles for selecting the most appropriate reporting guidelines for a study involving an AI intervention. As the main determinants of a high-quality study are contained within the methodology of the study design rather than the intervention, researchers are recommended to use reporting guidelines that are specific to the study design, and then supplement them with AI-specific guidance contained within available AI reporting guidelines.",,pdf:http://pure-oai.bham.ac.uk/ws/files/143736502/ceo.13943.pdf; doi:https://doi.org/10.1111/ceo.13943
 34032955,https://doi.org/10.1007/s11136-021-02876-4,"Health status after penetrating major trauma in Victoria, Australia: a registry-based cohort study.","Giummarra MJ, Dipnall JF, Gibson G, Beck B, Gabbe BJ.",,"Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation",2021,2021-05-25,N,Recovery; Health Status; Health-related Quality Of Life; Gunshot Wounds; Penetrating Trauma; Stab Wounds,,,"<h4>Purpose</h4>As few studies have examined long-term health after penetrating injury, this population-based registry study sought to assess health outcomes up to 24 months post-injury.<h4>Methods</h4>Major trauma patients with penetrating trauma (2009-2017) were included from the Victorian State Trauma Registry (N = 1,067; 102 died, 208 were lost to follow-up). The EQ-5D-3L was used to measure health status at 6, 12 and 24-months. Mixed linear and logistic regressions were used to examine predictors of summary scores, and problems versus no problems on each health dimension.<h4>Results</h4>Average health status summary scores were 0.70 (sd = 0.26) at 6 and 12 months, and 0.72 (sd = 0.26) at 24 months post-injury. Prevalence of problems was consistent over time: mobility (24-26%), self-care (17-20%), usual activities (47-50%), pain/discomfort (44-49%), and anxiety/depression (54-56%). Lower health status and reporting problems was associated with middle-older age, female sex, unemployment; pre-injury disability, comorbid conditions; and assault and firearm injury versus cutting/piercing.<h4>Conclusion</h4>Problems with usual activities, pain/discomfort and anxiety or depression are common after penetrating major trauma. Risk factor screening in hospital could be used to identify people at risk of poor health outcomes, and to link people at risk with services in hospital or early post-discharge to improve their longer-term health outcomes.",,doi:https://doi.org/10.1007/s11136-021-02876-4
 35072137,https://doi.org/10.1016/j.xgen.2021.100086,Machine learning optimized polygenic scores for blood cell traits identify sex-specific trajectories and genetic correlations with disease.,"Xu Y, Vuckovic D, Ritchie SC, Akbari P, Jiang T, Grealey J, Butterworth AS, Ouwehand WH, Roberts DJ, Di Angelantonio E, Danesh J, Soranzo N, Inouye M.",,Cell genomics,2022,2022-01-12,Y,Method; Machine Learning; Population Stratification; Polygenic Score; Blood Cell Trait; Disease Assocations,,,"Genetic association studies for blood cell traits, which are key indicators of health and immune function, have identified several hundred associations and defined a complex polygenic architecture. Polygenic scores (PGSs) for blood cell traits have potential clinical utility in disease risk prediction and prevention, but designing PGS remains challenging and the optimal methods are unclear. To address this, we evaluated the relative performance of 6 methods to develop PGS for 26 blood cell traits, including a standard method of pruning and thresholding (P + T) and 5 learning methods: LDpred2, elastic net (EN), Bayesian ridge (BR), multilayer perceptron (MLP) and convolutional neural network (CNN). We evaluated these optimized PGSs on blood cell trait data from UK Biobank and INTERVAL. We find that PGSs designed using common machine learning methods EN and BR show improved prediction of blood cell traits and consistently outperform other methods. Our analyses suggest EN/BR as the top choices for PGS construction, showing improved performance for 25 blood cell traits in the external validation, with correlations with the directly measured traits increasing by 10%-23%. Ten PGSs showed significant statistical interaction with sex, and sex-specific PGS stratification showed that all of them had substantial variation in the trajectories of blood cell traits with age. Genetic correlations between the PGSs for blood cell traits and common human diseases identified well-known as well as new associations. We develop machine learning-optimized PGS for blood cell traits, demonstrate their relationships with sex, age, and disease, and make these publicly available as a resource.",,doi:https://doi.org/10.1016/j.xgen.2021.100086; doi:https://doi.org/10.1016/j.xgen.2021.100086; html:https://europepmc.org/articles/PMC8758502; pdf:https://europepmc.org/articles/PMC8758502?pdf=render
-34348396,https://doi.org/10.1097/ede.0000000000001393,Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.,"Katsoulis M, Stavola BD, Diaz-Ordaz K, Gomes M, Lai A, Lagiou P, Wannamethee G, Tsilidis K, Lumbers RT, Denaxas S, Banerjee A, Parisinos CA, Batterham R, Patel R, Langenberg C, Hemingway H.",,"Epidemiology (Cambridge, Mass.)",2021,2021-09-01,Y,,,,"<h4>Background</h4>Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.<h4>Methods</h4>We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group.<h4>Results</h4>Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals.<h4>Conclusion</h4>Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.",,html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx; doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render
 31109684,https://doi.org/10.1016/j.injury.2019.05.004,Agreement between medical record and administrative coding of common comorbidities in orthopaedic trauma patients.,"Daly S, Nguyen TQ, Gabbe BJ, Braaf S, Simpson P, Ekegren CL.",,Injury,2019,2019-05-08,N,Trauma; Comorbidity; Agreement; Orthopaedic; Icd-10-am,,,"OBJECTIVE:To i) quantify the agreement between comorbidities documented within medical records and an orthopaedic trauma dataset; and ii) compare agreement between these sources before and after the introduction of new comorbidity coding rules in Australian hospitals. STUDY DESIGN AND SETTING:A random sample of adult (≥ 16 years) orthopaedic trauma patients (n = 400) were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). Diagnoses of obesity, arthritis, diabetes and cardiac conditions documented within patients' medical records were compared to ICD-10-AM comorbidity codes (provided by hospitals) for the same admission. Agreement was calculated (Cohen's kappa) before and after the introduction of new coding rules. RESULTS:All comorbidities had the same or higher prevalence in medical record data compared to coded data. Kappa values ranged from <0.001 (poor agreement) for coronary artery disease to 0.94 (excellent agreement) for type 2 diabetes. There was improvement in agreement between sources for most conditions following the introduction of new coding rules. CONCLUSION:There has been improvement in the coding of certain comorbidities since the introduction of new coding rules, suggesting that, since 2015, administrative data has improved capacity to capture patients' comorbidity profiles. Consideration must be taken when using the ICD-10-AM data due to its limitations.",,doi:https://doi.org/10.1016/j.injury.2019.05.004
+34348396,https://doi.org/10.1097/ede.0000000000001393,Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.,"Katsoulis M, Stavola BD, Diaz-Ordaz K, Gomes M, Lai A, Lagiou P, Wannamethee G, Tsilidis K, Lumbers RT, Denaxas S, Banerjee A, Parisinos CA, Batterham R, Patel R, Langenberg C, Hemingway H.",,"Epidemiology (Cambridge, Mass.)",2021,2021-09-01,Y,,,,"<h4>Background</h4>Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.<h4>Methods</h4>We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group.<h4>Results</h4>Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals.<h4>Conclusion</h4>Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.",,html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx; doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render
 32478737,https://doi.org/10.3791/60794,Implementation of a Real-Time Psychosis Risk Detection and Alerting System Based on Electronic Health Records using CogStack.,"Wang T, Oliver D, Msosa Y, Colling C, Spada G, Roguski Ł, Folarin A, Stewart R, Roberts A, Dobson RJB, Fusar-Poli P.",,Journal of visualized experiments : JoVE,2020,2020-05-15,N,,,,"Recent studies have shown that an automated, lifespan-inclusive, transdiagnostic, and clinically based, individualized risk calculator provides a powerful system for supporting the early detection of individuals at-risk of psychosis at a large scale, by leveraging electronic health records (EHRs). This risk calculator has been externally validated twice and is undergoing feasibility testing for clinical implementation. Integration of this risk calculator in clinical routine should be facilitated by prospective feasibility studies, which are required to address pragmatic challenges, such as missing data, and the usability of this risk calculator in a real-world and routine clinical setting. Here, we present an approach for a prospective implementation of a real-time psychosis risk detection and alerting service in a real-world EHR system. This method leverages the CogStack platform, which is an open-source, lightweight, and distributed information retrieval and text extraction system. The CogStack platform incorporates a set of services that allow for full-text search of clinical data, lifespan-inclusive, real-time calculation of psychosis risk, early risk-alerting to clinicians, and the visual monitoring of patients over time. Our method includes: 1) ingestion and synchronization of data from multiple sources into the CogStack platform, 2) implementation of a risk calculator, whose algorithm was previously developed and validated, for timely computation of a patient's risk of psychosis, 3) creation of interactive visualizations and dashboards to monitor patients' health status over time, and 4) building automated alerting systems to ensure that clinicians are notified of patients at-risk, so that appropriate actions can be pursued. This is the first ever study that has developed and implemented a similar detection and alerting system in clinical routine for early detection of psychosis.",,pdf:https://www.jove.com/pdf/60794/implementation-real-time-psychosis-risk-detection-alerting-system; doi:https://doi.org/10.3791/60794; html:https://europepmc.org/articles/PMC7272223; pdf:https://europepmc.org/articles/PMC7272223?pdf=render; doi:https://doi.org/10.3791/60794
 37750555,https://doi.org/10.1161/jaha.123.030766,Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.,"Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.",,Journal of the American Heart Association,2023,2023-09-26,N,Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs,,,"Background Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention. Methods and Results Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (£5830 [United Kingdom], $14 133 [US Medicare]), of myocardial infarction with urgent CRV procedure (£5614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (£4674/£4651 and $15 251/$17 539). Conclusions Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render; doi:https://doi.org/10.1161/jaha.123.030766
 33959646,https://doi.org/10.3389/fcvm.2021.658915,"Common Variants Associated With <i>OSMR</i> Expression Contribute to Carotid Plaque Vulnerability, but Not to Cardiovascular Disease in Humans.","van Keulen D, van Koeverden ID, Boltjes A, Princen HMG, van Gool AJ, de Borst GJ, Asselbergs FW, Tempel D, Pasterkamp G, van der Laan SW.",,Frontiers in cardiovascular medicine,2021,2021-04-20,Y,Genetics; Atherosclerosis; Cardiovascular disease; Plaque; Osm; Osmr; Lifr,,,"<b>Background and Aims:</b> Oncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants in <i>OSM</i> and its receptors, <i>OSMR</i> and <i>LIFR</i>, on overall plaque vulnerability, plaque phenotype, intraplaque <i>OSMR</i> and <i>LIFR</i> expression, coronary artery calcification burden and cardiovascular disease susceptibility. <b>Methods and Results:</b> We queried Genotype-Tissue Expression data and found that rs13168867 (C allele) was associated with decreased <i>OSMR</i> expression and that rs10491509 (A allele) was associated with increased <i>LIFR</i> expression in arterial tissues. No variant was significantly associated with <i>OSM</i> expression. We associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. After correction for multiple testing, rs13168867 was significantly associated with an increased overall plaque vulnerability (β = 0.118 ± s.e. = 0.040, <i>p</i> = 3.00 × 10<sup>-3</sup>, C allele). Looking at individual plaque characteristics, rs13168867 showed strongest associations with intraplaque fat (β = 0.248 ± s.e. = 0.088, <i>p</i> = 4.66 × 10<sup>-3</sup>, C allele) and collagen content (β = -0.259 ± s.e. = 0.095, <i>p</i> = 6.22 × 10<sup>-3</sup>, C allele), but these associations were not significant after correction for multiple testing. rs13168867 was not associated with intraplaque <i>OSMR</i> expression. Neither was intraplaque <i>OSMR</i> expression associated with plaque vulnerability and no known <i>OSMR</i> eQTLs were associated with coronary artery calcification burden, or cardiovascular disease susceptibility. No associations were found for rs10491509 in the <i>LIFR</i> locus. <b>Conclusions:</b> Our study suggests that rs1316887 in the OSMR locus is associated with increased plaque vulnerability, but not with coronary calcification or cardiovascular disease risk. It remains unclear through which precise biological mechanisms OSM signaling exerts its effects on plaque morphology. However, the OSM-OSMR/LIFR pathway is unlikely to be causally involved in lifetime cardiovascular disease susceptibility.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.658915/pdf; doi:https://doi.org/10.3389/fcvm.2021.658915; html:https://europepmc.org/articles/PMC8093786; pdf:https://europepmc.org/articles/PMC8093786?pdf=render
 36823471,https://doi.org/10.1038/s42255-023-00753-7,Proteogenomic links to human metabolic diseases.,"Koprulu M, Carrasco-Zanini J, Wheeler E, Lockhart S, Kerrison ND, Wareham NJ, Pietzner M, Langenberg C.",,Nature metabolism,2023,2023-02-23,Y,,,,"Studying the plasma proteome as the intermediate layer between the genome and the phenome has the potential to identify new disease processes. Here, we conducted a cis-focused proteogenomic analysis of 2,923 plasma proteins measured in 1,180 individuals using antibody-based assays. We (1) identify 256 unreported protein quantitative trait loci (pQTL); (2) demonstrate shared genetic regulation of 224 cis-pQTLs with 575 specific health outcomes, revealing examples for notable metabolic diseases (such as gastrin-releasing peptide as a potential therapeutic target for type 2 diabetes); (3) improve causal gene assignment at 40% (n = 192) of overlapping risk loci; and (4) observe convergence of phenotypic consequences of cis-pQTLs and rare loss-of-function gene burden for 12 proteins, such as TIMD4 for lipoprotein metabolism. Our findings demonstrate the value of integrating complementary proteomic technologies with genomics even at moderate scale to identify new mediators of metabolic diseases with the potential for therapeutic interventions.",,doi:https://doi.org/10.1038/s42255-023-00753-7; html:https://europepmc.org/articles/PMC7614946; pdf:https://europepmc.org/articles/PMC7614946?pdf=render
 34957541,https://doi.org/10.1111/bjh.18013,A novel algorithmic approach to generate consensus treatment guidelines in adult acute myeloid leukaemia.,"Coats T, Bean D, Basset A, Sirkis T, Brammeld J, Johnson S, Thomas I, Gilkes A, Raj K, Dennis M, Knapper S, Mehta P, Khwaja A, Hunter H, Tauro S, Bowen D, Jones G, Dobson R, Russell N, Dillon R.",,British journal of haematology,2022,2021-12-26,N,Myeloid Leukaemia; Classifications; Diagnostic Haematology; Clinical Haematology,,,"Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front-line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real-world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available.",,pdf:https://discovery.dundee.ac.uk/files/71382229/Br_J_Haematol_2022_Coats_A_novel_algorithmic_approach_to_generate_consensus_treatment_guidelines_in_adult_acute.pdf; doi:https://doi.org/10.1111/bjh.18013
 32685698,https://doi.org/10.12688/wellcomeopenres.15842.3,Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China.,"Endo A, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott S, Kucharski AJ, Funk S.",,Wellcome open research,2020,2020-07-10,Y,Branching Process; Overdispersion; Novel Coronavirus; Superspreading; Covid-19; Sars-cov-2,,,"<b>Background:</b> A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic reproduction number <i>R</i> <sub>0</sub>, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others. <b>Methods:</b> We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution. <b>Results:</b> Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of <i>R</i> <sub>0</sub> (2-3), the overdispersion parameter <i>k</i> of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for <i>R</i> <sub>0</sub> and <i>k</i> (95% CrIs: <i>R</i> <sub>0</sub> 1.4-12; <i>k</i> 0.04-0.2); however, the upper bound of <i>R</i> <sub>0</sub> was not well informed by the model and data, which did not notably differ from that of the prior distribution. <b>Conclusions:</b> Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.",,doi:https://doi.org/10.12688/wellcomeopenres.15842.3; html:https://europepmc.org/articles/PMC7338915; pdf:https://europepmc.org/articles/PMC7338915?pdf=render
-37699620,https://doi.org/10.1136/bmjopen-2023-074626,Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.,"Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne J, Sharp MK, Stuart EA, Hernan MA, Lee H, McAuley JH.",,BMJ open,2023,2023-09-12,Y,Retrospective studies; epidemiology; Statistics & Research Methods,,,"<h4>Background</h4>Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.<h4>Methods/design</h4>The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.<h4>Ethics and dissemination</h4>Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.",,doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?pdf=render
 31671849,https://doi.org/10.3390/ijerph16214178,Associations between the Home Physical Environment and Children's Home-Based Physical Activity and Sitting. ,"Sheldrick MP, Maitland C, Mackintosh KA, Rosenberg M, Griffiths LJ, Fry R, Stratton G.",,International journal of environmental research and public health,2019,2019-10-29,Y,,,,"It is important to understand the correlates of children's physical activity (PA) and sitting at home, where children spend significant time. The home social environment has an important influence; however, much less is known about the home physical environment. Therefore, the study aimed to assess relationships between the physical environment and children's sitting and PA at home. In total, 235 child-parent dyads were included in the analyses. Children spent 67% of their time at home sitting. Linear regression analyses examined associations between physical home environmental factors obtained via an audit and children's (55% girl, 10.2 ± 0.7) objective PA and sitting at home. Following adjustment for socio-demographics and social environmental factors, an open plan living area (OPLA), musical instrument accessibility and availability, and perceived house size were negatively and positively associated, whereas media equipment accessibility and availability was positively and negatively associated with sitting and standing, respectively. Additionally, an OPLA was positively associated with total and moderate-to-vigorous PA. Furthermore, sitting breaks were positively associated with objective garden size and negatively associated with digital TV. The physical home environment may have an important influence on children's sitting, standing and PA at home; therefore, interventions that target this environment are needed.",,pdf:https://www.mdpi.com/1660-4601/16/21/4178/pdf?version=1573119054; doi:https://doi.org/10.3390/ijerph16214178; html:https://europepmc.org/articles/PMC6862192; pdf:https://europepmc.org/articles/PMC6862192?pdf=render
+37699620,https://doi.org/10.1136/bmjopen-2023-074626,Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.,"Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne J, Sharp MK, Stuart EA, Hernan MA, Lee H, McAuley JH.",,BMJ open,2023,2023-09-12,Y,Retrospective studies; epidemiology; Statistics & Research Methods,,,"<h4>Background</h4>Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.<h4>Methods/design</h4>The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.<h4>Ethics and dissemination</h4>Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.",,doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?pdf=render
 37339333,https://doi.org/10.1002/jia2.26104,"COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.","Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.",,Journal of the International AIDS Society,2023,2023-06-01,Y,Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2,,,"<h4>Introduction</h4>While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.<h4>Methods</h4>We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.<h4>Results</h4>Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.<h4>Conclusions</h4>Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render
 33591280,https://doi.org/10.2196/16348,A Social Media Campaign (#datasaveslives) to Promote the Benefits of Using Health Data for Research Purposes: Mixed Methods Analysis.,"Hassan L, Nenadic G, Tully MP.",,Journal of medical Internet research,2021,2021-02-16,Y,Medical research; Public Engagement; Social Network Analysis; Social Media,,,"<h4>Background</h4>Social media provides the potential to engage a wide audience about scientific research, including the public. However, little empirical research exists to guide health scientists regarding what works and how to optimize impact. We examined the social media campaign #datasaveslives established in 2014 to highlight positive examples of the use and reuse of health data in research.<h4>Objective</h4>This study aims to examine how the #datasaveslives hashtag was used on social media, how often, and by whom; thus, we aim to provide insights into the impact of a major social media campaign in the UK health informatics research community and further afield.<h4>Methods</h4>We analyzed all publicly available posts (tweets) that included the hashtag #datasaveslives (N=13,895) on the microblogging platform Twitter between September 1, 2016, and August 31, 2017. Using a combination of qualitative and quantitative analyses, we determined the frequency and purpose of tweets. Social network analysis was used to analyze and visualize tweet sharing (retweet) networks among hashtag users.<h4>Results</h4>Overall, we found 4175 original posts and 9720 retweets featuring #datasaveslives by 3649 unique Twitter users. In total, 66.01% (2756/4175) of the original posts were retweeted at least once. Higher frequencies of tweets were observed during the weeks of prominent policy publications, popular conferences, and public engagement events. Cluster analysis based on retweet relationships revealed an interconnected series of groups of #datasaveslives users in academia, health services and policy, and charities and patient networks. Thematic analysis of tweets showed that #datasaveslives was used for a broader range of purposes than indexing information, including event reporting, encouraging participation and action, and showing personal support for data sharing.<h4>Conclusions</h4>This study shows that a hashtag-based social media campaign was effective in encouraging a wide audience of stakeholders to disseminate positive examples of health research. Furthermore, the findings suggest that the campaign supported community building and bridging practices within and between the interdisciplinary sectors related to the field of health data science and encouraged individuals to demonstrate personal support for sharing health data.",,pdf:https://www.jmir.org/2021/2/e16348/PDF; doi:https://doi.org/10.2196/16348; html:https://europepmc.org/articles/PMC7925154
 33372068,https://doi.org/10.1136/bmjopen-2020-038324,Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.,"Adesanya EI, Schonmann Y, Hayes JF, Mathur R, Mulick AR, Rayner L, Smeeth L, Smith CH, Langan SM, Mansfield KE.",,BMJ open,2020,2020-12-28,Y,Psoriasis; Mental health; Eczema; Anxiety Disorders; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders,,,"<h4>Introduction</h4>Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis.<h4>Methods and analysis</h4>We will conduct a systematic review of randomised controlled trials, cohort, case-control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.<h4>Ethics and dissemination</h4>Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.<h4>Prospero registration number</h4>CRD42020163941.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038324.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038324; html:https://europepmc.org/articles/PMC7772326; pdf:https://europepmc.org/articles/PMC7772326?pdf=render
 37348789,https://doi.org/10.1016/j.jhep.2023.05.046,Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.,"Roca-Fernandez A, Banerjee R, Thomaides-Brears H, Telford A, Sanyal A, Neubauer S, Nichols TE, Raman B, McCracken C, Petersen SE, Ntusi NA, Cuthbertson DJ, Lai M, Dennis A, Banerjee A.",,Journal of hepatology,2023,2023-06-20,N,Cardiac; MRI; Imaging; Hepatic; Heart Failure; liver disease; Cvd; Nafld; Atrial Fibrilliation,,,"<h4>Background & aims</h4>Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.<h4>Methods</h4>Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).<h4>Results</h4>A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m<sup>2</sup>, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).<h4>Conclusion</h4>Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.<h4>Impact and implications</h4>Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.",,pdf:https://discovery.ucl.ac.uk/id/eprint/10175737/1/1-s2.0-S0168827823004208-main.pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046
-37748493,https://doi.org/10.1016/s2213-2600(23)00262-x,"Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.",C-MORE/PHOSP-COVID Collaborative Group.,,The Lancet. Respiratory medicine,2023,2023-09-22,Y,,,,"<h4>Introduction</h4>The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.<h4>Methods</h4>In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.<h4>Findings</h4>Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5-5·8]; p<sub>adjusted</sub>=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32-4·82]; p<sub>adjusted</sub>=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23-11·88]; p<sub>adjusted</sub>=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.<h4>Interpretation</h4>After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.<h4>Funding</h4>UK Research and Innovation and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?pdf=render
 35115301,https://doi.org/10.1136/bjophthalmol-2021-319641,Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study.,"Gokhale KM, Adderley NJ, Subramanian A, Lee WH, Han D, Coker J, Braithwaite T, Denniston AK, Keane PA, Nirantharakumar K.",,The British journal of ophthalmology,2023,2022-02-03,N,Degeneration; epidemiology; Macula,,,"<h4>Background</h4>Age-related macular degeneration (AMD) in its late stages is a leading cause of sight loss in developed countries. Some previous studies have suggested that metformin may be associated with a reduced risk of developing AMD, but the evidence is inconclusive.<h4>Aims</h4>To explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.<h4>Methods</h4>A large, population-based retrospective open cohort study with a time-dependent exposure design was carried out using IQVIA Medical Research Data, 1995-2019. Patients aged ≥40 with diagnosed type 2 diabetes were included.The exposed group was those prescribed metformin (with or without any other antidiabetic medications); the comparator (unexposed) group was those prescribed other antidiabetic medications only. The exposure status was treated as time varying, collected at 3-monthly time intervals.Extended Cox proportional hazards regression was used to calculate the adjusted HRs for development of the outcome, newly diagnosed AMD.<h4>Results</h4>A total of 173 689 patients, 57% men, mean (SD) age 62.8 (11.6) years, with incident type 2 diabetes and a record of one or more antidiabetic medications were included in the study. Median follow-up was 4.8 (IQR 2.3-8.3, range 0.5-23.8) years. 3111 (1.8%) patients developed AMD. The adjusted HR for diagnosis of AMD was 1.02 (95% CI 0.92 to 1.12) in patients prescribed metformin (with or without other antidiabetic medications) compared with those prescribed any other antidiabetic medication only.<h4>Conclusion</h4>We found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.",,pdf:https://discovery.ucl.ac.uk/10143945/1/Keane_T2DM%20metformin%20and%20risk%20of%20AMD%20BJO%2020220111%20clean.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319641
+37748493,https://doi.org/10.1016/s2213-2600(23)00262-x,"Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.",C-MORE/PHOSP-COVID Collaborative Group.,,The Lancet. Respiratory medicine,2023,2023-09-22,Y,,,,"<h4>Introduction</h4>The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.<h4>Methods</h4>In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.<h4>Findings</h4>Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5-5·8]; p<sub>adjusted</sub>=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32-4·82]; p<sub>adjusted</sub>=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23-11·88]; p<sub>adjusted</sub>=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.<h4>Interpretation</h4>After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.<h4>Funding</h4>UK Research and Innovation and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?pdf=render
 31409800,https://doi.org/10.1038/s41467-019-11451-y,GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits.,"Pazoki R, Evangelou E, Mosen-Ansorena D, Pinto RC, Karaman I, Blakeley P, Gill D, Zuber V, Elliott P, Tzoulaki I, Dehghan A.",,Nature communications,2019,2019-08-13,Y,,Understanding the Causes of Disease,,"Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over-represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits.",,pdf:https://www.nature.com/articles/s41467-019-11451-y.pdf; doi:https://doi.org/10.1038/s41467-019-11451-y; html:https://europepmc.org/articles/PMC6692500; pdf:https://europepmc.org/articles/PMC6692500?pdf=render
 33788869,https://doi.org/10.1371/journal.pone.0249258,Using graphic modelling to identify modifiable mediators of the association between area-based deprivation at birth and offspring unemployment.,"Bogie J, Fleming M, Cullen B, Mackay D, Pell JP.",,PloS one,2021,2021-03-31,Y,,,,"<h4>Background</h4>Deprivation can perpetuate across generations; however, the causative pathways are not well understood. Directed acyclic graphs (DAG) with mediation analysis can help elucidate and quantify complex pathways in order to identify modifiable factors at which to target interventions.<h4>Methods and findings</h4>We linked ten Scotland-wide databases (six health and four education) to produce a cohort of 217,226 pupils who attended Scottish schools between 2009 and 2013. The DAG comprised 23 potential mediators of the association between area deprivation at birth and subsequent offspring 'not in education, employment or training' status, covering maternal, antenatal, perinatal and child health, school engagement, and educational factors. Analyses were performed using modified g-computation. Deprivation at birth was associated with a 7.3% increase in offspring 'not in education, employment or training'. The principal mediators of this association were smoking during pregnancy (natural indirect effect of 0·016, 95% CI 0·013, 0·019) and school absences (natural indirect effect of 0·021, 95% CI 0·018, 0·024), explaining 22% and 30% of the total effect respectively. The proportion of the association potentially eliminated by addressing these factors was 19% (controlled direct effect when set to non-smoker 0·058; 95% CI 0·053, 0·063) for smoking during pregnancy and 38% (controlled direct effect when set to no absences 0·043; 95% CI 0·037, 0·049) for school absences.<h4>Conclusions</h4>Combining a DAG with mediation analysis helped disentangle a complex public health problem and quantified the modifiable factors of maternal smoking and school absence that could be targeted for intervention. This study also demonstrates the general utility of DAGs in understanding complex public health problems.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0249258&type=printable; doi:https://doi.org/10.1371/journal.pone.0249258; html:https://europepmc.org/articles/PMC8011734; pdf:https://europepmc.org/articles/PMC8011734?pdf=render
 33521535,https://doi.org/10.1136/bmjnph-2020-000107,Genetic risk of obesity as a modifier of associations between neighbourhood environment and body mass index: an observational study of 335 046 UK Biobank participants.,"Mason KE, Palla L, Pearce N, Phelan J, Cummins S.",,"BMJ nutrition, prevention & health",2020,2020-10-05,Y,Malnutrition; Dietary Patterns,,,"<h4>Background</h4>There is growing recognition that recent global increases in obesity are the product of a complex interplay between genetic and environmental factors. However, in gene-environment studies of obesity, 'environment' usually refers to individual behavioural factors that influence energy balance, whereas more upstream environmental factors are overlooked. We examined gene-environment interactions between genetic risk of obesity and two neighbourhood characteristics likely to be associated with obesity (proximity to takeaway/fast-food outlets and availability of physical activity facilities).<h4>Methods</h4>We used data from 335 046 adults aged 40-70 in the UK Biobank cohort to conduct a population-based cross-sectional study of interactions between neighbourhood characteristics and genetic risk of obesity, in relation to body mass index (BMI). Proximity to a fast-food outlet was defined as distance from home address to nearest takeaway/fast-food outlet, and availability of physical activity facilities as the number of formal physical activity facilities within 1 km of home address. Genetic risk of obesity was operationalised by weighted Genetic Risk Scores of 91 or 69 single nucleotide polymorphisms (SNP), and by six individual SNPs considered separately. Multivariable, mixed-effects models with product terms for the gene-environment interactions were estimated.<h4>Results</h4>After accounting for likely confounding, the association between proximity to takeaway/fast-food outlets and BMI was stronger among those at increased genetic risk of obesity, with evidence of an interaction with polygenic risk scores (p=0.018 and p=0.028 for 69-SNP and 91-SNP scores, respectively) and in particular with a SNP linked to <i>MC4R</i> (p=0.009), a gene known to regulate food intake. We found very little evidence of gene-environment interaction for the availability of physical activity facilities.<h4>Conclusions</h4>Individuals at an increased genetic risk of obesity may be more sensitive to exposure to the local fast-food environment. Ensuring that neighbourhood residential environments are designed to promote a healthy weight may be particularly important for those with greater genetic susceptibility to obesity.",,pdf:https://nutrition.bmj.com/content/bmjnph/3/2/247.full.pdf; doi:https://doi.org/10.1136/bmjnph-2020-000107; html:https://europepmc.org/articles/PMC7841812; pdf:https://europepmc.org/articles/PMC7841812?pdf=render
 37755828,https://doi.org/10.1001/jamanetworkopen.2023.36023,Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.,"Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Douglas SRG, Rizzo RRN, Devonshire JJ, Williams SA, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne JAC, Sharp MK, Stuart EA, Hernán MA, Lee H, McAuley JH.",,JAMA network open,2023,2023-09-05,Y,,,,"<h4>Importance</h4>Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.<h4>Objective</h4>To assess the reporting of observational studies that explicitly aimed to emulate a target trial.<h4>Evidence review</h4>We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.<h4>Findings</h4>A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.<h4>Conclusion and relevance</h4>In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.",,doi:https://doi.org/10.1001/jamanetworkopen.2023.36023; html:https://europepmc.org/articles/PMC10534275
 36764723,https://doi.org/10.1136/bmjopen-2022-067254,Associations of remote mental healthcare with clinical outcomes: a natural language processing enriched electronic health record data study protocol.,"Ahmed MS, Kornblum D, Oliver D, Fusar-Poli P, Patel R.",,BMJ open,2023,2023-02-10,Y,Psychiatry; epidemiology; Telemedicine; Health Informatics,,,"<h4>Introduction</h4>People often experience significant difficulties in receiving mental healthcare due to insufficient resources, stigma and lack of access to care. Remote care technology has the potential to overcome these barriers by reducing travel time and increasing frequency of contact with patients. However, the safe delivery of remote mental healthcare requires evidence on which aspects of care are suitable for remote delivery and which are better served by in-person care. We aim to investigate clinical and demographic associations with remote mental healthcare in a large electronic health record (EHR) dataset and the degree to which remote care is associated with differences in clinical outcomes using natural language processing (NLP) derived EHR data.<h4>Methods and analysis</h4>Deidentified EHR data, derived from the South London and Maudsley (SLaM) National Health Service Foundation Trust Biomedical Research Centre (BRC) Case Register, will be extracted using the Clinical Record Interactive Search tool for all patients receiving mental healthcare between 1 January 2019 and 31 March 2022. First, data on a retrospective, longitudinal cohort of around 80 000 patients will be analysed using descriptive statistics to investigate clinical and demographic associations with remote mental healthcare and multivariable Cox regression to compare clinical outcomes of remote versus in-person assessments. Second, NLP models that have been previously developed to extract mental health symptom data will be applied to around 5 million documents to analyse the variation in content of remote versus in-person assessments.<h4>Ethics and dissemination</h4>The SLaM BRC Case Register and Clinical Record Interactive Search (CRIS) tool have received ethical approval as a deidentified dataset (including NLP-derived data from unstructured free text documents) for secondary mental health research from Oxfordshire REC C (Ref: 18/SC/0372). The study has received approval from the SLaM CRIS Oversight Committee. Study findings will be disseminated through peer-reviewed, open access journal articles and service user and carer advisory groups.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e067254.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067254; html:https://europepmc.org/articles/PMC9923317; pdf:https://europepmc.org/articles/PMC9923317?pdf=render
 31446403,https://doi.org/10.1136/bmjopen-2018-026677,Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements.,"Li Q, Li X, Wang J, Liu H, Kwong JS, Chen H, Li L, Chung SC, Shah A, Chen Y, An Z, Sun X, Hemingway H, Tian H, Li S.",,BMJ open,2019,2019-08-24,Y,Gout; Hyperuricemia; Systematic review; Clinical Practice Guideline,,,"<h4>Objectives</h4>Despite the publication of hundreds of trials on gout and hyperuricemia, management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for gout and hyperuricemia.<h4>Design</h4>Systematic review and quality assessment using the appraisal of guidelines for research and evaluation (AGREE) II methodology.<h4>Data sources</h4>PubMed and EMBASE (27 October 2016), two Chinese academic databases, eight guideline databases, and Google and Google scholar (July 2017).<h4>Eligibility criteria</h4>We included the latest version of international and national/regional clinical practice guidelines and consensus statements for diagnosis and/or treatment of hyperuricemia and gout, published in English or Chinese.<h4>Data extraction and synthesis</h4>Two reviewers independently screened searched items and extracted data. Four reviewers independently scored documents using AGREE II. Recommendations from all documents were tabulated and visualised in a coloured grid.<h4>Results</h4>Twenty-four guidance documents (16 clinical practice guidelines and 8 consensus statements) published between 2003 and 2017 were included. Included documents performed well in the domains of scope and purpose (median 85.4%, range 66.7%-100.0%) and clarity of presentation (median 79.2%, range 48.6%-98.6%), but unsatisfactory in applicability (median 10.9%, range 0.0%-66.7%) and editorial independence (median 28.1%, range 0.0%-83.3%). The 2017 British Society of Rheumatology guideline received the highest scores. Recommendations were concordant on the target serum uric acid level for long-term control, on some indications for urate-lowering therapy (ULT), and on the first-line drugs for ULT and for acute attack. Substantially inconsistent recommendations were provided for many items, especially for the timing of initiation of ULT and for treatment for asymptomatic hyperuricemia.<h4>Conclusions</h4>Methodological quality needs improvement in guidance documents on gout and hyperuricemia. Evidence for certain clinical questions is lacking, despite numerous trials in this field. Promoting standard guidance development methods and synthesising high-quality clinical evidence are potential approaches to reduce recommendation inconsistencies.<h4>Prospero registration number</h4>CRD42016046104.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e026677.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-026677; html:https://europepmc.org/articles/PMC6720466; pdf:https://europepmc.org/articles/PMC6720466?pdf=render
-33836256,https://doi.org/10.1016/j.jclinepi.2021.03.025,Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.,"Takada T, Nijman S, Denaxas S, Snell KIE, Uijl A, Nguyen TL, Asselbergs FW, Debray TPA.",,Journal of clinical epidemiology,2021,2021-04-06,N,Heterogeneity; Discrimination; Validation; Prediction model; calibration; Model Comparison,,,"<h4>Objective</h4>To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.<h4>Study design and setting</h4>We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices.<h4>Results</h4>Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke.<h4>Conclusion</h4>In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.",,pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025
 31994239,https://doi.org/10.1002/bimj.201900041,Estimating treatment effects with partially observed covariates using outcome regression with missing indicators.,"Blake HA, Leyrat C, Mansfield KE, Tomlinson LA, Carpenter J, Williamson EJ.",,Biometrical journal. Biometrische Zeitschrift,2020,2020-01-29,N,Average Treatment Effect; Outcome Regression; Missing Covariate Data; Missing Confounder Data; Missing Indicator,,,"Missing data is a common issue in research using observational studies to investigate the effect of treatments on health outcomes. When missingness occurs only in the covariates, a simple approach is to use missing indicators to handle the partially observed covariates. The missing indicator approach has been criticized for giving biased results in outcome regression. However, recent papers have suggested that the missing indicator approach can provide unbiased results in propensity score analysis under certain assumptions. We consider assumptions under which the missing indicator approach can provide valid inferences, namely, (1) no unmeasured confounding within missingness patterns; either (2a) covariate values of patients with missing data were conditionally independent of treatment or (2b) these values were conditionally independent of outcome; and (3) the outcome model is correctly specified: specifically, the true outcome model does not include interactions between missing indicators and fully observed covariates. We prove that, under the assumptions above, the missing indicator approach with outcome regression can provide unbiased estimates of the average treatment effect. We use a simulation study to investigate the extent of bias in estimates of the treatment effect when the assumptions are violated and we illustrate our findings using data from electronic health records. In conclusion, the missing indicator approach can provide valid inferences for outcome regression, but the plausibility of its assumptions must first be considered carefully.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4655332/1/Estimating-treatment-effects-with-partially-observed-covariates-using-outcome-regression-with-missing-indicators.pdf; doi:https://doi.org/10.1002/bimj.201900041
+33836256,https://doi.org/10.1016/j.jclinepi.2021.03.025,Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.,"Takada T, Nijman S, Denaxas S, Snell KIE, Uijl A, Nguyen TL, Asselbergs FW, Debray TPA.",,Journal of clinical epidemiology,2021,2021-04-06,N,Heterogeneity; Discrimination; Validation; Prediction model; calibration; Model Comparison,,,"<h4>Objective</h4>To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.<h4>Study design and setting</h4>We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices.<h4>Results</h4>Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke.<h4>Conclusion</h4>In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.",,pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025
 34931349,https://doi.org/10.1111/bcp.15191,Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R.,"Cupido AJ, Asselbergs FW, Natarajan P, CHARGE Inflammation Working Group, Ridker PM, Hovingh GK, Schmidt AF.",,British journal of clinical pharmacology,2022,2022-01-28,Y,IL-6; Cardiovascular disease; Trans-signalling; Classical Signalling,,,"<h4>Aims</h4>Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects.<h4>Methods</h4>We constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters.<h4>Results</h4>A 1 mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1 mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals.<h4>Conclusions</h4>IL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk.",,doi:https://doi.org/10.1111/bcp.15191; doi:https://doi.org/10.1111/bcp.15191; html:https://europepmc.org/articles/PMC9303316; pdf:https://europepmc.org/articles/PMC9303316?pdf=render
 34670038,https://doi.org/10.1056/nejmc2113864,BNT162b2 and ChAdOx1 nCoV-19 Vaccine Effectiveness against Death from the Delta Variant.,"Sheikh A, Robertson C, Taylor B.",,The New England journal of medicine,2021,2021-10-20,Y,,,,,,doi:https://doi.org/10.1056/nejmc2113864; doi:https://doi.org/10.1056/NEJMc2113864; html:https://europepmc.org/articles/PMC8552534; pdf:https://europepmc.org/articles/PMC8552534?pdf=render
 32846977,https://doi.org/10.3390/ijerph17176139,Agreement between the International Physical Activity Questionnaire and Accelerometry in Adults with Orthopaedic Injury. ,"Veitch WG, Climie RE, Gabbe BJ, Dunstan DW, Owen N, Ekegren CL.",,International journal of environmental research and public health,2020,2020-08-24,Y,,,,"Orthopaedic injury can lead to decreased physical activity. Valid measures for assessing physical activity are therefore needed in this population. The aim of this study was to determine the agreement and concordance between the International Physical Activity Questionnaire-Short Form (IPAQ) and device-measured physical activity and sitting time in orthopaedic injury patients. Adults with isolated upper or lower limb fracture (n = 46; mean age of 40.5 years) wore two activity monitors (ActiGraph wGT3X-BT and activPAL) for 10 days, from 2 weeks post-discharge. The IPAQ was also completed for a concurrent 7-day period. Lin's concordance correlation coefficients and Bland-Altman plots were calculated to compare walking/stepping time, total METmins, and sitting time. The IPAQ overestimated device-derived walking time (mean difference = 2.34 ± 7.33 h/week) and total METmins (mean difference = 767 ± 1659 METmins/week) and underestimated sitting time (mean difference = -2.26 ± 3.87 h/day). There was fair concordance between IPAQ-reported and device-measured walking (ρ = 0.34) and sitting time (ρ = 0.38) and moderate concordance between IPAQ-reported and device-measured METmins (ρ = 0.43). In patients with orthopaedic injury, the IPAQ overestimates physical activity and underestimates sitting time. Higher agreement was observed in the forms of activity (walking, total PA and sitting) commonly performed by this patient group.",,pdf:https://www.mdpi.com/1660-4601/17/17/6139/pdf?version=1598511551; doi:https://doi.org/10.3390/ijerph17176139; html:https://europepmc.org/articles/PMC7504024; pdf:https://europepmc.org/articles/PMC7504024?pdf=render
 36449515,https://doi.org/10.1371/journal.pcbi.1010726,Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.,"Cavallaro M, Coelho J, Ready D, Decraene V, Lamagni T, McCarthy ND, Todkill D, Keeling MJ.",,PLoS computational biology,2022,2022-11-30,Y,,,,"The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010726&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render
-36512045,https://doi.org/10.1007/s00330-022-09323-z,Prediction of incident cardiovascular events using machine learning and CMR radiomics.,"Pujadas ER, Raisi-Estabragh Z, Szabo L, McCracken C, Morcillo CI, Campello VM, Martín-Isla C, Atehortua AM, Vago H, Merkely B, Maurovich-Horvat P, Harvey NC, Neubauer S, Petersen SE, Lekadir K.",,European radiology,2023,2022-12-13,Y,Atrial fibrillation; Heart Failure; Preventive Medicine; Machine Learning; Radiomics,,,"<h4>Objectives</h4>Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), and stroke using machine learning techniques.<h4>Methods</h4>We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.<h4>Results</h4>AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.<h4>Conclusions</h4>Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.<h4>Key points</h4>• Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. • CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. • The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.",,pdf:https://link.springer.com/content/pdf/10.1007/s00330-022-09323-z.pdf; doi:https://doi.org/10.1007/s00330-022-09323-z; html:https://europepmc.org/articles/PMC10121487; pdf:https://europepmc.org/articles/PMC10121487?pdf=render
 33782427,https://doi.org/10.1038/s41598-021-86266-3,Analysis of temporal trends in potential COVID-19 cases reported through NHS Pathways England.,"Leclerc QJ, Nightingale ES, Abbott S, CMMID COVID-19 Working Group, Jombart T.",,Scientific reports,2021,2021-03-29,Y,,,,"The National Health Service (NHS) Pathways triage system collates data on enquiries to 111 and 999 services in England. Since the 18th of March 2020, these data have been made publically available for potential COVID-19 symptoms self-reported by members of the public. Trends in such reports over time are likely to reflect behaviour of the ongoing epidemic within the wider community, potentially capturing valuable information across a broader severity profile of cases than hospital admission data. We present a fully reproducible analysis of temporal trends in NHS Pathways reports until 14th May 2020, nationally and regionally, and demonstrate that rates of growth/decline and effective reproduction number estimated from these data may be useful in monitoring transmission. This is a particularly pressing issue as lockdown restrictions begin to be lifted and evidence of disease resurgence must be constantly reassessed. We further assess the correlation between NHS Pathways reports and a publicly available NHS dataset of COVID-19-associated deaths in England, finding that enquiries to 111/999 were strongly associated with daily deaths reported 16 days later. Our results highlight the potential of NHS Pathways as the basis of an early warning system. However, this dataset relies on self-reported symptoms, which are at risk of being severely biased. Further detailed work is therefore necessary to investigate potential behavioural issues which might otherwise explain our conclusions.",,pdf:https://www.nature.com/articles/s41598-021-86266-3.pdf; doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?pdf=render
+36512045,https://doi.org/10.1007/s00330-022-09323-z,Prediction of incident cardiovascular events using machine learning and CMR radiomics.,"Pujadas ER, Raisi-Estabragh Z, Szabo L, McCracken C, Morcillo CI, Campello VM, Martín-Isla C, Atehortua AM, Vago H, Merkely B, Maurovich-Horvat P, Harvey NC, Neubauer S, Petersen SE, Lekadir K.",,European radiology,2023,2022-12-13,Y,Atrial fibrillation; Heart Failure; Preventive Medicine; Machine Learning; Radiomics,,,"<h4>Objectives</h4>Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), and stroke using machine learning techniques.<h4>Methods</h4>We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.<h4>Results</h4>AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.<h4>Conclusions</h4>Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.<h4>Key points</h4>• Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. • CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. • The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.",,pdf:https://link.springer.com/content/pdf/10.1007/s00330-022-09323-z.pdf; doi:https://doi.org/10.1007/s00330-022-09323-z; html:https://europepmc.org/articles/PMC10121487; pdf:https://europepmc.org/articles/PMC10121487?pdf=render
 33692568,https://doi.org/10.1038/s41588-021-00783-5,The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation.,"Lambert SA, Gil L, Jupp S, Ritchie SC, Xu Y, Buniello A, McMahon A, Abraham G, Chapman M, Parkinson H, Danesh J, MacArthur JAL, Inouye M.",,Nature genetics,2021,2021-04-01,N,,,,,,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/05/23/2020.05.20.20108217.full.pdf; doi:https://doi.org/10.1038/s41588-021-00783-5
 34982094,https://doi.org/10.1167/tvst.11.1.3,OCT Assisted Quantification of Vitreous Inflammation in Uveitis.,"Liu X, Kale AU, Ometto G, Montesano G, Sitch AJ, Capewell N, Radovanovic C, Bucknall N, Beare NAV, Moore DJ, Keane PA, Crabb DP, Denniston AK.",,Translational vision science & technology,2022,2022-01-01,Y,,,,"<h4>Purpose</h4>Vitreous haze (VH) is a key marker of inflammation in uveitis but limited by its subjectivity. Optical coherence tomography (OCT) has potential as an objective, noninvasive method for quantifying VH. We test the hypotheses that OCT can reliably quantify VH and the measurement is associated with slit-lamp based grading of VH.<h4>Methods</h4>In this prospective study, participants underwent three repeated OCT macular scans to evaluate the within-eye reliability of the OCT vitreous intensity (VI). Association between OCT VI and clinical findings (including VH grade, phakic status, visual acuity [VA], anterior chamber cells, and macular thickness) were assessed.<h4>Results</h4>One hundred nineteen participants were included (41 healthy participants, 32 patients with uveitis without VH, and 46 patients with uveitis with VH). Within-eye test reliability of OCT VI was high in healthy eyes and in all grades of VH (intraclass correlation coefficient [ICC] > 0.79). Average OCT VI was significantly different between healthy eyes and uveitic eyes without and uveitic eyes with VH, and was associated with increasing clinical VH grade (P < 0.05). OCT VI was significantly associated with VA, whereas clinical VH grading was not. Cataract was also associated with higher OCT VI (P = 0.03).<h4>Conclusions</h4>OCT VI is a fast, noninvasive, objective, and automated method for measuring vitreous inflammation. It is associated with clinician grading of vitreous inflammation and VA, however, it can be affected by media opacities.<h4>Translational relevance</h4>OCT imaging for quantifying vitreous inflammation shows high within-eye repeatability and is associated with clinical grading of vitreous haze. OCT measurements are also associated with visual acuity but may be affected by structures anterior to the acquisition window, such as lens opacity and other anterior segment changes.",,doi:https://doi.org/10.1167/tvst.11.1.3; doi:https://doi.org/10.1167/tvst.11.1.3; html:https://europepmc.org/articles/PMC8742534; pdf:https://europepmc.org/articles/PMC8742534?pdf=render
 31479767,https://doi.org/10.1016/j.jaip.2019.08.030,Atopic Eczema in Adulthood and Risk of Depression and Anxiety: A Population-Based Cohort Study.,"Schonmann Y, Mansfield KE, Hayes JF, Abuabara K, Roberts A, Smeeth L, Langan SM.",,The journal of allergy and clinical immunology. In practice,2020,2019-08-31,Y,Depression; Anxiety; Atopic Eczema; Atopic Dermatitis; Severity; Population-based,Understanding the Causes of Disease,,"<h4>Background</h4>Atopic eczema is a common and debilitating condition associated with depression and anxiety, but the nature of this association remains unclear.<h4>Objective</h4>To explore the temporal relationship between atopic eczema and new depression/anxiety.<h4>Methods</h4>This matched cohort study used routinely collected data from the UK Clinical Practice Research Datalink, linked to hospital admissions data. We identified adults with atopic eczema (1998-2016) using a validated algorithm, and up to 5 individuals without atopic eczema matched on date of diagnosis, age, sex, and general practice. We estimated the hazard ratio (HR) for new depression/anxiety using stratified Cox regression to account for age, sex, calendar period, Index of Multiple Deprivation, glucocorticoid treatment, obesity, smoking, and harmful alcohol use.<h4>Results</h4>We identified 526,808 adults with atopic eczema who were matched to 2,569,030 without. Atopic eczema was associated with increased incidence of new depression (HR, 1.14; 99% CI, 1.12-1.16) and anxiety (HR, 1.17; 99% CI, 1.14-1.19). We observed a stronger effect of atopic eczema on depression with increasing atopic eczema severity (HR [99% CI] compared with no atopic eczema: mild, 1.10 [1.08-1.13]; moderate, 1.19 [1.15-1.23]; and severe, 1.26 [1.17-1.37]). A dose-response association, however, was less apparent for new anxiety diagnosis (HR [99% CI] compared with no atopic eczema: mild, 1.14 [1.11-1.18]; moderate, 1.21 [1.17-1.26]; and severe, 1.15; [1.05-1.25]).<h4>Conclusions</h4>Adults with atopic eczema are more likely to develop new depression and anxiety. For depression, we observed a dose-response relationship with atopic eczema severity.",,pdf:http://www.jaci-inpractice.org/article/S2213219819307536/pdf; doi:https://doi.org/10.1016/j.jaip.2019.08.030; html:https://europepmc.org/articles/PMC6947493; pdf:https://europepmc.org/articles/PMC6947493?pdf=render
@@ -1450,10 +1450,10 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33354439,https://doi.org/10.1109/jtehm.2020.3040236,Modeling Large Sparse Data for Feature Selection: Hospital Admission Predictions of the Dementia Patients Using Primary Care Electronic Health Records.,"Tsang G, Zhou SM, Xie X.",,IEEE journal of translational engineering in health and medicine,2021,2020-11-24,Y,Dementia; risk factors; Hospitalization; Feature Selection; Machine Learning; Electronic Health Records; Deep Learning; Weight Regularization,,,"A growing elderly population suffering from incurable, chronic conditions such as dementia present a continual strain on medical services due to mental impairment paired with high comorbidity resulting in increased hospitalization risk. The identification of at risk individuals allows for preventative measures to alleviate said strain. Electronic health records provide opportunity for big data analysis to address such applications. Such data however, provides a challenging problem space for traditional statistics and machine learning due to high dimensionality and sparse data elements. This article proposes a novel machine learning methodology: entropy regularization with ensemble deep neural networks (ECNN), which simultaneously provides high predictive performance of hospitalization of patients with dementia whilst enabling an interpretable heuristic analysis of the model architecture, able to identify individual features of importance within a large feature domain space. Experimental results on health records containing 54,647 features were able to identify 10 event indicators within a patient timeline: a collection of diagnostic events, medication prescriptions and procedural events, the highest ranked being essential hypertension. The resulting subset was still able to provide a highly competitive hospitalization prediction (Accuracy: 0.759) as compared to the full feature domain (Accuracy: 0.755) or traditional feature selection techniques (Accuracy: 0.737), a significant reduction in feature size. The discovery and heuristic evidence of correlation provide evidence for further clinical study of said medical events as potential novel indicators. There also remains great potential for adaption of ECNN within other medical big data domains as a data mining tool for novel risk factor identification.",,pdf:https://ieeexplore.ieee.org/ielx7/6221039/9246949/09268962.pdf; doi:https://doi.org/10.1109/JTEHM.2020.3040236; html:https://europepmc.org/articles/PMC7737850; pdf:https://europepmc.org/articles/PMC7737850?pdf=render
 33174528,https://doi.org/10.3310/hta24570,Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT.,"Gilbert R, Brown M, Faria R, Fraser C, Donohue C, Rainford N, Grosso A, Sinha AK, Dorling J, Gray J, Muller-Pebody B, Harron K, Moitt T, McGuire W, Bojke L, Gamble C, Oddie SJ.",,"Health technology assessment (Winchester, England)",2020,2020-11-01,Y,Infant; Newborn; Economic analysis; Central Venous Catheter; Bloodstream Infection; Randomised Controlled Trial; Generalisability; Antimicrobial-impregnated Catheter,,,"<h4>Background</h4>Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies.<h4>Objectives</h4>The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS.<h4>Design</h4>Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England.<h4>Setting</h4>The randomised controlled trial was conducted in 18 neonatal intensive care units in England.<h4>Participants</h4>Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size).<h4>Interventions</h4>The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation.<h4>Main outcome measure</h4>Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data.<h4>Results</h4>Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, <i>n</i> = 430; standard peripherally inserted central venous catheter, <i>n</i> = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; <i>p</i> = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; <i>p</i> = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days.<h4>Limitations</h4>The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance.<h4>Conclusions</h4>No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care.<h4>Trial registration</h4>Current Controlled Trials ISRCTN81931394.<h4>Funding</h4>This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in <i>Health Technology Assessment</i>; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.",,pdf:https://njl-admin.nihr.ac.uk/document/download/2034745; html:http://europepmc.org/books/NBK563908; doi:https://doi.org/10.3310/hta24570
 32023934,https://doi.org/10.3390/ijerph17030892,Identifying Homogeneous Patterns of Injury in Paediatric Trauma Patients to Improve Risk-Adjusted Models of Mortality and Functional Outcomes. ,"Dipnall JF, Gabbe BJ, Teague WJ, Beck B.",,International journal of environmental research and public health,2020,2020-01-31,Y,,Improving Public Health,injuries and accidents,"Injury is a leading cause of morbidity and mortality in the paediatric population and exhibits complex injury patterns. This study aimed to identify homogeneous groups of paediatric major trauma patients based on their profile of injury for use in mortality and functional outcomes risk-adjusted models. Data were extracted from the population-based Victorian State Trauma Registry for patients aged 0-15 years, injured 2006-2016. Four Latent Class Analysis (LCA) models with/without covariates of age/sex tested up to six possible latent classes. Five risk-adjusted models of in-hospital mortality and 6-month functional outcomes incorporated a combination of Injury Severity Score (ISS), New ISS (NISS), and LCA classes. LCA models replicated the best log-likelihood and entropy > 0.8 for all models (N = 1281). Four latent injury classes were identified: isolated head; isolated abdominal organ; multi-trauma injuries, and other injuries. The best models, in terms of goodness of fit statistics and model diagnostics, included the LCA classes and NISS. The identification of isolated head, isolated abdominal, multi-trauma and other injuries as key latent paediatric injury classes highlights areas for emphasis in planning prevention initiatives and paediatric trauma system development. Future risk-adjusted paediatric injury models that include these injury classes with the NISS when evaluating mortality and functional outcomes is recommended.",,pdf:https://www.mdpi.com/1660-4601/17/3/892/pdf?version=1580475934; doi:https://doi.org/10.3390/ijerph17030892; html:https://europepmc.org/articles/PMC7037699; pdf:https://europepmc.org/articles/PMC7037699?pdf=render
-36688706,https://doi.org/10.1093/rheumatology/kead038,Classification of patients with osteoarthritis through clusters of comorbidities using 633 330 individuals from Spain.,"Pineda-Moncusí M, Dernie F, Dell'Isola A, Kamps A, Runhaar J, Swain S, Zhang W, Englund M, Pitsillidou I, Strauss VY, Robinson DE, Prieto-Alhambra D, Khalid S.",,"Rheumatology (Oxford, England)",2023,2023-11-01,Y,Clustering; epidemiology; Comorbidities; Oa,,,"<h4>Objectives</h4>To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster.<h4>Methods</h4>This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.<h4>Results</h4>We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]).<h4>Conclusion</h4>Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead038/49101708/kead038.pdf; doi:https://doi.org/10.1093/rheumatology/kead038; html:https://europepmc.org/articles/PMC10629784; pdf:https://europepmc.org/articles/PMC10629784?pdf=render
 34002035,https://doi.org/10.1038/s41366-021-00807-4,Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis.,"Gill D, Zuber V, Dawson J, Pearson-Stuttard J, Carter AR, Sanderson E, Karhunen V, Levin MG, Wootton RE, Klarin D, Tsao PS, Tsilidis KK, Damrauer SM, Burgess S, Elliott P.",,International journal of obesity (2005),2021,2021-05-17,Y,,,,"<h4>Background</h4>Higher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not fully understood.<h4>Methods</h4>Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, Mendelian randomization mediation analysis was performed to investigate the degree to which systolic blood pressure (SBP), diabetes, lipid traits, and smoking mediated an effect of BMI and WHR on the risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke.<h4>Results</h4>The odds ratio of CAD per 1-standard deviation increase in genetically predicted BMI was 1.49 (95% CI 1.39 to 1.60). This attenuated to 1.34 (95% CI 1.24 to 1.45) after adjusting for genetically predicted SBP (proportion mediated 27%, 95% CI 3% to 50%), to 1.27 (95% CI 1.17 to 1.37) after adjusting for genetically predicted diabetes (41% mediated, 95% CI 18% to 63%), to 1.47 (95% CI 1.36 to 1.59) after adjusting for genetically predicted lipids (3% mediated, 95% -23% to 29%), and to 1.46 (95% CI 1.34 to 1.58) after adjusting for genetically predicted smoking (6% mediated, 95% CI -20% to 32%). Adjusting for all the mediators together, the estimate attenuated to 1.14 (95% CI 1.04 to 1.26; 66% mediated, 95% CI 42% to 91%). A similar pattern was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcome.<h4>Conclusions</h4>Measures to reduce obesity will lower the risk of cardiovascular disease primarily by impacting downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.",,pdf:https://www.nature.com/articles/s41366-021-00807-4.pdf; doi:https://doi.org/10.1038/s41366-021-00807-4; html:https://europepmc.org/articles/PMC8236409; pdf:https://europepmc.org/articles/PMC8236409?pdf=render
-37730620,https://doi.org/10.1186/s13643-023-02333-y,What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.,"Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",,Systematic reviews,2023,2023-09-20,Y,,,,"<h4>Background</h4>There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.<h4>Methods</h4>An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.<h4>Discussion</h4>The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render
 33654696,https://doi.org/10.1093/burnst/tkaa044,Venous thromboembolism prophylaxis practice and its association with outcomes in Australia and New Zealand burns patients.,"Tracy LM, Cameron PA, Singer Y, Earnest A, Wood F, Cleland H, Gabbe BJ.",,Burns & trauma,2021,2021-01-01,Y,Australia; New Zealand; Burn injury; Prophylaxis; Venous Thromboembolism,,,"<h4>Background</h4>Patients with burn injuries are considered to have an increased risk of venous thromboembolism (VTE). While untreated VTEs can be fatal, no studies have examined chemoprophylaxis effectiveness. This study aimed to quantify the variation in prevalence of VTE prophylaxis use in patients in Australian and New Zealand burns units and whether prophylaxis use is associated with in-hospital outcomes following burn injury.<h4>Methods</h4>Admission data for adult burns patients (aged ≥16 years) admitted between 1 July 2016 and 31 December 2018 were extracted from the Burns Registry of Australia and New Zealand. Mixed effects logistic regression modelling investigated whether VTE prophylaxis use was associated with the primary outcome of in-hospital mortality.<h4>Results</h4>There were 5066 admissions over the study period. Of these patients, 81% (n = 3799) with a valid response to the VTE prophylaxis data field received some form of VTE prophylaxis. Use of VTE prophylaxis ranged from 48.6% to 94.8% of patients between units. In-hospital death was recorded in <1% of patients (n = 33). After adjusting for confounders, receiving VTE prophylaxis was associated with a decrease in the adjusted odds of in-hospital mortality (adjusted odds ratio = 0.21; 95% CI, 0.07-0.63; <i>p</i> = 0.006).<h4>Conclusions</h4>Variation in the use of VTE prophylaxis was observed between the units, and prophylaxis use was associated with a decrease in the odds of mortality. These findings provide an opportunity to engage with units to further explore differences in prophylaxis use and develop future best practice guidelines.",,pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkaa044/37307900/tkaa044.pdf; doi:https://doi.org/10.1093/burnst/tkaa044; html:https://europepmc.org/articles/PMC7901708; pdf:https://europepmc.org/articles/PMC7901708?pdf=render
+36688706,https://doi.org/10.1093/rheumatology/kead038,Classification of patients with osteoarthritis through clusters of comorbidities using 633 330 individuals from Spain.,"Pineda-Moncusí M, Dernie F, Dell'Isola A, Kamps A, Runhaar J, Swain S, Zhang W, Englund M, Pitsillidou I, Strauss VY, Robinson DE, Prieto-Alhambra D, Khalid S.",,"Rheumatology (Oxford, England)",2023,2023-11-01,Y,Clustering; epidemiology; Comorbidities; Oa,,,"<h4>Objectives</h4>To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster.<h4>Methods</h4>This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.<h4>Results</h4>We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]).<h4>Conclusion</h4>Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead038/49101708/kead038.pdf; doi:https://doi.org/10.1093/rheumatology/kead038; html:https://europepmc.org/articles/PMC10629784; pdf:https://europepmc.org/articles/PMC10629784?pdf=render
+37730620,https://doi.org/10.1186/s13643-023-02333-y,What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.,"Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",,Systematic reviews,2023,2023-09-20,Y,,,,"<h4>Background</h4>There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.<h4>Methods</h4>An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.<h4>Discussion</h4>The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render
 34596018,https://doi.org/10.2807/1560-7917.es.2021.26.39.2001440,"Strategies to reduce the risk of SARS-CoV-2 importation from international travellers: modelling estimations for the United Kingdom, July 2020. ","Clifford S, Quilty BJ, Russell TW, Liu Y, Chan YD, Pearson CAB, Eggo RM, Endo A, CMMID COVID-19 Working Group, Flasche S, Edmunds WJ, Centre for Mathematical Modelling of Infectious Diseases (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-09-01,Y,,,,"BackgroundTo mitigate SARS-CoV-2 transmission risks from international air travellers, many countries implemented a combination of up to 14 days of self-quarantine upon arrival plus PCR testing in the early stages of the COVID-19 pandemic in 2020.AimTo assess the effectiveness of quarantine and testing of international travellers to reduce risk of onward SARS-CoV-2 transmission into a destination country in the pre-COVID-19 vaccination era.MethodsWe used a simulation model of air travellers arriving in the United Kingdom from the European Union or the United States, incorporating timing of infection stages while varying quarantine duration and timing and number of PCR tests.ResultsQuarantine upon arrival with a PCR test on day 7 plus a 1-day delay for results can reduce the number of infectious arriving travellers released into the community by a median 94% (95% uncertainty interval (UI): 89-98) compared with a no quarantine/no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median > 99%; 95% UI: 98-100). Even shorter quarantine periods can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (mean incubation period) in quarantine and have at least one negative test before release are highly effective (median reduction 89%; 95% UI: 83-95)).ConclusionThe effect of different screening strategies impacts asymptomatic and symptomatic individuals differently. The choice of an optimal quarantine and testing strategy for unvaccinated air travellers may vary based on the number of possible imported infections relative to domestic incidence.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/39/eurosurv-26-39-5.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.39.2001440&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.39.2001440; html:https://europepmc.org/articles/PMC8485583; pdf:https://europepmc.org/articles/PMC8485583?pdf=render
 36545235,https://doi.org/10.1177/26335565221145493,The DynAIRx Project Protocol: Artificial Intelligence for dynamic prescribing optimisation and care integration in multimorbidity.,"Walker LE, Abuzour AS, Bollegala D, Clegg A, Gabbay M, Griffiths A, Kullu C, Leeming G, Mair FS, Maskell S, Relton S, Ruddle RA, Shantsila E, Sperrin M, Van Staa T, Woodall A, Buchan I.",,Journal of multimorbidity and comorbidity,2022,2022-01-01,Y,Artificial intelligence; Frailty; Mental health; Polypharmacy; Multimorbidity; Medicines Optimisation,,,"<h4>Background</h4>Structured Medication Reviews (SMRs) are intended to help deliver the NHS Long Term Plan for medicines optimisation in people living with multiple long-term conditions and polypharmacy. It is challenging to gather the information needed for these reviews due to poor integration of health records across providers and there is little guidance on how to identify those patients most urgently requiring review.<h4>Objective</h4>To extract information from scattered clinical records on how health and medications change over time, apply interpretable artificial intelligence (AI) approaches to predict risks of poor outcomes and overlay this information on care records to inform SMRs. We will pilot this approach in primary care prescribing audit and feedback systems, and co-design future medicines optimisation decision support systems.<h4>Design</h4>DynAIRx will target potentially problematic polypharmacy in three key multimorbidity groups, namely, people with (a) mental and physical health problems, (b) four or more long-term conditions taking ten or more drugs and (c) older age and frailty. Structured clinical data will be drawn from integrated care records (general practice, hospital, and social care) covering an ∼11m population supplemented with Natural Language Processing (NLP) of unstructured clinical text. AI systems will be trained to identify patterns of conditions, medications, tests, and clinical contacts preceding adverse events in order to identify individuals who might benefit most from an SMR.<h4>Discussion</h4>By implementing and evaluating an AI-augmented visualisation of care records in an existing prescribing audit and feedback system we will create a learning system for medicines optimisation, co-designed throughout with end-users and patients.",,pdf:https://eprints.whiterose.ac.uk/197084/1/26335565221145493.pdf; doi:https://doi.org/10.1177/26335565221145493; html:https://europepmc.org/articles/PMC9761229; pdf:https://europepmc.org/articles/PMC9761229?pdf=render
 34970633,https://doi.org/10.23889/ijpds.v6i1.1674,Evaluation of the ASSIGN open-source deterministic address-matching algorithm for allocating unique property reference numbers to general practitioner-recorded patient addresses.,"Harper G, Stables D, Simon P, Ahmed Z, Smith K, Robson J, Dezateux C.",,International journal of population data science,2021,2021-12-08,Y,Quality assurance; Data Linkage; Population Health; Electronic Health Record; Addresses; Address-matching; Place-based Health,,,"<h4>Introduction</h4>Linking places to people is a core element of the UK government's geospatial strategy. Matching patient addresses in electronic health records to their Unique Property Reference Numbers (UPRNs) enables spatial linkage for research, innovation and public benefit. Available algorithms are not transparent or evaluated for use with addresses recorded by health care providers.<h4>Objectives</h4>To describe and quality assure the open-source deterministic ASSIGN address-matching algorithm applied to general practitioner-recorded patient addresses.<h4>Methods</h4>Best practice standards were used to report the ASSIGN algorithm match rate, sensitivity and positive predictive value using gold-standard datasets from London and Wales. We applied the ASSIGN algorithm to the recorded addresses of a sample of 1,757,018 patients registered with all general practices in north east London. We examined bias in match results for the study population using multivariable analyses to estimate the likelihood of an address-matched UPRN by demographic, registration, and organisational variables.<h4>Results</h4>We found a 99.5% and 99.6% match rate with high sensitivity (0.999,0.998) and positive predictive value (0.996,0.998) for the Welsh and London gold standard datasets respectively, and a 98.6% match rate for the study population.The 1.4% of the study population without a UPRN match were more likely to have changed registered address in the last 12 months (match rate: 95.4%), be from a Chinese ethnic background (95.5%), or registered with a general practice using the SystmOne clinical record system (94.4%). Conversely, people registered for more than 6.5 years with their general practitioner were more likely to have a match (99.4%) than those with shorter registration durations.<h4>Conclusions</h4>ASSIGN is a highly accurate open-source address-matching algorithm with a high match rate and minimal biases when evaluated against a large sample of general practice-recorded patient addresses. ASSIGN has potential to be used in other address-based datasets including those with information relevant to the wider determinants of health.",,pdf:https://ijpds.org/article/download/1674/3300; doi:https://doi.org/10.23889/ijpds.v6i1.1674; html:https://europepmc.org/articles/PMC8678979; pdf:https://europepmc.org/articles/PMC8678979?pdf=render
@@ -1465,14 +1465,14 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34237806,https://doi.org/10.1515/dmdi-2021-0104,Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. ,"Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Alsulaiman AA, Alabdulali MM, Alkhamis F, Alamri AS, Alali RA, Akhtar MS, Cyrus C, Claassens DMF, Asselbergs FW, Al-Ali AK.",,Drug metabolism and personalized therapy,2021,2021-07-08,N,,,,"To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.",,pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmdi-2021-0104
 35244709,https://doi.org/10.1093/europace/euac022,Impact of oral anticoagulation on the association between frailty and clinical outcomes in people with atrial fibrillation: nationwide primary care records on treatment analysis.,"Wilkinson C, Wu J, Clegg A, Nadarajah R, Rockwood K, Todd O, Gale CP.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2022,2022-07-01,Y,Bleeding; Atrial fibrillation; Stroke; Frailty; Outcome; Oral Anticoagulation; Oral Anticoagulation Prescription,,,"<h4>Aims</h4>People with atrial fibrillation (AF) frequently live with frailty, which increases the risk of mortality and stroke. This study reports the association between oral anticoagulation (OAC) and outcomes for people with frailty, and whether there is overall net benefit from treatment in people with AF.<h4>Methods and results</h4>Retrospective open cohort electronic records study. Frailty was identified using the electronic frailty index. Primary care electronic health records of 89 996 adults with AF and CHA2DS2-Vasc score of ≥2 were linked with secondary care and mortality data in the Clinical Practice Research Database (CPRD) from 1 January 1998 to 30 November 2018. The primary outcome was a composite of death, stroke, systemic embolism, or major bleeding. Secondary outcomes were stroke, major bleeding, all-cause mortality, transient ischaemic attack, and falls. Of 89 996 participants, 71 256 (79.2%) were living with frailty. The prescription of OAC increased with degree of frailty. For patients not prescribed OAC, rates of the primary outcome increased alongside frailty category. Prescription of OAC was associated with a reduction in the primary outcome for each frailty category [adjusted hazard ratio, 95% confidence interval, no OAC as reference; fit: vitamin K antagonist (VKA) 0.69, 0.64-0.75, direct oral anticoagulant (DOAC) 0.42, 0.33-0.53; mild frailty: VKA 0.52, 0.50-0.54, DOAC 0.57, 0.52-0.63; moderate: VKA 0.54, 0.52-0.56, DOAC 0.57, 0.52-0.63; severe: VKA 0.48, 0.45-0.51, DOAC 0.58, 0.52-0.65], with cumulative incidence function effects greater for DOAC than VKA.<h4>Conclusion</h4>Frailty among people with AF is common. The OAC was associated with a reduction in the primary endpoint across all degrees of frailty.",,doi:https://doi.org/10.1093/europace/euac022; doi:https://doi.org/10.1093/europace/euac022; html:https://europepmc.org/articles/PMC9326851; pdf:https://europepmc.org/articles/PMC9326851?pdf=render
 33072403,https://doi.org/10.1186/s40959-020-00079-3,Early- and late anthracycline-induced cardiac dysfunction: echocardiographic characterization and response to heart failure therapy.,"Kamphuis JAM, Linschoten M, Cramer MJ, Doevendans PA, Asselbergs FW, Teske AJ.",,"Cardio-oncology (London, England)",2020,2020-10-13,Y,Heart Failure; Anthracyclines; Cardiac Dysfunction; Cardiac Effects Of Cancer Treatment,,,"<h4>Background</h4>Anthracycline-induced cardiac dysfunction (ACD) is a notorious side effect of anticancer treatment. It has been described as a phenomenon of a continuous progressive decline of cardiac function, eventually leading to dilated cardiomyopathy (DCM). This progressive nature suggests that patients with a delayed ACD diagnosis have greater compromise of cardiac function and more adverse remodeling, with a poor response to heart failure (HF) treatment. This study aimed to delineate the impact of a delayed ACD diagnosis on echocardiographic characteristics and response to HF treatment.<h4>Methods and results</h4>From the population of our cardio-oncology outpatient clinic, 92 ACD patients were included in this study (age 51.6 ± 16.2 years, median cumulative anthracycline dose 329 [200-329] mg/m<sup>2</sup>), and a median follow-up of 25.0 [9.6-37.2] months after ACD diagnosis. Median time to ACD diagnosis for patients diagnosed early (< 1 year) and late (> 1 year) was 4.0 vs. 47.7 months respectively. There were no echocardiographic differences between patients diagnosed early vs. late (LVEF 43.6 ± 4.9% vs. 43.0 ± 6.2% and iEDV 63.6 vs. 62.9 mL/m<sup>2</sup>). Eighty-three percent of patients presented with mild LV dysfunction and in 79% the LV was not dilated. Patients diagnosed early were more likely to have (partial) recovery of cardiac function upon HF treatment initiation (<i>p</i> = 0.015).<h4>Conclusions</h4>In the setting of a cardio-oncology outpatient clinic, patients with ACD presented with a hypokinetic non-dilated cardiomyopathy, rather than typical DCM. Timing of ACD diagnosis did not impact HF disease severity. However, in patients receiving an early diagnosis, cardiac function was more likely to recover upon HF treatment.",,pdf:https://cardiooncologyjournal.biomedcentral.com/track/pdf/10.1186/s40959-020-00079-3; doi:https://doi.org/10.1186/s40959-020-00079-3; html:https://europepmc.org/articles/PMC7557080; pdf:https://europepmc.org/articles/PMC7557080?pdf=render
-36343994,https://doi.org/10.1136/bmjopen-2022-063159,"Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.","Cooper DJ, Lear S, Sithole N, Shaw A, Stark H, Ferris M, CITIID-NIHR BioResource COVID-19 collaboration consortium, Bradley J, Maxwell P, Goodfellow I, Weekes MP, Seaman S, Baker S.",,BMJ open,2022,2022-11-07,Y,Infection control; epidemiology; Public Health; Covid-19,,,"<h4>Objective</h4>Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs.<h4>Design/setting/participants</h4>HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model.<h4>Results</h4>Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p&lt;0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p&lt;0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p&lt;0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038).<h4>Conclusions</h4>The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render
 37671353,https://doi.org/10.23889/ijpds.v5i3.2133,Public Involvement & Engagement in health inequalities research on COVID-19 pandemic: a case study of CIDACS/FIOCRUZ BAHIA.,"Dos Anjos Fonseca A, Pimenta DM, de Almeida MRS, Lima RT, Barreto ML, Ichihara MYT.",,International journal of population data science,2020,2020-01-01,Y,Brazil; Pandemic; Policymakers; Social Inequalities; Public Engagement; Community Groups; Public Involvement,,,"<h4>Introduction</h4>Health inequalities in Brazil have deepened on Covid-19 pandemic, and the most vulnerable people were the more affected. A multidisciplinary team from Cidacs/Fiocruz Bahia developed a Social Disparities Index for Covid-19 (IDS-COVID-19) to support the evaluation of effects of health inequalities on the pandemic in Brazil. Public Involvement and Engagement were the pillars of this research because they allowed us to access first hand experiences about the social context in our country.<h4>Objectives</h4>This paper aims to describe our Public Involvement and Engagement experience by analysing our challenges, strategies, activities, results, and lessons learned during the construction of IDS-COVID-19.<h4>Methods</h4>The basis of the IDS-Covid-19 public engagement model was the participation of different social groups through methods and techniques that allow dialogue. Several activities and communication products supported the continuous interactions. Another guideline was the inclusion and the welcoming of participants from the beginning of the project to ensure that the participant's contributions could drive decision-making about the research.<h4>Results</h4>Participants made several contributions to the research as a new layer of information to the Index, and improvements were made to the interactive panel. They also compromised to support the dissemination and use of the product. Eight representatives of community groups and 29 policymakers participated in our engagement activities during the project. More than 500 people were in our open webinars. In addition, more than 140 news items about IDS-Covid-19 were published in national and international media.<h4>Conclusions</h4>We highlight as lessons learned the adaptation of some dissemination formats to the public, and the necessity of being flexible and accessible to participants. We strengthened the relationship with relevant stakeholders by exploring individual conversations by phone, WhatsApp, email, and interviews to produce a documentary that registered this whole experience. Cidacs/Fiocruz Bahia has also embedded public engagement and involvement in the study agenda.",,doi:https://doi.org/10.23889/ijpds.v5i3.2133; html:https://europepmc.org/articles/PMC10476697; pdf:https://europepmc.org/articles/PMC10476697?pdf=render
+36343994,https://doi.org/10.1136/bmjopen-2022-063159,"Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.","Cooper DJ, Lear S, Sithole N, Shaw A, Stark H, Ferris M, CITIID-NIHR BioResource COVID-19 collaboration consortium, Bradley J, Maxwell P, Goodfellow I, Weekes MP, Seaman S, Baker S.",,BMJ open,2022,2022-11-07,Y,Infection control; epidemiology; Public Health; Covid-19,,,"<h4>Objective</h4>Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs.<h4>Design/setting/participants</h4>HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model.<h4>Results</h4>Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p&lt;0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p&lt;0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p&lt;0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038).<h4>Conclusions</h4>The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render
 36351458,https://doi.org/10.1016/s0140-6736(22)02074-8,Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.,"Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium.",,"Lancet (London, England)",2022,2022-11-06,Y,,,,"<h4>Background</h4>Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.<h4>Methods</h4>We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.<h4>Findings</h4>We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [>99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 m<sup>2</sup>). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% CI 0·58-0·69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0·86, 0·81-0·92) but did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.<h4>Interpretation</h4>In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.<h4>Funding</h4>UK Medical Research Council and Kidney Research UK.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613836; doi:https://doi.org/10.1016/S0140-6736(22)02074-8; html:https://europepmc.org/articles/PMC7613836
 37719788,https://doi.org/10.1093/noajnl/vdad096,Development of a core outcome set for use in adult primary glioma phase III interventional trials: A mixed methods study.,"Retzer A, Baddeley E, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Rivera SC, Dirven L, Calvert M, Byrne A.",,Neuro-oncology advances,2023,2023-01-01,Y,trials; Outcomes; Neuro-oncology; Delphi; Primary Glioma,,,"<h4>Background</h4>Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution.<h4>Methods</h4>A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified.<h4>Results</h4>In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting.<h4>Conclusions</h4>A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS.",,pdf:https://academic.oup.com/noa/advance-article-pdf/doi/10.1093/noajnl/vdad096/51026152/vdad096.pdf; doi:https://doi.org/10.1093/noajnl/vdad096; html:https://europepmc.org/articles/PMC10503650; pdf:https://europepmc.org/articles/PMC10503650?pdf=render
 37025302,https://doi.org/10.1093/jacamr/dlad039,Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in <i>Mycobacterium tuberculosis</i>.,"Brankin AE, Fowler PW.",,JAC-antimicrobial resistance,2023,2023-04-04,Y,,,,"<h4>Objectives</h4>Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensitivities are often less than 90%. We hypothesize that this is partly because the bioinformatic pipelines used usually mask the recognition of minor alleles that have been implicated in fluoroquinolone resistance.<h4>Methods</h4>We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS <i>Mycobacterium tuberculosis</i> isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.<h4>Results</h4>Detecting minor alleles increased the sensitivity of WGS for moxifloxacin resistance prediction from 85.4% to 94.0%, without significantly reducing specificity. We also found no correlation between the proportion of an <i>M. tuberculosis</i> population containing a resistance-conferring allele and the magnitude of resistance.<h4>Conclusions</h4>Together our results highlight the importance of detecting minor resistance-conferring alleles when using WGS, or indeed any sequencing-based approach, to diagnose fluoroquinolone resistance.",,pdf:https://academic.oup.com/jacamr/article-pdf/5/2/dlad039/49747584/dlad039.pdf; doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render
 32810544,https://doi.org/10.1016/j.ijcard.2020.08.030,The relation between VLDL-cholesterol and risk of cardiovascular events in patients with manifest cardiovascular disease.,"Heidemann BE, Koopal C, Bots ML, Asselbergs FW, Westerink J, Visseren FLJ.",,International journal of cardiology,2021,2020-08-15,N,Inflammation; Vascular disease; Major Adverse Cardiovascular Events; Non-hdl-c; Vldl-c; Triglyceride Rich Lipoproteins,,,"<h4>Introduction</h4>Apolipoprotein B containing lipoproteins are atherogenic. There is evidence that with low plasma low density lipoprotein cholesterol (LDL-C) levels residual vascular risk might be caused by triglyceride rich lipoproteins such as very-low density lipoproteins (VLDL), chylomicrons and their remnants. We investigated the relationship between VLDL-cholesterol (VLDL-C) and recurrent major adverse cardiovascular events (MACE), major adverse limb events (MALE) and all-cause mortality in a cohort of patients with cardiovascular disease.<h4>Methods</h4>Prospective cohort study in 8057 patients with cardiovascular disease from the UCC-SMART study. The relation between calculated VLDL-C levels and the occurrence of MACE, MALE and all-cause mortality was analyzed with Cox regression models.<h4>Results</h4>Patients mean age was 60 ± 10 years, 74% were male, 4894 (61%) had coronary artery disease, 2445 (30%) stroke, 1425 (18%) peripheral arterial disease and 684 (8%) patients had an abdominal aorta aneurysm at baseline. A total of 1535 MACE, 571 MALE and 1792 deaths were observed during a median follow up of 8.2 years (interquartile range 4.512.2). VLDL-C was not associated with risk of MACE or all-cause mortality. In the highest quartile of VLDL-C the risk was higher for major adverse limb events (MALE) (HR 1.49; 95%CI 1.16-1.93) compared to the lowest quartile, after adjustment for confounders including LDL-C and lipid lowering medication.<h4>Conclusion</h4>In patients with clinically manifest cardiovascular disease plasma VLDL-C confers an increased risk for MALE, but not for MACE and all-cause mortality, independent of established risk factors including LDL-C and lipid-lowering medication.",,pdf:http://www.internationaljournalofcardiology.com/article/S0167527320335579/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.08.030
-35639667,https://doi.org/10.1093/eurheartj/ehac238,Critical appraisal of artificial intelligence-based prediction models for cardiovascular disease.,"van Smeden M, Heinze G, Van Calster B, Asselbergs FW, Vardas PE, Bruining N, de Jaegere P, Moore JH, Denaxas S, Boulesteix AL, Moons KGM.",,European heart journal,2022,2022-08-01,Y,Prediction; Artificial intelligence; Diagnosis; Prognosis; Machine Learning; Digital Health,,,"The medical field has seen a rapid increase in the development of artificial intelligence (AI)-based prediction models. With the introduction of such AI-based prediction model tools and software in cardiovascular patient care, the cardiovascular researcher and healthcare professional are challenged to understand the opportunities as well as the limitations of the AI-based predictions. In this article, we present 12 critical questions for cardiovascular health professionals to ask when confronted with an AI-based prediction model. We aim to support medical professionals to distinguish the AI-based prediction models that can add value to patient care from the AI that does not.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render
 34980174,https://doi.org/10.1186/s12967-021-03210-9,"Increased burden of cardiovascular disease in people with liver disease: unequal geographical variations, risk factors and excess years of life lost.","Chang WH, Mueller SH, Chung SC, Foster GR, Lai AG.",,Journal of translational medicine,2022,2022-01-03,Y,liver disease; Geographical variations; incidence; Cardiovascular Risk; Electronic Health Records; Years Of Life Lost,,,"<h4>Background</h4>People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes.<h4>Methods</h4>We employed population-wide electronic health records (EHRs; from 1998 to 2020) consisting of almost 4 million adults to assess regional variations in disease burden of five liver conditions, alcoholic liver disease (ALD), autoimmune liver disease, chronic hepatitis B infection (HBV), chronic hepatitis C infection (HCV) and NAFLD, in England. We analysed regional differences in incidence rates for 17 manifestations of CVD in people with or without liver disease. The associations between biomarkers and comorbidities and risk of CVD in patients with liver disease were estimated using Cox models. For each liver condition, we estimated excess years of life lost (YLL) attributable to CVD (i.e., difference in YLL between people with or without CVD).<h4>Results</h4>The age-standardised incidence rate for any liver disease was 114.5 per 100,000 person years. The highest incidence was observed in NAFLD (85.5), followed by ALD (24.7), HCV (6.0), HBV (4.1) and autoimmune liver disease (3.7). Regionally, the North West and North East regions consistently exhibited high incidence burden. Age-specific incidence rate analyses revealed that the peak incidence for liver disease of non-viral aetiology is reached in individuals aged 50-59 years. Patients with liver disease had a two-fold higher incidence burden of CVD (2634.6 per 100,000 persons) compared to individuals without liver disease (1339.7 per 100,000 persons). When comparing across liver diseases, atrial fibrillation was the most common initial CVD presentation while hypertrophic cardiomyopathy was the least common. We noted strong positive associations between body mass index and current smoking and risk of CVD. Patients who also had diabetes, hypertension, proteinuric kidney disease, chronic kidney disease, diverticular disease and gastro-oesophageal reflex disorders had a higher risk of CVD, as do patients with low albumin, raised C-reactive protein and raised International Normalized Ratio levels. All types of CVD were associated with shorter life expectancies. When evaluating excess YLLs by age of CVD onset and by liver disease type, differences in YLLs, when comparing across CVD types, were more pronounced at younger ages.<h4>Conclusions</h4>We developed a public online app ( https://lailab.shinyapps.io/cvd_in_liver_disease/ ) to showcase results interactively. We provide a blueprint that revealed previously underappreciated clinical factors related to the risk of CVD, which differed in the magnitude of effects across liver diseases. We found significant geographical variations in the burden of liver disease and CVD, highlighting the need to devise local solutions. Targeted policies and regional initiatives addressing underserved communities might help improve equity of access to CVD screening and treatment.",,pdf:https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-021-03210-9; doi:https://doi.org/10.1186/s12967-021-03210-9; html:https://europepmc.org/articles/PMC8722174; pdf:https://europepmc.org/articles/PMC8722174?pdf=render
+35639667,https://doi.org/10.1093/eurheartj/ehac238,Critical appraisal of artificial intelligence-based prediction models for cardiovascular disease.,"van Smeden M, Heinze G, Van Calster B, Asselbergs FW, Vardas PE, Bruining N, de Jaegere P, Moore JH, Denaxas S, Boulesteix AL, Moons KGM.",,European heart journal,2022,2022-08-01,Y,Prediction; Artificial intelligence; Diagnosis; Prognosis; Machine Learning; Digital Health,,,"The medical field has seen a rapid increase in the development of artificial intelligence (AI)-based prediction models. With the introduction of such AI-based prediction model tools and software in cardiovascular patient care, the cardiovascular researcher and healthcare professional are challenged to understand the opportunities as well as the limitations of the AI-based predictions. In this article, we present 12 critical questions for cardiovascular health professionals to ask when confronted with an AI-based prediction model. We aim to support medical professionals to distinguish the AI-based prediction models that can add value to patient care from the AI that does not.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render
 32763829,https://doi.org/10.1016/j.ebiom.2020.102932,Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: An IMI DIRECT study.,"Eriksen R, Perez IG, Posma JM, Haid M, Sharma S, Prehn C, Thomas LE, Koivula RW, Bizzotto R, Prehn C, Mari A, Giordano GN, Pavo I, Schwenk JM, De Masi F, Tsirigos KD, Brunak S, Viñuela A, Mahajan A, McDonald TJ, Kokkola T, Rutter F, Teare H, Hansen TH, Fernandez J, Jones A, Jennison C, Walker M, McCarthy MI, Pedersen O, Ruetten H, Forgie I, Bell JD, Pearson ER, Franks PW, Adamski J, Holmes E, Frost G.",,EBioMedicine,2020,2020-08-04,Y,Type 2 diabetes; metabolic profiling; Dietary Patterns; Cardiometabolic Health,,,"<h4>Background</h4>Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D.<h4>Methods</h4>We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (T<sub>pred</sub>) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous T<sub>pred</sub> score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models.<h4>Findings</h4>A higher T<sub>pred</sub> score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=-0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher T<sub>pred</sub> score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the T<sub>pred</sub> score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher T<sub>pred</sub> score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2.<h4>Interpretation</h4>Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health.<h4>Funding</h4>This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies.",,pdf:http://www.thelancet.com/article/S235239642030308X/pdf; doi:https://doi.org/10.1016/j.ebiom.2020.102932; html:https://europepmc.org/articles/PMC7406914; pdf:https://europepmc.org/articles/PMC7406914?pdf=render
 35869125,https://doi.org/10.1038/s41598-022-16375-0,Minimising multi-centre radiomics variability through image normalisation: a pilot study.,"Campello VM, Martín-Isla C, Izquierdo C, Guala A, Palomares JFR, Viladés D, Descalzo ML, Karakas M, Çavuş E, Raisi-Estabragh Z, Petersen SE, Escalera S, Seguí S, Lekadir K.",,Scientific reports,2022,2022-07-22,Y,,,,"Radiomics is an emerging technique for the quantification of imaging data that has recently shown great promise for deeper phenotyping of cardiovascular disease. Thus far, the technique has been mostly applied in single-centre studies. However, one of the main difficulties in multi-centre imaging studies is the inherent variability of image characteristics due to centre differences. In this paper, a comprehensive analysis of radiomics variability under several image- and feature-based normalisation techniques was conducted using a multi-centre cardiovascular magnetic resonance dataset. 218 subjects divided into healthy (n = 112) and hypertrophic cardiomyopathy (n = 106, HCM) groups from five different centres were considered. First and second order texture radiomic features were extracted from three regions of interest, namely the left and right ventricular cavities and the left ventricular myocardium. Two methods were used to assess features' variability. First, feature distributions were compared across centres to obtain a distribution similarity index. Second, two classification tasks were proposed to assess: (1) the amount of centre-related information encoded in normalised features (centre identification) and (2) the generalisation ability for a classification model when trained on these features (healthy versus HCM classification). The results showed that the feature-based harmonisation technique ComBat is able to remove the variability introduced by centre information from radiomic features, at the expense of slightly degrading classification performance. Piecewise linear histogram matching normalisation gave features with greater generalisation ability for classification ( balanced accuracy in between 0.78 ± 0.08 and 0.79 ± 0.09). Models trained with features from images without normalisation showed the worst performance overall ( balanced accuracy in between 0.45 ± 0.28 and 0.60 ± 0.22). In conclusion, centre-related information removal did not imply good generalisation ability for classification.",,pdf:https://www.nature.com/articles/s41598-022-16375-0.pdf; doi:https://doi.org/10.1038/s41598-022-16375-0; html:https://europepmc.org/articles/PMC9307565; pdf:https://europepmc.org/articles/PMC9307565?pdf=render
 35641524,https://doi.org/10.1038/s41533-022-00280-0,Development and validation of a multivariable mortality risk prediction model for COPD in primary care.,"Shah SA, Nwaru BI, Sheikh A, Simpson CR, Kotz D.",,NPJ primary care respiratory medicine,2022,2022-05-31,Y,,,,"Risk stratification of chronic obstructive pulmonary disease (COPD) patients is important to enable targeted management. Existing disease severity classification systems, such as GOLD staging, do not take co-morbidities into account despite their high prevalence in COPD patients. We sought to develop and validate a prognostic model to predict 10-year mortality in patients with diagnosed COPD. We constructed a longitudinal cohort of 37,485 COPD patients (149,196 person-years) from a UK-wide primary care database. The risk factors included in the model pertained to demographic and behavioural characteristics, co-morbidities, and COPD severity. The outcome of interest was all-cause mortality. We fitted an extended Cox-regression model to estimate hazard ratios (HR) with 95% confidence intervals (CI), used machine learning-based data modelling approaches including k-fold cross-validation to validate the prognostic model, and assessed model fitting and discrimination. The inter-quartile ranges of the three metrics on the validation set suggested good performance: 0.90-1.06 for model fit, 0.80-0.83 for Harrel's c-index, and 0.40-0.46 for Royston and Saurebrei's [Formula: see text] with a strong overlap of these metrics on the training dataset. According to the validated prognostic model, the two most important risk factors of mortality were heart failure (HR 1.92; 95% CI 1.87-1.96) and current smoking (HR 1.68; 95% CI 1.66-1.71). We have developed and validated a national, population-based prognostic model to predict 10-year mortality of patients diagnosed with COPD. This model could be used to detect high-risk patients and modify risk factors such as optimising heart failure management and offering effective smoking cessation interventions.",,pdf:https://www.nature.com/articles/s41533-022-00280-0.pdf; doi:https://doi.org/10.1038/s41533-022-00280-0; html:https://europepmc.org/articles/PMC9156666; pdf:https://europepmc.org/articles/PMC9156666?pdf=render
@@ -1492,8 +1492,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33824163,https://doi.org/10.3399/bjgp20x714161,Post-bariatric surgery nutritional follow-up in primary care: a population-based cohort study.,"Parretti HM, Subramanian A, Adderley NJ, Abbott S, Tahrani AA, Nirantharakumar K.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-05-27,Y,Nutrition; Followup; Cohort studies; General Practice; Bariatric Surgery; The Health Improvement Network,,,"<h4>Background</h4>Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.<h4>Aim</h4>To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.<h4>Design and setting</h4>Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).<h4>Method</h4>Participants were adults who had had bariatric surgery with a minimum of 3 years' follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.<h4>Results</h4>A total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2-7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% (<i>n</i> = 629/1400) and 61.2% (<i>n</i> = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (<i>n</i> = 10/818) and 1.5% (<i>n</i> = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low.<h4>Conclusion</h4>This study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.",,pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf; doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?pdf=render
 32238333,https://doi.org/10.2196/16400,Low-Density Lipoprotein Cholesterol Target Attainment in Patients With Established Cardiovascular Disease: Analysis of Routine Care Data.,"Groenhof TKJ, Kofink D, Bots ML, Nathoe HM, Hoefer IE, Van Solinge WW, Lely AT, Asselbergs FW, Haitjema S.",,JMIR medical informatics,2020,2020-04-02,Y,LDL-C; Cardiovascular Risk Management; Learning Health Care System; Routine Clinical Data,Better Care,cardiovascular,"<h4>Background</h4>Direct feedback on quality of care is one of the key features of a learning health care system (LHS), enabling health care professionals to improve upon the routine clinical care of their patients during practice.<h4>Objective</h4>This study aimed to evaluate the potential of routine care data extracted from electronic health records (EHRs) in order to obtain reliable information on low-density lipoprotein cholesterol (LDL-c) management in cardiovascular disease (CVD) patients referred to a tertiary care center.<h4>Methods</h4>We extracted all LDL-c measurements from the EHRs of patients with a history of CVD referred to the University Medical Center Utrecht. We assessed LDL-c target attainment at the time of referral and per year. In patients with multiple measurements, we analyzed LDL-c trajectories, truncated at 6 follow-up measurements. Lastly, we performed a logistic regression analysis to investigate factors associated with improvement of LDL-c at the next measurement.<h4>Results</h4>Between February 2003 and December 2017, 250,749 LDL-c measurements were taken from 95,795 patients, of whom 23,932 had a history of CVD. At the time of referral, 51% of patients had not reached their LDL-c target. A large proportion of patients (55%) had no follow-up LDL-c measurements. Most of the patients with repeated measurements showed no change in LDL-c levels over time: the transition probability to remain in the same category was up to 0.84. Sequence clustering analysis showed more women (odds ratio 1.18, 95% CI 1.07-1.10) in the cluster with both most measurements off target and the most LDL-c measurements furthest from the target. Timing of drug prescription was difficult to determine from our data, limiting the interpretation of results regarding medication management.<h4>Conclusions</h4>Routine care data can be used to provide feedback on quality of care, such as LDL-c target attainment. These routine care data show high off-target prevalence and little change in LDL-c over time. Registrations of diagnosis; follow-up trajectory, including primary and secondary care; and medication use need to be improved in order to enhance usability of the EHR system for adequate feedback.",,pdf:https://medinform.jmir.org/2020/4/e16400/PDF; doi:https://doi.org/10.2196/16400; html:https://europepmc.org/articles/PMC7163416
 32393804,https://doi.org/10.1038/s41591-020-0916-2,Real-time tracking of self-reported symptoms to predict potential COVID-19.,"Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, Ganesh S, Varsavsky T, Cardoso MJ, El-Sayed Moustafa JS, Visconti A, Hysi P, Bowyer RCE, Mangino M, Falchi M, Wolf J, Ourselin S, Chan AT, Steves CJ, Spector TD.",,Nature medicine,2020,2020-05-11,N,,,,"A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.",,pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf; doi:https://doi.org/10.1038/s41591-020-0916-2; html:https://europepmc.org/articles/PMC7751267; pdf:https://europepmc.org/articles/PMC7751267?pdf=render; doi:https://doi.org/10.1038/s41591-020-0916-2
-36423925,https://doi.org/10.1136/thorax-2022-219591,Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).,"Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe D, Davies G, Lyons RA, Griffiths C, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,Thorax,2023,2022-11-23,Y,Asthma; Covid-19,,,"<h4>Background</h4>The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.<h4>Methods</h4>We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.<h4>Results</h4>Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31).<h4>Conclusions</h4>Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.<h4>Study registration number</h4>NCT04330599.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render
 34040552,https://doi.org/10.3389/fpsyt.2021.627996,Optimising a Simple Fully Convolutional Network for Accurate Brain Age Prediction in the PAC 2019 Challenge.,"Gong W, Beckmann CF, Vedaldi A, Smith SM, Peng H.",,Frontiers in psychiatry,2021,2021-05-10,Y,Brain imaging; Predictive Analysis; Big Data; Deep Learning; Convolution Neural Network; Brain Age Prediction,,,"Brain age prediction from brain MRI scans not only helps improve brain ageing modelling generally, but also provides benchmarks for predictive analysis methods. Brain-age delta, which is the difference between a subject's predicted age and true age, has become a meaningful biomarker for the health of the brain. Here, we report the details of our brain age prediction models and results in the Predictive Analysis Challenge 2019. The aim of the challenge was to use T1-weighted brain MRIs to predict a subject's age in multicentre datasets. We apply a lightweight deep convolutional neural network architecture, Simple Fully Convolutional Neural Network (SFCN), and combined several techniques including data augmentation, transfer learning, model ensemble, and bias correction for brain age prediction. The model achieved first place in both of the two objectives in the PAC 2019 brain age prediction challenge: Mean absolute error (MAE) = 2.90 years without bias removal (Second Place = 3.09 yrs; Third Place = 3.33 yrs), and MAE = 2.95 years with bias removal, leading by a large margin (Second Place = 3.80 yrs; Third Place = 3.92 yrs).",,pdf:https://www.frontiersin.org/articles/10.3389/fpsyt.2021.627996/pdf; doi:https://doi.org/10.3389/fpsyt.2021.627996; html:https://europepmc.org/articles/PMC8141616; pdf:https://europepmc.org/articles/PMC8141616?pdf=render
+36423925,https://doi.org/10.1136/thorax-2022-219591,Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).,"Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe D, Davies G, Lyons RA, Griffiths C, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,Thorax,2023,2022-11-23,Y,Asthma; Covid-19,,,"<h4>Background</h4>The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.<h4>Methods</h4>We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.<h4>Results</h4>Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31).<h4>Conclusions</h4>Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.<h4>Study registration number</h4>NCT04330599.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render
 33933530,https://doi.org/10.1016/j.jinf.2021.04.027,Early observations on the impact of a healthcare worker COVID-19 vaccination programme at a major UK tertiary centre.,"Garvey MI, Wilkinson MAC, Holden E, Shields A, Robertson A, Richter A, Ball S.",,The Journal of infection,2021,2021-04-29,Y,Vaccination; Healthcare Workers; Lateral Flow; Covid-19,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081749; doi:https://doi.org/10.1016/j.jinf.2021.04.027; html:https://europepmc.org/articles/PMC8081749; pdf:https://europepmc.org/articles/PMC8081749?pdf=render
 31168069,https://doi.org/10.1038/s41380-019-0439-8,"The genomic basis of mood instability: identification of 46 loci in 363,705 UK Biobank participants, genetic correlation with psychiatric disorders, and association with gene expression and function.","Ward J, Tunbridge EM, Sandor C, Lyall LM, Ferguson A, Strawbridge RJ, Lyall DM, Cullen B, Graham N, Johnston KJA, Webber C, Escott-Price V, O'Donovan M, Pell JP, Bailey MES, Harrison PJ, Smith DJ.",,Molecular psychiatry,2020,2019-06-05,Y,,,,"Genome-wide association studies (GWAS) of psychiatric phenotypes have tended to focus on categorical diagnoses, but to understand the biology of mental illness it may be more useful to study traits which cut across traditional boundaries. Here, we report the results of a GWAS of mood instability as a trait in a large population cohort (UK Biobank, n = 363,705). We also assess the clinical and biological relevance of the findings, including whether genetic associations show enrichment for nervous system pathways. Forty six unique loci associated with mood instability were identified with a SNP heritability estimate of 9%. Linkage Disequilibrium Score Regression (LDSR) analyses identified genetic correlations with Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia, anxiety, and Post Traumatic Stress Disorder (PTSD). Gene-level and gene set analyses identified 244 significant genes and 6 enriched gene sets. Tissue expression analysis of the SNP-level data found enrichment in multiple brain regions, and eQTL analyses highlighted an inversion on chromosome 17 plus two brain-specific eQTLs. In addition, we used a Phenotype Linkage Network (PLN) analysis and community analysis to assess for enrichment of nervous system gene sets using mouse orthologue databases. The PLN analysis found enrichment in nervous system PLNs for a community containing serotonin and melatonin receptors. In summary, this work has identified novel loci, tissues and gene sets contributing to mood instability. These findings may be relevant for the identification of novel trans-diagnostic drug targets and could help to inform future stratified medicine innovations in mental health.",,pdf:https://eprints.gla.ac.uk/185493/1/185493.pdf; doi:https://doi.org/10.1038/s41380-019-0439-8; html:https://europepmc.org/articles/PMC7116257; pdf:https://europepmc.org/articles/PMC7116257?pdf=render
 32735547,https://doi.org/10.2196/20169,Can Robots Improve Testing Capacity for SARS-CoV-2?,"Cresswell K, Ramalingam S, Sheikh A.",,Journal of medical Internet research,2020,2020-08-12,Y,Virus; Infectious disease; Testing; Robotics; Pandemic; Covid-19; Sars-cov-2,,,"There is currently increasing interest internationally in deploying robotic applications for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, as these can help to reduce the risk of transmission of the virus to health care staff and patients. We provide an overview of key recent developments in this area. We argue that, although there is some potential for deploying robots to help with SARS-CoV-2 testing, the potential of patient-facing applications is likely to be limited. This is due to the high costs associated with patient-facing functionality, and risks of potentially adverse impacts on health care staff work practices and patient interactions. In contrast, back-end laboratory-based robots dealing with sample extraction and amplification, that effectively integrate with established processes, software, and interfaces to process samples, are much more likely to result in safety and efficiency gains. Consideration should therefore be given to deploying these at scale.",,pdf:https://www.jmir.org/2020/8/e20169/PDF; doi:https://doi.org/10.2196/20169; html:https://europepmc.org/articles/PMC7450371
@@ -1508,10 +1508,10 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 35047182,https://doi.org/10.7189/jogh.11.01010,"The COVID-19 pandemic in children and young people during 2020-2021: Learning about clinical presentation, patterns of spread, viral load, diagnosis and treatment.","Rudan I, Adeloye D, Katikireddi SV, Murray J, Simpson C, Shah SA, Robertson C, Sheikh A, EAVE II collaboration.",,Journal of global health,2021,2021-12-25,Y,,,,,,doi:https://doi.org/10.7189/jogh.11.01010; doi:https://doi.org/10.7189/jogh.11.01010; html:https://europepmc.org/articles/PMC8763336; pdf:https://europepmc.org/articles/PMC8763336?pdf=render
 35210596,https://doi.org/10.1038/s41591-022-01736-z,Modeling comparative cost-effectiveness of SARS-CoV-2 vaccine dose fractionation in India.,"Du Z, Wang L, Pandey A, Lim WW, Chinazzi M, Piontti APY, Lau EHY, Wu P, Malani A, Cobey S, Cowling BJ.",,Nature medicine,2022,2022-02-24,Y,,,,"Given global Coronavirus Disease 2019 (COVID-19) vaccine shortages and inequity of vaccine distributions, fractionation of vaccine doses might be an effective strategy for reducing public health and economic burden, notwithstanding the emergence of new variants of concern. In this study, we developed a multi-scale model incorporating population-level transmission and individual-level vaccination to estimate the costs of hospitalization and vaccination and the economic benefits of reducing COVID-19 deaths due to dose-fractionation strategies in India. We used large-scale survey data of the willingness to pay together with data of vaccine and hospital admission costs to build the model. We found that fractional doses of vaccines could be an economically viable vaccination strategy compared to alternatives of either full-dose vaccination or no vaccination. Dose-sparing strategies could save a large number of lives, even with the emergence of new variants with higher transmissibility.",,pdf:https://www.nature.com/articles/s41591-022-01736-z.pdf; doi:https://doi.org/10.1038/s41591-022-01736-z; html:https://europepmc.org/articles/PMC9117137; pdf:https://europepmc.org/articles/PMC9117137?pdf=render
 33036417,https://doi.org/10.3390/ijerph17197320,"Prognostic Role of Demographic, Injury and Claim Factors in Disabling Pain and Mental Health Conditions 12 Months after Compensable Injury. ","Nguyen TL, Baker KS, Ioannou L, Hassani-Mahmooei B, Gibson SJ, Collie A, Ponsford J, Cameron PA, Gabbe BJ, Giummarra MJ.",,International journal of environmental research and public health,2020,2020-10-07,Y,,,,"Identifying who might develop disabling pain or poor mental health after injury is a high priority so that healthcare providers can provide targeted preventive interventions. This retrospective cohort study aimed to identify predictors of disabling pain or probable mental health conditions at 12 months post-injury. Participants were recruited 12-months after admission to a major trauma service for a compensable transport or workplace injury (n = 157). Injury, compensation claim, health services and medication information were obtained from the Victorian Orthopaedic Trauma Outcome Registry, Victorian State Trauma Registry and Compensation Research Database. Participants completed questionnaires about pain, and mental health (anxiety, depression, posttraumatic stress disorder) at 12 months post-injury. One third had disabling pain, one third had at least one probable mental health condition and more than one in five had both disabling pain and a mental health condition at 12 months post-injury. Multivariable logistic regression found mental health treatment 3-6 months post-injury, persistent work disability and opioid use at 6-12 months predicted disabling pain at 12 months post-injury. The presence of opioid use at 3-6 months, work disability and psychotropic medications at 6-12 months predicted a mental health condition at 12 months post-injury. These factors could be used to identify at risk of developing disabling pain who could benefit from timely interventions to better manage both pain and mental health post-injury. Implications for healthcare and compensation system are discussed.",,pdf:https://www.mdpi.com/1660-4601/17/19/7320/pdf?version=1602228180; doi:https://doi.org/10.3390/ijerph17197320; html:https://europepmc.org/articles/PMC7579145; pdf:https://europepmc.org/articles/PMC7579145?pdf=render
-35513530,https://doi.org/10.1038/s41591-022-01781-8,Patient reported outcome assessment must be inclusive and equitable.,"Calvert MJ, Cruz Rivera S, Retzer A, Hughes SE, Campbell L, Molony-Oates B, Aiyegbusi OL, Stover AM, Wilson R, McMullan C, Anderson NE, Turner GM, Davies EH, Verdi R, Velikova G, Kamudoni P, Muslim S, Gheorghe A, O'Connor D, Liu X, Wu AW, Denniston AK.",,Nature medicine,2022,2022-06-01,N,,,,,,pdf:https://www.nature.com/articles/s41591-022-01781-8.pdf; doi:https://doi.org/10.1038/s41591-022-01781-8
 31089183,https://doi.org/10.1038/s41598-019-43861-9,Genetic variation in CADM2 as a link between psychological traits and obesity.,"Morris J, Bailey MES, Baldassarre D, Cullen B, de Faire U, Ferguson A, Gigante B, Giral P, Goel A, Graham N, Hamsten A, Humphries SE, Johnston KJA, Lyall DM, Lyall LM, Sennblad B, Silveira A, Smit AJ, Tremoli E, Veglia F, Ward J, Watkins H, Smith DJ, Strawbridge RJ.",,Scientific reports,2019,2019-05-14,Y,,Understanding the Causes of Disease,,"CADM2 has been associated with a range of behavioural and metabolic traits, including physical activity, risk-taking, educational attainment, alcohol and cannabis use and obesity. Here, we set out to determine whether CADM2 contributes to mechanisms shared between mental and physical health disorders. We assessed genetic variants in the CADM2 locus for association with phenotypes in the UK Biobank, IMPROVE, PROCARDIS and SCARFSHEEP studies, before performing meta-analyses. A wide range of metabolic phenotypes were meta-analysed. Psychological phenotypes analysed in UK Biobank only were major depressive disorder, generalised anxiety disorder, bipolar disorder, neuroticism, mood instability and risk-taking behaviour. In UK Biobank, four, 88 and 172 genetic variants were significantly (p < 1 × 10<sup>-5</sup>) associated with neuroticism, mood instability and risk-taking respectively. In meta-analyses of 4 cohorts, we identified 362, 63 and 11 genetic variants significantly (p < 1 × 10<sup>-5</sup>) associated with BMI, SBP and CRP respectively. Genetic effects on BMI, CRP and risk-taking were all positively correlated, and were consistently inversely correlated with genetic effects on SBP, mood instability and neuroticism. Conditional analyses suggested an overlap in the signals for physical and psychological traits. Many significant variants had genotype-specific effects on CADM2 expression levels in adult brain and adipose tissues. CADM2 variants influence a wide range of both psychological and metabolic traits, suggesting common biological mechanisms across phenotypes via regulation of CADM2 expression levels in adipose tissue. Functional studies of CADM2 are required to fully understand mechanisms connecting mental and physical health conditions.",,pdf:https://www.nature.com/articles/s41598-019-43861-9.pdf; doi:https://doi.org/10.1038/s41598-019-43861-9; html:https://europepmc.org/articles/PMC6517397; pdf:https://europepmc.org/articles/PMC6517397?pdf=render
-35681241,https://doi.org/10.1186/s12933-022-01525-5,Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study.,"Patel RS, Pasea L, Soran H, Downie P, Jones R, Hingorani AD, Neely D, Denaxas S, Hemingway H.",,Cardiovascular diabetology,2022,2022-06-09,Y,Lipids; Triglycerides; Myocardial infarction; Diabetes; Pancreatitis,,,"<h4>Background</h4>Assessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes.<h4>Methods</h4>We used linked data from primary and secondary care for 15 M people, to explore the association between triglyceride concentration and risk of acute pancreatitis, chronic pancreatitis, new onset diabetes, myocardial infarction and all-cause mortality, over a median of 6-7 years follow up.<h4>Results</h4>Triglyceride concentration was available for 1,530,411 individuals (mean age 56·6 ± 15·6 years, 51·4% female), with a median of 1·3 mmol/L (IQR: 0.9.to 1.9). Severe hypertriglyceridemia, defined as > 10 mmol/L, was identified in 3289 (0·21%) individuals including 620 with > 20 mmol/L. In multivariable analyses, a triglyceride concentration > 20 mmol/L was associated with very high risk for acute pancreatitis (Hazard ratio (HR) 13·55 (95% CI 9·15-20·06)); chronic pancreatitis (HR 25·19 (14·91-42·55)); and high risk for diabetes (HR 5·28 (4·51-6·18)) and all-cause mortality (HR 3·62 (2·82-4·65)) when compared to the reference category of ≤ 1·7 mmol/L. An association with myocardial infarction, however, was only observed for more moderate hypertriglyceridaemia between 1.7 and 10 mmol/L. We found a risk interaction with age, with higher risks for all outcomes including mortality among those ≤ 40 years compared to > 40 years.<h4>Conclusions</h4>We highlight an exponential association between severe hypertriglyceridaemia and risk of incident acute and chronic pancreatitis, new diabetes, and mortality, especially at younger ages, but not for myocardial infarction for which only moderate hypertriglyceridemia conferred risk.",,pdf:https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-022-01525-5; doi:https://doi.org/10.1186/s12933-022-01525-5; html:https://europepmc.org/articles/PMC9185961; pdf:https://europepmc.org/articles/PMC9185961?pdf=render
+35513530,https://doi.org/10.1038/s41591-022-01781-8,Patient reported outcome assessment must be inclusive and equitable.,"Calvert MJ, Cruz Rivera S, Retzer A, Hughes SE, Campbell L, Molony-Oates B, Aiyegbusi OL, Stover AM, Wilson R, McMullan C, Anderson NE, Turner GM, Davies EH, Verdi R, Velikova G, Kamudoni P, Muslim S, Gheorghe A, O'Connor D, Liu X, Wu AW, Denniston AK.",,Nature medicine,2022,2022-06-01,N,,,,,,pdf:https://www.nature.com/articles/s41591-022-01781-8.pdf; doi:https://doi.org/10.1038/s41591-022-01781-8
 32079223,https://doi.org/10.3390/jcm9020545,Quantitative Approach to Fragmented QRS in Arrhythmogenic Cardiomyopathy: From Disease towards Asymptomatic Carriers of Pathogenic Variants. ,"Roudijk RW, Bosman LP, van der Heijden JF, de Bakker JMT, Hauer RNW, van Tintelen JP, Asselbergs FW, Te Riele ASJM, Loh P.",,Journal of clinical medicine,2020,2020-02-17,Y,,Understanding the Causes of Disease,cardiovascular,"Fragmented QRS complexes (fQRS) are common in patients with arrhythmogenic cardiomyopathy (ACM). A new method of fQRS quantification may aid early disease detection in pathogenic variant carriers and assessment of prognosis in patients with early stage ACM. Patients with definite ACM (n = 221, 66%), carriers of a pathogenic ACM-associated variant without a definite ACM diagnosis (n = 57, 17%) and control subjects (n = 58, 17%) were included. Quantitative fQRS (Q-fQRS) was defined as the total amount of deflections in the QRS complex in all 12 electrocardiography (ECG) leads. Q-fQRS was scored by a single observer and reproducibility was determined by three independent observers. Q-fQRS count was feasible with acceptable intra- and inter-observer agreement. Q-fQRS count is significantly higher in patients with definite ACM (54 ± 15) and pathogenic variant carriers (55 ± 10) compared to controls (35 ± 5) (p < 0.001). In patients with ACM, Q-fQRS was not associated with sustained ventricular arrhythmia (p = 0.701) at baseline or during follow-up (p = 0.335). Both definite ACM patients and pathogenic variant carriers not fulfilling ACM diagnosis have a higher Q-fQRS than controls. This may indicate that increased Q-fQRS is an early sign of disease penetrance. In concealed and early stages of ACM the role of Q-fQRS for risk stratification is limited.",,pdf:https://www.mdpi.com/2077-0383/9/2/545/pdf?version=1581938622; doi:https://doi.org/10.3390/jcm9020545; html:https://europepmc.org/articles/PMC7073517; pdf:https://europepmc.org/articles/PMC7073517?pdf=render
+35681241,https://doi.org/10.1186/s12933-022-01525-5,Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study.,"Patel RS, Pasea L, Soran H, Downie P, Jones R, Hingorani AD, Neely D, Denaxas S, Hemingway H.",,Cardiovascular diabetology,2022,2022-06-09,Y,Lipids; Triglycerides; Myocardial infarction; Diabetes; Pancreatitis,,,"<h4>Background</h4>Assessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes.<h4>Methods</h4>We used linked data from primary and secondary care for 15 M people, to explore the association between triglyceride concentration and risk of acute pancreatitis, chronic pancreatitis, new onset diabetes, myocardial infarction and all-cause mortality, over a median of 6-7 years follow up.<h4>Results</h4>Triglyceride concentration was available for 1,530,411 individuals (mean age 56·6 ± 15·6 years, 51·4% female), with a median of 1·3 mmol/L (IQR: 0.9.to 1.9). Severe hypertriglyceridemia, defined as > 10 mmol/L, was identified in 3289 (0·21%) individuals including 620 with > 20 mmol/L. In multivariable analyses, a triglyceride concentration > 20 mmol/L was associated with very high risk for acute pancreatitis (Hazard ratio (HR) 13·55 (95% CI 9·15-20·06)); chronic pancreatitis (HR 25·19 (14·91-42·55)); and high risk for diabetes (HR 5·28 (4·51-6·18)) and all-cause mortality (HR 3·62 (2·82-4·65)) when compared to the reference category of ≤ 1·7 mmol/L. An association with myocardial infarction, however, was only observed for more moderate hypertriglyceridaemia between 1.7 and 10 mmol/L. We found a risk interaction with age, with higher risks for all outcomes including mortality among those ≤ 40 years compared to > 40 years.<h4>Conclusions</h4>We highlight an exponential association between severe hypertriglyceridaemia and risk of incident acute and chronic pancreatitis, new diabetes, and mortality, especially at younger ages, but not for myocardial infarction for which only moderate hypertriglyceridemia conferred risk.",,pdf:https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-022-01525-5; doi:https://doi.org/10.1186/s12933-022-01525-5; html:https://europepmc.org/articles/PMC9185961; pdf:https://europepmc.org/articles/PMC9185961?pdf=render
 36100927,https://doi.org/10.28920/dhm52.3.164-174,Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial.,"Millar IL, Lind FG, Jansson KÅ, Hájek M, Smart DR, Fernandes TD, McGinnes RA, Williamson OD, Miller RK, Martin CA, Gabbe BJ, Myles PS, Cameron PA, HOLLT investigator group.",,Diving and hyperbaric medicine,2022,2022-09-01,N,Injuries; Wounds; Fractures; Orthopaedics; Outcome; Hyperbaric Oxygen Treatment; Musculo-skeletal,,,"<h4>Introduction</h4>Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes.<h4>Methods</h4>Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury.<h4>Results</h4>One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05.<h4>Conclusions</h4>In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536848; doi:https://doi.org/10.28920/dhm52.3.164-174; html:https://europepmc.org/articles/PMC9536848; pdf:https://europepmc.org/articles/PMC9536848?pdf=render; doi:https://doi.org/10.28920/dhm52.3.164-174
 30848519,https://doi.org/10.1111/dme.13945,Impact of glycaemic control on fracture risk in 5368 people with newly diagnosed Type 1 diabetes: a time-dependent analysis.,"Thayakaran R, Perrins M, Gokhale KM, Kumaran S, Narendran P, Price MJ, Nirantharakumar K, Toulis KA.",,Diabetic medicine : a journal of the British Diabetic Association,2019,2019-04-05,N,,,,"<h4>Aims</h4>To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes.<h4>Methods</h4>People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA<sub>1c</sub> measurements from diagnosis to fracture or study end or loss to follow-up were collected. A Cox proportional hazards model with HbA<sub>1c</sub> included as a time-dependent variable was fitted to these data.<h4>Results</h4>Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA<sub>1c</sub> was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002-1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03-1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA<sub>1c</sub> .<h4>Conclusions</h4>In people with newly diagnosed Type 1 diabetes, higher HbA<sub>1c</sub> is associated with an increased risk for fractures.",,doi:https://doi.org/10.1111/dme.13945
 34173614,https://doi.org/10.1016/s2666-7568(20)30012-x,Evolution and effects of COVID-19 outbreaks in care homes: a population analysis in 189 care homes in one geographical region of the UK.,"Burton JK, Bayne G, Evans C, Garbe F, Gorman D, Honhold N, McCormick D, Othieno R, Stevenson JE, Swietlik S, Templeton KE, Tranter M, Willocks L, Guthrie B.",,The lancet. Healthy longevity,2020,2020-10-20,Y,,,,"<h4>Background</h4>COVID-19 has affected care home residents internationally, but detailed information on outbreaks is scarce. We aimed to describe the evolution of outbreaks of COVID-19 in all care homes in one large health region in Scotland.<h4>Methods</h4>We did a population analysis of testing, cases, and deaths in care homes in the National Health Service (NHS) Lothian health region of the UK. We obtained data for COVID-19 testing (PCR testing of nasopharyngeal swabs for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) and deaths (COVID-19-related and non-COVID-19-related), and we analysed data by several variables including type of care home, number of beds, and locality. Outcome measures were timing of outbreaks, number of confirmed cases of COVID-19 in care home residents, care home characteristics associated with the presence of an outbreak, and deaths of residents in both care homes and hospitals. We calculated excess deaths (both COVID-19-related and non-COVID-19-related), which we defined as the sum of deaths over and above the historical average in the same period over the past 5 years.<h4>Findings</h4>Between March 10 and Aug 2, 2020, residents at 189 care homes (5843 beds) were tested for COVID-19 when symptomatic. A COVID-19 outbreak was confirmed at 69 (37%) care homes, of which 66 (96%) were care homes for older people. The size of care homes for older people was strongly associated with a COVID-19 outbreak (odds ratio per 20-bed increase 3·35, 95% CI 1·99-5·63). 907 confirmed cases of SARS-CoV-2 infection were recorded during the study period, and 432 COVID-19-related deaths. 229 (25%) COVID-19-related cases and 99 (24%) COVID-related deaths occurred in five (3%) of 189 care homes, and 441 (49%) cases and 207 (50%) deaths were in 13 (7%) care homes. 411 (95%) COVID-19-related deaths occurred in the 69 care homes with a confirmed COVID-19 outbreak, 19 (4%) deaths were in hospital, and two (<1%) were in one of the 120 care homes without a confirmed COVID-19 outbreak. At the 69 care homes with a confirmed COVID-19 outbreak, 74 excess non-COVID-19-related deaths were reported, whereas ten non-COVID-19-related excess deaths were observed in the 120 care homes without a confirmed COVID-19 outbreak. 32 fewer non-COVID-19-related deaths than expected were reported among care home residents in hospital.<h4>Interpretation</h4>The effect of COVID-19 on care homes has been substantial but concentrated in care homes with known outbreaks. A key implication from our findings is that, if community incidence of COVID-19 increases again, many care home residents will be susceptible. Shielding care home residents from potential sources of SARS-CoV-2 infection, and ensuring rapid action to minimise outbreak size if infection is introduced, will be important for any second wave.<h4>Funding</h4>None.",,doi:https://doi.org/10.1016/s2666-7568(20)30012-x; doi:https://doi.org/10.1016/S2666-7568(20)30012-X; html:https://europepmc.org/articles/PMC7574931; pdf:https://europepmc.org/articles/PMC7574931?pdf=render
@@ -1531,9 +1531,9 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 31242963,https://doi.org/10.1016/j.vaccine.2019.06.019,An online decision tree for vaccine efficacy trial design during infectious disease epidemics: The InterVax-Tool.,"Bellan SE, Eggo RM, Gsell PS, Kucharski AJ, Dean NE, Donohue R, Zook M, Edmunds WJ, Odhiambo F, Longini IM, Brisson M, Mahon BE, Henao-Restrepo AM.",,Vaccine,2019,2019-06-24,Y,Vaccines; Decision support system; epidemics; Outbreaks; Emerging Infectious Diseases; Phase Iii Trial; Scientific Communication; Public Health Emergency; Vaccine Trial Design,"Applied Analytics, Better Care, Better, Faster and More Efficient Clinical Trials",,"<h4>Background</h4>Licensed vaccines are urgently needed for emerging infectious diseases, but the nature of these epidemics causes challenges for the design of phase III trials to evaluate vaccine efficacy. Designing and executing rigorous, fast, and ethical, vaccine efficacy trials is difficult, and the decisions and limitations in the design of these trials encompass epidemiological, logistical, regulatory, statistical, and ethical dimensions.<h4>Results</h4>Trial design decisions are complex and interrelated, but current guidance documents do not lend themselves to efficient decision-making. We created InterVax-Tool (http://vaxeval.com), an online, interactive decision-support tool, to help diverse stakeholders navigate the decisions in the design of phase III vaccine trials. InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of the: (1) Primary Endpoint, (2) Target Population, (3) Randomization Scheme, and, (4) Comparator. We provide guidance on how key considerations - grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural - inform each decision in the trial design process.<h4>Conclusions</h4>InterVax-Tool facilitates structured, transparent, and collaborative discussion of trial design, while recording the decision-making process. Users can save and share their decisions, which is useful both for comparing proposed trial designs, and for justifying particular design choices. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.",,doi:https://doi.org/10.1016/j.vaccine.2019.06.019; doi:https://doi.org/10.1016/j.vaccine.2019.06.019; html:https://europepmc.org/articles/PMC6620503
 32573463,https://doi.org/10.2196/18185,Superusers' Engagement in Asthma Online Communities: Asynchronous Web-Based Interview Study.,"De Simoni A, Shah AT, Fulton O, Parkinson J, Sheikh A, Panzarasa P, Pagliari C, Coulson NS, Griffiths CJ.",,Journal of medical Internet research,2020,2020-06-23,Y,Asthma; Misinformation; Social Networks; Leadership; Social Support; Self-management; Social Media; Ehealth; Online Health Communities; Superusers; Online Forums; Peer-to-peer Support,,,"<h4>Background</h4>Superusers, defined as the 1% of users who write a large number of posts, play critical roles in online health communities (OHCs), catalyzing engagement and influencing other users' self-care. Their unique online behavior is key to sustaining activity in OHCs and making them flourish. Our previous work showed the presence of 20 to 30 superusers active on a weekly basis among 3345 users in the nationwide Asthma UK OHC and that the community would disintegrate if superusers were removed. Recruiting these highly skilled individuals for research purposes can be challenging, and little is known about superusers.<h4>Objective</h4>This study aimed to explore superusers' motivation to actively engage in OHCs, the difficulties they may face, and their interactions with health care professionals (HCPs).<h4>Methods</h4>An asynchronous web-based structured interview study was conducted. Superusers of the Asthma UK OHC and Facebook groups were recruited through Asthma UK staff to pilot and subsequently complete the questionnaire. Open-ended questions were analyzed using content analysis.<h4>Results</h4>There were 17 superusers recruited for the study (14 patients with asthma and 3 carers); the majority were female (15/17). The age range of participants was 18 to 75 years. They were active in OHCs for 1 to 6 years and spent between 1 and 20 hours per week reading and 1 and 3 hours per week writing posts. Superusers' participation in OHCs was prompted by curiosity about asthma and its medical treatment and by the availability of spare time when they were off work due to asthma exacerbations or retired. Their engagement increased over time as participants furthered their familiarity with the OHCs and their knowledge of asthma and its self-management. Financial or social recognition of the superuser role was not important; their reward came from helping and interacting with others. According to the replies provided, they showed careful judgment to distinguish what can be dealt with through peer advice and what needs input from HCPs. Difficulties were encountered when dealing with misunderstandings about asthma and its treatment, patients not seeking advice from HCPs when needed, and miracle cures or dangerous ideas. Out of 17 participants, only 3 stated that their HCPs were aware of their engagement with OHCs. All superusers thought that HCPs should direct patients to OHCs, provided they are trusted and moderated. In addition, 9 users felt that HCPs themselves should take part in OHCs.<h4>Conclusions</h4>Superusers from a UK-wide online community are highly motivated, altruistic, and mostly female individuals who exhibit judgment about the complexity of coping with asthma and the limits of their advice. Engagement with OHCs satisfies their psychosocial needs. Future research should explore how to address their unmet needs, their interactions with HCPs, and the potential integration of OHCs in traditional healthcare.",,pdf:https://www.jmir.org/2020/6/e18185/PDF; doi:https://doi.org/10.2196/18185; html:https://europepmc.org/articles/PMC7381072
 32935062,https://doi.org/10.23889/ijpds.v5i2.1383,Prospective data linkage to facilitate COVID-19 trials - A call to action.,"Paprica PA, Sydes MR, McGrail KM, Morris AD, Schull MJ, Walker R.",,International journal of population data science,2020,2020-08-11,Y,,,,,,pdf:https://ijpds.org/article/download/1383/2566; doi:https://doi.org/10.23889/ijpds.v5i2.1383; html:https://europepmc.org/articles/PMC7473253; pdf:https://europepmc.org/articles/PMC7473253?pdf=render
-37808344,https://doi.org/10.1016/j.jacadv.2023.100573,<i>CYP2C19</i> Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With Clopidogrel.,"Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,JACC. Advances,2023,2023-09-01,Y,Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology,,,"<h4>Background</h4>Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in <i>CYP2C19</i> and their relationship with clinical efficacy have not included South Asian populations.<h4>Objectives</h4>The objective of this study was to assess prevalence of common <i>CYP2C19</i> genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.<h4>Methods</h4>The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. <i>CYP2C19</i> diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.<h4>Results</h4>Genes & Health cohort participants (N = 44,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function <i>CYP2C19</i> allele. The prevalence of poor metabolizers carrying 2 <i>CYP2C19</i> loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; <i>P</i> = 0.019).<h4>Conclusions</h4>A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",,doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render
 32909959,https://doi.org/10.1136/bmj.m3164,Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI Extension.,"Liu X, Rivera SC, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"The CONSORT 2010 (Consolidated Standards of Reporting Trials) statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency when evaluating new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes.The CONSORT-AI extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI. Both guidelines were developed through a staged consensus process, involving a literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed on in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The CONSORT-AI extension includes 14 new items, which were considered sufficiently important for AI interventions, that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and providing analysis of error cases.CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3164.full.pdf; doi:https://doi.org/10.1136/bmj.m3164; html:https://europepmc.org/articles/PMC7490784
 32878619,https://doi.org/10.1186/s12916-020-01726-3,COVID-19 length of hospital stay: a systematic review and data synthesis.,"Rees EM, Nightingale ES, Jafari Y, Waterlow NR, Clifford S, B Pearson CA, Group CW, Jombart T, Procter SR, Knight GM.",,BMC medicine,2020,2020-09-03,Y,Length Of Stay; Hospitalisation; Icu Capacity; Covid-19; Sars-cov-2; Bed Demand,,,"<h4>Background</h4>The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care.<h4>Methods</h4>We performed a systematic review of early evidence on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach, we provide distributions for total hospital and ICU LoS from studies in China and elsewhere, for use by the community.<h4>Results</h4>We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies-four each within and outside China-with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR 10-19) days for China, compared with 5 (IQR 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date.<h4>Conclusion</h4>Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01726-3; doi:https://doi.org/10.1186/s12916-020-01726-3; html:https://europepmc.org/articles/PMC7467845; pdf:https://europepmc.org/articles/PMC7467845?pdf=render
+37808344,https://doi.org/10.1016/j.jacadv.2023.100573,<i>CYP2C19</i> Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With Clopidogrel.,"Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,JACC. Advances,2023,2023-09-01,Y,Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology,,,"<h4>Background</h4>Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in <i>CYP2C19</i> and their relationship with clinical efficacy have not included South Asian populations.<h4>Objectives</h4>The objective of this study was to assess prevalence of common <i>CYP2C19</i> genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.<h4>Methods</h4>The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. <i>CYP2C19</i> diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.<h4>Results</h4>Genes & Health cohort participants (N = 44,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function <i>CYP2C19</i> allele. The prevalence of poor metabolizers carrying 2 <i>CYP2C19</i> loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; <i>P</i> = 0.019).<h4>Conclusions</h4>A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",,doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render
 33306713,https://doi.org/10.1371/journal.pone.0243383,"Health, educational and employment outcomes among children treated for a skin disorder: Scotland-wide retrospective record linkage cohort study of 766,244 children.","Fleming M, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,PloS one,2020,2020-12-11,Y,,,,"<h4>Background</h4>To compare health, educational and employment outcomes of schoolchildren receiving medication for a skin disorder with peers.<h4>Methods</h4>This retrospective population cohort study linked eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, school examinations, school absences/exclusions and unemployment to investigate educational (absence, exclusion, special educational need, academic attainment), employment, and health (admissions and mortality) outcomes of 766,244 children attending local authority run primary, secondary and special schools in Scotland between 2009 and 2013.<h4>Results</h4>After adjusting for sociodemographic and maternity confounders the 130,087 (17.0%) children treated for a skin disorder had increased hospitalisation, particularly within one year of commencing treatment (IRR 1.38, 95% CI 1.35-1.41, p<0.001) and mortality (HR 1.50, 95% CI 1.18-1.90, p<0.001). They had greater special educational need (OR 1.19, 95% CI 1.17-1.21, p<0.001) and more frequent absences from school (IRR 1.07, 95% CI 1.06-1.08, p<0.001) but did not exhibit poorer exam attainment or increased post-school unemployment. The associations remained after further adjustment for comorbid chronic conditions.<h4>Conclusions</h4>Despite increased hospitalisation, school absenteeism, and special educational need, children treated for a skin disorder did not have poorer exam attainment or employment outcomes. Whilst findings relating to educational and employment outcomes are reassuring, the association with increased risk of mortality is alarming and merits further investigation.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243383&type=printable; doi:https://doi.org/10.1371/journal.pone.0243383; html:https://europepmc.org/articles/PMC7732076; pdf:https://europepmc.org/articles/PMC7732076?pdf=render
 32679111,https://doi.org/10.1016/s0140-6736(20)31356-8,COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England.,"Mafham MM, Spata E, Goldacre R, Gair D, Curnow P, Bray M, Hollings S, Roebuck C, Gale CP, Mamas MA, Deanfield JE, de Belder MA, Luescher TF, Denwood T, Landray MJ, Emberson JR, Collins R, Morris EJA, Casadei B, Baigent C.",,"Lancet (London, England)",2020,2020-07-14,Y,,,,"<h4>Background</h4>Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.<h4>Methods</h4>We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.<h4>Findings</h4>Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37-43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13-20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38-46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12-29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29-45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2-9) in 2019 to 3 days (1-5) by the end of March, 2020.<h4>Interpretation</h4>Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.<h4>Funding</h4>UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.",,doi:https://doi.org/10.1016/s0140-6736(20)31356-8; doi:https://doi.org/10.1016/S0140-6736(20)31356-8; html:https://europepmc.org/articles/PMC7429983; pdf:https://europepmc.org/articles/PMC7429983?pdf=render
 35434685,https://doi.org/10.1016/j.lanepe.2022.100381,Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.,"Liu Y, Pearson CAB, Sandmann FG, Barnard RC, Kim JH, CMMID COVID-19 Working Group, Flasche S, Jit M, Abbas K.",,The Lancet regional health. Europe,2022,2022-04-11,Y,"Quantitative Methods; Mathematical Modelling; Public Health Intervention; Vaccine Policy; Ve, Vaccine Efficacy; Covid-19; Sars-cov-2; Voc, Variant Of Concern; Aefi, Adverse Events Following Immunisation; Mic, Middle Income Country",,,"<h4>Background</h4>In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.<h4>Methods</h4>We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.<h4>Findings</h4>In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.<h4>Interpretation</h4>We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.<h4>Funding</h4>World Health Organization.",,doi:https://doi.org/10.1016/j.lanepe.2022.100381; doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render
@@ -1543,8 +1543,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34859219,https://doi.org/10.1093/braincomms/fcab275,Maternal immune activation downregulates schizophrenia genes in the foetal mouse brain.,"Handunnetthi L, Saatci D, Hamley JC, Knight JC.",,Brain communications,2021,2021-11-15,Y,Infection; Genetics; Schizophrenia; Immune; Maternal,,,"Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Maternal immune activation by infections during pregnancy is hypothesized to be a key environmental risk factor. However, little is known about how maternal immune activation contributes to schizophrenia pathogenesis. In this study, we investigated if maternal immune activation influences the expression of genes associated with schizophrenia in foetal mouse brains. We found that two sets of schizophrenia genes were downregulated more than expected by chance in the foetal mouse brain following maternal immune activation, namely those genes associated with schizophrenia through genome-wide association study (fold change = 1.93, false discovery rate = 4 × 10<sup>-4</sup>) and downregulated genes in adult schizophrenia brains (fold change = 1.51, false discovery rate = 4 × 10<sup>-10</sup>). We found that these genes mapped to key biological processes, such as neuronal cell adhesion. We also identified cortical excitatory neurons and inhibitory interneurons as the most vulnerable cell types to the deleterious effects of this interaction. Subsequently, we used gene expression information from herpes simplex virus 1 infection of neuronal precursor cells as orthogonal evidence to support our findings and to demonstrate that schizophrenia-associated cell adhesion genes, <i>PCDHA2, PCDHA3</i> and <i>PCDHA5</i>, were downregulated following herpes simplex virus 1 infection. Collectively, our results provide novel evidence for a link between genetic and environmental risk factors in schizophrenia pathogenesis. These findings carry important implications for early preventative strategies in schizophrenia.",,pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab275/41365065/fcab275.pdf; doi:https://doi.org/10.1093/braincomms/fcab275; html:https://europepmc.org/articles/PMC8633770; pdf:https://europepmc.org/articles/PMC8633770?pdf=render
 35365070,https://doi.org/10.1186/s12879-022-07268-8,Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study.,"Rosello A, Barnard RC, Smith DRM, Evans S, Grimm F, Davies NG, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Modelling Working Group, Deeny SR, Knight GM, Edmunds WJ.",,BMC infectious diseases,2022,2022-04-01,Y,PCR; Testing; mathematical model; Long-term Care Facility; Care Home; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2,,,"<h4>Background</h4>COVID-19 outbreaks still occur in English care homes despite the interventions in place.<h4>Methods</h4>We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (PCR), enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics.<h4>Results</h4>The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing.<h4>Conclusions</h4>Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks.",,pdf:https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-022-07268-8; doi:https://doi.org/10.1186/s12879-022-07268-8; html:https://europepmc.org/articles/PMC8972713; pdf:https://europepmc.org/articles/PMC8972713?pdf=render
 33986429,https://doi.org/10.1038/s41598-021-89743-x,Predicting sex from retinal fundus photographs using automated deep learning.,"Korot E, Pontikos N, Liu X, Wagner SK, Faes L, Huemer J, Balaskas K, Denniston AK, Khawaja A, Keane PA.",,Scientific reports,2021,2021-05-13,Y,,,,"Deep learning may transform health care, but model development has largely been dependent on availability of advanced technical expertise. Herein we present the development of a deep learning model by clinicians without coding, which predicts reported sex from retinal fundus photographs. A model was trained on 84,743 retinal fundus photos from the UK Biobank dataset. External validation was performed on 252 fundus photos from a tertiary ophthalmic referral center. For internal validation, the area under the receiver operating characteristic curve (AUROC) of the code free deep learning (CFDL) model was 0.93. Sensitivity, specificity, positive predictive value (PPV) and accuracy (ACC) were 88.8%, 83.6%, 87.3% and 86.5%, and for external validation were 83.9%, 72.2%, 78.2% and 78.6% respectively. Clinicians are currently unaware of distinct retinal feature variations between males and females, highlighting the importance of model explainability for this task. The model performed significantly worse when foveal pathology was present in the external validation dataset, ACC: 69.4%, compared to 85.4% in healthy eyes, suggesting the fovea is a salient region for model performance OR (95% CI): 0.36 (0.19, 0.70) p = 0.0022. Automated machine learning (AutoML) may enable clinician-driven automated discovery of novel insights and disease biomarkers.",,pdf:https://www.nature.com/articles/s41598-021-89743-x.pdf; doi:https://doi.org/10.1038/s41598-021-89743-x; html:https://europepmc.org/articles/PMC8119673; pdf:https://europepmc.org/articles/PMC8119673?pdf=render
-36962407,https://doi.org/10.1371/journal.pgph.0000292,Health worker experiences of implementing TB infection prevention and control: A qualitative evidence synthesis to inform implementation recommendations.,"van der Westhuizen HM, Dorward J, Roberts N, Greenhalgh T, Ehrlich R, Butler CC, Tonkin-Crine S.",,PLOS global public health,2022,2022-07-07,Y,,,,"Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render
 31220083,https://doi.org/10.1371/journal.pmed.1002833,Associations of genetically determined iron status across the phenome: A mendelian randomization study.,"Gill D, Benyamin B, Moore LSP, Monori G, Zhou A, Koskeridis F, Evangelou E, Laffan M, Walker AP, Tsilidis KK, Dehghan A, Elliott P, Hyppönen E, Tzoulaki I.",,PLoS medicine,2019,2019-06-20,Y,,Understanding the Causes of Disease,,"<h4>Background</h4>Iron is integral to many physiological processes, and variations in its levels, even within the normal range, can have implications for health. The objective of this study was to explore the broad clinical effects of varying iron status.<h4>Methods and findings</h4>Genome-wide association study (GWAS) summary data obtained from 48,972 European individuals (55% female) across 19 cohorts in the Genetics of Iron Status Consortium were used to identify 3 genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene [HFE] and rs855791 in the transmembrane protease serine 6 gene [TMPRSS6]) that associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, thus serving as instruments for systemic iron status. Phenome-wide association study (PheWAS) of these instruments was performed on 424,439 European individuals (54% female) in the UK Biobank who were aged 40-69 years when recruited from 2006 to 2010, with their genetic data linked to Hospital Episode Statistics (HES) from April, 1995 to March, 2016. Two-sample summary data mendelian randomization (MR) analysis was performed to investigate the effect of varying iron status on outcomes across the human phenome. MR-PheWAS analysis for the 3 iron status genetic instruments was performed separately and then pooled by meta-analysis. Correction was made for testing of multiple correlated phenotypes using a 5% false discovery rate (FDR) threshold. Heterogeneity between MR estimates for different instruments was used to indicate possible bias due to effects of the genetic variants through pathways unrelated to iron status. There were 904 distinct phenotypes included in the MR-PheWAS analyses. After correcting for multiple testing, the 3 genetic instruments for systemic iron status demonstrated consistent evidence of a causal effect of higher iron status on decreasing risk of traits related to anemia (iron deficiency anemia: odds ratio [OR] scaled to a standard deviation [SD] increase in genetically determined serum iron levels 0.72, 95% confidence interval [CI] 0.64-0.81, P = 4 × 10-8) and hypercholesterolemia (hypercholesterolemia: OR 0.88, 95% CI 0.83-0.93, P = 2 × 10-5) and increasing risk of traits related to infection of the skin and related structures (cellulitis and abscess of the leg: OR 1.25, 95% CI 1.10-1.42, P = 6 × 10-4). The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and misclassification of diagnoses in the HES data. Furthermore, this work only investigated participants with European ancestry, and the findings may not be applicable to other ethnic groups.<h4>Conclusions</h4>Our findings offer novel, to our knowledge, insight into previously unreported effects of iron status, highlighting a potential protective effect of higher iron status on hypercholesterolemia and a detrimental role on risk of skin and skin structure infections. Given the modifiable and variable nature of iron status, these findings warrant further investigation.",,doi:https://doi.org/10.1371/journal.pmed.1002833; doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render
+36962407,https://doi.org/10.1371/journal.pgph.0000292,Health worker experiences of implementing TB infection prevention and control: A qualitative evidence synthesis to inform implementation recommendations.,"van der Westhuizen HM, Dorward J, Roberts N, Greenhalgh T, Ehrlich R, Butler CC, Tonkin-Crine S.",,PLOS global public health,2022,2022-07-07,Y,,,,"Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render
 36210800,https://doi.org/10.1038/s43856-022-00189-2,Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.,"Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.",,Communications medicine,2022,2022-10-06,Y,epigenomics; epidemiology,,,"<h4>Background</h4>Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.<h4>Methods</h4>We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.<h4>Results</h4>Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.<h4>Conclusions</h4>Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.",,pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?pdf=render
 35241573,https://doi.org/10.1136/bmjqs-2020-012108,Comparing antibiotic prescribing between clinicians in UK primary care: an analysis in a cohort study of eight different measures of antibiotic prescribing.,"Van Staa T, Li Y, Gold N, Chadborn T, Welfare W, Palin V, Ashcroft DM, Bircher J.",,BMJ quality & safety,2022,2022-03-03,Y,General Practice; Antibiotic Management; Healthcare Quality Improvement,,,"<h4>Background</h4>There is a need to reduce antimicrobial uses in humans. Previous studies have found variations in antibiotic (AB) prescribing between practices in primary care. This study assessed variability of AB prescribing between clinicians.<h4>Methods</h4>Clinical Practice Research Datalink, which collects electronic health records in primary care, was used to select anonymised clinicians providing 500+ consultations during 2012-2017. Eight measures of AB prescribing were assessed, such as overall and incidental AB prescribing, repeat AB courses and extent of risk-based prescribing. Poisson regression models with random effect for clinicians were fitted.<h4>Results</h4>6111 clinicians from 466 general practices were included. Considerable variability between individual clinicians was found for most AB measures. For example, the rate of AB prescribing varied between 77.4 and 350.3 per 1000 consultations; percentage of repeat AB courses within 30 days ranged from 13.1% to 34.3%; predicted patient risk of hospital admission for infection-related complications in those prescribed AB ranged from 0.03% to 0.32% (5th and 95th percentiles). The adjusted relative rate between clinicians in rates of AB prescribing was 5.23. Weak correlation coefficients (<0.5) were found between most AB measures. There was considerable variability in case mix seen by clinicians. The largest potential impact to reduce AB prescribing could be around encouraging risk-based prescribing and addressing repeat issues of ABs. Reduction of repeat AB courses to prescribing habit of median clinician would save 21 813 AB prescriptions per 1000 clinicians per year.<h4>Conclusions</h4>The wide variation seen in all measures of AB prescribing and weak correlation between them suggests that a single AB measure, such as prescribing rate, is not sufficient to underpin the optimisation of AB prescribing.",,pdf:https://qualitysafety.bmj.com/content/qhc/early/2022/03/02/bmjqs-2020-012108.full.pdf; doi:https://doi.org/10.1136/bmjqs-2020-012108; html:https://europepmc.org/articles/PMC9606525; pdf:https://europepmc.org/articles/PMC9606525?pdf=render
 36936592,https://doi.org/10.1136/bmjmed-2022-000151,Covid-19 variants of concern and pregnancy.,"Stock SJ, Harmer C, Calvert C.",,BMJ medicine,2022,2022-03-02,Y,Pregnancy complications; Covid-19,,,,,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000151.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000151; html:https://europepmc.org/articles/PMC9951363; pdf:https://europepmc.org/articles/PMC9951363?pdf=render
@@ -1560,8 +1560,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 35861818,https://doi.org/10.1161/jaha.121.025473,Interatrial Block Predicts Life-Threatening Arrhythmias in Dilated Cardiomyopathy.,"Henkens MTHM, López Martínez H, Weerts J, Sammani A, Raafs AG, Verdonschot JAJ, van de Leur RR, Sikking MA, Stroeks S, van Empel VPM, Brunner-La Rocca HP, van Stipdonk AMW, Farmakis D, Hazebroek MR, Vernooy K, Bayés-de-Luna A, Asselbergs FW, Bayés-Genís A, Heymans SRB.",,Journal of the American Heart Association,2022,2022-07-15,Y,Electrocardiography; Dilated cardiomyopathy; Sudden Cardiac Death; Interatrial Block; Non‐ischemic Cardiomyopathy; Life‐threatening Arrhythmias,,,"Background Interatrial block (IAB) has been associated with supraventricular arrhythmias and stroke, and even with sudden cardiac death in the general population. Whether IAB is associated with life-threatening arrhythmias (LTA) and sudden cardiac death in dilated cardiomyopathy (DCM) remains unknown. This study aimed to determine the association between IAB and LTA in ambulant patients with DCM. Methods and Results A derivation cohort (Maastricht Dilated Cardiomyopathy Registry; N=469) and an external validation cohort (Utrecht Cardiomyopathy Cohort; N=321) were used for this study. The presence of IAB (P-wave duration>120 milliseconds) or atrial fibrillation (AF) was determined using digital calipers by physicians blinded to the study data. In the derivation cohort, IAB and AF were present in 291 (62%) and 70 (15%) patients with DCM, respectively. LTA (defined as sudden cardiac death, justified shock from implantable cardioverter-defibrillator or anti-tachypacing, or hemodynamic unstable ventricular fibrillation/tachycardia) occurred in 49 patients (3 with no IAB, 35 with IAB, and 11 patients with AF, respectively; median follow-up, 4.4 years [2.1; 7.4]). The LTA-free survival distribution significantly differed between IAB or AF versus no IAB (both <i>P</i><0.01), but not between IAB versus AF (<i>P</i>=0.999). This association remained statistically significant in the multivariable model (IAB: HR, 4.8 (1.4-16.1), <i>P</i>=0.013; AF: HR, 6.4 (1.7-24.0), <i>P</i>=0.007). In the external validation cohort, the survival distribution was also significantly worse for IAB or AF versus no IAB (<i>P</i>=0.037; <i>P</i>=0.005), but not for IAB versus AF (<i>P</i>=0.836). Conclusions IAB is an easy to assess, widely applicable marker associated with LTA in DCM. IAB and AF seem to confer similar risk of LTA. Further research on IAB in DCM, and on the management of IAB in DCM is warranted.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025473; doi:https://doi.org/10.1161/JAHA.121.025473; html:https://europepmc.org/articles/PMC9707810; pdf:https://europepmc.org/articles/PMC9707810?pdf=render
 36048760,https://doi.org/10.1371/journal.pgen.1010294,Neurocognitive trajectory and proteomic signature of inherited risk for Alzheimer's disease.,"Paranjpe MD, Chaffin M, Zahid S, Ritchie S, Rotter JI, Rich SS, Gerszten R, Guo X, Heckbert S, Tracy R, Danesh J, Lander ES, Inouye M, Kathiresan S, Butterworth AS, Khera AV.",,PLoS genetics,2022,2022-09-01,Y,,,,"For Alzheimer's disease-a leading cause of dementia and global morbidity-improved identification of presymptomatic high-risk individuals and identification of new circulating biomarkers are key public health needs. Here, we tested the hypothesis that a polygenic predictor of risk for Alzheimer's disease would identify a subset of the population with increased risk of clinically diagnosed dementia, subclinical neurocognitive dysfunction, and a differing circulating proteomic profile. Using summary association statistics from a recent genome-wide association study, we first developed a polygenic predictor of Alzheimer's disease comprised of 7.1 million common DNA variants. We noted a 7.3-fold (95% CI 4.8 to 11.0; p < 0.001) gradient in risk across deciles of the score among 288,289 middle-aged participants of the UK Biobank study. In cross-sectional analyses stratified by age, minimal differences in risk of Alzheimer's disease and performance on a digit recall test were present according to polygenic score decile at age 50 years, but significant gradients emerged by age 65. Similarly, among 30,541 participants of the Mass General Brigham Biobank, we again noted no significant differences in Alzheimer's disease diagnosis at younger ages across deciles of the score, but for those over 65 years we noted an odds ratio of 2.0 (95% CI 1.3 to 3.2; p = 0.002) in the top versus bottom decile of the polygenic score. To understand the proteomic signature of inherited risk, we performed aptamer-based profiling in 636 blood donors (mean age 43 years) with very high or low polygenic scores. In addition to the well-known apolipoprotein E biomarker, this analysis identified 27 additional proteins, several of which have known roles related to disease pathogenesis. Differences in protein concentrations were consistent even among the youngest subset of blood donors (mean age 33 years). Of these 28 proteins, 7 of the 8 proteins with concentrations available were similarly associated with the polygenic score in participants of the Multi-Ethnic Study of Atherosclerosis. These data highlight the potential for a DNA-based score to identify high-risk individuals during the prolonged presymptomatic phase of Alzheimer's disease and to enable biomarker discovery based on profiling of young individuals in the extremes of the score distribution.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010294&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010294; html:https://europepmc.org/articles/PMC9436054; pdf:https://europepmc.org/articles/PMC9436054?pdf=render
 37178708,https://doi.org/10.1016/s1470-2045(23)00156-0,Utility of polygenic risk scores in UK cancer screening: a modelling analysis.,"Huntley C, Torr B, Sud A, Rowlands CF, Way R, Snape K, Hanson H, Swanton C, Broggio J, Lucassen A, McCartney M, Houlston RS, Hingorani AD, Jones ME, Turnbull C.",,The Lancet. Oncology,2023,2023-05-10,N,,,,"<h4>Background</h4>It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension into new age ranges and disease types. To address this proposition, we present an overview of the performance of PRS tools (ie, models and sets of single nucleotide polymorphisms) alongside harms and benefits of PRS-stratified cancer screening for eight example cancers (breast, prostate, colorectal, pancreas, ovary, kidney, lung, and testicular cancer).<h4>Methods</h4>For this modelling analysis, we used age-stratified cancer incidences for the UK population from the National Cancer Registration Dataset (2016-18) and published estimates of the area under the receiver operating characteristic curve for current, future, and optimised PRS for each of the eight cancer types. For each of five PRS-defined high-risk quantiles (ie, the top 50%, 20%, 10%, 5%, and 1%) and according to each of the three PRS tools (ie, current, future, and optimised) for the eight cancers, we calculated the relative proportion of cancers arising, the odds ratios of a cancer arising compared with the UK population average, and the lifetime cancer risk. We examined maximal attainable rates of cancer detection by age stratum from combining PRS-based stratification with cancer screening tools and modelled the maximal impact on cancer-specific survival of hypothetical new UK programmes of PRS-stratified screening.<h4>Findings</h4>The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases. Extending UK screening programmes to a PRS-defined high-risk quintile including people aged 40-49 years for breast cancer, 50-59 years for colorectal cancer, and 60-69 years for prostate cancer has the potential to avert, respectively, a maximum of 102, 188, and 158 deaths annually. Unstratified screening of the full population aged 48-49 years for breast cancer, 58-59 years for colorectal cancer, and 68-69 years for prostate cancer would use equivalent resources and avert, respectively, an estimated maximum of 80, 155, and 95 deaths annually. These maximal modelled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors.<h4>Interpretation</h4>Under favourable assumptions, our modelling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programmes for breast, prostate, and colorectal cancer. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being low-risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomised trials are required.<h4>Funding</h4>The Wellcome Trust.",,pdf:http://www.thelancet.com/article/S1470204523001560/pdf; doi:https://doi.org/10.1016/S1470-2045(23)00156-0
-34791170,https://doi.org/10.1093/eurheartj/ehab759,A sex-specific prediction model is not enough to achieve equality for women in preventative cardiovascular medicine.,"Kimenai DM, Shah ASV, Mills NL.",,European heart journal,2022,2022-01-01,Y,,,,,,pdf:https://academic.oup.com/eurheartj/article-pdf/43/3/239/42296399/ehab759.pdf; doi:https://doi.org/10.1093/eurheartj/ehab759; html:https://europepmc.org/articles/PMC8790764; pdf:https://europepmc.org/articles/PMC8790764?pdf=render
 32781946,https://doi.org/10.1098/rspb.2020.1405,Key questions for modelling COVID-19 exit strategies.,"Thompson RN, Hollingsworth TD, Isham V, Arribas-Bel D, Ashby B, Britton T, Challenor P, Chappell LHK, Clapham H, Cunniffe NJ, Dawid AP, Donnelly CA, Eggo RM, Funk S, Gilbert N, Glendinning P, Gog JR, Hart WS, Heesterbeek H, House T, Keeling M, Kiss IZ, Kretzschmar ME, Lloyd AL, McBryde ES, McCaw JM, McKinley TJ, Miller JC, Morris M, O'Neill PD, Parag KV, Pearson CAB, Pellis L, Pulliam JRC, Ross JV, Tomba GS, Silverman BW, Struchiner CJ, Tildesley MJ, Trapman P, Webb CR, Mollison D, Restif O.",,Proceedings. Biological sciences,2020,2020-08-12,Y,Uncertainty; Mathematical Modelling; Epidemic Control; Exit Strategy; Covid-19; Sars-cov-2,,,"Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.",,doi:https://doi.org/10.1098/rspb.2020.1405; doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render
+34791170,https://doi.org/10.1093/eurheartj/ehab759,A sex-specific prediction model is not enough to achieve equality for women in preventative cardiovascular medicine.,"Kimenai DM, Shah ASV, Mills NL.",,European heart journal,2022,2022-01-01,Y,,,,,,pdf:https://academic.oup.com/eurheartj/article-pdf/43/3/239/42296399/ehab759.pdf; doi:https://doi.org/10.1093/eurheartj/ehab759; html:https://europepmc.org/articles/PMC8790764; pdf:https://europepmc.org/articles/PMC8790764?pdf=render
 37075078,https://doi.org/10.1371/journal.pmed.1004223,The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.,"Sheppard JP, Koshiaris C, Stevens R, Lay-Flurrie S, Banerjee A, Bellows BK, Clegg A, Hobbs FDR, Payne RA, Swain S, Usher-Smith JA, McManus RJ.",,PLoS medicine,2023,2023-04-19,Y,,,,"<h4>Background</h4>Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data.<h4>Methods and findings</h4>This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out.<h4>Conclusions</h4>Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004223&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004223; html:https://europepmc.org/articles/PMC10155987; pdf:https://europepmc.org/articles/PMC10155987?pdf=render
 34347787,https://doi.org/10.1371/journal.pone.0253809,Developing a Natural Language Processing tool to identify perinatal self-harm in electronic healthcare records.,"Ayre K, Bittar A, Kam J, Verma S, Howard LM, Dutta R.",,PloS one,2021,2021-08-04,Y,,,,"<h4>Background</h4>Self-harm occurring within pregnancy and the postnatal year (""perinatal self-harm"") is a clinically important yet under-researched topic. Current research likely under-estimates prevalence due to methodological limitations. Electronic healthcare records (EHRs) provide a source of clinically rich data on perinatal self-harm.<h4>Aims</h4>(1) To create a Natural Language Processing (NLP) tool that can, with acceptable precision and recall, identify mentions of acts of perinatal self-harm within EHRs. (2) To use this tool to identify service-users who have self-harmed perinatally, based on their EHRs.<h4>Methods</h4>We used the Clinical Record Interactive Search system to extract de-identified EHRs of secondary mental healthcare service-users at South London and Maudsley NHS Foundation Trust. We developed a tool that applied several layers of linguistic processing based on the spaCy NLP library for Python. We evaluated mention-level performance in the following domains: span, status, temporality and polarity. Evaluation was done against a manually coded reference standard. Mention-level performance was reported as precision, recall, F-score and Cohen's kappa for each domain. Performance was also assessed at 'service-user' level and explored whether a heuristic rule improved this. We report per-class statistics for service-user performance, as well as likelihood ratios and post-test probabilities.<h4>Results</h4>Mention-level performance: micro-averaged F-score, precision and recall for span, polarity and temporality >0.8. Kappa for status 0.68, temporality 0.62, polarity 0.91. Service-user level performance with heuristic: F-score, precision, recall of minority class 0.69, macro-averaged F-score 0.81, positive LR 9.4 (4.8-19), post-test probability 69.0% (53-82%). Considering the task difficulty, the tool performs well, although temporality was the attribute with the lowest level of annotator agreement.<h4>Conclusions</h4>It is feasible to develop an NLP tool that identifies, with acceptable validity, mentions of perinatal self-harm within EHRs, although with limitations regarding temporality. Using a heuristic rule, it can also function at a service-user-level.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0253809&type=printable; doi:https://doi.org/10.1371/journal.pone.0253809; html:https://europepmc.org/articles/PMC8336818; pdf:https://europepmc.org/articles/PMC8336818?pdf=render
 30993728,https://doi.org/10.1111/cen.13990,Risk of incident circulatory disease in patients treated for differentiated thyroid carcinoma with no history of cardiovascular disease.,"Toulis KA, Viola D, Gkoutos G, Keerthy D, Boelaert K, Nirantharakumar K.",,Clinical endocrinology,2019,2019-05-17,N,Atrial fibrillation; Cardiovascular events; Thyroid cancer; Differentiated Thyroid Carcinoma,,,"<h4>Context</h4>The incidence of differentiated thyroid cancer (DTC) is increasing, yet the prognosis is favourable and long-term survival is expected. Exogenous TSH suppression has been used for many years to prevent DTC recurrence and may be associated with increased risks of circulatory diseases.<h4>Design</h4>Risks of circulatory disease in patients treated for DTC were compared to randomly matched patients without DTC (controls) up to a 1:5 ratio using age, sex, body mass index (BMI) and smoking as the matching parameters in a population-based, open cohort study using The Health Improvement Network.<h4>Patients</h4>A total of 3009 patients treated for DTC with no pre-existing cardiovascular disease were identified and matched to 11 303 controls, followed up to median of 5 years.<h4>Results</h4>A total of 1259 incident circulatory events were recorded during the observation period. No difference in the risk of ischaemic heart disease (IHD) (adjusted hazards ratio [aHR]: 1.04, 95% CI: 0.80-1.36) or heart failure (HF) (aHR: 1.27, 95% CI: 0.89-1.81) was detected. The risk of atrial fibrillation (AF) and stroke was significantly higher in patients with DTC (aHR: 1.71, 95% CI: 1.36-2.15 and aHR: 1.34, 95% CI: 1.05-1.72, respectively). In a sensitivity analysis limited to newly diagnosed patients with DTC, only the risk of AF was consistently elevated (aHR: 1.86, 95% CI: 1.33-2.60).<h4>Conclusions</h4>The increased risk of AF in patients who have undergone treatment for DTC but without pre-existing CVD may warrant periodic screening for this arrhythmia. Whereas no evidence of increased risk of IHD or HF was observed, the increased risk of stroke/TIA warrants further investigation.",,doi:https://doi.org/10.1111/cen.13990
@@ -1586,9 +1586,9 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 35184736,https://doi.org/10.1186/s12916-022-02271-x,Comparative assessment of methods for short-term forecasts of COVID-19 hospital admissions in England at the local level.,"Meakin S, Abbott S, Bosse N, Munday J, Gruson H, Hellewell J, Sherratt K, CMMID COVID-19 Working Group, Funk S.",,BMC medicine,2022,2022-02-21,Y,Forecasting; Infectious disease; outbreak; Real-time; Ensemble; Healthcare Demand; Covid-19,,,"<h4>Background</h4>Forecasting healthcare demand is essential in epidemic settings, both to inform situational awareness and facilitate resource planning. Ideally, forecasts should be robust across time and locations. During the COVID-19 pandemic in England, it is an ongoing concern that demand for hospital care for COVID-19 patients in England will exceed available resources.<h4>Methods</h4>We made weekly forecasts of daily COVID-19 hospital admissions for National Health Service (NHS) Trusts in England between August 2020 and April 2021 using three disease-agnostic forecasting models: a mean ensemble of autoregressive time series models, a linear regression model with 7-day-lagged local cases as a predictor, and a scaled convolution of local cases and a delay distribution. We compared their point and probabilistic accuracy to a mean-ensemble of them all and to a simple baseline model of no change from the last day of admissions. We measured predictive performance using the weighted interval score (WIS) and considered how this changed in different scenarios (the length of the predictive horizon, the date on which the forecast was made, and by location), as well as how much admissions forecasts improved when future cases were known.<h4>Results</h4>All models outperformed the baseline in the majority of scenarios. Forecasting accuracy varied by forecast date and location, depending on the trajectory of the outbreak, and all individual models had instances where they were the top- or bottom-ranked model. Forecasts produced by the mean-ensemble were both the most accurate and most consistently accurate forecasts amongst all the models considered. Forecasting accuracy was improved when using future observed, rather than forecast, cases, especially at longer forecast horizons.<h4>Conclusions</h4>Assuming no change in current admissions is rarely better than including at least a trend. Using confirmed COVID-19 cases as a predictor can improve admissions forecasts in some scenarios, but this is variable and depends on the ability to make consistently good case forecasts. However, ensemble forecasts can make forecasts that make consistently more accurate forecasts across time and locations. Given minimal requirements on data and computation, our admissions forecasting ensemble could be used to anticipate healthcare needs in future epidemic or pandemic settings.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02271-x; doi:https://doi.org/10.1186/s12916-022-02271-x; html:https://europepmc.org/articles/PMC8858706; pdf:https://europepmc.org/articles/PMC8858706?pdf=render
 32916155,https://doi.org/10.1016/j.molmet.2020.101072,"Corrigendum to ""Genome-wide association study of adipocyte lipolysis in the GENetics of adipocyte lipolysis (GENiAL) cohort"" [Molecular Metabolism 34 (2020) 85-96].","Kulyté A, Lundbäck V, Lindgren CM, Luan J, Lotta LA, Langenberg C, Arner P, Strawbridge RJ, Dahlman I.",,Molecular metabolism,2020,2020-09-08,Y,,,,,,doi:https://doi.org/10.1016/j.molmet.2020.101072; doi:https://doi.org/10.1016/j.molmet.2020.101072; html:https://europepmc.org/articles/PMC7492984; pdf:https://europepmc.org/articles/PMC7492984?pdf=render
 32170038,https://doi.org/10.1136/heartjnl-2019-316088,Cardiovascular risk factors and the risk of major adverse limb events in patients with symptomatic cardiovascular disease.,"Hageman SHJ, de Borst GJ, Dorresteijn JAN, Bots ML, Westerink J, Asselbergs FW, Visseren FLJ, UCC-SMART Study Group.",,Heart (British Cardiac Society),2020,2020-03-13,N,Hypertension; Smoking Cessation; Peripheral Vascular Disease; Cardiac Risk Factors And Prevention; Lipoproteins And Hyperlipidaemia,,,"<h4>Aim</h4>To determine the relationship between non-high-density lipoprotein cholesterol (non-HDL-c), systolic blood pressure (SBP) and smoking and the risk of major adverse limb events (MALE) and the combination with major adverse cardiovascular events (MALE/MACE) in patients with symptomatic vascular disease.<h4>Methods</h4>Patients with symptomatic vascular disease from the Utrecht Cardiovascular Cohort - Secondary Manifestations of ARTerial disease (1996-2017) study were included. The effects of non-HDL-c, SBP and smoking on the risk of MALE were analysed with Cox proportional hazard models stratified for presence of peripheral artery disease (PAD). MALE was defined as major amputation, peripheral revascularisation or thrombolysis in the lower limb.<h4>Results</h4>In 8139 patients (median follow-up 7.8 years, IQR 4.0-11.8), 577 MALE (8.7 per 1000 person-years) and 1933 MALE/MACE were observed (29.1 per 1000 person-years). In patients with PAD there was no relation between non-HDL-c and MALE, and in patients with coronary artery disease (CAD), cerebrovascular disease (CVD) or abdominal aortic aneurysm (AAA) the risk of MALE was higher per 1 mmol/L non-HDL-c (HR 1.14, 95% CI 1.01 to 1.29). Per 10 mm Hg SBP, the risk of MALE was higher in patients with PAD (HR 1.06, 95% CI 1.01 to 1.12) and in patients with CVD/CAD/AAA (HR 1.15, 95% CI 1.08 to 1.22). The risk of MALE was higher in smokers with PAD (HR 1.45, 95% CI 0.97 to 2.14) and CAD/CVD/AAA (HR 7.08, 95% CI 3.99 to 12.57).<h4>Conclusions</h4>The risk of MALE and MALE/MACE in patients with symptomatic vascular disease differs according to vascular disease location and is associated with non-HDL-c, SBP and smoking. These findings confirm the importance of MALE as an outcome and underline the importance of risk factor management in patients with vascular disease.",,pdf:https://discovery.ucl.ac.uk/10096914/1/Hageman_Manuscript_MALE_20200211_clean.pdf; doi:https://doi.org/10.1136/heartjnl-2019-316088
-37605204,https://doi.org/10.1186/s12916-023-03013-3,The development of a core outcome set for studies of pregnant women with multimorbidity.,"Lee SI, Hanley S, Vowles Z, Plachcinski R, Moss N, Singh M, Gale C, Fagbamigbe AF, Azcoaga-Lorenzo A, Subramanian A, Taylor B, Nelson-Piercy C, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Dolk H, Hope H, Phillips K, Abel KM, Eastwood KA, Kent L, Locock L, Loane M, Mhereeg M, Brocklehurst P, McCann S, Brophy S, Wambua S, Hemali Sudasinghe SPB, Thangaratinam S, Nirantharakumar K, Black M, MuM-PreDiCT Group.",,BMC medicine,2023,2023-08-21,Y,Pregnancy; Maternity; Outcome; Multimorbidity; Multiple Chronic Conditions; Core Outcome Set; Multiple Long-term Conditions,,,"<h4>Background</h4>Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity.<h4>Methods</h4>We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations.<h4>Results</h4>Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs.<h4>Conclusions</h4>Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.",,doi:https://doi.org/10.1186/s12916-023-03013-3; html:https://europepmc.org/articles/PMC10441728; pdf:https://europepmc.org/articles/PMC10441728?pdf=render
 34062542,https://doi.org/10.1159/000517521,Structural Endpoints and Outcome Measures in Uveitis.,"Wintergerst MWM, Liu X, Terheyden JH, Pohlmann D, Li JQ, Montesano G, Ometto G, Holz FG, Crabb DP, Pleyer U, Heinz C, Denniston AK, Finger RP.",,Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde,2021,2021-06-01,N,Biomarker; Uveitis; Outcome; Outcome Measure; Endpoint; Imaging Biomarker; Inflammatory Eye Diseases; Instrument-based Measure,,,"Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and ""core outcomes"" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current ""core modalities"" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far.",,pdf:https://www.karger.com/Article/Pdf/517521; doi:https://doi.org/10.1159/000517521
 33017023,https://doi.org/10.1001/jamaneurol.2020.3502,Trends in Optic Neuritis Incidence and Prevalence in the UK and Association With Systemic and Neurologic Disease.,"Braithwaite T, Subramanian A, Petzold A, Galloway J, Adderley NJ, Mollan SP, Plant GT, Nirantharakumar K, Denniston AK.",,JAMA neurology,2020,2020-12-01,N,,,,"<h4>Importance</h4>Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse.<h4>Objective</h4>To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom.<h4>Design, setting, and participants</h4>This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10 937 511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls.<h4>Exposures</h4>Optic neuritis.<h4>Main outcomes and measures</h4>Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs.<h4>Results</h4>A total of 10 937 511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100 000 person-years. Annual point prevalence (per 100 000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR, 98.22; 95% CI, 65.40-147.52), syphilis (OR, 5.76; 95% CI, 1.39-23.96), Mycoplasma (OR, 3.90; 95% CI, 1.09-13.93), vasculitis (OR, 3.70; 95% CI, 1.68-8.15), sarcoidosis (OR, 2.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR, 2.29; 95% CI, 1.80-2.92), Crohn disease (OR, 1.97; 95% CI, 1.13-3.43), and psoriasis (OR, 1.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR, 284.97; 95% CI, 167.85-483.81), Behçet disease (HR, 17.39; 95% CI, 1.55-195.53), sarcoidosis (HR, 14.80; 95% CI, 4.86-45.08), vasculitis (HR, 4.89; 95% CI, 1.82-13.10), Sjögren syndrome (HR, 3.48; 95% CI, 1.38-8.76), and herpetic infection (HR, 1.68; 95% CI, 1.24-2.28).<h4>Conclusions and relevance</h4>The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.",,pdf:http://pure-oai.bham.ac.uk/ws/files/100688542/NEU20_1602R_Merged_PDF.pdf; doi:https://doi.org/10.1001/jamaneurol.2020.3502; html:https://europepmc.org/articles/PMC7536630; doi:https://doi.org/10.1001/jamaneurol.2020.3502
+37605204,https://doi.org/10.1186/s12916-023-03013-3,The development of a core outcome set for studies of pregnant women with multimorbidity.,"Lee SI, Hanley S, Vowles Z, Plachcinski R, Moss N, Singh M, Gale C, Fagbamigbe AF, Azcoaga-Lorenzo A, Subramanian A, Taylor B, Nelson-Piercy C, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Dolk H, Hope H, Phillips K, Abel KM, Eastwood KA, Kent L, Locock L, Loane M, Mhereeg M, Brocklehurst P, McCann S, Brophy S, Wambua S, Hemali Sudasinghe SPB, Thangaratinam S, Nirantharakumar K, Black M, MuM-PreDiCT Group.",,BMC medicine,2023,2023-08-21,Y,Pregnancy; Maternity; Outcome; Multimorbidity; Multiple Chronic Conditions; Core Outcome Set; Multiple Long-term Conditions,,,"<h4>Background</h4>Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity.<h4>Methods</h4>We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations.<h4>Results</h4>Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs.<h4>Conclusions</h4>Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.",,doi:https://doi.org/10.1186/s12916-023-03013-3; html:https://europepmc.org/articles/PMC10441728; pdf:https://europepmc.org/articles/PMC10441728?pdf=render
 31363735,https://doi.org/10.1093/hmg/ddz187,Towards clinical utility of polygenic risk scores.,"Lambert SA, Abraham G, Inouye M.",,Human molecular genetics,2019,2019-11-01,N,,,,"Prediction of disease risk is an essential part of preventative medicine, often guiding clinical management. Risk prediction typically includes risk factors such as age, sex, family history of disease and lifestyle (e.g. smoking status); however, in recent years, there has been increasing interest to include genomic information into risk models. Polygenic risk scores (PRS) aggregate the effects of many genetic variants across the human genome into a single score and have recently been shown to have predictive value for multiple common diseases. In this review, we summarize the potential use cases for seven common diseases (breast cancer, prostate cancer, coronary artery disease, obesity, type 1 diabetes, type 2 diabetes and Alzheimer's disease) where PRS has or could have clinical utility. PRS analysis for these diseases frequently revolved around (i) risk prediction performance of a PRS alone and in combination with other non-genetic risk factors, (ii) estimation of lifetime risk trajectories, (iii) the independent information of PRS and family history of disease or monogenic mutations and (iv) estimation of the value of adding a PRS to specific clinical risk prediction scenarios. We summarize open questions regarding PRS usability, ancestry bias and transferability, emphasizing the need for the next wave of studies to focus on the implementation and health-economic value of PRS testing. In conclusion, it is becoming clear that PRS have value in disease risk prediction and there are multiple areas where this may have clinical utility.",,pdf:https://academic.oup.com/hmg/article-pdf/28/R2/R133/31081033/ddz187.pdf; doi:https://doi.org/10.1093/hmg/ddz187
 35279265,https://doi.org/10.1016/s2213-2600(21)00511-7,"Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis.","Adeloye D, Song P, Zhu Y, Campbell H, Sheikh A, Rudan I, NIHR RESPIRE Global Respiratory Health Unit.",,The Lancet. Respiratory medicine,2022,2022-03-10,Y,,,,"<h4>Background</h4>Chronic obstructive pulmonary disease (COPD) is an increasingly important cause of morbidity, disability, and mortality worldwide. We aimed to estimate global, regional, and national COPD prevalence and risk factors to guide policy and population interventions.<h4>Methods</h4>For this systematic review and modelling study, we searched MEDLINE, Embase, Global Health, and CINAHL, for population-based studies on COPD prevalence published between Jan 1, 1990, and Dec 31, 2019. We included data reported using the two main case definitions: the Global Initiative for Chronic Obstructive Lung Disease fixed ratio (GOLD; FEV<sub>1</sub>/FVC<0·7) and the lower limit of normal (LLN; FEV<sub>1</sub>/FVC<LLN). We employed a multilevel multivariable mixed-effects meta-regression approach to generate the age-specific and sex-specific prevalence of COPD in 2019 for high-income countries (HICs) and low-income and middle-income countries (LMICs) according to the World Bank definition. Common risk factors for GOLD-COPD were evaluated using a random-effects meta-analysis.<h4>Findings</h4>We identified 162 articles reporting population-based studies conducted across 260 sites in 65 countries. In 2019, the global prevalence of COPD among people aged 30-79 years was 10·3% (95% CI 8·2-12·8) using the GOLD case definition, which translates to 391·9 million people (95% CI 312·6-487·9), and 7·6% (5·8-10·1) using the LLN definition, which translates to 292·0 million people (219·8-385·6). Using the GOLD definition, we estimated that 391·9 million (95% CI 312·6-487·9) people aged 30-79 years had COPD worldwide in 2019, with most (315·5 million [246·7-399·6]; 80·5%) living in LMICs. The overall prevalence of GOLD-COPD among people aged 30-79 years was the highest in the Western Pacific region (11·7% [95% CI 9·3-14·6]) and lowest in the region of the Americas (6·8% [95% CI 5·6-8·2]). Globally, male sex (OR 2·1 [95% CI 1·8-2·3]), smoking (current smoker 3·2 [2·5-4·0]; ever smoker 2·3 [2·0-2·5]), body-mass index of less than 18·5 kg/m<sup>2</sup> (2·2 [1·7-2·7]), biomass exposure (1·4 [1·2-1·7]), and occupational exposure to dust or smoke (1·4 [1·3-1·6]) were all substantial risk factors for COPD.<h4>Interpretation</h4>With more than three-quarters of global COPD cases in LMICs, tackling this chronic condition is a major and increasing challenge for health systems in these settings. In the absence of targeted population-wide efforts and health system reforms in these settings, many of which are under-resourced, achieving a substantial reduction in the burden of COPD globally might remain a difficult task.<h4>Funding</h4>National Institute for Health Research and Health Data Research UK.",,doi:https://doi.org/10.1016/s2213-2600(21)00511-7; doi:https://doi.org/10.1016/S2213-2600(21)00511-7; html:https://europepmc.org/articles/PMC9050565
 33928785,https://doi.org/10.1161/circulationaha.120.049844,Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.,"Feyen DAM, Perea-Gil I, Maas RGC, Harakalova M, Gavidia AA, Arthur Ataam J, Wu TH, Vink A, Pei J, Vadgama N, Suurmeijer AJ, Te Rijdt WP, Vu M, Amatya PL, Prado M, Zhang Y, Dunkenberger L, Sluijter JPG, Sallam K, Asselbergs FW, Mercola M, Karakikes I.",,Circulation,2021,2021-04-30,N,"Unfolded protein response; Models, Biological; Induced Pluripotent Stem Cells; Phospholamban; Cardiomyopathy, Dilated; Sequence Analysis, Rna",,,"<h4>Background</h4>Phospholamban (PLN) is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in PLN (R14del) is associated with dilated cardiomyopathy with a high prevalence of ventricular arrhythmias. How the R14 deletion causes dilated cardiomyopathy is poorly understood, and there are no disease-specific therapies.<h4>Methods</h4>We used single-cell RNA sequencing to uncover PLN R14del disease mechanisms in human induced pluripotent stem cells (hiPSC-CMs). We used both 2-dimensional and 3-dimensional functional contractility assays to evaluate the impact of modulating disease-relevant pathways in PLN R14del hiPSC-CMs.<h4>Results</h4>Modeling of the PLN R14del cardiomyopathy with isogenic pairs of hiPSC-CMs recapitulated the contractile deficit associated with the disease in vitro. Single-cell RNA sequencing revealed the induction of the unfolded protein response (UPR) pathway in PLN R14del compared with isogenic control hiPSC-CMs. The activation of UPR was also evident in the hearts from PLN R14del patients. Silencing of each of the 3 main UPR signaling branches (IRE1, ATF6, or PERK) by siRNA exacerbated the contractile dysfunction of PLN R14del hiPSC-CMs. We explored the therapeutic potential of activating the UPR with a small molecule activator, BiP (binding immunoglobulin protein) inducer X. PLN R14del hiPSC-CMs treated with BiP protein inducer X showed a dose-dependent amelioration of the contractility deficit in both 2-dimensional cultures and 3-dimensional engineered heart tissues without affecting calcium homeostasis.<h4>Conclusions</h4>Together, these findings suggest that the UPR exerts a protective effect in the setting of PLN R14del cardiomyopathy and that modulation of the UPR might be exploited therapeutically.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.049844; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.049844; html:https://europepmc.org/articles/PMC8667423; pdf:https://europepmc.org/articles/PMC8667423?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.049844
@@ -1601,26 +1601,26 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 30537243,https://doi.org/10.1002/ejhf.1370,"Can advanced analytics fix modern medicine's problem of uncertainty, imprecision, and inaccuracy?","Ahmad T, Freeman JV, Asselbergs FW.",,European journal of heart failure,2019,2018-12-10,N,,,,,,doi:https://doi.org/10.1002/ejhf.1370
 32619549,https://doi.org/10.1016/j.cels.2020.05.012,Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection.,"Messner CB, Demichev V, Wendisch D, Michalick L, White M, Freiwald A, Textoris-Taube K, Vernardis SI, Egger AS, Kreidl M, Ludwig D, Kilian C, Agostini F, Zelezniak A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, von Kalle C, Campbell A, Hayward C, Porteous DJ, Marioni RE, Langenberg C, Lilley KS, Kuebler WM, Mülleder M, Drosten C, Suttorp N, Witzenrath M, Kurth F, Sander LE, Ralser M.",,Cell systems,2020,2020-06-02,Y,Mass spectrometry; High-throughput Proteomics; Swath-ms; Antiviral Immune Response; Clinical Classifiers; Covid-19 Infection,,,"The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up to 180 samples per day, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, this work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.",,doi:https://doi.org/10.1016/j.cels.2020.05.012; doi:https://doi.org/10.1016/j.cels.2020.05.012; html:https://europepmc.org/articles/PMC7264033
 35189884,https://doi.org/10.1186/s12913-022-07607-0,Factors influencing follow-up care post-TIA and minor stroke: a qualitative study using the theoretical domains framework.,"Turner GM, Aquino MRJV, Atkins L, Foy R, Mant J, Calvert M.",,BMC health services research,2022,2022-02-21,Y,Follow-up; Transient Ischaemic Attack; Tia; Minor Stroke; Theoretical Domains Framework,,,"<h4>Background</h4>Follow-up care after transient ischaemic attack (TIA) and minor stroke has been found to be sub-optimal, with individuals often feeling abandoned. We aimed to explore factors influencing holistic follow-up care after TIA and minor stroke.<h4>Methods</h4>Qualitative semi-structured interviews with 24 healthcare providers (HCPs): 5 stroke doctors, 4 nurses, 9 allied health professionals and 6 general practitioners. Participants were recruited from three TIA clinics, seven general practices and one community care trust in the West Midlands, England. Interview transcripts were deductively coded using the Theoretical Domains Framework and themes were generated from coded data.<h4>Results</h4>There was no clear pathway for supporting people with TIA or minor stroke after rapid specialist review in hospital; consequently, these patients had limited access to HCPs from all settings ('Environmental context and resources'). There was lack of understanding of potential needs post-TIA/minor stroke, in particular residual problems such as anxiety/fatigue ('Knowledge'). Identification and management of needs was largely influenced by HCPs' perceived role, professional training ('Social professional role and identity') and time constraints ('Environmental context and resources'). Follow-up was often passive - with onerous on patients to seek support - and predominantly focused on acute medical management ('Intentions'/'Goal').<h4>Conclusions</h4>Follow-up care post-TIA/minor stroke is currently sub-optimal. Through identifying factors which influence follow-up, we can inform guidelines and practical strategies to improve holistic healthcare.",,pdf:https://bmchealthservres.biomedcentral.com/track/pdf/10.1186/s12913-022-07607-0; doi:https://doi.org/10.1186/s12913-022-07607-0; html:https://europepmc.org/articles/PMC8859903; pdf:https://europepmc.org/articles/PMC8859903?pdf=render
-35193920,https://doi.org/10.1136/bmjopen-2021-055773,Investigating the optimal handling of uncertain pregnancy episodes in the CPRD GOLD Pregnancy Register: a methodological study using UK primary care data.,"Campbell J, Bhaskaran K, Thomas S, Williams R, McDonald HI, Minassian C.",,BMJ open,2022,2022-02-22,Y,epidemiology; Public Health; Maternal Medicine,,,"<h4>Objectives</h4>To investigate why episodes of pregnancy identified from electronic health records may be incomplete or conflicting (overlapping), and provide guidance on how to handle them.<h4>Setting</h4>Pregnancy Register generated from the Clinical Practice Research Datalink (CPRD) GOLD UK primary care database.<h4>Participants</h4>Female patients with at least one pregnancy episode in the Register (01 January 1937-31 December 2017) which had no recorded outcome or conflicted with another episode.<h4>Design</h4>We identified multiple scenarios potentially explaining why uncertain episodes occur. Criteria were established and systematically applied to determine whether episodes had evidence of each scenario. Linked Hospital Episode Statistics were used to identify pregnancy events not captured in primary care.<h4>Results</h4>Of 5.8 million pregnancy episodes in the Register, 932 604 (16%) had no recorded outcome, and 478 341 (8.5%) conflicted with another episode (251 026 distinct conflicting pairs of episodes among 210 593 women). 826 146 (89%) of the episodes without outcome recorded in primary care and 215 577 (86%) of the conflicting pairs were consistent with one or more of our proposed scenarios. For 689 737 (74%) episodes with recorded outcome missing and 215 544 (86%) of the conflicting pairs (at least one episode), supportive evidence (eg, antenatal records, linked hospital records) suggested they were true and current pregnancies. Furthermore, 516 818 (55 %) and 160 936 (64%), respectively, were during research quality follow-up time. For a sizeable proportion of uncertain episode, there is evidence to suggest that historical outcomes being recorded by the general practitioner during an ongoing pregnancy may offer explanation (73 208 (29.2%) and 349 874 (37.5%)).<h4>Conclusions</h4>This work provides insight to users of the CPRD Pregnancy Register on why uncertain pregnancy episodes exist and indicates that most of these episodes are likely to be real pregnancies. Guidance is given to help researchers consider whether to include/exclude uncertain pregnancies from their studies, and how to tailor approaches to minimise underestimation and bias.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055773.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055773; html:https://europepmc.org/articles/PMC8867343; pdf:https://europepmc.org/articles/PMC8867343?pdf=render
 31443926,https://doi.org/10.1016/s0140-6736(19)31674-5,Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases.,"Strongman H, Gadd S, Matthews A, Mansfield KE, Stanway S, Lyon AR, Dos-Santos-Silva I, Smeeth L, Bhaskaran K.",,"Lancet (London, England)",2019,2019-08-20,Y,,Understanding the Causes of Disease,,"<h4>Background</h4>The past few decades have seen substantial improvements in cancer survival, but concerns exist about long-term cardiovascular disease risk in survivors. Evidence is scarce on the risks of specific cardiovascular diseases in survivors of a wide range of cancers to inform prevention and management. In this study, we used large-scale electronic health records data from multiple linked UK databases to address these evidence gaps.<h4>Methods</h4>For this population-based cohort study, we used linked primary care, hospital, and cancer registry data from the UK Clinical Practice Research Datalink to identify cohorts of survivors of the 20 most common cancers who were 18 years or older and alive 12 months after diagnosis and controls without history of cancer, matched for age, sex, and general practice. We compared risks for a range of cardiovascular disease outcomes using crude and adjusted Cox models. We fitted interactions to investigate effect modification, and flexible parametric survival models to estimate absolute excess risks over time.<h4>Findings</h4>Between Jan 1, 1990, and Dec 31, 2015, 126 120 individuals with a diagnosis of a cancer of interest still being followed up at least 1 year later were identified and matched to 630 144 controls. After exclusions, 108 215 cancer survivors and 523 541 controls were included in the main analyses. Venous thromboembolism risk was elevated in survivors of 18 of 20 site-specific cancers compared with that of controls; adjusted hazard ratios (HRs) ranged from 1·72 (95% CI 1·57-1·89) in patients after prostate cancer to 9·72 (5·50-17·18) after pancreatic cancer. HRs decreased over time, but remained elevated more than 5 years after diagnosis. We observed increased risks of heart failure or cardiomyopathy in patients after ten of 20 cancers, including haematological (adjusted HR 1·94, 1·66-2·25, with non-Hodgkin lymphoma; 1·77, 1·50-2·09, with leukaemia; and 3·29, 2·59-4·18, with multiple myeloma), oesophageal (1·96, 1·46-2·64), lung (1·82, 1·52-2·17) kidney (1·73, 1·38-2·17) and ovarian (1·59, 1·19-2·12). Elevated risks of arrhythmia, pericarditis, coronary artery disease, stroke, and valvular heart disease were also observed for multiple cancers, including haematological malignancies. HRs for heart failure or cardiomyopathy and venous thromboembolism were greater in patients without previous cardiovascular disease and in younger patients. However, absolute excess risks were generally greater with increasing age. Increased risks of these outcomes seemed most pronounced in patients who had received chemotherapy.<h4>Interpretation</h4>Survivors of most site-specific cancers had increased medium-term to long-term risk for one or more cardiovascular diseases compared with that for the general population, with substantial variations between cancer sites.<h4>Funding</h4>Wellcome Trust and Royal Society.",,pdf:http://www.thelancet.com/article/S0140673619316745/pdf; doi:https://doi.org/10.1016/S0140-6736(19)31674-5; html:https://europepmc.org/articles/PMC6857444; pdf:https://europepmc.org/articles/PMC6857444?pdf=render
+35193920,https://doi.org/10.1136/bmjopen-2021-055773,Investigating the optimal handling of uncertain pregnancy episodes in the CPRD GOLD Pregnancy Register: a methodological study using UK primary care data.,"Campbell J, Bhaskaran K, Thomas S, Williams R, McDonald HI, Minassian C.",,BMJ open,2022,2022-02-22,Y,epidemiology; Public Health; Maternal Medicine,,,"<h4>Objectives</h4>To investigate why episodes of pregnancy identified from electronic health records may be incomplete or conflicting (overlapping), and provide guidance on how to handle them.<h4>Setting</h4>Pregnancy Register generated from the Clinical Practice Research Datalink (CPRD) GOLD UK primary care database.<h4>Participants</h4>Female patients with at least one pregnancy episode in the Register (01 January 1937-31 December 2017) which had no recorded outcome or conflicted with another episode.<h4>Design</h4>We identified multiple scenarios potentially explaining why uncertain episodes occur. Criteria were established and systematically applied to determine whether episodes had evidence of each scenario. Linked Hospital Episode Statistics were used to identify pregnancy events not captured in primary care.<h4>Results</h4>Of 5.8 million pregnancy episodes in the Register, 932 604 (16%) had no recorded outcome, and 478 341 (8.5%) conflicted with another episode (251 026 distinct conflicting pairs of episodes among 210 593 women). 826 146 (89%) of the episodes without outcome recorded in primary care and 215 577 (86%) of the conflicting pairs were consistent with one or more of our proposed scenarios. For 689 737 (74%) episodes with recorded outcome missing and 215 544 (86%) of the conflicting pairs (at least one episode), supportive evidence (eg, antenatal records, linked hospital records) suggested they were true and current pregnancies. Furthermore, 516 818 (55 %) and 160 936 (64%), respectively, were during research quality follow-up time. For a sizeable proportion of uncertain episode, there is evidence to suggest that historical outcomes being recorded by the general practitioner during an ongoing pregnancy may offer explanation (73 208 (29.2%) and 349 874 (37.5%)).<h4>Conclusions</h4>This work provides insight to users of the CPRD Pregnancy Register on why uncertain pregnancy episodes exist and indicates that most of these episodes are likely to be real pregnancies. Guidance is given to help researchers consider whether to include/exclude uncertain pregnancies from their studies, and how to tailor approaches to minimise underestimation and bias.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055773.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055773; html:https://europepmc.org/articles/PMC8867343; pdf:https://europepmc.org/articles/PMC8867343?pdf=render
 33724919,https://doi.org/10.2196/26627,Artificial Intelligence-Enabled Analysis of Public Attitudes on Facebook and Twitter Toward COVID-19 Vaccines in the United Kingdom and the United States: Observational Study.,"Hussain A, Tahir A, Hussain Z, Sheikh Z, Gogate M, Dashtipour K, Ali A, Sheikh A.",,Journal of medical Internet research,2021,2021-04-05,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Twitter; Sentiment Analysis; Deep Learning; Covid-19; Infodemiology; Facebook; Social Media,,,"<h4>Background</h4>Global efforts toward the development and deployment of a vaccine for COVID-19 are rapidly advancing. To achieve herd immunity, widespread administration of vaccines is required, which necessitates significant cooperation from the general public. As such, it is crucial that governments and public health agencies understand public sentiments toward vaccines, which can help guide educational campaigns and other targeted policy interventions.<h4>Objective</h4>The aim of this study was to develop and apply an artificial intelligence-based approach to analyze public sentiments on social media in the United Kingdom and the United States toward COVID-19 vaccines to better understand the public attitude and concerns regarding COVID-19 vaccines.<h4>Methods</h4>Over 300,000 social media posts related to COVID-19 vaccines were extracted, including 23,571 Facebook posts from the United Kingdom and 144,864 from the United States, along with 40,268 tweets from the United Kingdom and 98,385 from the United States from March 1 to November 22, 2020. We used natural language processing and deep learning-based techniques to predict average sentiments, sentiment trends, and topics of discussion. These factors were analyzed longitudinally and geospatially, and manual reading of randomly selected posts on points of interest helped identify underlying themes and validated insights from the analysis.<h4>Results</h4>Overall averaged positive, negative, and neutral sentiments were at 58%, 22%, and 17% in the United Kingdom, compared to 56%, 24%, and 18% in the United States, respectively. Public optimism over vaccine development, effectiveness, and trials as well as concerns over their safety, economic viability, and corporation control were identified. We compared our findings to those of nationwide surveys in both countries and found them to correlate broadly.<h4>Conclusions</h4>Artificial intelligence-enabled social media analysis should be considered for adoption by institutions and governments alongside surveys and other conventional methods of assessing public attitude. Such analyses could enable real-time assessment, at scale, of public confidence and trust in COVID-19 vaccines, help address the concerns of vaccine sceptics, and help develop more effective policies and communication strategies to maximize uptake.",,pdf:https://www.jmir.org/2021/4/e26627/PDF; doi:https://doi.org/10.2196/26627; html:https://europepmc.org/articles/PMC8023383
 36005401,https://doi.org/10.3390/jcdd9080237,The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses.,"Taylor K, McBride N, Zhao J, Oddie S, Azad R, Wright J, Andreassen OA, Stewart ID, Langenberg C, Magnus MC, Borges MC, Caputo M, Lawlor DA.",,Journal of cardiovascular development and disease,2022,2022-07-27,Y,Metabolites; Congenital heart disease; Alspac; Moba; Born In Bradford,,,"Background: It is plausible that maternal pregnancy metabolism influences the risk of offspring congenital heart disease (CHD). We sought to explore this through a systematic approach using different methods and data. Methods: We undertook multivariable logistic regression of the odds of CHD for 923 mass spectrometry (MS)-derived metabolites in a sub-sample of a UK birth cohort (Born in Bradford (BiB); N = 2605, 46 CHD cases). We considered metabolites reaching a p-value threshold <0.05 to be suggestively associated with CHD. We sought validation of our findings, by repeating the multivariable regression analysis within the BiB cohort for any suggestively associated metabolite that was measured by nuclear magnetic resonance (NMR) or clinical chemistry (N = 7296, 87 CHD cases), and by using genetic risk scores (GRS: weighted genetic risk scores of single nucleotide polymorphisms (SNPs) that were associated with any suggestive metabolite) in Mendelian randomization (MR) analyses. The MR analyses were performed in BiB and two additional European birth cohorts (N = 38,662, 319 CHD cases). Results: In the main multivariable analyses, we identified 44 metabolites suggestively associated with CHD, including those from the following super pathways: amino acids, lipids, co-factors and vitamins, xenobiotics, nucleotides, energy, and several unknown molecules. Of these 44, isoleucine and leucine were available in the larger BiB cohort (NMR), and for these the results were validated. The MR analyses were possible for 27/44 metabolites and for 11 there was consistency with the multivariable regression results. Conclusions: In summary, we have used complimentary data sources and statistical techniques to construct layers of evidence. We found that pregnancy amino acid metabolism, androgenic steroid lipids, and levels of succinylcarnitine could be important contributing factors for CHD.",,pdf:https://www.mdpi.com/2308-3425/9/8/237/pdf?version=1658976309; doi:https://doi.org/10.3390/jcdd9080237; html:https://europepmc.org/articles/PMC9410051; pdf:https://europepmc.org/articles/PMC9410051?pdf=render
 37789377,https://doi.org/10.1186/s12943-023-01863-2,Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.,"Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.",,Molecular cancer,2023,2023-10-03,Y,prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures,,,"Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.",,pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render
-37814053,https://doi.org/10.1038/s41588-023-01522-8,Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.,"Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.",,Nature genetics,2023,2023-10-09,N,,,,"The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.",,doi:https://doi.org/10.1038/s41588-023-01522-8
 35251129,https://doi.org/10.3389/fgene.2022.818574,Calculating Polygenic Risk Scores (PRS) in UK Biobank: A Practical Guide for Epidemiologists.,"Collister JA, Liu X, Clifton L.",,Frontiers in genetics,2022,2022-02-18,Y,Polygenic Score; Genetic Risk Score; Uk Biobank; Polygenic Risk Score; Worked Example,,,"A polygenic risk score estimates the genetic risk of an individual for some disease or trait, calculated by aggregating the effect of many common variants associated with the condition. With the increasing availability of genetic data in large cohort studies such as the UK Biobank, inclusion of this genetic risk as a covariate in statistical analyses is becoming more widespread. Previously this required specialist knowledge, but as tooling and data availability have improved it has become more feasible for statisticians and epidemiologists to calculate existing scores themselves for use in analyses. While tutorial resources exist for conducting genome-wide association studies and generating of new polygenic risk scores, fewer guides exist for the simple calculation and application of existing genetic scores. This guide outlines the key steps of this process: selection of suitable polygenic risk scores from the literature, extraction of relevant genetic variants and verification of their quality, calculation of the risk score and key considerations of its inclusion in statistical models, using the UK Biobank imputed data as a model data set. Many of the techniques in this guide will generalize to other datasets, however we also focus on some of the specific techniques required for using data in the formats UK Biobank have selected. This includes some of the challenges faced when working with large numbers of variants, where the computation time required by some tools is impractical. While we have focused on only a couple of tools, which may not be the best ones for every given aspect of the process, one barrier to working with genetic data is the sheer volume of tools available, and the difficulty for a novice to assess their viability. By discussing in depth a couple of tools that are adequate for the calculation even at large scale, we hope to make polygenic risk scores more accessible to a wider range of researchers.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2022.818574/pdf; doi:https://doi.org/10.3389/fgene.2022.818574; html:https://europepmc.org/articles/PMC8894758; pdf:https://europepmc.org/articles/PMC8894758?pdf=render
+37814053,https://doi.org/10.1038/s41588-023-01522-8,Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.,"Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.",,Nature genetics,2023,2023-10-09,N,,,,"The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.",,doi:https://doi.org/10.1038/s41588-023-01522-8
 33560344,https://doi.org/10.1210/clinem/dgab067,Association of Metformin with Susceptibility to COVID-19 in People with Type 2 Diabetes.,"Wang J, Cooper JM, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, Chandan JS, Anand A, Okoth K, Subramanian A, Bangash MN, Jackson T, Zemedikun D, Taverner T, Hanif W, Ghosh S, Narendran P, Toulis KA, Tahrani AA, Surenthirakumaran R, Adderley NJ, Haroon S, Khunti K, Sainsbury C, Thomas GN, Nirantharakumar K.",,The Journal of clinical endocrinology and metabolism,2021,2021-04-01,Y,Type 2 diabetes mellitus; Metformin; Covid-19; Sars-cov-2 Infection,,,"<h4>Objective</h4>Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes.<h4>Research design and methods</h4>We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed.<h4>Results</h4>There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding.<h4>Conclusion</h4>Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.",,pdf:https://academic.oup.com/jcem/article-pdf/106/5/1255/41848481/dgab067.pdf; doi:https://doi.org/10.1210/clinem/dgab067; html:https://europepmc.org/articles/PMC7928949
 33825703,https://doi.org/10.1107/s2059798321000826,Vagabond: bond-based parametrization reduces overfitting for refinement of proteins.,Ginn HM.,,"Acta crystallographica. Section D, Structural biology",2021,2021-03-30,Y,Models; X-ray diffraction; Protein Flexibility; Bonds; Refinement Software,,,"Structural biology methods have delivered over 150 000 high-resolution structures of macromolecules, which have fundamentally altered our understanding of biology and our approach to developing new medicines. However, the description of molecular flexibility is instrinsically flawed and in almost all cases, regardless of the experimental method used for structure determination, there remains a strong overfitting bias during molecular model building and refinement. In the worst case this can lead to wholly incorrect structures and thus incorrect biological interpretations. Here, by reparametrizing the description of these complex structures in terms of bonds rather than atomic positions, and by modelling flexibility using a deterministic ensemble of structures, it is demonstrated that structures can be described using fewer parameters than in conventional refinement. The current implementation, applied to X-ray diffraction data, significantly reduces the extent of overfitting, allowing the experimental data to reveal more biological information in electron-density maps.",,pdf:https://journals.iucr.org/d/issues/2021/04/00/qj5007/qj5007.pdf; doi:https://doi.org/10.1107/S2059798321000826; html:https://europepmc.org/articles/PMC8025884; pdf:https://europepmc.org/articles/PMC8025884?pdf=render
 33782080,https://doi.org/10.1136/thoraxjnl-2020-216512,Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data.,"Shah SA, Quint JK, Nwaru BI, Sheikh A.",,Thorax,2021,2021-03-29,Y,Asthma; Asthma Epidemiology; Covid-19,,,"<h4>Background</h4>The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear.<h4>Methods</h4>We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016-2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting.<h4>Results</h4>From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016-2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (-0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005-0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210-0.277 (sex), 0.159-0.367 (age), 0.068-0.590 (region).<h4>Conclusions</h4>There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.",,pdf:https://thorax.bmj.com/content/thoraxjnl/76/9/860.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-216512; html:https://europepmc.org/articles/PMC8011425; pdf:https://europepmc.org/articles/PMC8011425?pdf=render
 31234639,https://doi.org/10.1161/circulationaha.118.038814,Use of Genetic Variants Related to Antihypertensive Drugs to Inform on Efficacy and Side Effects.,"Gill D, Georgakis MK, Koskeridis F, Jiang L, Feng Q, Wei WQ, Theodoratou E, Elliott P, Denny JC, Malik R, Evangelou E, Dehghan A, Dichgans M, Tzoulaki I.",,Circulation,2019,2019-06-25,Y,Antihypertensive drugs; Mendelian Randomization Analysis,"Better Care, The Human Phenome",,"<h4>Background</h4>Drug effects can be investigated through natural variation in the genes for their protein targets. The present study aimed to use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs, which are among the most commonly used medications worldwide.<h4>Methods</h4>Genetic proxies for the effect of antihypertensive drug classes were identified as variants in the genes for the corresponding targets that associated with systolic blood pressure at genome-wide significance. Mendelian randomization estimates for drug effects on coronary heart disease and stroke risk were compared with randomized, controlled trial results. A phenome-wide association study in the UK Biobank was performed to identify potential side effects and repurposing opportunities, with findings investigated in the Vanderbilt University biobank (BioVU) and in observational analysis of the UK Biobank.<h4>Results</h4>Suitable genetic proxies for angiotensin-converting enzyme inhibitors, β-blockers, and calcium channel blockers (CCBs) were identified. Mendelian randomization estimates for their effect on coronary heart disease and stroke risk, respectively, were comparable to results from randomized, controlled trials against placebo. A phenome-wide association study in the UK Biobank identified an association of the CCB standardized genetic risk score with increased risk of diverticulosis (odds ratio, 1.02 per standard deviation increase; 95% CI, 1.01-1.04), with a consistent estimate found in BioVU (odds ratio, 1.01; 95% CI, 1.00-1.02). Cox regression analysis of drug use in the UK Biobank suggested that this association was specific to nondihydropyridine CCBs (hazard ratio 1.49 considering thiazide diuretic agents as a comparator; 95% CI, 1.04-2.14) but not dihydropyridine CCBs (hazard ratio, 1.04; 95% CI, 0.83-1.32).<h4>Conclusions</h4>Genetic variants can be used to explore the efficacy and side effects of antihypertensive medications. The identified potential effect of nondihydropyridine CCBs on diverticulosis risk could have clinical implications and warrants further investigation.",,doi:https://doi.org/10.1161/circulationaha.118.038814; doi:https://doi.org/10.1161/CIRCULATIONAHA.118.038814; html:https://europepmc.org/articles/PMC6687408; pdf:https://europepmc.org/articles/PMC6687408?pdf=render
 33184391,https://doi.org/10.1038/s41598-020-76816-6,Prediction of vascular aging based on smartphone acquired PPG signals.,"Dall'Olio L, Curti N, Remondini D, Safi Harb Y, Asselbergs FW, Castellani G, Uh HW.",,Scientific reports,2020,2020-11-12,Y,,,,"Photoplethysmography (PPG) measured by smartphone has the potential for a large scale, non-invasive, and easy-to-use screening tool. Vascular aging is linked to increased arterial stiffness, which can be measured by PPG. We investigate the feasibility of using PPG to predict healthy vascular aging (HVA) based on two approaches: machine learning (ML) and deep learning (DL). We performed data preprocessing, including detrending, demodulating, and denoising on the raw PPG signals. For ML, ridge penalized regression has been applied to 38 features extracted from PPG, whereas for DL several convolutional neural networks (CNNs) have been applied to the whole PPG signals as input. The analysis has been conducted using the crowd-sourced Heart for Heart data. The prediction performance of ML using two features (AUC of 94.7%) - the a wave of the second derivative PPG and tpr, including four covariates, sex, height, weight, and smoking - was similar to that of the best performing CNN, 12-layer ResNet (AUC of 95.3%). Without having the heavy computational cost of DL, ML might be advantageous in finding potential biomarkers for HVA prediction. The whole workflow of the procedure is clearly described, and open software has been made available to facilitate replication of the results.",,pdf:https://www.nature.com/articles/s41598-020-76816-6.pdf; doi:https://doi.org/10.1038/s41598-020-76816-6; html:https://europepmc.org/articles/PMC7661535; pdf:https://europepmc.org/articles/PMC7661535?pdf=render
 33043790,https://doi.org/10.1177/0141076820961776,Advancing UK regulatory science and innovation in healthcare.,"Calvert MJ, Marston E, Samuels M, Rivera SC, Torlinska B, Oliver K, Denniston AK, Hoare S.",,Journal of the Royal Society of Medicine,2021,2020-10-12,Y,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0141076820961776; doi:https://doi.org/10.1177/0141076820961776; html:https://europepmc.org/articles/PMC7809339; pdf:https://europepmc.org/articles/PMC7809339?pdf=render
-36446465,https://doi.org/10.1136/bmjopen-2022-065142,"Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.","Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ.",,BMJ open,2022,2022-11-29,Y,epidemiology; Public Health; Protocols & Guidelines; Covid-19,,,"<h4>Introduction</h4>The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.<h4>Methods and analysis</h4>Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.<h4>Ethics and dissemination</h4>Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.<h4>Trial registration number</h4>NCT05240742.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render
 32212911,https://doi.org/10.1161/jaha.119.013684,Prognostic significance of troponin level in 3121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study).,"Kaura A, Arnold AD, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Lefroy DC, Francis DP, Shah AM, Kharbanda R, Perera D, Patel RS, Mayet J.",,Journal of the American Heart Association,2020,2020-03-26,Y,Troponin; Mortality; Atrial fibrillation; coronary artery disease; angiography,,,"Background Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all-cause mortality in real-world patients presenting with AF. Methods and Results We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median follow-up of 1462 (interquartile range, 929-1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associated with a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01-1.43; <i>P</i><0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9-3.4) at ≈250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography. The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42-0.89; <i>P</i>=0.01). Conclusions Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013684; doi:https://doi.org/10.1161/JAHA.119.013684; html:https://europepmc.org/articles/PMC7428631; pdf:https://europepmc.org/articles/PMC7428631?pdf=render
+36446465,https://doi.org/10.1136/bmjopen-2022-065142,"Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.","Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ.",,BMJ open,2022,2022-11-29,Y,epidemiology; Public Health; Protocols & Guidelines; Covid-19,,,"<h4>Introduction</h4>The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.<h4>Methods and analysis</h4>Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.<h4>Ethics and dissemination</h4>Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.<h4>Trial registration number</h4>NCT05240742.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render
 37208429,https://doi.org/10.1038/s41598-023-33391-w,Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom.,"Zöllner J, Finer S, Linton KJ, Genes and Health Research Team, van Heel DA, Williamson C, Dixon PH.",,Scientific reports,2023,2023-05-19,Y,,,,"This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research.",,doi:https://doi.org/10.1038/s41598-023-33391-w; doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?pdf=render
 34632432,https://doi.org/10.1016/s2666-5247(21)00128-2,Epidemiology of <i>Mycobacterium abscessus</i> in England: an observational study.,"Lipworth S, Hough N, Weston N, Muller-Pebody B, Phin N, Myers R, Chapman S, Flight W, Alexander E, Smith EG, Robinson E, Peto TEA, Crook DW, Walker AS, Hopkins S, Eyre DW, Walker TM.",,The Lancet. Microbe,2021,2021-10-01,Y,,,,"<h4>Background</h4><i>Mycobacterium abscessus</i> has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England.<h4>Methods</h4>In this retrospective observational study, we analysed consecutive <i>M abscessus</i> whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [SNPs]).<h4>Findings</h4>2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0·38). High-density phylogenetic clusters were randomly distributed over a wide geographical area. Most isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age (adjusted odds ratio 1·14 per 10 years, 95% CI 1·04-1·26), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis.<h4>Interpretation</h4>Previously identified widely disseminated dominant clones of <i>M abscessus</i> are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for <i>M abscessus</i> dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis health-care-associated niche.<h4>Funding</h4>The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.",,pdf:http://www.thelancet.com/article/S2666524721001282/pdf; doi:https://doi.org/10.1016/S2666-5247(21)00128-2; html:https://europepmc.org/articles/PMC8481905
 34581777,https://doi.org/10.1182/bloodadvances.2021005453,G protein-coupled receptor kinase 5 regulates thrombin signaling in platelets via PAR-1.,"Downes K, Zhao X, Gleadall NS, McKinney H, Kempster C, Batista J, Thomas PL, Cooper M, Michael JV, Kreuzhuber R, Wedderburn K, Waller K, Varney B, Verdier H, Kriek N, Ashford SE, Stirrups KE, Dunster JL, McKenzie SE, Ouwehand WH, Gibbins JM, Yang J, Astle WJ, Ma P.",,Blood advances,2022,2022-04-01,Y,,,,"The interindividual variation in the functional response of platelets to activation by agonists is heritable. Genome-wide association studies (GWASs) of quantitative measures of platelet function have identified fewer than 20 distinctly associated variants, some with unknown mechanisms. Here, we report GWASs of pathway-specific functional responses to agonism by adenosine 5'-diphosphate, a glycoprotein VI-specific collagen mimetic, and thrombin receptor-agonist peptides, each specific to 1 of the G protein-coupled receptors PAR-1 and PAR-4, in subsets of 1562 individuals. We identified an association (P = 2.75 × 10-40) between a common intronic variant, rs10886430, in the G protein-coupled receptor kinase 5 gene (GRK5) and the sensitivity of platelets to activate through PAR-1. The variant resides in a megakaryocyte-specific enhancer that is bound by the transcription factors GATA1 and MEIS1. The minor allele (G) is associated with fewer GRK5 transcripts in platelets and the greater sensitivity of platelets to activate through PAR-1. We show that thrombin-mediated activation of human platelets causes binding of GRK5 to PAR-1 and that deletion of the mouse homolog Grk5 enhances thrombin-induced platelet activation sensitivity and increases platelet accumulation at the site of vascular injury. This corroborates evidence that the human G allele of rs10886430 is associated with a greater risk for cardiovascular disease. In summary, by combining the results of pathway-specific GWASs and expression quantitative trait locus studies in humans with the results from platelet function studies in Grk5-/- mice, we obtain evidence that GRK5 regulates the human platelet response to thrombin via the PAR-1 pathway.",,pdf:https://ashpublications.org/bloodadvances/article-pdf/6/7/2319/1886257/advancesadv2021005453.pdf; doi:https://doi.org/10.1182/bloodadvances.2021005453; html:https://europepmc.org/articles/PMC9006276; pdf:https://europepmc.org/articles/PMC9006276?pdf=render
-34468736,https://doi.org/10.1093/europace/euab162,Comparing clinical performance of current implantable cardioverter-defibrillator implantation recommendations in arrhythmogenic right ventricular cardiomyopathy.,"Bosman LP, Bosman LP, Nielsen Gerlach CL, Cadrin-Tourigny J, Orgeron G, Tichnell C, Murray B, Bourfiss M, van der Heijden JF, Yap SC, Zeppenfeld K, van den Berg MP, Wilde AAM, Asselbergs FW, Tandri H, Calkins H, van Tintelen JP, James CA, Te Riele ASJM.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2022,2022-02-01,Y,Prognosis; Risk stratification; Ventricular Arrhythmias; Implantable Cardioverter-defibrillator; Arrhythmogenic Right Ventricular Cardiomyopathy,,,"<h4>Aims</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation algorithms are available The International Task Force Consensus ('ITFC'), an ITFC modification by Orgeron et al. ('mITFC'), the AHA/HRS/ACC guideline for VA management ('AHA'), and the HRS expert consensus statement ('HRS'). This study aims to validate and compare the performance of these algorithms in ARVC.<h4>Methods and results</h4>We classified 617 definite ARVC patients (38.5 ± 15.1 years, 52.4% male, 39.2% prior sustained VA) according to four algorithms. Clinical performance was evaluated by sensitivity, specificity, ROC-analysis, and decision curve analysis for any sustained VA and for fast VA (>250 b.p.m.). During 6.4 [2.8-11.5] years follow-up, 282 (45.7%) patients experienced any sustained VA, and 63 (10.2%) fast VA. For any sustained VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (94.0-97.8% vs. 76.7-83.5%), but lower specificity (15.9-32.0% vs. 42.7%-60.1%). Similarly, for fast VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (95.2-97.1% vs. 76.7-78.4%) but lower specificity (42.7-43.1 vs. 76.7-78.4%). Decision curve analysis showed ITFC and mITFC to be superior for a 5-year sustained VA risk ICD indication threshold between 5-25% or 2-9% for fast VA.<h4>Conclusion</h4>The ITFC and mITFC provide the highest protection rates, whereas AHA and HRS decrease unnecessary ICD placements. ITFC or mITFC should be used if we consider the 5-year threshold for ICD indication to lie within 5-25% for sustained VA or 2-9% for fast VA. These data will inform decision-making for ICD placement in ARVC.",,pdf:https://academic.oup.com/europace/article-pdf/24/2/296/42370389/euab162.pdf; doi:https://doi.org/10.1093/europace/euab162; html:https://europepmc.org/articles/PMC8824519; pdf:https://europepmc.org/articles/PMC8824519?pdf=render
 31657946,https://doi.org/10.1164/rccm.201903-0673oc,Long-Term Outcomes after Severe Traumatic Brain Injury in Older Adults. A Registry-based Cohort Study.,"Maiden MJ, Cameron PA, Rosenfeld JV, Cooper DJ, McLellan S, Gabbe BJ.",,American journal of respiratory and critical care medicine,2020,2020-01-01,N,Elderly; Brain trauma; Functional Performance; Critical Care Outcomes,,,"Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients.Objectives: To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates.Methods: This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI. Functional status was assessed with Glasgow Outcome Scale Extended (GOSE) 6, 12, and 24 months after injury. Cohort subgroups were defined by admission to an ICU. Features associated with functional outcome were assessed from the ICU subgroup.Measurements and Main Results: The study included 540 older adults who had been hospitalized with severe TBI over the 10-year period; 428 (79%) patients died in hospital, and 456 (84%) died 6 months after injury. There were 277 patients who had not been admitted to an ICU; at 6 months, 268 (97%) had died, 8 (3%) were dependent (GOSE 2-4), and 1 (0.4%) was functionally independent (GOSE 5-8). There were 263 patients who had been admitted to an ICU; at 6 months, 188 (73%) had died, 39 (15%) were dependent, and 32 (12%) were functionally independent. These proportions did not change over longer follow-up. The only clinical features associated with a lower rate of functional independence were Injury Severity Score ≥25 (adjusted odds ratio, 0.24 [95% confidence interval, 0.09-0.67]; P = 0.007) and older age groups (P = 0.017).Conclusions: Severe TBI in older adults is a condition with very high mortality, and few recover to functional independence.",,doi:https://doi.org/10.1164/rccm.201903-0673OC
+34468736,https://doi.org/10.1093/europace/euab162,Comparing clinical performance of current implantable cardioverter-defibrillator implantation recommendations in arrhythmogenic right ventricular cardiomyopathy.,"Bosman LP, Bosman LP, Nielsen Gerlach CL, Cadrin-Tourigny J, Orgeron G, Tichnell C, Murray B, Bourfiss M, van der Heijden JF, Yap SC, Zeppenfeld K, van den Berg MP, Wilde AAM, Asselbergs FW, Tandri H, Calkins H, van Tintelen JP, James CA, Te Riele ASJM.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2022,2022-02-01,Y,Prognosis; Risk stratification; Ventricular Arrhythmias; Implantable Cardioverter-defibrillator; Arrhythmogenic Right Ventricular Cardiomyopathy,,,"<h4>Aims</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation algorithms are available The International Task Force Consensus ('ITFC'), an ITFC modification by Orgeron et al. ('mITFC'), the AHA/HRS/ACC guideline for VA management ('AHA'), and the HRS expert consensus statement ('HRS'). This study aims to validate and compare the performance of these algorithms in ARVC.<h4>Methods and results</h4>We classified 617 definite ARVC patients (38.5 ± 15.1 years, 52.4% male, 39.2% prior sustained VA) according to four algorithms. Clinical performance was evaluated by sensitivity, specificity, ROC-analysis, and decision curve analysis for any sustained VA and for fast VA (>250 b.p.m.). During 6.4 [2.8-11.5] years follow-up, 282 (45.7%) patients experienced any sustained VA, and 63 (10.2%) fast VA. For any sustained VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (94.0-97.8% vs. 76.7-83.5%), but lower specificity (15.9-32.0% vs. 42.7%-60.1%). Similarly, for fast VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (95.2-97.1% vs. 76.7-78.4%) but lower specificity (42.7-43.1 vs. 76.7-78.4%). Decision curve analysis showed ITFC and mITFC to be superior for a 5-year sustained VA risk ICD indication threshold between 5-25% or 2-9% for fast VA.<h4>Conclusion</h4>The ITFC and mITFC provide the highest protection rates, whereas AHA and HRS decrease unnecessary ICD placements. ITFC or mITFC should be used if we consider the 5-year threshold for ICD indication to lie within 5-25% for sustained VA or 2-9% for fast VA. These data will inform decision-making for ICD placement in ARVC.",,pdf:https://academic.oup.com/europace/article-pdf/24/2/296/42370389/euab162.pdf; doi:https://doi.org/10.1093/europace/euab162; html:https://europepmc.org/articles/PMC8824519; pdf:https://europepmc.org/articles/PMC8824519?pdf=render
 34661196,https://doi.org/10.1093/ehjopen/oeab019,Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.,"Wall C, Huang Y, Le EPV, Ćorović A, Uy CP, Gopalan D, Ma C, Manavaki R, Fryer TD, Aloj L, Graves MJ, Tombetti E, Ariff B, Bambrough P, Hoole SP, Rusk RA, Jayne DR, Dweck MR, Newby D, Fayad ZA, Bennett MR, Peters JE, Slomka P, Dey D, Mason JC, Rudd JHF, Tarkin JM.",,European heart journal open,2021,2021-08-06,Y,coronary artery disease; Takayasu Arteritis; Pericoronary Adipose Tissue Density,,,"<h4>Aims</h4>To examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.<h4>Methods and results</h4>PCAT and PAAT density was measured in coronary (<i>n</i> = 1016) and aortic (<i>n</i> = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), <i>n</i> = 36; TAK, <i>n</i> = 18; atherosclerotic CAD, <i>n</i> = 32; matched controls, <i>n</i> = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: <i>P</i> < 0.0001; PAAT: <i>P</i> = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients (<i>P</i> = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (<i>P</i> = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (<i>r</i> = 0.43, <i>P</i> = 0.001) and C-reactive protein (<i>r</i> = 0.41, <i>P</i> < 0.0001) and was higher in active vs. inactive TAK (<i>P</i> = 0.002). mPCAT density above -74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97-1)]. The association of PCAT density and coronary arterial inflammation measured by <sup>68</sup>Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in <sup>68</sup>Ga-DOTATATE maximum tissue-to-blood ratio (<i>P</i> = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.<h4>Conclusions</h4>PCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK.",,pdf:https://academic.oup.com/ehjopen/article-pdf/1/2/oeab019/41727950/oeab019.pdf; doi:https://doi.org/10.1093/ehjopen/oeab019; html:https://europepmc.org/articles/PMC8508012; pdf:https://europepmc.org/articles/PMC8508012?pdf=render
 35144751,https://doi.org/10.1016/j.jacc.2021.11.045,Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies: JACC Review Topic of the Week.,"Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.",,Journal of the American College of Cardiology,2022,2022-02-01,N,Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy,,,"Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.",,doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045
 35913736,https://doi.org/10.1093/ehjqcco/qcac045,Impact of cancer diagnosis on distribution and trends of cardiovascular hospitalizations in the USA between 2004 and 2017.,"Kobo O, Raisi-Estabragh Z, Gevaert S, Rana JS, Van Spall HGC, Roguin A, Petersen SE, Ky B, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2022,2022-10-01,N,Prognosis; trends; Cardio- Oncology,,,"<h4>Background and aims</h4>There is limited data on temporal trends of cardiovascular hospitalizations and outcomes amongst cancer patients. We describe the distribution, trends of admissions, and in-hospital mortality associated with key cardiovascular diseases among cancer patients in the USA between 2004 and 2017.<h4>Methods</h4>Using the Nationwide Inpatient Sample we, identified admissions with five cardiovascular diseases of interest: acute myocardial infarction (AMI), pulmonary embolism (PE), ischaemic stroke, heart failure, atrial fibrillation (AF) or atrial flutter, and intracranial haemorrhage. Patients were stratified by cancer status and type. We estimated crude annual rates of hospitalizations and annual in-hospital all-cause mortality rates.<h4>Results</h4>From &gt;42.5 million hospitalizations with a primary cardiovascular diagnosis, 1.9 million (4.5%) had a concurrent record of cancer. Between 2004 and 2017, cardiovascular admission rates increased by 23.2% in patients with cancer, whilst decreasing by 10.9% in patients without cancer. The admission rate increased among cancer patients across all admission causes and cancer types except prostate cancer. Patients with haematological (9.7-13.5), lung (7.4-8.9), and GI cancer (4.6-6.3) had the highest crude rates of cardiovascular hospitalizations per 100 000 US population. Heart failure was the most common reason for cardiovascular admission in patients across all cancer types, except GI cancer (crude admission rates of 13.6-16.6 per 100 000 US population for patients with cancer).<h4>Conclusions</h4>In contrast to declining trends in patients without cancer, primary cardiovascular admissions in patients with cancer is increasing. The highest admission rates are in patients with haematological cancer, and the most common cause of admission is heart failure.",,pdf:https://biblio.ugent.be/publication/01GTEZMFA3PQ4FR2HWVVMJE1PP/file/01GTEZP5YQ68PC7TFPP52TS6QR.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac045; html:https://europepmc.org/articles/PMC9603542; pdf:https://europepmc.org/articles/PMC9603542?pdf=render; doi:https://doi.org/10.1093/ehjqcco/qcac045
@@ -1681,8 +1681,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 37117760,https://doi.org/10.1038/s43587-021-00166-9,"Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank.","Codd V, Denniff M, Swinfield C, Warner SC, Papakonstantinou M, Sheth S, Nanus DE, Budgeon CA, Musicha C, Bountziouka V, Wang Q, Bramley R, Allara E, Kaptoge S, Stoma S, Jiang T, Butterworth AS, Wood AM, Di Angelantonio E, Thompson JR, Danesh JN, Nelson CP, Samani NJ.",,Nature aging,2022,2022-02-17,N,,,,"Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.",,pdf:https://figshare.com/articles/journal_contribution/Measurement_and_initial_characterization_of_leukocyte_telomere_length_in_474_074_participants_in_UK_Biobank/19228749/1/files/34165107.pdf; doi:https://doi.org/10.1038/s43587-021-00166-9
 37117689,https://doi.org/10.1038/s43016-021-00309-6,Author Correction: Nutriome-metabolome relationships provide insights into dietary intake and metabolism.,"Posma JM, Garcia-Perez I, Frost G, Aljuraiban GS, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson JK.",,Nature food,2021,2021-07-01,N,,,,,,pdf:https://www.nature.com/articles/s43016-021-00309-6.pdf; doi:https://doi.org/10.1038/s43016-021-00309-6
 32564639,https://doi.org/10.1177/0300060520931298,Mortality statistics in England and Wales: the SARS-CoV-2 paradox.,"Harrison G, Newport D, Robbins T, Arvanitis TN, Stein A.",,The Journal of international medical research,2020,2020-06-01,Y,Respiratory disease; United Kingdom; Mortality Rate; Paradox; Covid-19; Sars-cov-2,,,"<h4>Objective</h4>To analyse mortality statistics in the United Kingdom during the initial phases of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic and to understand the impact of the pandemic on national mortality.<h4>Methods</h4>Retrospective review of weekly national mortality statistics in the United Kingdom over the past 5 years, including subgroup analysis of respiratory mortality rates.<h4>Results</h4>During the early phases of the SARS-CoV-2 pandemic in the first months of 2020, there were consistently fewer deaths per week compared with the preceding 5 years. This pattern was not observed at any other time within the past 5 years. We have termed this phenomenon the ""SARS-CoV-2 paradox."" We postulate potential explanations for this seeming paradox and explore the implications of these data.<h4>Conclusions</h4>Paradoxically, but potentially importantly, lower rather than higher weekly mortality rates were observed during the early stages of the SARS-CoV-2 pandemic. This paradox may have implications for current and future healthcare utilisation. A rebound increase in non-SARS-CoV-2 mortality later this year might coincide with the peak of SARS-CoV-2 admissions and mortality.",,doi:https://doi.org/10.1177/0300060520931298; doi:https://doi.org/10.1177/0300060520931298; html:https://europepmc.org/articles/PMC7307394; pdf:https://europepmc.org/articles/PMC7307394?pdf=render
-35834561,https://doi.org/10.1371/journal.pmed.1004039,"Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses.","Topiwala A, Wang C, Ebmeier KP, Burgess S, Bell S, Levey DF, Zhou H, McCracken C, Roca-Fernández A, Petersen SE, Raman B, Husain M, Gelernter J, Miller KL, Smith SM, Nichols TE.",,PLoS medicine,2022,2022-07-14,Y,,,,"<h4>Background</h4>Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits.<h4>Methods and findings</h4>Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-sample mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 ± 1.10 years after baseline) was used to ascertain iron content of each brain region (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Main outcomes were susceptibility (χ) and T2*, measures used as indices of iron deposition. Brain regions of interest included putamen, caudate, hippocampi, thalami, and substantia nigra. Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation analysis. Cognition was assessed at the scan and in online follow-up (5.82 ± 0.86 years after baseline). Executive function was assessed with the trail-making test, fluid intelligence with puzzle tasks, and reaction time by a task based on the ""Snap"" card game. Mean age was 54.8 ± 7.4 years and 48.6% were female. Weekly alcohol consumption was 17.7 ± 15.9 units and never drinkers comprised 2.7% of the sample. Alcohol consumption was associated with markers of higher iron (χ) in putamen (β = 0.08 standard deviation (SD) [95% confidence interval (CI) 0.06 to 0.09], p < 0.001), caudate (β = 0.05 [0.04 to 0.07], p < 0.001), and substantia nigra (β = 0.03 [0.02 to 0.05], p < 0.001) and lower iron in the thalami (β = -0.06 [-0.07 to -0.04], p < 0.001). Quintile-based analyses found these associations in those consuming >7 units (56 g) alcohol weekly. MR analyses provided weak evidence these relationships are causal. Genetically predicted alcoholic drinks weekly positively associated with putamen and hippocampus susceptibility; however, these associations did not survive multiple testing corrections. Weak evidence for a causal relationship between genetically predicted alcohol use disorder and higher putamen susceptibility was observed; however, this was not robust to multiple comparisons correction. Genetically predicted alcohol use disorder was associated with serum iron and transferrin saturation. Elevated liver iron was observed at just >11 units (88 g) alcohol weekly c.f. <7 units (56 g). Systemic iron levels partially mediated associations of alcohol intake with brain iron. Markers of higher basal ganglia iron associated with slower executive function, lower fluid intelligence, and slower reaction times. The main limitations of the study include that χ and T2* can reflect changes in myelin as well as iron, alcohol use was self-reported, and MR estimates can be influenced by genetic pleiotropy.<h4>Conclusions</h4>To the best of our knowledge, this study represents the largest investigation of moderate alcohol consumption and iron homeostasis to date. Alcohol consumption above 7 units weekly associated with higher brain iron. Iron accumulation represents a potential mechanism for alcohol-related cognitive decline.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004039&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004039; html:https://europepmc.org/articles/PMC9282660; pdf:https://europepmc.org/articles/PMC9282660?pdf=render
 34645794,https://doi.org/10.1038/s41467-021-25914-8,A cross-sectional analysis of meteorological factors and SARS-CoV-2 transmission in 409 cities across 26 countries.,"Sera F, Armstrong B, Abbott S, Meakin S, O'Reilly K, von Borries R, Schneider R, Royé D, Hashizume M, Pascal M, Tobias A, Vicedo-Cabrera AM, MCC Collaborative Research Network, CMMID COVID-19 Working Group, Gasparrini A, Lowe R.",,Nature communications,2021,2021-10-13,Y,,,,"There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (R<sub>e</sub>) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10 °C increase. Early interventions have a greater effect on R<sub>e</sub> with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission.",,pdf:https://www.nature.com/articles/s41467-021-25914-8.pdf; doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render
+35834561,https://doi.org/10.1371/journal.pmed.1004039,"Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses.","Topiwala A, Wang C, Ebmeier KP, Burgess S, Bell S, Levey DF, Zhou H, McCracken C, Roca-Fernández A, Petersen SE, Raman B, Husain M, Gelernter J, Miller KL, Smith SM, Nichols TE.",,PLoS medicine,2022,2022-07-14,Y,,,,"<h4>Background</h4>Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits.<h4>Methods and findings</h4>Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-sample mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 ± 1.10 years after baseline) was used to ascertain iron content of each brain region (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Main outcomes were susceptibility (χ) and T2*, measures used as indices of iron deposition. Brain regions of interest included putamen, caudate, hippocampi, thalami, and substantia nigra. Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation analysis. Cognition was assessed at the scan and in online follow-up (5.82 ± 0.86 years after baseline). Executive function was assessed with the trail-making test, fluid intelligence with puzzle tasks, and reaction time by a task based on the ""Snap"" card game. Mean age was 54.8 ± 7.4 years and 48.6% were female. Weekly alcohol consumption was 17.7 ± 15.9 units and never drinkers comprised 2.7% of the sample. Alcohol consumption was associated with markers of higher iron (χ) in putamen (β = 0.08 standard deviation (SD) [95% confidence interval (CI) 0.06 to 0.09], p < 0.001), caudate (β = 0.05 [0.04 to 0.07], p < 0.001), and substantia nigra (β = 0.03 [0.02 to 0.05], p < 0.001) and lower iron in the thalami (β = -0.06 [-0.07 to -0.04], p < 0.001). Quintile-based analyses found these associations in those consuming >7 units (56 g) alcohol weekly. MR analyses provided weak evidence these relationships are causal. Genetically predicted alcoholic drinks weekly positively associated with putamen and hippocampus susceptibility; however, these associations did not survive multiple testing corrections. Weak evidence for a causal relationship between genetically predicted alcohol use disorder and higher putamen susceptibility was observed; however, this was not robust to multiple comparisons correction. Genetically predicted alcohol use disorder was associated with serum iron and transferrin saturation. Elevated liver iron was observed at just >11 units (88 g) alcohol weekly c.f. <7 units (56 g). Systemic iron levels partially mediated associations of alcohol intake with brain iron. Markers of higher basal ganglia iron associated with slower executive function, lower fluid intelligence, and slower reaction times. The main limitations of the study include that χ and T2* can reflect changes in myelin as well as iron, alcohol use was self-reported, and MR estimates can be influenced by genetic pleiotropy.<h4>Conclusions</h4>To the best of our knowledge, this study represents the largest investigation of moderate alcohol consumption and iron homeostasis to date. Alcohol consumption above 7 units weekly associated with higher brain iron. Iron accumulation represents a potential mechanism for alcohol-related cognitive decline.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004039&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004039; html:https://europepmc.org/articles/PMC9282660; pdf:https://europepmc.org/articles/PMC9282660?pdf=render
 35717168,https://doi.org/10.1186/s12879-022-07490-4,The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.,"Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.",,BMC infectious diseases,2022,2022-06-18,Y,Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2,,,"<h4>Background</h4>SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown.<h4>Methods</h4>We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset > 7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020.<h4>Results</h4>In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases.<h4>Conclusions</h4>Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the ""first wave"" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07490-4; doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render
 34991479,https://doi.org/10.1186/s12877-021-02684-y,The dynamics of frailty development and progression in older adults in primary care in England (2006-2017): a retrospective cohort profile.,"Fogg C, Fraser SDS, Roderick P, de Lusignan S, Clegg A, Brailsford S, Barkham A, Patel HP, Windle V, Harris S, Zhu S, England T, Evenden D, Lambert F, Walsh B, Frailty Dynamics study team.",,BMC geriatrics,2022,2022-01-06,Y,Adults; Frailty; Cohort study; Primary Care; Service Use; Electronic Health Records; Computer Simulation Modelling; Trajectories,,,"<h4>Background</h4>Frailty is a common condition in older adults and has a major impact on patient outcomes and service use. Information on the prevalence in middle-aged adults and the patterns of progression of frailty at an individual and population level is scarce. To address this, a cohort was defined from a large primary care database in England to describe the epidemiology of frailty and understand the dynamics of frailty within individuals and across the population. This article describes the structure of the dataset, cohort characteristics and planned analyses.<h4>Methods</h4>Retrospective cohort study using electronic health records. Participants were aged ≥50 years registered in practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre between 2006 to 2017. Data include GP practice details, patient sociodemographic and clinical characteristics, twice-yearly electronic Frailty Index (eFI), deaths, medication use and primary and secondary care health service use. Participants in each cohort year by age group, GP and patient characteristics at cohort entry are described.<h4>Results</h4>The cohort includes 2,177,656 patients, contributing 15,552,946 person-years, registered at 419 primary care practices in England. The mean age was 61 years, 52.1% of the cohort was female, and 77.6% lived in urban environments. Frailty increased with age, affecting 10% of adults aged 50-64 and 43.7% of adults aged ≥65. The prevalence of long-term conditions and specific frailty deficits increased with age, as did the eFI and the severity of frailty categories.<h4>Conclusion</h4>A comprehensive understanding of frailty dynamics will inform predictions of current and future care needs to facilitate timely planning of appropriate interventions, service configurations and workforce requirements. Analysis of this large, nationally representative cohort including participants aged ≥50 will capture earlier transitions to frailty and enable a detailed understanding of progression and impact. These results will inform novel simulation models which predict future health and service needs of older people living with frailty.<h4>Study registration</h4>Registered on www.clinicaltrials.gov October 25th 2019, NCT04139278 .",,pdf:https://bmcgeriatr.biomedcentral.com/counter/pdf/10.1186/s12877-021-02684-y; doi:https://doi.org/10.1186/s12877-021-02684-y; html:https://europepmc.org/articles/PMC8740419; pdf:https://europepmc.org/articles/PMC8740419?pdf=render
 35188939,https://doi.org/10.1097/pts.0000000000000867,Optimizing Hospital Electronic Prescribing Systems: A Systematic Scoping Review.,"Williams J, Malden S, Heeney C, Bouamrane M, Holder M, Perera U, Bates DW, Sheikh A.",,Journal of patient safety,2022,2022-03-01,Y,,,,"<h4>Objective</h4>Considerable international investment in hospital electronic prescribing (ePrescribing) systems has been made, but despite this, it is proving difficult for most organizations to realize safety, quality, and efficiency gains in prescribing. The objective of this work was to develop policy-relevant insights into the optimization of hospital ePrescribing systems to maximize the benefits and minimize the risks of these expensive digital health infrastructures.<h4>Methods</h4>We undertook a systematic scoping review of the literature by searching MEDLINE, Embase, and CINAHL databases. We searched for primary studies reporting on ePrescribing optimization strategies and independently screened and abstracted data until saturation was achieved. Findings were theoretically and thematically synthesized taking a medicine life-cycle perspective, incorporating consultative phases with domain experts.<h4>Results</h4>We identified 23,609 potentially eligible studies from which 1367 satisfied our inclusion criteria. Thematic synthesis was conducted on a data set of 76 studies, of which 48 were based in the United States. Key approaches to optimization included the following: stakeholder engagement, system or process redesign, technological innovations, and education and training packages. Single-component interventions (n = 26) described technological optimization strategies focusing on a single, specific step in the prescribing process. Multicomponent interventions (n = 50) used a combination of optimization strategies, typically targeting multiple steps in the medicines management process.<h4>Discussion</h4>We identified numerous optimization strategies for enhancing the performance of ePrescribing systems. Key considerations for ePrescribing optimization include meaningful stakeholder engagement to reconceptualize the service delivery model and implementing technological innovations with supporting training packages to simultaneously impact on different facets of the medicines management process.",,html:https://journals.lww.com/journalpatientsafety/Fulltext/2022/03000/Optimizing_Hospital_Electronic_Prescribing.36.aspx; doi:https://doi.org/10.1097/PTS.0000000000000867; html:https://europepmc.org/articles/PMC8855945; pdf:https://europepmc.org/articles/PMC8855945?pdf=render
@@ -1721,13 +1721,13 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33325834,https://doi.org/10.2196/23530,Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application.,"Wolfe C, Pestian T, Gecili E, Su W, Keogh RH, Pestian JP, Seid M, Diggle PJ, Ziady A, Clancy JP, Grossoehme DH, Szczesniak RD, Brokamp C.",,JMIR medical informatics,2020,2020-12-16,Y,Chronic disease; Clinical Decision Support; Medical Monitoring; Clinical Decision Rules; Application Programming Interface,,,"<h4>Background</h4>Despite steady gains in life expectancy, individuals with cystic fibrosis (CF) lung disease still experience rapid pulmonary decline throughout their clinical course, which can ultimately end in respiratory failure. Point-of-care tools for accurate and timely information regarding the risk of rapid decline is essential for clinical decision support.<h4>Objective</h4>This study aims to translate a novel algorithm for earlier, more accurate prediction of rapid lung function decline in patients with CF into an interactive web-based application that can be integrated within electronic health record systems, via collaborative development with clinicians.<h4>Methods</h4>Longitudinal clinical history, lung function measurements, and time-invariant characteristics were obtained for 30,879 patients with CF who were followed in the US Cystic Fibrosis Foundation Patient Registry (2003-2015). We iteratively developed the application using the R Shiny framework and by conducting a qualitative study with care provider focus groups (N=17).<h4>Results</h4>A clinical conceptual model and 4 themes were identified through coded feedback from application users: (1) ambiguity in rapid decline, (2) clinical utility, (3) clinical significance, and (4) specific suggested revisions. These themes were used to revise our application to the currently released version, available online for exploration. This study has advanced the application's potential prognostic utility for monitoring individuals with CF lung disease. Further application development will incorporate additional clinical characteristics requested by the users and also a more modular layout that can be useful for care provider and family interactions.<h4>Conclusions</h4>Our framework for creating an interactive and visual analytics platform enables generalized development of applications to synthesize, model, and translate electronic health data, thereby enhancing clinical decision support and improving care and health outcomes for chronic diseases and disorders. A prospective implementation study is necessary to evaluate this tool's effectiveness regarding increased communication, enhanced shared decision-making, and improved clinical outcomes for patients with CF.",,pdf:https://medinform.jmir.org/2020/12/e23530/PDF; doi:https://doi.org/10.2196/23530; html:https://europepmc.org/articles/PMC7773511
 33025017,https://doi.org/10.1093/schbul/sbaa126,Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.,"Irving J, Patel R, Oliver D, Colling C, Pritchard M, Broadbent M, Baldwin H, Stahl D, Stewart R, Fusar-Poli P.",,Schizophrenia bulletin,2021,2021-03-01,N,Prediction; Prevention; Psychosis; Machine Learning; Electronic Health Records; Natural Language Processing,,,"<h4>Background</h4>Using novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis.<h4>Method</h4>The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell's C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia.<h4>Results</h4>A total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3-3.6). External validation indicated strong performance on unseen data (Harrell's C 0.85, 95% CI 0.84-0.86), an increase of 0.06 from the original model.<h4>Conclusions</h4>Using NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.",,pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/405/36620462/sbaa126.pdf; doi:https://doi.org/10.1093/schbul/sbaa126; html:https://europepmc.org/articles/PMC7965059; pdf:https://europepmc.org/articles/PMC7965059?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa126
 33185016,https://doi.org/10.1002/art.41593,Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.,"Chandan JS, Zemedikun DT, Thayakaran R, Byne N, Dhalla S, Acosta-Mena D, Gokhale KM, Thomas T, Sainsbury C, Subramanian A, Cooper J, Anand A, Okoth KO, Wang J, Adderley NJ, Taverner T, Denniston AK, Lord J, Thomas GN, Buckley CD, Raza K, Bhala N, Nirantharakumar K, Haroon S.",,"Arthritis & rheumatology (Hoboken, N.J.)",2021,2021-05-01,Y,,,,"<h4>Objective</h4>To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.<h4>Methods</h4>We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.<h4>Results</h4>During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex.<h4>Conclusion</h4>No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/art.41593; doi:https://doi.org/10.1002/art.41593; html:https://europepmc.org/articles/PMC8252419; pdf:https://europepmc.org/articles/PMC8252419?pdf=render
+31564467,https://doi.org/10.1016/s2215-0366(19)30369-4,"The burden of mental ill health associated with childhood maltreatment in the UK, using The Health Improvement Network database: a population-based retrospective cohort study.","Chandan JS, Thomas T, Gokhale KM, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,The lancet. Psychiatry,2019,2019-09-26,N,,,,"<h4>Background</h4>Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health.<h4>Methods</h4>In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients.<h4>Findings</h4>The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11 831 850 patients were eligible to participate. Of these patients, we identified 217 758 (1·8%) patients with any recorded childhood maltreatment. These patients were matched to 423 410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1·8 years (IQR 0·6-4·3) versus 3·2 years (1·3-6·1) in the unexposed group. During the study period, 11 665 (5·9%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16·8 events per 1000 person-years versus 15 301 (3·7%) new recorded diagnoses at an incidence rate of 8·3 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2·14 (95% CI 2·08-2·19). 30 911 (14·8%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46·5 events per 1000 person-years) versus 36 390 (8·9%) patients in the unexposed group (20·5 per 1000 person-years) resulting in an adjusted IRR of 2·44 (95% CI 2·40-2·48).<h4>Interpretation</h4>Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health.<h4>Funding</h4>None.",,pdf:http://pure-oai.bham.ac.uk/ws/files/77236664/Chandan_et_al_The_burden_of_mental_ill_health_associated_with_childhood_maltreatment_in_the_UK_using_The_Health_Improvement_Network_database_The_Lancet_Psychiatry_2019.pdf; doi:https://doi.org/10.1016/S2215-0366(19)30369-4
 35507331,https://doi.org/10.1002/art.42154,Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling.,"Soomro M, Stadler M, Dand N, Bluett J, Jadon D, Jalali-Najafabadi F, Duckworth M, Ho P, Marzo-Ortega H, Helliwell PS, Ryan AW, Kane D, Korendowych E, Simpson MA, Packham J, McManus R, Gabay C, Lamacchia C, Nissen MJ, Brown MA, Verstappen SMM, Van Staa T, Barker JN, Smith CH, BADBIR Study Group, BSTOP study group, FitzGerald O, McHugh N, Warren RB, Bowes J, Barton A.",,"Arthritis & rheumatology (Hoboken, N.J.)",2022,2022-08-04,Y,,,,"<h4>Objectives</h4>Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models.<h4>Methods</h4>Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h<sup>2</sup> <sub>SNP</sub> ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation.<h4>Results</h4>We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10<sup>-9</sup> ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10<sup>-45</sup> ) and Wnt signaling (adjusted P = 9.5 × 10<sup>-58</sup> ). The heritability of PsA in this cohort was found to be moderate (h<sup>2</sup> <sub>SNP</sub>  = 0.63), which was similar to the heritability of PsC (h<sup>2</sup> <sub>SNP</sub>  = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data.<h4>Conclusion</h4>Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.",,pdf:https://eprints.whiterose.ac.uk/191095/1/Arthritis%20%20%20Rheumatology%20-%202022%20-%20Soomro%20-%20Comparative%20Genetic%20Analysis%20of%20Psoriatic%20Arthritis%20and%20Psoriasis%20for%20the.pdf; doi:https://doi.org/10.1002/art.42154; html:https://europepmc.org/articles/PMC9539852; pdf:https://europepmc.org/articles/PMC9539852?pdf=render
 35606928,https://doi.org/10.1111/bjd.21677,Biomarkers of systemic treatment response in people with psoriasis: a scoping review.,"Corbett M, Ramessur R, Marshall D, Acencio ML, Ostaszewski M, Barbosa IA, Dand N, Di Meglio P, Haddad S, Jensen AHM, Koopmann W, Mahil SK, Rahmatulla S, Rastrick J, Saklatvala J, Weidinger S, Wright K, Eyerich K, Barker JN, Ndlovu M, Conrad C, Skov L, Smith CH, BIOMAP consortium.",,The British journal of dermatology,2022,2022-07-20,Y,,,,"<h4>Background</h4>Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare.<h4>Objectives</h4>To perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community.<h4>Methods</h4>A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with systemic treatment response. The main outcomes were any measure of systemic treatment efficacy or safety. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise and mapped to relevant cellular and molecular pathways.<h4>Results</h4>Of 71 included studies (67 studying effectiveness outcomes and eight safety outcomes; four studied both), most reported genomic or proteomic biomarkers associated with response to biologics (48 studies). Methodological or reporting limitations frequently compromised the interpretation of findings, including inadequate control for key covariates, lack of adjustment for multiple testing, and selective outcome reporting. We identified candidate biomarkers of efficacy to tumour necrosis factor inhibitors [variation in CARD14, CDKAL1, IL1B, IL12B and IL17RA loci, and lipopolysaccharide-induced phosphorylation of nuclear factor (NF)-κB in type 2 dendritic cells] and ustekinumab (HLA-C*06:02 and variation in an IL1B locus). None were supported by sufficient evidence for clinical use without further validation studies. Candidate biomarkers were found to be involved in the immune cellular crosstalk implicated in psoriasis pathogenesis, most notably antigen presentation, T helper (Th)17 cell differentiation, positive regulation of NF-κB, and Th17 cell activation.<h4>Conclusions</h4>This comprehensive catalogue provides a key resource for researchers and reveals a diverse range of biomarker types and outcomes in the included studies. The candidate biomarkers identified require further evaluation in methodologically robust studies to establish potential clinical utility. Future studies should aim to address the common methodological limitations highlighted in this review to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare. What does this study add? This review provides a comprehensive catalogue of investigated biomarkers of systemic treatment response in psoriasis. A diverse range of biomarker types and outcomes was found in the included studies, serving as a key resource for the translational research community.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796396; doi:https://doi.org/10.1111/bjd.21677; html:https://europepmc.org/articles/PMC9796396; pdf:https://europepmc.org/articles/PMC9796396?pdf=render
-31564467,https://doi.org/10.1016/s2215-0366(19)30369-4,"The burden of mental ill health associated with childhood maltreatment in the UK, using The Health Improvement Network database: a population-based retrospective cohort study.","Chandan JS, Thomas T, Gokhale KM, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,The lancet. Psychiatry,2019,2019-09-26,N,,,,"<h4>Background</h4>Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health.<h4>Methods</h4>In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients.<h4>Findings</h4>The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11 831 850 patients were eligible to participate. Of these patients, we identified 217 758 (1·8%) patients with any recorded childhood maltreatment. These patients were matched to 423 410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1·8 years (IQR 0·6-4·3) versus 3·2 years (1·3-6·1) in the unexposed group. During the study period, 11 665 (5·9%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16·8 events per 1000 person-years versus 15 301 (3·7%) new recorded diagnoses at an incidence rate of 8·3 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2·14 (95% CI 2·08-2·19). 30 911 (14·8%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46·5 events per 1000 person-years) versus 36 390 (8·9%) patients in the unexposed group (20·5 per 1000 person-years) resulting in an adjusted IRR of 2·44 (95% CI 2·40-2·48).<h4>Interpretation</h4>Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health.<h4>Funding</h4>None.",,pdf:http://pure-oai.bham.ac.uk/ws/files/77236664/Chandan_et_al_The_burden_of_mental_ill_health_associated_with_childhood_maltreatment_in_the_UK_using_The_Health_Improvement_Network_database_The_Lancet_Psychiatry_2019.pdf; doi:https://doi.org/10.1016/S2215-0366(19)30369-4
 34767555,https://doi.org/10.1371/journal.pmed.1003832,Educational and health outcomes of schoolchildren in local authority care in Scotland: A retrospective record linkage study.,"Fleming M, McLay JS, Clark D, King A, Mackay DF, Minnis H, Pell JP.",,PLoS medicine,2021,2021-11-12,Y,,,,"<h4>Background</h4>Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders.<h4>Methods and findings</h4>Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care.<h4>Conclusions</h4>Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003832&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003832; html:https://europepmc.org/articles/PMC8589203; pdf:https://europepmc.org/articles/PMC8589203?pdf=render
 34432797,https://doi.org/10.1371/journal.pone.0255748,Regional performance variation in external validation of four prediction models for severity of COVID-19 at hospital admission: An observational multi-centre cohort study.,"Wickstrøm KE, Vitelli V, Carr E, Holten AR, Bendayan R, Reiner AH, Bean D, Searle T, Shek A, Kraljevic Z, Teo J, Dobson R, Tonby K, Köhn-Luque A, Amundsen EK.",,PloS one,2021,2021-08-25,Y,,,,"<h4>Background</h4>Prediction models should be externally validated to assess their performance before implementation. Several prediction models for coronavirus disease-19 (COVID-19) have been published. This observational cohort study aimed to validate published models of severity for hospitalized patients with COVID-19 using clinical and laboratory predictors.<h4>Methods</h4>Prediction models fitting relevant inclusion criteria were chosen for validation. The outcome was either mortality or a composite outcome of mortality and ICU admission (severe disease). 1295 patients admitted with symptoms of COVID-19 at Kings Cross Hospital (KCH) in London, United Kingdom, and 307 patients at Oslo University Hospital (OUH) in Oslo, Norway were included. The performance of the models was assessed in terms of discrimination and calibration.<h4>Results</h4>We identified two models for prediction of mortality (referred to as Xie and Zhang1) and two models for prediction of severe disease (Allenbach and Zhang2). The performance of the models was variable. For prediction of mortality Xie had good discrimination at OUH with an area under the receiver-operating characteristic (AUROC) 0.87 [95% confidence interval (CI) 0.79-0.95] and acceptable discrimination at KCH, AUROC 0.79 [0.76-0.82]. In prediction of severe disease, Allenbach had acceptable discrimination (OUH AUROC 0.81 [0.74-0.88] and KCH AUROC 0.72 [0.68-0.75]). The Zhang models had moderate to poor discrimination. Initial calibration was poor for all models but improved with recalibration.<h4>Conclusions</h4>The performance of the four prediction models was variable. The Xie model had the best discrimination for mortality, while the Allenbach model had acceptable results for prediction of severe disease.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0255748&type=printable; doi:https://doi.org/10.1371/journal.pone.0255748; html:https://europepmc.org/articles/PMC8386866; pdf:https://europepmc.org/articles/PMC8386866?pdf=render
-35331425,https://doi.org/10.1016/j.jacep.2021.09.001,Clinical Characteristics and Follow-Up of Pediatric-Onset Arrhythmogenic Right Ventricular Cardiomyopathy.,"Roudijk RW, Verheul L, Bosman LP, Bourfiss M, Breur JMPJ, Slieker MG, Blank AC, Dooijes D, van der Heijden JF, van den Heuvel F, Clur SA, Udink Ten Cate FEA, van den Berg MP, Wilde AAM, Asselbergs FW, Peter van Tintelen J, Te Riele ASJM.",,JACC. Clinical electrophysiology,2022,2021-12-22,N,Genetics; Ventricular tachycardia; Heart Failure; Sudden Cardiac Death; Arrhythmogenic Right Ventricular Cardiomyopathy; Pediatric-onset; Cascade Screening,,,"<h4>Objectives</h4>The goal of this study was to describe characteristics, cascade screening results, and predictors of adverse outcome in pediatric-onset arrhythmogenic right ventricular cardiomyopathy (ARVC).<h4>Background</h4>Although ARVC is increasingly recognized in children, pediatric ARVC cohorts remain underrepresented in the literature.<h4>Methods</h4>This study included 12 probands with pediatric-onset ARVC (aged <18 years at diagnosis) and 68 pediatric relatives (aged <18 years at first evaluation) referred for cascade screening. ARVC diagnosis was based on 2010 Task Force Criteria. Clinical presentation, diagnostic testing, and outcomes (sustained ventricular tachycardia [VT]; heart failure) were ascertained. Predictors of adverse outcome were determined by using univariable logistic regression.<h4>Results</h4>Pediatric-onset ARVC was diagnosed in 12 probands and 12 (18%) relatives at a median age of 16.6 years (interquartile range: 13.8-17.4 years), whereas 12 (18%) relatives reached ARVC diagnosis as adults (median age, 22.0 years; interquartile range: 20.0-26.7 years). Sudden cardiac death/arrest was the first disease manifestation in 3 (25%) probands and 3 (4%) relatives. In patients without ARVC diagnosis at presentation (n = 61), electrocardiogram and Holter monitoring abnormalities occurred before development of imaging Task Force Criteria (7.3 ± 5.0 years vs 8.4 ± 5.0 years). Clinical course was characterized by sustained VT (91%) and heart failure (36%) in probands, which were rare in relatives (2% and 0%, respectively). Male sex (P < 0.01), T-wave inversion V<sub>1</sub>-V<sub>3</sub> (P < 0.01), premature ventricular complexes/runs (P ≤ 0.01), and decrease in biventricular ejection fraction (P ≤ 0.01) were associated with VT occurrence.<h4>Conclusions</h4>Pediatric ARVC carries high arrhythmic risk, especially in probands. Disease progression is particularly observed on electrocardiogram or Holter monitoring. Arrhythmic events are associated with male sex, T-wave inversions, premature ventricular complexes/runs, and reduced biventricular ejection fraction.",,doi:https://doi.org/10.1016/j.jacep.2021.09.001; doi:https://doi.org/10.1016/j.jacep.2021.09.001
 32951912,https://doi.org/10.1016/j.jhep.2020.08.030,"Corrigendum to: ""Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis"" [J Hepatol (2020) 241-251].","Parisinos CA, Wilman HR, Thomas EL, Kelly M, Nicholls RC, McGonigle J, Neubauer S, Hingorani AD, Patel RS, Hemingway H, Bell JD, Banerjee R, Yaghootkar H.",,Journal of hepatology,2020,2020-09-18,Y,,,,,,pdf:http://www.journal-of-hepatology.eu/article/S0168827820336035/pdf; doi:https://doi.org/10.1016/j.jhep.2020.08.030; html:https://europepmc.org/articles/PMC8055539; pdf:https://europepmc.org/articles/PMC8055539?pdf=render
+35331425,https://doi.org/10.1016/j.jacep.2021.09.001,Clinical Characteristics and Follow-Up of Pediatric-Onset Arrhythmogenic Right Ventricular Cardiomyopathy.,"Roudijk RW, Verheul L, Bosman LP, Bourfiss M, Breur JMPJ, Slieker MG, Blank AC, Dooijes D, van der Heijden JF, van den Heuvel F, Clur SA, Udink Ten Cate FEA, van den Berg MP, Wilde AAM, Asselbergs FW, Peter van Tintelen J, Te Riele ASJM.",,JACC. Clinical electrophysiology,2022,2021-12-22,N,Genetics; Ventricular tachycardia; Heart Failure; Sudden Cardiac Death; Arrhythmogenic Right Ventricular Cardiomyopathy; Pediatric-onset; Cascade Screening,,,"<h4>Objectives</h4>The goal of this study was to describe characteristics, cascade screening results, and predictors of adverse outcome in pediatric-onset arrhythmogenic right ventricular cardiomyopathy (ARVC).<h4>Background</h4>Although ARVC is increasingly recognized in children, pediatric ARVC cohorts remain underrepresented in the literature.<h4>Methods</h4>This study included 12 probands with pediatric-onset ARVC (aged <18 years at diagnosis) and 68 pediatric relatives (aged <18 years at first evaluation) referred for cascade screening. ARVC diagnosis was based on 2010 Task Force Criteria. Clinical presentation, diagnostic testing, and outcomes (sustained ventricular tachycardia [VT]; heart failure) were ascertained. Predictors of adverse outcome were determined by using univariable logistic regression.<h4>Results</h4>Pediatric-onset ARVC was diagnosed in 12 probands and 12 (18%) relatives at a median age of 16.6 years (interquartile range: 13.8-17.4 years), whereas 12 (18%) relatives reached ARVC diagnosis as adults (median age, 22.0 years; interquartile range: 20.0-26.7 years). Sudden cardiac death/arrest was the first disease manifestation in 3 (25%) probands and 3 (4%) relatives. In patients without ARVC diagnosis at presentation (n = 61), electrocardiogram and Holter monitoring abnormalities occurred before development of imaging Task Force Criteria (7.3 ± 5.0 years vs 8.4 ± 5.0 years). Clinical course was characterized by sustained VT (91%) and heart failure (36%) in probands, which were rare in relatives (2% and 0%, respectively). Male sex (P < 0.01), T-wave inversion V<sub>1</sub>-V<sub>3</sub> (P < 0.01), premature ventricular complexes/runs (P ≤ 0.01), and decrease in biventricular ejection fraction (P ≤ 0.01) were associated with VT occurrence.<h4>Conclusions</h4>Pediatric ARVC carries high arrhythmic risk, especially in probands. Disease progression is particularly observed on electrocardiogram or Holter monitoring. Arrhythmic events are associated with male sex, T-wave inversions, premature ventricular complexes/runs, and reduced biventricular ejection fraction.",,doi:https://doi.org/10.1016/j.jacep.2021.09.001; doi:https://doi.org/10.1016/j.jacep.2021.09.001
 37118290,https://doi.org/10.1038/s43587-022-00293-x,Immune system-wide Mendelian randomization and triangulation analyses support autoimmunity as a modifiable component in dementia-causing diseases.,"Lindbohm JV, Mars N, Sipilä PN, Singh-Manoux A, Runz H, FinnGen, Livingston G, Seshadri S, Xavier R, Hingorani AD, Ripatti S, Kivimäki M.",,Nature aging,2022,2022-10-14,Y,,,,"Immune system and blood-brain barrier dysfunction are implicated in the development of Alzheimer's and other dementia-causing diseases, but their causal role remains unknown. We performed Mendelian randomization for 1,827 immune system- and blood-brain barrier-related biomarkers and identified 127 potential causal risk factors for dementia-causing diseases. Pathway analyses linked these biomarkers to amyloid-β, tau and α-synuclein pathways and to autoimmunity-related processes. A phenome-wide analysis using Mendelian randomization-based polygenic risk score in the FinnGen study (n = 339,233) for the biomarkers indicated shared genetic background for dementias and autoimmune diseases. This association was further supported by human leukocyte antigen analyses. In inverse-probability-weighted analyses that simulate randomized controlled drug trials in observational data, anti-inflammatory methotrexate treatment reduced the incidence of Alzheimer's disease in high-risk individuals (hazard ratio compared with no treatment, 0.64, 95% confidence interval 0.49-0.88, P = 0.005). These converging results from different lines of human research suggest that autoimmunity is a modifiable component in dementia-causing diseases.",,pdf:https://www.nature.com/articles/s43587-022-00293-x.pdf; doi:https://doi.org/10.1038/s43587-022-00293-x; html:https://europepmc.org/articles/PMC10154235; pdf:https://europepmc.org/articles/PMC10154235?pdf=render
 31912232,https://doi.org/10.1007/s00394-019-02170-7,Adherence to the Dutch dietary guidelines and 15-year incidence of heart failure in the EPIC-NL cohort.,"Harbers MC, de Kroon AM, Boer JMA, Asselbergs FW, Geleijnse JM, Verschuren WMM, van der Schouw YT, Sluijs I.",,European journal of nutrition,2020,2020-01-07,N,Heart Failure; Dietary Patterns; Dutch Healthy Diet 2015 Index; Dutch Dietary Guidelines,,,"<h4>Purpose</h4>A healthy diet may contribute to the primary prevention of heart failure (HF), but evidence is still inconclusive. We aimed to study the association between adherence to the Dutch dietary guidelines and incidence of HF.<h4>Methods</h4>We studied 37,468 participants aged 20-70 years and free of HF at baseline from the EPIC-NL cohort. At baseline (1993-1997), data were collected on demographics, lifestyle, and presence of chronic diseases. Dietary intake was assessed using a 178-item validated food frequency questionnaire. Dietary intake data were used to calculate scores on the Dutch Healthy Diet 2015 Index (DHD15-index) measuring adherence to the Dutch dietary guidelines. The DHD15-index is based on the average daily intake of 14 food groups resulting in a total score ranging between 0 and 140, with higher scores indicating better adherence. HF morbidity and mortality during follow-up were ascertained through linkage with national registries. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between DHD15 adherence and HF risk, adjusting for sociodemographic and lifestyle characteristics.<h4>Results</h4>The average score on the DHD15-index was 71 (SD = 15). During a median follow-up of 15.2 years (IQR 14.1-16.5), 674 HF events occurred. After adjustment for demographic and lifestyle characteristics, higher scores on the DHD15-index were associated with lower risk of HF (HR<sub>Q4vsQ1</sub> 0.73; 95% CI 0.58-0.93; P<sub>trend</sub> 0.001).<h4>Conclusion</h4>In a large Dutch population of middle-aged adults, higher adherence to the Dutch dietary guidelines was associated with lower risk of HF.",,pdf:https://discovery.ucl.ac.uk/id/eprint/10104999/1/Harbers%20et%20al.%202019%20Adh%20do%20Dutch%20dietary%20guidelines%20and%20HF.pdf; doi:https://doi.org/10.1007/s00394-019-02170-7
 33769566,https://doi.org/10.1111/bph.15459,Emerging therapies and their delivery for treating age-related macular degeneration.,"Thomas CN, Sim DA, Lee WH, Alfahad N, Dick AD, Denniston AK, Hill LJ.",,British journal of pharmacology,2022,2021-05-12,N,Retina; Complement; Immunotherapy; Age-related macular degeneration; Drug Delivery; Anti-vegf; Ocular Disease,,,"Age-related macular degeneration (AMD) is the most common cause of blindness in the Western world and is characterised in its latter stages by retinal cell death and neovascularisation and earlier stages with the loss of parainflammatory homeostasis. Patients with neovascular AMD (nAMD) are treated with frequent intraocular injections of anti-vascular endothelial growth factor (VEGF) therapies, which are not only unpopular with patients but carry risks of sight-threatening complications. A minority of patients are unresponsive with no alternative treatment available, and some patients who respond initially eventually develop a tolerance to treatment. New therapeutics with improved delivery methods and sustainability of clinical effects are required, in particular for non-neovascular AMD (90% of cases and no current approved treatments). There are age-related and disease-related changes that occur which can affect ocular drug delivery. Here, we review the latest emerging therapies for AMD, their delivery routes and implications for translating to clinical practice. LINKED ARTICLES: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bph.15459; doi:https://doi.org/10.1111/bph.15459
@@ -1735,12 +1735,12 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34192199,https://doi.org/10.1136/bmjpo-2021-001049,Staff-pupil SARS-CoV-2 infection pathways in schools in Wales: a population-level linked data approach.,"Thompson DA, Abbasizanjani H, Fry R, Marchant E, Griffiths L, Akbari A, Hollinghurst J, North L, Lyons J, Torabi F, Davies G, Gravenor MB, Lyons RA.",,BMJ paediatrics open,2021,2021-05-10,Y,Disease transmission; Schools; Public Health; Sars-cov-2,,,"<h4>Background</h4>Better understanding of the role that children and school staff play in the transmission of SARS-CoV-2 is essential to guide policy development on controlling infection while minimising disruption to children's education and well-being.<h4>Methods</h4>Our national e-cohort (n=464531) study used anonymised linked data for pupils, staff and associated households linked via educational settings in Wales. We estimated the odds of testing positive for SARS-CoV-2 infection for staff and pupils over the period August- December 2020, dependent on measures of recent exposure to known cases linked to their educational settings.<h4>Results</h4>The total number of cases in a school was not associated with a subsequent increase in the odds of testing positive (staff OR per case: 0.92, 95% CI 0.85 to 1.00; pupil OR per case: 0.98, 95% CI 0.93 to 1.02). Among pupils, the number of recent cases within the same year group was significantly associated with subsequent increased odds of testing positive (OR per case: 1.12, 95% CI 1.08 to 1.15). These effects were adjusted for a range of demographic covariates, and in particular any known cases within the same household, which had the strongest association with testing positive (staff OR: 39.86, 95% CI 35.01 to 45.38; pupil OR: 9.39, 95% CI 8.94 to 9.88).<h4>Conclusions</h4>In a national school cohort, the odds of staff testing positive for SARS-CoV-2 infection were not significantly increased in the 14-day period after case detection in the school. However, pupils were found to be at increased odds, following cases appearing within their own year group, where most of their contacts occur. Strong mitigation measures over the whole of the study period may have reduced wider spread within the school environment.",,pdf:https://bmjpaedsopen.bmj.com/content/bmjpo/5/1/e001049.full.pdf; doi:https://doi.org/10.1136/bmjpo-2021-001049; html:https://europepmc.org/articles/PMC8111870; pdf:https://europepmc.org/articles/PMC8111870?pdf=render
 32285648,https://doi.org/10.1002/ehf2.12689,Predicting sustained ventricular arrhythmias in dilated cardiomyopathy: a meta-analysis and systematic review.,"Sammani A, Kayvanpour E, Bosman LP, Sedaghat-Hamedani F, Proctor T, Gi WT, Broezel A, Jensen K, Katus HA, Te Riele ASJM, Meder B, Asselbergs FW.",,ESC heart failure,2020,2020-04-14,Y,Prognosis; Dilated cardiomyopathy; risk; Sudden Cardiac Death; Implantable Cardiac-defibrillator,,,"<h4>Aims</h4>Patients with non-ischaemic dilated cardiomyopathy (DCM) are at increased risk of sudden cardiac death. Identification of patients that may benefit from implantable cardioverter-defibrillator implantation remains challenging. In this study, we aimed to determine predictors of sustained ventricular arrhythmias in patients with DCM.<h4>Methods and results</h4>We searched MEDLINE/Embase for studies describing predictors of sustained ventricular arrhythmias in patients with DCM. Quality and bias were assessed using the Quality in Prognostic Studies tool, articles with high risk of bias in ≥2 areas were excluded. Unadjusted hazard ratios (HRs) of uniformly defined predictors were pooled, while all other predictors were evaluated in a systematic review. We included 55 studies (11 451 patients and 3.7 ± 2.3 years follow-up). Crude annual event rate was 4.5%. Younger age [HR 0.82; 95% CI (0.74-1.00)], hypertension [HR 1.95; 95% CI (1.26-3.00)], prior sustained ventricular arrhythmia [HR 4.15; 95% CI (1.32-13.02)], left ventricular ejection fraction on ultrasound [HR 1.45; 95% CI (1.19-1.78)], left ventricular dilatation (HR 1.10), and presence of late gadolinium enhancement [HR 5.55; 95% CI (4.02-7.67)] were associated with arrhythmic outcome in pooled analyses. Prior non-sustained ventricular arrhythmia and several genotypes [mutations in Phospholamban (PLN), Lamin A/C (LMNA), and Filamin-C (FLNC)] were associated with arrhythmic outcome in non-pooled analyses. Quality of evidence was moderate, and heterogeneity among studies was moderate to high.<h4>Conclusions</h4>In patients with DCM, the annual event rate of sustained ventricular arrhythmias is approximately 4.5%. This risk is considerably higher in younger patients with hypertension, prior (non-)sustained ventricular arrhythmia, decreased left ventricular ejection fraction, left ventricular dilatation, late gadolinium enhancement, and genetic mutations (PLN, LMNA, and FLNC). These results may help determine appropriate candidates for implantable cardioverter-defibrillator implantation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.12689; doi:https://doi.org/10.1002/ehf2.12689; html:https://europepmc.org/articles/PMC7373946; pdf:https://europepmc.org/articles/PMC7373946?pdf=render
 32680743,https://doi.org/10.1016/j.jphys.2020.06.008,"Adaptation, self-motivation and support services are key to physical activity participation three to five years after major trauma: a qualitative study.","Ekegren CL, Braaf S, Ameratunga S, Ponsford J, Nunn A, Cameron P, Lyons RA, Gabbe BJ.",,Journal of physiotherapy,2020,2020-07-14,N,Trauma; Recovery; Exercise; wounds and injuries; Sedentary Lifestyle,,,"<h4>Questions</h4>What are the perceived long-term impacts of major trauma on physical activity participation over time? What factors influence physical activity participation in people recovering from major trauma?<h4>Design</h4>Longitudinal qualitative study.<h4>Participants</h4>Sixty-six people aged ≥ 16 years with non-neurological major trauma.<h4>Methods</h4>Participants were interviewed 3 years (n = 66), 4 years (n = 63) and 5 years (n = 57) after their injury. A thematic analysis was performed.<h4>Results</h4>Despite wanting to be physically active, many participants experienced significant, long-term physical activity restriction after their injury, which persisted over time. Restrictions were often related to a fear of re-injury or of exacerbating pain and fatigue levels. These restrictions were a source of distress and frustration for many participants, given the perceived impacts on their social life, family roles and enjoyment of life. Participants were also concerned about weight gain, health decline and reduced physical fitness. Participants valued the support of insurers and specialised services in facilitating access to modified activities, such as clinical Pilates and hydrotherapy. Many participants also recognised the importance of adaptation, goal-setting, self-motivation and determination to be physically active despite limitations.<h4>Conclusion</h4>People recovering from major trauma experienced significant and persistent physical activity restriction after their injury. Given the high prevalence of activity restrictions, distress and health concerns that were reported, there is an urgent need to develop and evaluate support strategies to improve physical activity participation in this group.",,doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008
-36470992,https://doi.org/10.1038/s41375-022-01773-0,Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.,"Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",,Leukemia,2023,2022-12-05,Y,,,,"The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n = 107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",,pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render
 33692554,https://doi.org/10.1038/s41586-021-03243-6,Improving reporting standards for polygenic scores in risk prediction studies.,"Wand H, Lambert SA, Tamburro C, Iacocca MA, O'Sullivan JW, Sillari C, Kullo IJ, Rowley R, Dron JS, Brockman D, Venner E, McCarthy MI, Antoniou AC, Easton DF, Hegele RA, Khera AV, Chatterjee N, Kooperberg C, Edwards K, Vlessis K, Kinnear K, Danesh JN, Parkinson H, Ramos EM, Roberts MC, Ormond KE, Khoury MJ, Janssens ACJW, Goddard KAB, Kraft P, MacArthur JAL, Inouye M, Wojcik GL.",,Nature,2021,2021-03-10,N,,,,"Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609771; doi:https://doi.org/10.1038/s41586-021-03243-6; html:https://europepmc.org/articles/PMC8609771; pdf:https://europepmc.org/articles/PMC8609771?pdf=render; doi:https://doi.org/10.1038/s41586-021-03243-6
 33678251,https://doi.org/10.1016/j.jaci.2020.08.026,"The intersect of genetics, environment, and microbiota in asthma-perspectives and challenges.","Tang HHF, Teo SM, Sly PD, Holt PG, Inouye M.",,The Journal of allergy and clinical immunology,2021,2021-03-01,N,Environment; Genomics; Asthma; Microbiota; systems biology; Gene-environment Interaction; Allergy And Immunology,,,"In asthma, a significant portion of the interaction between genetics and environment occurs through microbiota. The proposed mechanisms behind this interaction are complex and at times contradictory. This review covers recent developments in our understanding of this interaction: the ""microbial hypothesis"" and the ""farm effect""; the role of endotoxin and genetic variation in pattern recognition systems; the interaction with allergen exposure; the additional involvement of host gut and airway microbiota; the role of viral respiratory infections in interaction with the 17q21 and CDHR3 genetic loci; and the importance of in utero and early-life timing of exposures. We propose a unified framework for understanding how all these phenomena interact to drive asthma pathogenesis. Finally, we point out some future challenges for continued research in this field, in particular the need for multiomic integration, as well as the potential utility of asthma endotyping.",,doi:https://doi.org/10.1016/j.jaci.2020.08.026
+36470992,https://doi.org/10.1038/s41375-022-01773-0,Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.,"Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",,Leukemia,2023,2022-12-05,Y,,,,"The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n = 107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",,pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render
 33222494,https://doi.org/10.1177/2048872620974605,Cardiac complications in patients hospitalised with COVID-19.,"Linschoten M, Peters S, van Smeden M, Jewbali LS, Schaap J, Siebelink HM, Smits PC, Tieleman RG, van der Harst P, van Gilst WH, Asselbergs FW, CAPACITY-COVID collaborative consortium.",,European heart journal. Acute cardiovascular care,2020,2020-11-21,Y,Pulmonary embolism; Cohorts; Cardiac Complications; Patient Registry; Covid-19/coronavirus,,,"<h4>Aims</h4>To determine the frequency and pattern of cardiac complications in patients hospitalised with coronavirus disease (COVID-19).<h4>Methods and results</h4>CAPACITY-COVID is an international patient registry established to determine the role of cardiovascular disease in the COVID-19 pandemic. In this registry, data generated during routine clinical practice are collected in a standardised manner for patients with a (highly suspected) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring hospitalisation. For the current analysis, consecutive patients with laboratory confirmed COVID-19 registered between 28 March and 3 July 2020 were included. Patients were followed for the occurrence of cardiac complications and pulmonary embolism from admission to discharge. In total, 3011 patients were included, of which 1890 (62.8%) were men. The median age was 67 years (interquartile range 56-76); 937 (31.0%) patients had a history of cardiac disease, with pre-existent coronary artery disease being most common (<i>n</i>=463, 15.4%). During hospitalisation, 595 (19.8%) patients died, including 16 patients (2.7%) with cardiac causes. Cardiac complications were diagnosed in 349 (11.6%) patients, with atrial fibrillation (<i>n</i>=142, 4.7%) being most common. The incidence of other cardiac complications was 1.8% for heart failure (<i>n</i>=55), 0.5% for acute coronary syndrome (<i>n</i>=15), 0.5% for ventricular arrhythmia (<i>n</i>=14), 0.1% for bacterial endocarditis (<i>n</i>=4) and myocarditis (<i>n</i>=3), respectively, and 0.03% for pericarditis (<i>n</i>=1). Pulmonary embolism was diagnosed in 198 (6.6%) patients.<h4>Conclusion</h4>This large study among 3011 hospitalised patients with COVID-19 shows that the incidence of cardiac complications during hospital admission is low, despite a frequent history of cardiovascular disease. Long-term cardiac outcomes and the role of pre-existing cardiovascular disease in COVID-19 outcome warrants further investigation.",,pdf:https://academic.oup.com/ehjacc/article-pdf/9/8/817/49790126/ehjacc0817.pdf; doi:https://doi.org/10.1177/2048872620974605; html:https://europepmc.org/articles/PMC7734244; pdf:https://europepmc.org/articles/PMC7734244?pdf=render
-34708157,https://doi.org/10.12688/wellcomeopenres.16701.3,Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.,"Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",,Wellcome open research,2021,2021-12-21,Y,Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus,,,"<b>Background:</b> The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. <b>Methods:</b> Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. <b>Results:</b> We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. <b>Conclusions:</b> These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",,doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render
 33437953,https://doi.org/10.1016/j.eclinm.2020.100658,"Education, biological ageing, all-cause and cause-specific mortality and morbidity: UK biobank cohort study.","Chadeau-Hyam M, Bodinier B, Vermeulen R, Karimi M, Zuber V, Castagné R, Elliott J, Muller D, Petrovic D, Whitaker M, Stringhini S, Tzoulaki I, Kivimäki M, Vineis P, Elliott P, Kelly-Irving M, Delpierre C.",,EClinicalMedicine,2020,2020-11-19,Y,Biomarkers; Prospective Cohort; Uk Biobank; Mendelian Randomisation; Biological Ageing; Social Embedding; Allostatic Load Mortality; Incidentpathologies,,,"<h4>Background</h4>Socioeconomic position as measured by education may be embodied and affect the functioning of key physiological systems. Links between social disadvantage, its biological imprint, and cause-specific mortality and morbidity have not been investigated in large populations, and yet may point towards areas for public health interventions beyond targeting individual behaviours.<h4>Methods</h4>Using data from 366,748 UK Biobank participants with 13 biomarker measurements, we calculated a Biological Health Score (BHS, ranging from 0 to 1) capturing the level of functioning of five physiological systems. Associations between BHS and incidence of cardiovascular disease (CVD) and cancer, and mortality from all, CVD, cancer, and external causes were examined. We explored the role of education in these associations. Mendelian randomisation using genetic evidence was used to triangulate these findings.<h4>Findings</h4>An increase in BHS of 0.1 was associated with all-cause (HR = 1.14 [1.12-1.16] and 1.09 [1.07-1.12] in men and women respectively), cancer (HR = 1.11 [1.09-1.14] and 1.07 [1.04-1.10]) and CVD (HR = 1.25 [1.20-1.31] and 1.21 [1.11-1.31]) mortality, CVD incidence (HR = 1.15 [1.13-1.16] and 1.17 [1.15-1.19]). These associations survived adjustment for education, lifestyle-behaviours, body mass index (BMI), co-morbidities and medical treatments. Mendelian randomisation further supported the link between the BHS and CVD incidence (HR = 1.31 [1.21-1.42]). The BHS contributed to CVD incidence prediction (age-adjusted C-statistic = 0.58), other than through education and health behaviours.<h4>Interpretation</h4>The BHS captures features of the embodiment of education, health behaviours, and more proximal unknown factors which all complementarily contribute to all-cause, cancer and CVD morbidity and premature death.",,pdf:http://www.thelancet.com/article/S2589537020304028/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100658; html:https://europepmc.org/articles/PMC7788440; pdf:https://europepmc.org/articles/PMC7788440?pdf=render
+34708157,https://doi.org/10.12688/wellcomeopenres.16701.3,Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.,"Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",,Wellcome open research,2021,2021-12-21,Y,Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus,,,"<b>Background:</b> The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. <b>Methods:</b> Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. <b>Results:</b> We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. <b>Conclusions:</b> These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",,doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render
 34310590,https://doi.org/10.1371/journal.pcbi.1009098,Projecting contact matrices in 177 geographical regions: An update and comparison with empirical data for the COVID-19 era.,"Prem K, Zandvoort KV, Klepac P, Eggo RM, Davies NG, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Cook AR, Jit M.",,PLoS computational biology,2021,2021-07-26,Y,,,,"Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009098&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009098; html:https://europepmc.org/articles/PMC8354454; pdf:https://europepmc.org/articles/PMC8354454?pdf=render
 33905882,https://doi.org/10.1016/j.media.2021.102050,Phenotype discovery from population brain imaging.,"Gong W, Beckmann CF, Smith SM.",,Medical image analysis,2021,2021-03-31,Y,Neuroimaging; Uk Biobank; Behaviour Prediction; Phenotype Discovery; Multimodal Independent Component Analysis,,,"Neuroimaging allows for the non-invasive study of the brain in rich detail. Data-driven discovery of patterns of population variability in the brain has the potential to be extremely valuable for early disease diagnosis and understanding the brain. The resulting patterns can be used as imaging-derived phenotypes (IDPs), and may complement existing expert-curated IDPs. However, population datasets, comprising many different structural and functional imaging modalities from thousands of subjects, provide a computational challenge not previously addressed. Here, for the first time, a multimodal independent component analysis approach is presented that is scalable for data fusion of voxel-level neuroimaging data in the full UK Biobank (UKB) dataset, that will soon reach 100,000 imaged subjects. This new computational approach can estimate modes of population variability that enhance the ability to predict thousands of phenotypic and behavioural variables using data from UKB and the Human Connectome Project. A high-dimensional decomposition achieved improved predictive power compared with widely-used analysis strategies, single-modality decompositions and existing IDPs. In UKB data (14,503 subjects with 47 different data modalities), many interpretable associations with non-imaging phenotypes were identified, including multimodal spatial maps related to fluid intelligence, handedness and disease, in some cases where IDP-based approaches failed.",,doi:https://doi.org/10.1016/j.media.2021.102050; doi:https://doi.org/10.1016/j.media.2021.102050; html:https://europepmc.org/articles/PMC8850869; pdf:https://europepmc.org/articles/PMC8850869?pdf=render
 32413819,https://doi.org/10.1016/j.dsx.2020.04.050,Vitamin D concentrations and COVID-19 infection in UK Biobank.,"Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, Jani BD, Welsh P, Mair FS, Gray SR, O'Donnell CA, Gill JM, Sattar N, Pell JP.",,Diabetes & metabolic syndrome,2020,2020-05-07,N,Vitamin D; Ethnicity; Covid-19,,,"<h4>Background and aims</h4>COVID-19 and low levels of vitamin D appear to disproportionately affect black and minority ethnic individuals. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk, and whether it explained the higher incidence of COVID-19 in black and South Asian people.<h4>Methods</h4>UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration and ethnicity, were linked to COVID-19 test results. Univariable and multivariable logistic regression analyses were performed for the association between 25(OH)D and confirmed COVID-19, and the association between ethnicity and both 25(OH)D and COVID-19.<h4>Results</h4>Complete data were available for 348,598 UK Biobank participants. Of these, 449 had confirmed COVID-19 infection. Vitamin D was associated with COVID-19 infection univariably (OR = 0.99; 95% CI 0.99-0.999; p = 0.013), but not after adjustment for confounders (OR = 1.00; 95% CI = 0.998-1.01; p = 0.208). Ethnicity was associated with COVID-19 infection univariably (blacks versus whites OR = 5.32, 95% CI = 3.68-7.70, p-value<0.001; South Asians versus whites OR = 2.65, 95% CI = 1.65-4.25, p-value<0.001). Adjustment for 25(OH)D concentration made little difference to the magnitude of the association.<h4>Conclusions</h4>Our findings do not support a potential link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration may explain ethnic differences in COVID-19 infection.","This study aimed to investigate if low levels of vitamin D were associated with a higher likelihood of having COVID-19, which could be a cause of higher rates of COVID infection amoung black and South Asian people.",doi:https://doi.org/10.1016/j.dsx.2020.04.050; doi:https://doi.org/10.1016/j.dsx.2020.04.050; html:https://europepmc.org/articles/PMC7204679; doi:https://doi.org/10.1016/j.dsx.2020.04.050
@@ -1748,18 +1748,18 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34091032,https://doi.org/10.1016/j.neuroimage.2021.118235,Subspace-constrained approaches to low-rank fMRI acceleration.,"Mason HT, Graedel NN, Miller KL, Chiew M.",,NeuroImage,2021,2021-06-03,Y,fMRI; Tikhonov regularization; Acceleration; temporal resolution; Low Rank; Temporal Smoothing; K-t Faster; Low Resolution Priors,,,"Acceleration methods in fMRI aim to reconstruct high fidelity images from under-sampled k-space, allowing fMRI datasets to achieve higher temporal resolution, reduced physiological noise aliasing, and increased statistical degrees of freedom. While low levels of acceleration are typically part of standard fMRI protocols through parallel imaging, there exists the potential for approaches that allow much greater acceleration. One such existing approach is k-t FASTER, which exploits the inherent low-rank nature of fMRI. In this paper, we present a reformulated version of k-t FASTER which includes additional L2 constraints within a low-rank framework. We evaluated the effect of three different constraints against existing low-rank approaches to fMRI reconstruction: Tikhonov constraints, low-resolution priors, and temporal subspace smoothness. The different approaches are separately tested for robustness to under-sampling and thermal noise levels, in both retrospectively and prospectively-undersampled finger-tapping task fMRI data. Reconstruction quality is evaluated by accurate reconstruction of low-rank subspaces and activation maps. The use of L2 constraints was found to achieve consistently improved results, producing high fidelity reconstructions of statistical parameter maps at higher acceleration factors and lower SNR values than existing methods, but at a cost of longer computation time. In particular, the Tikhonov constraint proved very robust across all tested datasets, and the temporal subspace smoothness constraint provided the best reconstruction scores in the prospectively-undersampled dataset. These results demonstrate that regularized low-rank reconstruction of fMRI data can recover functional information at high acceleration factors without the use of any model-based spatial constraints.",,doi:https://doi.org/10.1016/j.neuroimage.2021.118235; doi:https://doi.org/10.1016/j.neuroimage.2021.118235; html:https://europepmc.org/articles/PMC7611820; pdf:https://europepmc.org/articles/PMC7611820?pdf=render
 36401199,https://doi.org/10.1186/s12888-022-04275-6,Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.,"Rayner C, Coleman JRI, Skelton M, Armour C, Bradley J, Buckman JEJ, Davies MR, Hirsch CR, Hotopf M, Hübel C, Jones IR, Kalsi G, Kingston N, Krebs G, Lin Y, Monssen D, McIntosh AM, Mundy JR, Peel AJ, Rimes KA, Rogers HC, Smith DJ, Ter Kuile AR, Thompson KN, Veale D, Wingrove J, Walters JTR, Breen G, Eley TC.",,BMC psychiatry,2022,2022-11-18,Y,Counselling; Cognitive Behavioral Therapy; Minimal Phenotyping,,,"<h4>Background</h4>Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature.<h4>Methods</h4>Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n = 2890).<h4>Results</h4>Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR = 1.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR = 0.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR = 0.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR = 1.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios.<h4>Conclusion</h4>Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.",,pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04275-6; doi:https://doi.org/10.1186/s12888-022-04275-6; html:https://europepmc.org/articles/PMC9675224; pdf:https://europepmc.org/articles/PMC9675224?pdf=render
 31780306,https://doi.org/10.1016/s2215-0366(19)30298-6,Pharmacoepidemiology research: delivering evidence about drug safety and effectiveness in mental health.,"Davis KAS, Farooq S, Hayes JF, John A, Lee W, MacCabe JH, McIntosh A, Osborn DPJ, Stewart RJ, Woelbert E.",,The lancet. Psychiatry,2020,2019-11-25,N,,,,"Research that provides an evidence base for the pharmacotherapy of people with mental disorders is needed. The abundance of digital data has facilitated pharmacoepidemiology and, in particular, observational research on the effectiveness of real-world medication. Advantages of pharmacoepidemiological research are the availability of large patient samples, and coverage of under-researched subpopulations in their naturalistic conditions. Such research is also cheaper and quicker to do than randomised controlled trials, meaning that issues regarding generic medication, stopping medication (deprescribing), and long-term outcomes are more likely to be addressed. Pharmacoepidemiological methods can also be extended to pharmacovigilance and to aid the development of new purposes for existing drugs. Drawbacks of observational pharmacoepidemiological studies come from the non-randomised nature of treatment selection, leading to confounding by indication. Potential methods for managing this drawback include active comparison groups, within-individual designs, and propensity scoring. Many of the more rigorous pharmacoepidemiology studies have been strengthened through multiple analytical approaches triangulated to improve confidence in inferred causal relationships. With developments in data resources and analytical techniques, it is encouraging that guidelines are beginning to include evidence from robust observational pharmacoepidemiological studies alongside randomised controlled trials. Collaboration between guideline writers and researchers involved in pharmacoepidemiology could help researchers to answer the questions that are important to policy makers and ensure that results are integrated into the evidence base. Further development of statistical and data science techniques, alongside public engagement and capacity building (data resources and researcher base), will be necessary to take full advantage of future opportunities.",,html:https://eprints.keele.ac.uk/6650/1/Pharamcoepidemiology%20Lancet%20Psych%202019%20submitted%20version.docx; doi:https://doi.org/10.1016/S2215-0366(19)30298-6
-37315048,https://doi.org/10.1371/journal.pone.0287091,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,PloS one,2023,2023-06-14,Y,,,,"<h4>Background</h4>Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.<h4>Methods</h4>Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.<h4>Results</h4>We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.<h4>Conclusion</h4>The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287091&type=printable; doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render
 33299071,https://doi.org/10.1038/s41746-020-00357-5,Belief of having had unconfirmed Covid-19 infection reduces willingness to participate in app-based contact tracing.,"Bachtiger P, Adamson A, Quint JK, Peters NS.",,NPJ digital medicine,2020,2020-11-06,Y,,,,"Contact tracing and lockdown are health policies being used worldwide to combat the coronavirus (COVID-19). The UK National Health Service (NHS) Track and Trace Service has plans for a nationwide app that notifies the need for self-isolation to those in contact with a person testing positive for COVID-19. To be successful, such an app will require high uptake, the determinants and willingness for which are unclear but essential to understand for effective public health benefit. The objective of this study was to measure the determinants of willingness to participate in an NHS app-based contact-tracing programme using a questionnaire within the Care Information Exchange (CIE)-the largest patient-facing electronic health record in the NHS. Among 47,708 registered NHS users of the CIE, 27% completed a questionnaire asking about willingness to participate in app-based contact tracing, understanding of government advice, mental and physical wellbeing and their healthcare utilisation-related or not to COVID-19. Descriptive statistics are reported alongside univariate and multivariable logistic regression models, with positive or negative responses to a question on app-based contact tracing as the dependent variable. 26.1% of all CIE participants were included in the analysis (N = 12,434, 43.0% male, mean age 55.2). 60.3% of respondents were willing to participate in app-based contact tracing. Out of those who responded 'no', 67.2% stated that this was due to privacy concerns. In univariate analysis, worsening mood, fear and anxiety in relation to changes in government rules around lockdown were associated with lower willingness to participate. Multivariable analysis showed that difficulty understanding government rules was associated with a decreased inclination to download the app, with those scoring 1-2 and 3-4 in their understanding of the new government rules being 45% and 27% less inclined to download the contact-tracing app, respectively; when compared to those who rated their understanding as 5-6/10 (OR for 1-2/10 = 0.57 [CI 0.48-0.67]; OR for 3-4/10 = 0.744 [CI 0.64-0.87]), whereas scores of 7-8 and 9-10 showed a 43% and 31% respective increase. Those reporting an unconfirmed belief of having previously had and recovered from COVID-19 were 27% less likely to be willing to download the app; belief of previous recovery from COVID-19 infection OR 0.727 [0.585-0.908]). In this large UK-wide questionnaire of wellbeing in lockdown, a willingness for app-based contact tracing over an appropriate age range is 60%-close to the estimated 56% population uptake, and substantially less than the smartphone-user uptake considered necessary for an app-based contact tracing to be an effective intervention to help suppress an epidemic. Difficulty comprehending government advice and uncertainty of diagnosis, based on a public health policy of not testing to confirm self-reported COVID-19 infection during lockdown, therefore reduce willingness to adopt a government contact-tracing app to a level below the threshold for effectiveness as a tool to suppress an epidemic.",,pdf:https://www.nature.com/articles/s41746-020-00357-5.pdf; doi:https://doi.org/10.1038/s41746-020-00357-5; html:https://europepmc.org/articles/PMC7648058; pdf:https://europepmc.org/articles/PMC7648058?pdf=render
-37918923,https://doi.org/10.1136/bmjopen-2023-072531,Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.,"Zylbersztejn A, Lewis K, Nguyen V, Matthews J, Winterburn I, Karwatowska L, Barnes S, Lilliman M, Saxton J, Stone A, Boddy K, Downs J, Logan S, Rahi J, Black-Hawkins K, Dearden L, Ford T, Harron K, De Stavola B, Gilbert R.",,BMJ open,2023,2023-11-02,Y,epidemiology; Public Health; Qualitative Research; Health Informatics; Statistics & Research Methods; Health Equity,,,"<h4>Introduction</h4>One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes.<h4>Methods</h4>The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation.<h4>Ethics and dissemination</h4>Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.",,doi:https://doi.org/10.1136/bmjopen-2023-072531; html:https://europepmc.org/articles/PMC10626865; pdf:https://europepmc.org/articles/PMC10626865?pdf=render
+37315048,https://doi.org/10.1371/journal.pone.0287091,LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.,"Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",,PloS one,2023,2023-06-14,Y,,,,"<h4>Background</h4>Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.<h4>Methods</h4>Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.<h4>Results</h4>We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV ≥0.99) who could be rapidly discharged using information collected at initial assessment.<h4>Conclusion</h4>The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287091&type=printable; doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render
+30887727,https://doi.org/10.1002/ppul.24314,Physical activity among children with asthma: Cross-sectional analysis in the UK millennium cohort.,"Pike KC, Griffiths LJ, Dezateux C, Pearce A.",,Pediatric pulmonology,2019,2019-03-18,Y,Children; Cohort study; epidemiology; Physical Activity; Asthma And Early Wheeze,Improving Public Health,,"<h4>Background</h4>Although beneficial for health and well-being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap.<h4>Methods</h4>We analyzed cross-sectional associations between physical activity and parent-reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7-year-old participants (3321, [49%] girls). Primary outcomes were daily moderate-to-vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60 minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent-reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors.<h4>Results</h4>Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: -0.18 [-0.27, -0.08]; -0.14 [-0.24, -0.05]; -0.15, [-0.28, -0.02], respectively) and hospital admission with lower total activity (-48 cpm [-68, -28]).<h4>Conclusion</h4>Children with asthma are as physically active as their asthma-free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ppul.24314; doi:https://doi.org/10.1002/ppul.24314; html:https://europepmc.org/articles/PMC6617805; pdf:https://europepmc.org/articles/PMC6617805?pdf=render
 33782396,https://doi.org/10.1038/s41467-021-22213-0,Implications of the school-household network structure on SARS-CoV-2 transmission under school reopening strategies in England.,"Munday JD, Sherratt K, Meakin S, Endo A, Pearson CAB, Hellewell J, Abbott S, Bosse NI, CMMID COVID-19 Working Group, Atkins KE, Wallinga J, Edmunds WJ, van Hoek AJ, Funk S.",,Nature communications,2021,2021-03-29,Y,,,,"In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.",,pdf:https://www.nature.com/articles/s41467-021-22213-0.pdf; doi:https://doi.org/10.1038/s41467-021-22213-0; html:https://europepmc.org/articles/PMC8007691; pdf:https://europepmc.org/articles/PMC8007691?pdf=render
 33939619,https://doi.org/10.2196/29072,Predicting Risk of Hospital Admission in Patients With Suspected COVID-19 in a Community Setting: Protocol for Development and Validation of a Multivariate Risk Prediction Tool.,"Espinosa-Gonzalez AB, Neves AL, Fiorentino F, Prociuk D, Husain L, Ramtale SC, Mi E, Mi E, Macartney J, Anand SN, Sherlock J, Saravanakumar K, Mayer E, de Lusignan S, Greenhalgh T, Delaney BC.",,JMIR research protocols,2021,2021-05-25,Y,Primary Care; Hospital Admission; Electronic Health Records; Early Warning Score; Risk Prediction Tool; Covid-19 Severity,,,"<h4>Background</h4>During the pandemic, remote consultations have become the norm for assessing patients with signs and symptoms of COVID-19 to decrease the risk of transmission. This has intensified the clinical uncertainty already experienced by primary care clinicians when assessing patients with suspected COVID-19 and has prompted the use of risk prediction scores, such as the National Early Warning Score (NEWS2), to assess severity and guide treatment. However, the risk prediction tools available have not been validated in a community setting and are not designed to capture the idiosyncrasies of COVID-19 infection.<h4>Objective</h4>The objective of this study is to produce a multivariate risk prediction tool, RECAP-V1 (Remote COVID-19 Assessment in Primary Care), to support primary care clinicians in the identification of those patients with COVID-19 that are at higher risk of deterioration and facilitate the early escalation of their treatment with the aim of improving patient outcomes.<h4>Methods</h4>The study follows a prospective cohort observational design, whereby patients presenting in primary care with signs and symptoms suggestive of COVID-19 will be followed and their data linked to hospital outcomes (hospital admission and death). Data collection will be carried out by primary care clinicians in four arms: North West London Clinical Commissioning Groups (NWL CCGs), Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), Covid Clinical Assessment Service (CCAS), and South East London CCGs (Doctaly platform). The study involves the use of an electronic template that incorporates a list of items (known as RECAP-V0) thought to be associated with disease outcome according to previous qualitative work. Data collected will be linked to patient outcomes in highly secure environments. We will then use multivariate logistic regression analyses for model development and validation.<h4>Results</h4>Recruitment of participants started in October 2020. Initially, only the NWL CCGs and RCGP RSC arms were active. As of March 24, 2021, we have recruited a combined sample of 3827 participants in these two arms. CCAS and Doctaly joined the study in February 2021, with CCAS starting the recruitment process on March 15, 2021. The first part of the analysis (RECAP-V1 model development) is planned to start in April 2021 using the first half of the NWL CCGs and RCGP RSC combined data set. Posteriorly, the model will be validated with the rest of the NWL CCGs and RCGP RSC data as well as the CCAS and Doctaly data sets. The study was approved by the Research Ethics Committee on May 27, 2020 (Integrated Research Application System number: 283024, Research Ethics Committee reference number: 20/NW/0266) and badged as National Institute of Health Research Urgent Public Health Study on October 14, 2020.<h4>Conclusions</h4>We believe the validated RECAP-V1 early warning score will be a valuable tool for the assessment of severity in patients with suspected COVID-19 in the community, either in face-to-face or remote consultations, and will facilitate the timely escalation of treatment with the potential to improve patient outcomes.<h4>Trial registration</h4>ISRCTN registry ISRCTN13953727; https://www.isrctn.com/ISRCTN13953727.<h4>International registered report identifier (irrid)</h4>DERR1-10.2196/29072.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i5e29072_app1.pdf&filename=e079f888f9036dd40808005eb7b49b6f.pdf; doi:https://doi.org/10.2196/29072; html:https://europepmc.org/articles/PMC8153031
-30887727,https://doi.org/10.1002/ppul.24314,Physical activity among children with asthma: Cross-sectional analysis in the UK millennium cohort.,"Pike KC, Griffiths LJ, Dezateux C, Pearce A.",,Pediatric pulmonology,2019,2019-03-18,Y,Children; Cohort study; epidemiology; Physical Activity; Asthma And Early Wheeze,Improving Public Health,,"<h4>Background</h4>Although beneficial for health and well-being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap.<h4>Methods</h4>We analyzed cross-sectional associations between physical activity and parent-reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7-year-old participants (3321, [49%] girls). Primary outcomes were daily moderate-to-vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60 minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent-reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors.<h4>Results</h4>Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: -0.18 [-0.27, -0.08]; -0.14 [-0.24, -0.05]; -0.15, [-0.28, -0.02], respectively) and hospital admission with lower total activity (-48 cpm [-68, -28]).<h4>Conclusion</h4>Children with asthma are as physically active as their asthma-free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ppul.24314; doi:https://doi.org/10.1002/ppul.24314; html:https://europepmc.org/articles/PMC6617805; pdf:https://europepmc.org/articles/PMC6617805?pdf=render
 34173574,https://doi.org/10.1016/j.puhip.2020.100039,Schools and COVID-19: Reopening Pandora's box?,"Ziauddeen N, Woods-Townsend K, Saxena S, Gilbert R, Alwan NA.",,"Public health in practice (Oxford, England)",2020,2020-11-01,Y,Safety; Covid-19; School Re-Opening,,,"Schools in countries across the world are reopening as lockdown to slow progression of COVID-19 is eased. The UK government ordered school closures in England from March 20, 2020, later than the rest of Europe. A temporary and limited return for some year groups was trialled from June 2020. Teachers, school governors, the public and doctors have openly challenged the decision. The UK government has struggled to provide enough detailed information to convince the public, teachers and health practitioners, that effective systems for protection, including test, trace and isolate, are in place to prevent and manage outbreaks in schools. Risks of infection on reopening to children, staff and families must be weighed against the harms of closure to children's education and social development. The potential consequences, if the re-opening of schools is managed badly, is subsequent waves of COVID-19 infection leading to more deaths, further school closures and prolonged restrictions, losing any ground gained thus far. This article weighs the evidence for risks and benefits of reopening schools during the pandemic.",,doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?pdf=render
+37918923,https://doi.org/10.1136/bmjopen-2023-072531,Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.,"Zylbersztejn A, Lewis K, Nguyen V, Matthews J, Winterburn I, Karwatowska L, Barnes S, Lilliman M, Saxton J, Stone A, Boddy K, Downs J, Logan S, Rahi J, Black-Hawkins K, Dearden L, Ford T, Harron K, De Stavola B, Gilbert R.",,BMJ open,2023,2023-11-02,Y,epidemiology; Public Health; Qualitative Research; Health Informatics; Statistics & Research Methods; Health Equity,,,"<h4>Introduction</h4>One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes.<h4>Methods</h4>The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation.<h4>Ethics and dissemination</h4>Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.",,doi:https://doi.org/10.1136/bmjopen-2023-072531; html:https://europepmc.org/articles/PMC10626865; pdf:https://europepmc.org/articles/PMC10626865?pdf=render
 35710247,https://doi.org/10.1136/bmjopen-2021-060280,Structured follow-up pathway to support people after transient ischaemic attack and minor stroke (SUPPORT TIA): protocol for a feasibility study and process evaluation.,"Turner GM, Jones R, Collis P, Patel S, Jowett S, Tearne S, Foy R, Atkins L, Mant J, Calvert M.",,BMJ open,2022,2022-06-16,Y,Qualitative Research; Rehabilitation Medicine; Stroke Medicine; Protocols & Guidelines; Organisation Of Health Services; Depression & Mood Disorders,,,"<h4>Introduction</h4>People who experience transient ischaemic attack (TIA) and minor stroke have limited follow-up despite rapid specialist review in hospital. This means they often have unmet needs and feel abandoned following discharge. Care needs after TIA/minor stroke include information provision (diagnosis and stroke risk), stroke prevention (medication and lifestyle change) and holistic care (residual problems and return to work or usual activities). This protocol describes a feasibility study and process evaluation of an intervention to support people after TIA/minor stroke. The study aims to assess the feasibility and acceptability of (1) the intervention and (2) the trial procedures for a future randomised controlled trial of this intervention.<h4>Methods and analysis</h4>This is a multicentre, randomised (1:1) feasibility study with a mixed-methods process evaluation. Sixty participants will be recruited from TIA clinics or stroke wards at three hospital sites (England). Intervention arm participants will be offered a nurse or allied health professional-led follow-up appointment 4 weeks after TIA/minor stroke. The multifaceted intervention includes: a needs checklist, action plan, resources to support management of needs, a general practitioner letter and training to deliver the intervention. Control arm participants will receive usual care. Follow-up will be self-completed questionnaires (12 weeks and 24 weeks) and a clinic appointment (24 weeks). Follow-up questionnaires will measure anxiety, depression, fatigue, health related quality of life, self-efficacy and medication adherence. The clinic appointment will collect body mass index, blood pressure, cholesterol and medication. Assessment of feasibility and acceptability will include quantitative process variables (such as recruitment and questionnaire response rates), structured observations of study processes, and interviews with a subsample of participants and clinical staff.<h4>Ethics and dissemination</h4>Favourable ethical opinion was gained from the Wales Research Ethics Committee (REC) 1 (23 February 2021, REC reference: 21/WA/0036). Study results will be published in peer-reviewed journals and presented at conferences. A lay summary and dissemination strategy will be codesigned with consumers. The lay summary and journal publication will be distributed on social media.<h4>Trial registration number</h4>ISRCTN39864003.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/6/e060280.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render
 31196949,https://doi.org/10.1183/13993003.02309-2018,Educational and health outcomes of children treated for asthma: Scotland-wide record linkage study of 683 716 children. ,"Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,The European respiratory journal,2019,2019-09-05,Y,,Improving Public Health,,"The global prevalence of childhood asthma is increasing. The condition impacts physical and psychosocial morbidity; therefore, wide-ranging effects on health and education outcomes are plausible. Linkage of eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions and unemployment, provided data on 683 716 children attending Scottish schools between 2009 and 2013. We compared schoolchildren on medication for asthma with peers, adjusting for sociodemographic, maternity and comorbidity confounders, and explored effect modifiers and mediators. The 45 900 (6.0%) children treated for asthma had an increased risk of hospitalisation, particularly within the first year of treatment (incidence rate ratio 1.98, 95% CI 1.93-2.04), and increased mortality (HR 1.77, 95% CI 1.30-2.40). They were more likely to have special educational need for mental (OR 1.76, 95% CI 1.49-2.08) and physical (OR 2.76, 95% CI 2.57-2.95) health reasons, and performed worse in school exams (OR 1.11, 95% CI 1.06-1.16). Higher absenteeism (incidence rate ratio 1.25, 95% CI 1.24-1.26) partially explained their poorer attainment. Children with treated asthma have poorer education and health outcomes than their peers. Educational interventions that mitigate the adverse effects of absenteeism should be considered.",,pdf:https://erj.ersjournals.com/content/erj/54/3/1802309.full.pdf; doi:https://doi.org/10.1183/13993003.02309-2018; html:https://europepmc.org/articles/PMC6727030; pdf:https://europepmc.org/articles/PMC6727030?pdf=render
 32845538,https://doi.org/10.1634/theoncologist.2020-0572,Cancer and Risk of COVID-19 Through a General Community Survey.,"Lee KA, Ma W, Sikavi DR, Drew DA, Nguyen LH, Bowyer RCE, Cardoso MJ, Fall T, Freidin MB, Gomez M, Graham M, Guo CG, Joshi AD, Kwon S, Lo CH, Lochlainn MN, Menni C, Murray B, Mehta R, Song M, Sudre CH, Bataille V, Varsavsky T, Visconti A, Franks PW, Wolf J, Steves CJ, Ourselin S, Spector TD, Chan AT, COPE consortium.",,The oncologist,2021,2020-09-07,Y,,,,"Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65 years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.",,pdf:https://academic.oup.com/oncolo/article-pdf/26/1/e182/41923952/oncolo_26_1_n_a.pdf; doi:https://doi.org/10.1634/theoncologist.2020-0572; html:https://europepmc.org/articles/PMC7460944; pdf:https://europepmc.org/articles/PMC7460944?pdf=render
-35288697,https://doi.org/10.1038/s41591-022-01750-1,COVID-19 and resilience of healthcare systems in ten countries.,"Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar Á, Pérez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Guiñez F, Bauhoff S, Kruk ME.",,Nature medicine,2022,2022-03-14,Y,,,,"Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.",,pdf:https://www.nature.com/articles/s41591-022-01750-1.pdf; doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render
 30649175,https://doi.org/10.1001/jamacardio.2018.4537,Cardiovascular Risk Factors Associated With Venous Thromboembolism.,"Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Zöller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, Völzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Després JP, Simons L, Barrett-Connor E, Björkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundström J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, Gómez de la Cámara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Njølstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration.",,JAMA cardiology,2019,2019-02-01,Y,,Understanding the Causes of Disease,,"<h4>Importance</h4>It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).<h4>Objective</h4>To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.<h4>Design, setting, and participants</h4>This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.<h4>Exposures</h4>A panel of several established cardiovascular risk factors.<h4>Main outcomes and measures</h4>Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).<h4>Results</h4>Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.<h4>Conclusions and relevance</h4>Older age, smoking, and adiposity were consistently associated with higher VTE risk.",,pdf:https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=1451&context=sph_facpub; doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140
+35288697,https://doi.org/10.1038/s41591-022-01750-1,COVID-19 and resilience of healthcare systems in ten countries.,"Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar Á, Pérez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Guiñez F, Bauhoff S, Kruk ME.",,Nature medicine,2022,2022-03-14,Y,,,,"Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.",,pdf:https://www.nature.com/articles/s41591-022-01750-1.pdf; doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render
 35505938,https://doi.org/10.1016/j.eclinm.2022.101417,Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort.,"Hampshire A, Chatfield DA, MPhil AM, Jolly A, Trender W, Hellyer PJ, Giovane MD, Newcombe VFJ, Outtrim JG, Warne B, Bhatti J, Pointon L, Elmer A, Sithole N, Bradley J, Kingston N, Sawcer SJ, Bullmore ET, Rowe JB, Menon DK, Cambridge NeuroCOVID Group, the NIHR COVID-19 BioResource, and Cambridge NIHR Clinical Research Facility.",,EClinicalMedicine,2022,2022-04-28,Y,Memory; Cognition; Attention; Planning; Cognitive Assessment; Reasoning; Covid-19,,,"<h4>Background</h4>Preliminary evidence has highlighted a possible association between severe COVID-19 and persistent cognitive deficits. Further research is required to confirm this association, determine whether cognitive deficits relate to clinical features from the acute phase or to mental health status at the point of assessment, and quantify rate of recovery.<h4>Methods</h4>46 individuals who received critical care for COVID-19 at Addenbrooke's hospital between 10th March 2020 and 31st July 2020 (16 mechanically ventilated) underwent detailed computerised cognitive assessment alongside scales measuring anxiety, depression and post-traumatic stress disorder under supervised conditions at a mean follow up of 6.0 (± 2.1) months following acute illness. Patient and matched control (<i>N</i> = 460) performances were transformed into standard deviation from expected scores, accounting for age and demographic factors using <i>N</i> = 66,008 normative datasets. Global accuracy and response time composites were calculated (G_SScore & G_RT). Linear modelling predicted composite score deficits from acute severity, mental-health status at assessment, and time from hospital admission. The pattern of deficits across tasks was qualitatively compared with normal age-related decline, and early-stage dementia.<h4>Findings</h4>COVID-19 survivors were less accurate (G_SScore=-0.53SDs) and slower (G_RT=+0.89SDs) in their responses than expected compared to their matched controls. Acute illness, but not chronic mental health, significantly predicted cognitive deviation from expected scores (G_SScore (<i>p</i>=​​0.0037) and G_RT (<i>p</i> = 0.0366)). The most prominent task associations with COVID-19 were for higher cognition and processing speed, which was qualitatively distinct from the profiles of normal ageing and dementia and similar in magnitude to the effects of ageing between 50 and 70 years of age. A trend towards reduced deficits with time from illness (r∼=0.15) did not reach statistical significance.<h4>Interpretation</h4>Cognitive deficits after severe COVID-19 relate most strongly to acute illness severity, persist long into the chronic phase, and recover slowly if at all, with a characteristic profile highlighting higher cognitive functions and processing speed.<h4>Funding</h4>This work was funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC), NIHR Cambridge Clinical Research Facility (BRC-1215-20014), the Addenbrooke's Charities Trust and NIHR COVID-19 BioResource RG9402. AH is funded by the UK Dementia Research Institute Care Research and Technology Centre and Imperial College London Biomedical Research Centre. ETB and DKM are supported by NIHR Senior Investigator awards. JBR is supported by the Wellcome Trust (220258) and Medical Research Council (SUAG/051 G101400). VFJN is funded by an Academy of Medical Sciences/ The Health Foundation Clinician Scientist Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S258953702200147X/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101417; html:https://europepmc.org/articles/PMC9048584; pdf:https://europepmc.org/articles/PMC9048584?pdf=render
 31163036,https://doi.org/10.1371/journal.pone.0217158,Differences in the epidemiology of out-of-hospital and in-hospital trauma deaths.,"Beck B, Smith K, Mercier E, Gabbe B, Bassed R, Mitra B, Teague W, Siedenburg J, McLellan S, Cameron P.",,PloS one,2019,2019-06-04,Y,,Improving Public Health,,"<h4>Background</h4>Trauma is a leading cause of mortality. Holistic views of trauma systems consider injury as a public health problem that requires efforts in primary, secondary and tertiary prevention. However, the performance of trauma systems is commonly judged on the in-hospital mortality rate. Such a focus misses opportunities to consider all deaths within a population, to understand differences in in-hospital and out-of-hospital trauma deaths and to inform population-level injury prevention efforts. The aim of this study was to provide an epidemiological overview of out-of-hospital and in-hospital trauma deaths in a geographically-defined area over a 10-year period.<h4>Methods</h4>We performed a population-based review of out-of-hospital and in-hospital trauma deaths over the period of 01 July 2006 to 30 June 2016 in Victoria, Australia, using data from the National Coronial Information System and the Victorian State Trauma Registry. Temporal trends in population-based incidence rates were evaluated.<h4>Results</h4>Over the study period, there were 11,246 trauma deaths, of which 71% were out-of-hospital deaths. Out-of-hospital trauma deaths commonly resulted from intentional self-harm events (50%) and transport events (35%), while in-hospital trauma deaths commonly resulted from low falls (≤1 metre) (50%). The incidence of overall trauma deaths did not change over the study period (incidence rate ratio 0.998; 95%CI: 0.991, 1.004; P = 0.56).<h4>Conclusions</h4>Out-of-hospital deaths accounted for most trauma deaths. Given the notable differences between out-of-hospital and in-hospital trauma deaths, monitoring of all trauma deaths is necessary to inform injury prevention activities and to reduce trauma mortality. The absence of a change in the incidence of both out-of-hospital and in-hospital trauma deaths demonstrates the need for enhanced activities across all aspects of injury prevention.",,doi:https://doi.org/10.1371/journal.pone.0217158; doi:https://doi.org/10.1371/journal.pone.0217158; html:https://europepmc.org/articles/PMC6548370; pdf:https://europepmc.org/articles/PMC6548370?pdf=render
 34139154,https://doi.org/10.1016/j.cels.2021.05.005,A time-resolved proteomic and prognostic map of COVID-19.,"Demichev V, Tober-Lau P, Lemke O, Nazarenko T, Thibeault C, Whitwell H, Röhl A, Freiwald A, Szyrwiel L, Ludwig D, Correia-Melo C, Aulakh SK, Helbig ET, Stubbemann P, Lippert LJ, Grüning NM, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Mittermaier M, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, Bosquillon de Jarcy L, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Enghard P, Zelezniak A, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Müller-Redetzky H, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, PA-COVID-19 Study group, Ralser M, Kurth F.",,Cell systems,2021,2021-06-14,Y,Proteomics; Biomarkers; Physiological parameters; Machine Learning; Disease Prognosis; Clinical Disease Progression; Covid-19; Patient Trajectories; Longitudinal Profiling,,,"COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.",,pdf:http://www.cell.com/article/S2405471221001605/pdf; doi:https://doi.org/10.1016/j.cels.2021.05.005; html:https://europepmc.org/articles/PMC8201874
@@ -1771,8 +1771,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33480434,https://doi.org/10.1093/pubmed/fdaa267,"Complex differences in infection rates between ethnic groups in Scotland: a retrospective, national census-linked cohort study of 1.65 million cases.","Gruer LD, Cézard GI, Wallace LA, Hutchinson SJ, Douglas AF, Buchanan D, Katikireddi SV, Millard AD, Goldberg DJ, Sheikh A, Bhopal RS.",,"Journal of public health (Oxford, England)",2022,2022-03-01,Y,Infectious disease; epidemiology; Ethnicity,,,"<h4>Background</h4>Ethnicity can influence susceptibility to infection, as COVID-19 has shown. Few countries have systematically investigated ethnic variations in infection.<h4>Methods</h4>We linked the Scotland 2001 Census, including ethnic group, to national databases of hospitalizations/deaths and serological diagnoses of bloodborne viruses for 2001-2013. We calculated age-adjusted rate ratios (RRs) in 12 ethnic groups for all infections combined, 15 infection categories, and human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses.<h4>Results</h4>We analysed over 1.65 million infection-related hospitalisations/deaths. Compared with White Scottish, RRs for all infections combined were 0.8 or lower for Other White British, Other White and Chinese males and females, and 1.2-1.4 for Pakistani and African males and females. Adjustment for socioeconomic status or birthplace had little effect. RRs for specific infection categories followed similar patterns with striking exceptions. For HIV, RRs were 136 in African females and 14 in males; for HBV, 125 in Chinese females and 59 in males, 55 in African females and 24 in males; and for HCV, 2.3-3.1 in Pakistanis and Africans.<h4>Conclusions</h4>Ethnic differences were found in overall rates and many infection categories, suggesting multiple causative pathways. We recommend census linkage as a powerful method for studying the disproportionate impact of COVID-19.",,pdf:https://academic.oup.com/jpubhealth/advance-article-pdf/doi/10.1093/pubmed/fdaa267/36684631/fdaa267.pdf; doi:https://doi.org/10.1093/pubmed/fdaa267; html:https://europepmc.org/articles/PMC7928762; pdf:https://europepmc.org/articles/PMC7928762?pdf=render
 34568585,https://doi.org/10.23889/ijpds.v6i1.1671,Linking education and hospital data in England: linkage process and quality.,"Libuy N, Harron K, Gilbert R, Caulton R, Cameron E, Blackburn R.",,International journal of population data science,2021,2021-09-16,Y,Bias; Data Linkage; Record Linkage; Administrative Data; Hospital Records; Linkage Error; Educational Records,,,"<h4>Introduction</h4>Linkage of administrative data for universal state education and National Health Service (NHS) hospital care would enable research into the inter-relationships between education and health for all children in England.<h4>Objectives</h4>We aim to describe the linkage process and evaluate the quality of linkage of four one-year birth cohorts within the National Pupil Database (NPD) and Hospital Episode Statistics (HES).<h4>Methods</h4>We used multi-step deterministic linkage algorithms to link longitudinal records from state schools to the chronology of records in the NHS Personal Demographics Service (PDS; linkage stage 1), and HES (linkage stage 2). We calculated linkage rates and compared pupil characteristics in linked and unlinked samples for each stage of linkage and each cohort (1990/91, 1996/97, 1999/00, and 2004/05).<h4>Results</h4>Of the 2,287,671 pupil records, 2,174,601 (95%) linked to HES. Linkage rates improved over time (92% in 1990/91 to 99% in 2004/05). Ethnic minority pupils and those living in more deprived areas were less likely to be matched to hospital records, but differences in pupil characteristics between linked and unlinked samples were moderate to small.<h4>Conclusion</h4>We linked nearly all pupils to at least one hospital record. The high coverage of the linkage represents a unique opportunity for wide-scale analyses across the domains of health and education. However, missed links disproportionately affected ethnic minorities or those living in the poorest neighbourhoods: selection bias could be mitigated by increasing the quality and completeness of identifiers recorded in administrative data or the application of statistical methods that account for missed links.<h4>Highlights</h4>Longitudinal administrative records for all children attending state school and acute hospital services in England have been used for research for more than two decades, but lack of a shared unique identifier has limited scope for linkage between these databases.We applied multi-step deterministic linkage algorithms to 4 one-year cohorts of children born 1 September-31 August in 1990/91, 1996/97, 1999/00 and 2004/05. In stage 1, full names, date of birth, and postcode histories from education data in the National Pupil Database were linked to the NHS Personal Demographic Service. In stage 2, NHS number, postcode, date of birth and sex were linked to hospital records in Hospital Episode Statistics.Between 92% and 99% of school pupils linked to at least one hospital record. Ethnic minority pupils and pupils who were living in the most deprived areas were least likely to link. Ethnic minority pupils were less likely than white children to link at the first step in both algorithms.Bias due to linkage errors could lead to an underestimate of the health needs in disadvantaged groups. Improved data quality, more sensitive linkage algorithms, and/or statistical methods that account for missed links in analyses, should be considered to reduce linkage bias.",,pdf:https://ijpds.org/article/download/1671/3248; doi:https://doi.org/10.23889/ijpds.v6i1.1671; html:https://europepmc.org/articles/PMC8445153; pdf:https://europepmc.org/articles/PMC8445153?pdf=render
 31588514,https://doi.org/10.1093/ptj/pzz151,Physical Activity and Sedentary Behavior 6 Months After Musculoskeletal Trauma: What Factors Predict Recovery?,"Ekegren CL, Climie RE, Simpson PM, Owen N, Dunstan DW, Veitch W, Gabbe BJ.",,Physical therapy,2020,2020-02-01,N,,,,"<h4>Background</h4>Physical activity is increasingly recognized as an important marker of functional recovery following fracture.<h4>Objective</h4>The objectives of this study were to measure sedentary behavior and physical activity 2 weeks and 6 months following fracture and to determine associated demographic and injury factors.<h4>Design</h4>This was an observational study.<h4>Methods</h4>Two weeks and 6 months following fracture, 83 adults who were 18 to 69 years old and had upper limb (UL) or lower limb (LL) fractures wore an accelerometer and an inclinometer for 10 days. We calculated sitting time, steps, moderate-intensity physical activity (MPA), and vigorous-intensity physical activity and conducted linear mixed-effects multivariable regression analyses to determine factors associated with temporal changes in activity.<h4>Results</h4>At 6 months versus 2 weeks after fracture, participants sat less, took more steps, and engaged in more MPA. Participants with LL fractures sat 2 hours more, took 66% fewer steps, and engaged in 77% less MPA than participants with UL fractures. Greater reductions in sitting time were observed for participants in the youngest age group and with LL fractures, participants with high preinjury activity, and participants who were overweight or obese. For steps, greater improvement was observed for participants in the youngest and middle-aged groups and those with LL fractures. For MPA, greater improvement was observed for middle-aged participants and those with LL fractures.<h4>Limitations</h4>Although this study was sufficiently powered for the analysis of major categories, a convenience sample that may not be representative of all people with musculoskeletal trauma was used.<h4>Conclusions</h4>Working-age adults with LL fractures had lower levels of physical activity 6 months after fracture than those with UL fractures. Older adults showed less improvement over time, suggesting that they are an important target group for interventions aimed at regaining preinjury activity levels.",,pdf:https://academic.oup.com/ptj/article-pdf/100/2/332/32901113/pzz151.pdf; doi:https://doi.org/10.1093/ptj/pzz151
-36539756,https://doi.org/10.1186/s12888-022-04429-6,ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol.,"Denyer H, Ramos-Quiroga JA, Folarin A, Ramos C, Nemeth P, Bilbow A, Woodward E, Whitwell S, Müller-Sedgwick U, Larsson H, Dobson RJ, Kuntsi J.",,BMC psychiatry,2022,2022-12-20,Y,ADHD; Cardiovascular disease; Attention Deficit Hyperactivity Disorder; Medication Adherence; Remote Monitoring; Mhealth; Digital Phenotyping; Remote Measurement Technology,,,"<h4>Background</h4>Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD.<h4>Methods</h4>ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration 'TIMESPAN' (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform.<h4>Discussion</h4>The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.",,pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04429-6; doi:https://doi.org/10.1186/s12888-022-04429-6; html:https://europepmc.org/articles/PMC9764531; pdf:https://europepmc.org/articles/PMC9764531?pdf=render
 32887683,https://doi.org/10.1136/annrheumdis-2020-217421,Genomic risk scores for juvenile idiopathic arthritis and its subtypes.,"Cánovas R, Cobb J, Brozynska M, Bowes J, Li YR, Smith SL, Hakonarson H, Thomson W, Ellis JA, Abraham G, Munro JE, Inouye M.",,Annals of the rheumatic diseases,2020,2020-09-04,Y,Polymorphism; Arthritis; Genetic; Juvenile; Rheumatoid,,,"<h4>Objectives</h4>Juvenile idiopathic arthritis (JIA) is an autoimmune disease and a common cause of chronic disability in children. Diagnosis of JIA is based purely on clinical symptoms, which can be variable, leading to diagnosis and treatment delays. Despite JIA having substantial heritability, the construction of genomic risk scores (GRSs) to aid or expedite diagnosis has not been assessed. Here, we generate GRSs for JIA and its subtypes and evaluate their performance.<h4>Methods</h4>We examined three case/control cohorts (UK, US-based and Australia) with genome-wide single nucleotide polymorphism (SNP) genotypes. We trained GRSs for JIA and its subtypes using lasso-penalised linear models in cross-validation on the UK cohort, and externally tested it in the other cohorts.<h4>Results</h4>The JIA GRS alone achieved cross-validated area under the receiver operating characteristic curve (AUC)=0.670 in the UK cohort and externally-validated AUCs of 0.657 and 0.671 in the US-based and Australian cohorts, respectively. In logistic regression of case/control status, the corresponding odds ratios (ORs) per standard deviation (SD) of GRS were 1.831 (1.685 to 1.991) and 2.008 (1.731 to 2.345), and were unattenuated by adjustment for sex or the top 10 genetic principal components. Extending our analysis to JIA subtypes revealed that the enthesitis-related JIA had both the longest time-to-referral and the subtype GRS with the strongest predictive capacity overall across data sets: AUCs 0.82 in UK; 0.84 in Australian; and 0.70 in US-based. The particularly common oligoarthritis JIA also had a GRS that outperformed those for JIA overall, with AUCs of 0.72, 0.74 and 0.77, respectively.<h4>Conclusions</h4>A GRS for JIA has potential to augment clinical JIA diagnosis protocols, prioritising higher-risk individuals for follow-up and treatment. Consistent with JIA heterogeneity, subtype-specific GRSs showed particularly high performance for enthesitis-related and oligoarthritis JIA.",,pdf:https://ard.bmj.com/content/annrheumdis/79/12/1572.full.pdf; doi:https://doi.org/10.1136/annrheumdis-2020-217421; html:https://europepmc.org/articles/PMC7677485; pdf:https://europepmc.org/articles/PMC7677485?pdf=render
+36539756,https://doi.org/10.1186/s12888-022-04429-6,ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol.,"Denyer H, Ramos-Quiroga JA, Folarin A, Ramos C, Nemeth P, Bilbow A, Woodward E, Whitwell S, Müller-Sedgwick U, Larsson H, Dobson RJ, Kuntsi J.",,BMC psychiatry,2022,2022-12-20,Y,ADHD; Cardiovascular disease; Attention Deficit Hyperactivity Disorder; Medication Adherence; Remote Monitoring; Mhealth; Digital Phenotyping; Remote Measurement Technology,,,"<h4>Background</h4>Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD.<h4>Methods</h4>ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration 'TIMESPAN' (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform.<h4>Discussion</h4>The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.",,pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04429-6; doi:https://doi.org/10.1186/s12888-022-04429-6; html:https://europepmc.org/articles/PMC9764531; pdf:https://europepmc.org/articles/PMC9764531?pdf=render
 35073907,https://doi.org/10.1186/s12916-021-02218-8,Association between hypertensive disorders of pregnancy and later risk of cardiovascular outcomes.,"Oliver-Williams C, Stevens D, Payne RA, Wilkinson IB, Smith GCS, Wood A.",,BMC medicine,2022,2022-01-25,Y,Pregnancy; Cardiovascular disease; Pre-eclampsia; Women; Gestational Hypertension,,,"<h4>Background</h4>Hypertensive disorders of pregnancy are common pregnancy complications that are associated with greater cardiovascular disease risk for mothers. However, risk of cardiovascular disease subtypes associated with gestational hypertension or pre-eclampsia is unclear. The present study aims to compare the risk of cardiovascular disease outcomes for women with and without a history of gestational hypertension and pre-eclampsia using national hospital admissions data.<h4>Methods</h4>This was a retrospective cohort study of national medical records from all National Health Service hospitals in England. Women who had one or more singleton live births in England between 1997 and 2015 were included in the analysis. Risk of total cardiovascular disease and 19 pre-specified cardiovascular disease subtypes, including stroke, coronary heart disease, cardiomyopathy and peripheral arterial disease, was calculated separately for women with a history of gestational hypertension and pre-eclampsia compared to normotensive pregnancies.<h4>Results</h4>Amongst 2,359,386 first live births, there were 85,277 and 74,542 hospital admissions with a diagnosis of gestational hypertension and pre-eclampsia, respectively. During 18 years (16,309,386 person-years) of follow-up, the number and incidence of total CVD for normotensive women, women with prior gestational hypertension and women with prior pre-eclampsia were n = 8668, 57.1 (95% CI: 55.9-58.3) per 100,000 person-years; n = 521, 85.8 (78.6-93.5) per 100,000 person-years; and n = 518, 99.3 (90.9-108.2) per 100,000 person-years, respectively. Adjusted HRs (aHR) for total CVD were aHR (95% CI) = 1.45 (1.33-1.59) for women with prior gestational hypertension and aHR = 1.62 (1.48-1.78) for women with prior pre-eclampsia. Gestational hypertension was strongly associated with dilated cardiomyopathy, aHR = 2.85 (1.67-4.86), and unstable angina, aHR = 1.92 (1.33-2.77). Pre-eclampsia was strongly associated with hypertrophic cardiomyopathy, aHR = 3.27 (1.49-7.19), and acute myocardial infarction, aHR = 2.46 (1.72-3.53). Associations were broadly homogenous across cardiovascular disease subtypes and increased with a greater number of affected pregnancies.<h4>Conclusions</h4>Women with either previous gestational hypertension or pre-eclampsia are at greater risk of a range of cardiovascular outcomes. These women may benefit from clinical risk assessment or early interventions to mitigate their greater risk of various cardiovascular outcomes.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02218-8; doi:https://doi.org/10.1186/s12916-021-02218-8; html:https://europepmc.org/articles/PMC8787919; pdf:https://europepmc.org/articles/PMC8787919?pdf=render
 35416614,https://doi.org/10.1007/s43441-022-00394-0,Opportunities and Risks of UK Medical Device Reform.,"Han JED, Ibrahim H, Aiyegbusi OL, Liu X, Marston E, Denniston AK, Calvert MJ.",,Therapeutic innovation & regulatory science,2022,2022-04-13,Y,Regulations; Medical devices; In Vitro Diagnostics; Ce Mark; Ukca,,,"<h4>Objectives</h4>To identify the potential opportunities and risks around future UK regulatory reform of medical devices.<h4>Design</h4>A mixed methods approach, comprising a rapid literature review, one-to-one, semi-structured interviews with key stakeholders, a multidisciplinary stakeholder workshop, and a post-workshop survey.<h4>Setting</h4>United Kingdom.<h4>Participants</h4>32 key stakeholders across the medical device sector were identified both from the public and private sectors.<h4>Results</h4>Opportunities relating to regulatory independence were identified, including the potential to create and implement a regulatory framework that ensures availability of medical devices; innovation and investment potential; and safety to the citizens of the UK. The most significant risks identified included threats to the safety of individual patients and the wider health system arising from the delay in awaiting regulatory approval due to the shortage of approved bodies; and reduced competitiveness of UK market and device manufacturers. Recommendations were identified to mitigate risks, centred on harnessing broader cross-sector collaborations, promoting patient and public partnership, and maximizing international engagement.<h4>Conclusions</h4>The UK's medical device sector is at a time-critical juncture to construct a regulatory framework to navigate its exit of Europe and respond to Europe's transition to new medical device regulations whilst also addressing the ongoing demand for rapid approval for new devices in response to the global pandemic. Investment, capacity-building, and international engagement will play a central role in mitigating risks and maximizing opportunities for medical device regulation.",,pdf:https://link.springer.com/content/pdf/10.1007/s43441-022-00394-0.pdf; doi:https://doi.org/10.1007/s43441-022-00394-0; html:https://europepmc.org/articles/PMC9007047; pdf:https://europepmc.org/articles/PMC9007047?pdf=render
 33550229,https://doi.org/10.1136/bmjopen-2020-040167,Assessing public support for extending smoke-free policies beyond enclosed public places and workplaces: protocol for a systematic review and meta-analysis.,"Boderie NW, Mölenberg FJ, Sheikh A, Bramer WM, Burdorf A, van Lenthe FJ, Been JV.",,BMJ open,2021,2021-02-05,Y,Tobacco smoke pollution; Attitude; Smoke-free Policy,,,"<h4>Introduction</h4>Smoke-free enclosed public environments are effective in reducing exposure to secondhand smoke and yield major public health benefits. Building on this, many countries are now implementing smoke-free policies regulating smoking beyond enclosed public places and workplaces. In order to successfully implement such 'novel smoke-free policies', public support is essential. We aim to provide the first comprehensive systematic review and meta-analysis assessing levels and determinants of public support for novel smoke-free policies.<h4>Methods and analysis</h4>The primary objective of this review is to summarise the level of public support for novel smoke-free policies. Eight online databases (Embase.com, Medline ALL Ovid, Web of Science Core Collection, WHO Library Database, Latin American and Caribbean Health Sciences Literature, Scientific Online Library Online, PsychINFO and Google Scholar) will be searched from 1 January 2004 by two independent researchers with no language restrictions. The initial search was performed on 15 April 2020 and will be updated prior to finalisation of the report. Studies are eligible if assessing support for novel smoke-free policies in the general population (age ≥16 years) and have a sample size of n≥400. Studies funded by the tobacco industry or evaluating support among groups with vested interest are excluded. The primary outcome is proportion of public support for smoke-free policies, subdivided according to the spaces covered: (1) indoor private spaces (eg, cars) (2) indoor semiprivate spaces (eg, multi-unit housing) (3) outdoor (semi)private spaces (eg, courtyards) (4) non-hospitality outdoor public spaces (eg, parks, hospital grounds, playgrounds) and (5) hospitality outdoor public spaces (eg, restaurant terraces). The secondary objective is to identify determinants associated with public support on three levels: (1) within-study determinants (eg, smoking status) (2) between-study determinants (eg, survey year) and (3) context-specific determinants (eg, social norms). Risk of bias will be assessed using the Mixed Methods Appraisal Tool and a sensitivity analysis will be performed excluding studies at high risk of bias.<h4>Ethics and dissemination</h4>No formal ethical approval is required. Findings will be disseminated to academics, policymakers and the general public.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/2/e040167.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-040167; html:https://europepmc.org/articles/PMC7925902; pdf:https://europepmc.org/articles/PMC7925902?pdf=render
@@ -1795,8 +1795,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 31950165,https://doi.org/10.1093/pubmed/fdz188,Is child weight status correctly reported to parents? Cross-sectional analysis of National Child Measurement Programme data using ethnic-specific BMI adjustments.,"Firman N, Boomla K, Hudda MT, Robson J, Whincup P, Dezateux C.",,"Journal of public health (Oxford, England)",2020,2020-11-01,Y,Obesity; Children; Ethnicity,,,"<h4>Background</h4>BMI underestimates and overestimates body fat in children from South Asian and Black ethnic groups, respectively.<h4>Methods</h4>We used cross-sectional NCMP data (2015-17) for 38 270 children in three inner-London local authorities: City & Hackney, Newham and Tower Hamlets (41% South Asian, 18.8% Black): 20 439 4-5 year-olds (48.9% girls) and 17 831 10-11 year-olds (49.1% girls). We estimated the proportion of parents who would have received different information about their child's weight status, and the area-level prevalence of obesity-defined as ≥98th centile-had ethnic-specific BMI adjustments been employed in the English National Child Measurement Programme (NCMP).<h4>Results</h4>Had ethnic-specific adjustment been employed, 19.7% (3112/15 830) of parents of children from South Asian backgrounds would have been informed that their child was in a heavier weight category, and 19.1% (1381/7217) of parents of children from Black backgrounds would have been informed that their child was in a lighter weight category. Ethnic-specific adjustment increased obesity prevalence from 7.9% (95% CI: 7.6, 8.3) to 9.1% (8.7, 9.5) amongst 4-5 year-olds and from 17.5% (16.9, 18.1) to 18.8% (18.2, 19.4) amongst 10-11 year-olds.<h4>Conclusions</h4>Ethnic-specific adjustment in the NCMP would ensure equitable categorization of weight status, provide correct information to parents and support local service provision for families.",,pdf:https://academic.oup.com/jpubhealth/article-pdf/42/4/e541/34469388/fdz188.pdf; doi:https://doi.org/10.1093/pubmed/fdz188; html:https://europepmc.org/articles/PMC7685848; pdf:https://europepmc.org/articles/PMC7685848?pdf=render
 30382236,https://doi.org/10.1038/s41433-018-0229-6,The diagnostic accuracy of OCT angiography in naive and treated neovascular age-related macular degeneration: a review.,"Perrott-Reynolds R, Cann R, Cronbach N, Neo YN, Ho V, McNally O, Madi HA, Cochran C, Chakravarthy U.",,"Eye (London, England)",2019,2018-10-31,N,,,,"Optical coherence tomography angiography (OCTA) is a non-invasive retinal imaging innovation that has been gaining popularity for the evaluation of the retinal vasculature. Of clinical importance is its current use either as an alternative or in conjunction with conventional dye-based angiography in neovascular age-related macular degeneration. OCTA is not without limitations and these include image artefact, a relatively small field of view and failure of the segmentation algorithms, which can confound the interpretation of findings. While there are numerous publications on OCTA in neovascular AMD, few have examined the diagnostic accuracy of this new technology compared with the accepted gold standard of fundus fluorescein angiography (FFA). In this review, we summarise the literature on the clinical application of OCTA in nAMD. In particular, we have reviewed the published articles that have reported the sensitivity and specificity of OCTA in the diagnosis of nAMD, and those that have described and or correlated the morphological findings and compared them to dye-based angiography.",Perrott et al. reviewed strengths and limitations of an eye (retinal) imagining method for diagnosis of a condition affecting the central part of the retina (the macula). This degenerative condition may result in loss of central vision in older adults. Perrott et al. concluded that diagnostic accuracy depends on both method and equipment. ,pdf:https://www.nature.com/articles/s41433-018-0229-6.pdf; doi:https://doi.org/10.1038/s41433-018-0229-6; html:https://europepmc.org/articles/PMC6367454; pdf:https://europepmc.org/articles/PMC6367454?pdf=render; doi:https://doi.org/10.1038/s41433-018-0229-6
 33407780,https://doi.org/10.1186/s13063-020-04951-6,Reporting guidelines for clinical trials of artificial intelligence interventions: the SPIRIT-AI and CONSORT-AI guidelines.,"Ibrahim H, Liu X, Rivera SC, Moher D, Chan AW, Sydes MR, Calvert MJ, Denniston AK.",,Trials,2021,2021-01-06,Y,Artificial intelligence; Checklist; RANDOMISED CONTROLLED TRIALS; Research Report; Clinical Trials; Guidelines; Research Design; Machine Learning,,,"<h4>Background</h4>The application of artificial intelligence (AI) in healthcare is an area of immense interest. The high profile of 'AI in health' means that there are unusually strong drivers to accelerate the introduction and implementation of innovative AI interventions, which may not be supported by the available evidence, and for which the usual systems of appraisal may not yet be sufficient.<h4>Main text</h4>We are beginning to see the emergence of randomised clinical trials evaluating AI interventions in real-world settings. It is imperative that these studies are conducted and reported to the highest standards to enable effective evaluation because they will potentially be a key part of the evidence that is used when deciding whether an AI intervention is sufficiently safe and effective to be approved and commissioned. Minimum reporting guidelines for clinical trial protocols and reports have been instrumental in improving the quality of clinical trials and promoting completeness and transparency of reporting for the evaluation of new health interventions. The current guidelines-SPIRIT and CONSORT-are suited to traditional health interventions but research has revealed that they do not adequately address potential sources of bias specific to AI systems. Examples of elements that require specific reporting include algorithm version and the procedure for acquiring input data. In response, the SPIRIT-AI and CONSORT-AI guidelines were developed by a multidisciplinary group of international experts using a consensus building methodological process. The extensions include a number of new items that should be reported in addition to the core items. Each item, where possible, was informed by challenges identified in existing studies of AI systems in health settings.<h4>Conclusion</h4>The SPIRIT-AI and CONSORT-AI guidelines provide the first international standards for clinical trials of AI systems. The guidelines are designed to ensure complete and transparent reporting of clinical trial protocols and reports involving AI interventions and have the potential to improve the quality of these clinical trials through improvements in their design and delivery. Their use will help to efficiently identify the safest and most effective AI interventions and commission them with confidence for the benefit of patients and the public.",,pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04951-6; doi:https://doi.org/10.1186/s13063-020-04951-6; html:https://europepmc.org/articles/PMC7788716; pdf:https://europepmc.org/articles/PMC7788716?pdf=render
-35477539,https://doi.org/10.1136/gutjnl-2021-326183,Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer.,"Corry SM, McCorry AM, Lannagan TR, Leonard NA, Fisher NC, Byrne RM, Tsantoulis P, Cortes-Lavaud X, Amirkhah R, Redmond KL, McCooey AJ, Malla SB, Rogan E, Sakhnevych S, Gillespie MA, White M, Richman SD, Jackstadt RF, Campbell AD, Maguire S, S:CORT and ACRCelerate consortia, McDade SS, Longley DB, Loughrey MB, Coleman HG, Kerr EM, Tejpar S, Maughan T, Leedham SJ, Small DM, Ryan AE, Sansom OJ, Lawler M, Dunne PD.",,Gut,2022,2022-04-27,Y,Cancer; Colorectal Cancer; Adjuvant Treatment; Colon Carcinogenesis,,,"<h4>Objective</h4>Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy.<h4>Design</h4>To address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series of <i>in vitro</i> and stroma-rich <i>in vivo</i> models to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours.<h4>Results</h4>By performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Using <i>in silico, in vitro</i> and <i>in vivo</i> models, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype across <i>in vitro</i> and <i>in vivo</i> models. In an <i>in vivo</i> model of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002).<h4>Conclusion</h4>This study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.",,pdf:https://gut.bmj.com/content/gutjnl/early/2022/04/10/gutjnl-2021-326183.full.pdf; doi:https://doi.org/10.1136/gutjnl-2021-326183; html:https://europepmc.org/articles/PMC9664095; pdf:https://europepmc.org/articles/PMC9664095?pdf=render
 33742045,https://doi.org/10.1038/s41598-021-85354-8,Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma.,"Roberts HE, Lopopolo M, Pagnamenta AT, Sharma E, Parkes D, Lonie L, Freeman C, Knight SJL, Lunter G, Dreau H, Lockstone H, Taylor JC, Schuh A, Bowden R, Buck D.",,Scientific reports,2021,2021-03-19,Y,,,,"Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.",,pdf:https://www.nature.com/articles/s41598-021-85354-8.pdf; doi:https://doi.org/10.1038/s41598-021-85354-8; html:https://europepmc.org/articles/PMC7979876; pdf:https://europepmc.org/articles/PMC7979876?pdf=render
+35477539,https://doi.org/10.1136/gutjnl-2021-326183,Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer.,"Corry SM, McCorry AM, Lannagan TR, Leonard NA, Fisher NC, Byrne RM, Tsantoulis P, Cortes-Lavaud X, Amirkhah R, Redmond KL, McCooey AJ, Malla SB, Rogan E, Sakhnevych S, Gillespie MA, White M, Richman SD, Jackstadt RF, Campbell AD, Maguire S, S:CORT and ACRCelerate consortia, McDade SS, Longley DB, Loughrey MB, Coleman HG, Kerr EM, Tejpar S, Maughan T, Leedham SJ, Small DM, Ryan AE, Sansom OJ, Lawler M, Dunne PD.",,Gut,2022,2022-04-27,Y,Cancer; Colorectal Cancer; Adjuvant Treatment; Colon Carcinogenesis,,,"<h4>Objective</h4>Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy.<h4>Design</h4>To address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series of <i>in vitro</i> and stroma-rich <i>in vivo</i> models to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours.<h4>Results</h4>By performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Using <i>in silico, in vitro</i> and <i>in vivo</i> models, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype across <i>in vitro</i> and <i>in vivo</i> models. In an <i>in vivo</i> model of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002).<h4>Conclusion</h4>This study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.",,pdf:https://gut.bmj.com/content/gutjnl/early/2022/04/10/gutjnl-2021-326183.full.pdf; doi:https://doi.org/10.1136/gutjnl-2021-326183; html:https://europepmc.org/articles/PMC9664095; pdf:https://europepmc.org/articles/PMC9664095?pdf=render
 32073627,https://doi.org/10.1093/ije/dyaa002,Educational and health outcomes of children and adolescents receiving antidepressant medication: Scotland-wide retrospective record linkage cohort study of 766 237 schoolchildren.,"Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,International journal of epidemiology,2020,2020-08-01,Y,Depression; Health; Prescribing; Educational Outcomes; Record Linkage; Population Cohort,,,"<h4>Background</h4>Childhood depression is relatively common, under-researched and can impact social and cognitive function and self-esteem.<h4>Methods</h4>Record linkage of routinely collected Scotland-wide administrative databases covering prescriptions [prescribing information system (PIS)], hospitalizations (Scottish Morbidity Records 01 and 04), maternity records (Scottish Morbidity Records 02), deaths (National Records of Scotland), annual pupil census, school absences/exclusions, special educational needs (Scottish Exchange of Educational Data; ScotXed), examinations (Scottish Qualifications Authority) and (un)employment (ScotXed) provided data on 766 237 children attending Scottish schools between 2009 and 2013 inclusively. We compared educational and health outcomes of children receiving antidepressant medication with their peers, adjusting for confounders (socio-demographic, maternity and comorbidity) and explored effect modifiers and mediators.<h4>Results</h4>Compared with peers, children receiving antidepressants were more likely to be absent [adjusted incidence rate ratio (IRR) 1.90, 95% confidence interval (CI) 1.85-1.95] or excluded (adjusted IRR 1.48, 95% CI 1.29-1.69) from school, have special educational needs [adjusted odds ratio (OR) 1.77, 95% CI 1.65-1.90], have the lowest level of academic attainment (adjusted OR 3.00, 95% CI 2.51-3.58) and be unemployed after leaving school (adjusted OR 1.88, 95% CI 1.71-2.08). They had increased hospitalization [adjusted hazard ratio (HR) 2.07, 95% CI 1.98-2.18] and mortality (adjusted HR 2.73, 95% CI 1.73-4.29) over 5 years' follow-up. Higher absenteeism partially explained poorer attainment and unemployment. Treatment with antidepressants was less common among boys than girls (0.5% vs 1.0%) but the associations with special educational need and unemployment were stronger in boys.<h4>Conclusions</h4>Children receiving antidepressants fare worse than their peers across a wide range of education and health outcomes. Interventions to reduce absenteeism or mitigate its effects should be investigated.",,pdf:https://academic.oup.com/ije/article-pdf/49/4/1380/34275416/dyaa002.pdf; doi:https://doi.org/10.1093/ije/dyaa002; html:https://europepmc.org/articles/PMC7660154; pdf:https://europepmc.org/articles/PMC7660154?pdf=render
 30351417,https://doi.org/10.1093/bioinformatics/bty837,pJRES Binning Algorithm (JBA): a new method to facilitate the recovery of metabolic information from pJRES 1H NMR spectra.,"Rodriguez-Martinez A, Ayala R, Posma JM, Harvey N, Jiménez B, Sonomura K, Sato TA, Matsuda F, Zalloua P, Gauguier D, Nicholson JK, Dumas ME.",,"Bioinformatics (Oxford, England)",2019,2019-06-01,Y,,Applied Analytics,,"<h4>Motivation</h4>Data processing is a key bottleneck for 1H NMR-based metabolic profiling of complex biological mixtures, such as biofluids. These spectra typically contain several thousands of signals, corresponding to possibly few hundreds of metabolites. A number of binning-based methods have been proposed to reduce the dimensionality of 1 D 1H NMR datasets, including statistical recoupling of variables (SRV). Here, we introduce a new binning method, named JBA (""pJRES Binning Algorithm""), which aims to extend the applicability of SRV to pJRES spectra.<h4>Results</h4>The performance of JBA is comprehensively evaluated using 617 plasma 1H NMR spectra from the FGENTCARD cohort. The results presented here show that JBA exhibits higher sensitivity than SRV to detect peaks from low-abundance metabolites. In addition, JBA allows a more efficient removal of spectral variables corresponding to pure electronic noise, and this has a positive impact on multivariate model building.<h4>Availability and implementation</h4>The algorithm is implemented using the MWASTools R/Bioconductor package.<h4>Supplementary information</h4>Supplementary data are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/35/11/1916/28759353/bty837.pdf; doi:https://doi.org/10.1093/bioinformatics/bty837; html:https://europepmc.org/articles/PMC6546129; pdf:https://europepmc.org/articles/PMC6546129?pdf=render
 35265823,https://doi.org/10.1016/j.eclinm.2022.101317,Variation in global COVID-19 symptoms by geography and by chronic disease: A global survey using the COVID-19 Symptom Mapper.,"Kadirvelu B, Burcea G, Quint JK, Costelloe CE, Faisal AA.",,EClinicalMedicine,2022,2022-03-06,Y,"Comorbidities; Pcr, Polymerase Chain Reaction; Covid-19; Covid-19 Symptoms; Covid Symptom Profile; Covid Symptoms Mapper; Covid Symptoms Survey; Covid-19, The Coronavirus Disease That First Appeared In 2019 Caused By The Sars-cov-2 Coronavirus.; Who, World Health Organization, A Specialized Agency Of The United Nations Responsible For International Public Health.",,,"<h4>Background</h4>COVID-19 is typically characterised by a triad of symptoms: cough, fever and loss of taste and smell, however, this varies globally. This study examines variations in COVID-19 symptom profiles based on underlying chronic disease and geographical location.<h4>Methods</h4>Using a global online symptom survey of 78,299 responders in 190 countries between 09/04/2020 and 22/09/2020, we conducted an exploratory study to examine symptom profiles associated with a positive COVID-19 test result by country and underlying chronic disease (single, co- or multi-morbidities) using statistical and machine learning methods.<h4>Findings</h4>From the results of 7980 COVID-19 tested positive responders, we find that symptom patterns differ by country. For example, India reported a lower proportion of headache (22.8% vs 47.8%, p<1e-13) and itchy eyes (7.3% vs. 16.5%, p=2e-8) than other countries. As with geographic location, we find people differed in their reported symptoms if they suffered from specific chronic diseases. For example, COVID-19 positive responders with asthma (25.3% vs. 13.7%, p=7e-6) were more likely to report shortness of breath compared to those with no underlying chronic disease.<h4>Interpretation</h4>We have identified variation in COVID-19 symptom profiles depending on geographic location and underlying chronic disease. Failure to reflect this symptom variation in public health messaging may contribute to asymptomatic COVID-19 spread and put patients with chronic diseases at a greater risk of infection. Future work should focus on symptom profile variation in the emerging variants of the SARS-CoV-2 virus. This is crucial to speed up clinical diagnosis, predict prognostic outcomes and target treatment.<h4>Funding</h4>We acknowledge funding to AAF by a UKRI Turing AI Fellowship and to CEC by a personal NIHR Career Development Fellowship (grant number NIHR-2016-090-015). JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, Asthma UK-British Lung Foundation, IQVIA, Chiesi AZ, and Insmed. This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004]. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Imperial College London is grateful for the support from the Northwest London NIHR Applied Research Collaboration. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S2589537022000475/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101317; html:https://europepmc.org/articles/PMC8898170; pdf:https://europepmc.org/articles/PMC8898170?pdf=render
@@ -1808,8 +1808,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 32835195,https://doi.org/10.1016/s2589-7500(20)30134-5,The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK.,"Drake TM, Docherty AB, Weiser TG, Yule S, Sheikh A, Harrison EM.",,The Lancet. Digital health,2020,2020-06-12,Y,,,,,,doi:https://doi.org/10.1016/s2589-7500(20)30134-5; doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render
 37719470,https://doi.org/10.3390/rs14143429,What you see is what you breathe? Estimating air pollution spatial variation using street level imagery.,"Suel E, Sorek-Hamer M, Moise I, von Pohle M, Sahasrabhojanee A, Asanjan AA, Arku RE, Alli AS, Barratt B, Clark SN, Middel A, Deardorff E, Lingenfelter V, Oza N, Yadav N, Ezzati M, Brauer M.",,Remote sensing,2022,2022-07-01,Y,Air pollution; Computer vision; Urban pollution; transferability; Deep Learning; Data Science; Street Images,,,"High spatial resolution information on urban air pollution levels is unavailable in many areas globally, partially due to high input data needs of existing estimation approaches. Here we introduce a computer vision method to estimate annual means for air pollution levels from street level images. We used annual mean estimates of NO<sub>2</sub> and PM<sub>2.5</sub> concentrations from locally calibrated models as labels from London, New York, and Vancouver to allow for compilation of a sufficiently large dataset (~250k images for each city). Our experimental setup is designed to quantify intra and intercity transferability of image-based model estimates. Performances were high and comparable to traditional land-use regression (LUR) and dispersion models when training and testing on images from the same city (R<sup>2</sup> values between 0.51 and 0.95 when validated on data from ground monitoring stations). Like LUR models, transferability of models between cities in different geographies is more difficult. Specifically, transferability between the three cities i.e., London, New York, and Vancouver, which have similar pollution source profiles were moderately successful (R<sup>2</sup> values between zero and 0.67). Comparatively, performances when transferring models trained on these cities with very different source profiles i.e., Accra in Ghana and Hong Kong were lower (R<sup>2</sup> between zero and 0.21) suggesting the need for local calibration with local calibration using additional measurement data from cities that share similar source profiles.",,pdf:https://www.mdpi.com/2072-4292/14/14/3429/pdf?version=1658213065; doi:https://doi.org/10.3390/rs14143429; html:https://europepmc.org/articles/PMC7615101; pdf:https://europepmc.org/articles/PMC7615101?pdf=render
 29780001,https://doi.org/10.1016/s2352-3026(18)30053-x,Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.,"Lane WJ, Westhoff CM, Gleadall NS, Aguad M, Smeland-Wagman R, Vege S, Simmons DP, Mah HH, Lebo MS, Walter K, Soranzo N, Di Angelantonio E, Danesh J, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Kaufman RM, Rehm HL, Silberstein LE, Green RC, MedSeq Project.",,The Lancet. Haematology,2018,2018-05-17,N,,The Human Phenome,,"<h4>Background</h4>There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens.<h4>Methods</h4>This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons.<h4>Findings</h4>We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage).<h4>Interpretation</h4>By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine.<h4>Funding</h4>National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S235230261830053X/pdf; doi:https://doi.org/10.1016/S2352-3026(18)30053-X; html:https://europepmc.org/articles/PMC6438177; pdf:https://europepmc.org/articles/PMC6438177?pdf=render; doi:https://doi.org/10.1016/s2352-3026(18)30053-x
-37418234,https://doi.org/10.1007/s12265-023-10403-8,A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.,"Nagyova E, Hoorntje ET, Te Rijdt WP, Bosman LP, Syrris P, Protonotarios A, Elliott PM, Tsatsopoulou A, Mestroni L, Taylor MRG, Sinagra G, Merlo M, Wada Y, Horie M, Mogensen J, Christensen AH, Gerull B, Song L, Yao Y, Fan S, Saguner AM, Duru F, Koskenvuo JW, Cruz Marino T, Tichnell C, Judge DP, Dooijes D, Lekanne Deprez RH, Basso C, Pilichou K, Bauce B, Wilde AAM, Charron P, Fressart V, van der Heijden JF, van den Berg MP, Asselbergs FW, James CA, Jongbloed JDH, Harakalova M, van Tintelen JP.",,Journal of cardiovascular translational research,2023,2023-07-07,N,Genetics; Arrhythmia; Arvc; Composite Endpoint; Multiple Variants; Desmosomal Genes,,,"The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.",,doi:https://doi.org/10.1007/s12265-023-10403-8
 32888427,https://doi.org/10.1016/j.ajhg.2020.08.009,Inferring Gene-by-Environment Interactions with a Bayesian Whole-Genome Regression Model.,"Kerin M, Marchini J.",,American journal of human genetics,2020,2020-09-03,Y,Linear Mixed Model; Gxe Interactions; Whole-genome Regression; Gxe Heritability,,,"The contribution of gene-by-environment (GxE) interactions for many human traits and diseases is poorly characterized. We propose a Bayesian whole-genome regression model for joint modeling of main genetic effects and GxE interactions in large-scale datasets, such as the UK Biobank, where many environmental variables have been measured. The method is called LEMMA (Linear Environment Mixed Model Analysis) and estimates a linear combination of environmental variables, called an environmental score (ES), that interacts with genetic markers throughout the genome. The ES provides a readily interpretable way to examine the combined effect of many environmental variables. The ES can be used both to estimate the proportion of phenotypic variance attributable to GxE effects and to test for GxE effects at genetic variants across the genome. GxE effects can induce heteroskedasticity in quantitative traits, and LEMMA accounts for this by using robust standard error estimates when testing for GxE effects. When applied to body mass index, systolic blood pressure, diastolic blood pressure, and pulse pressure in the UK Biobank, we estimate that 9.3%, 3.9%, 1.6%, and 12.5%, respectively, of phenotypic variance is explained by GxE interactions and that low-frequency variants explain most of this variance. We also identify three loci that interact with the estimated environmental scores (-log<sub>10</sub>p>7.3).",,pdf:http://www.cell.com/article/S0002929720302779/pdf; doi:https://doi.org/10.1016/j.ajhg.2020.08.009; html:https://europepmc.org/articles/PMC7536582; pdf:https://europepmc.org/articles/PMC7536582?pdf=render
+37418234,https://doi.org/10.1007/s12265-023-10403-8,A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.,"Nagyova E, Hoorntje ET, Te Rijdt WP, Bosman LP, Syrris P, Protonotarios A, Elliott PM, Tsatsopoulou A, Mestroni L, Taylor MRG, Sinagra G, Merlo M, Wada Y, Horie M, Mogensen J, Christensen AH, Gerull B, Song L, Yao Y, Fan S, Saguner AM, Duru F, Koskenvuo JW, Cruz Marino T, Tichnell C, Judge DP, Dooijes D, Lekanne Deprez RH, Basso C, Pilichou K, Bauce B, Wilde AAM, Charron P, Fressart V, van der Heijden JF, van den Berg MP, Asselbergs FW, James CA, Jongbloed JDH, Harakalova M, van Tintelen JP.",,Journal of cardiovascular translational research,2023,2023-07-07,N,Genetics; Arrhythmia; Arvc; Composite Endpoint; Multiple Variants; Desmosomal Genes,,,"The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.",,doi:https://doi.org/10.1007/s12265-023-10403-8
 32678323,https://doi.org/10.1038/s41366-020-0642-3,"Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank.","Zhu P, Lewington S, Haynes R, Emberson J, Landray MJ, Cherney D, Woodward M, Baigent C, Herrington WG, Staplin N.",,International journal of obesity (2005),2020,2020-07-16,Y,,,,"<h4>Background</h4>Whether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain.<h4>Methods</h4>Ordinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators.<h4>Results</h4>Levels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53-57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30-34%). Each 5 kg/m<sup>2</sup> higher BMI was associated with a 47% (46-49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33-37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure.<h4>Conclusions</h4>Conventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity-albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.",,pdf:https://www.nature.com/articles/s41366-020-0642-3.pdf; doi:https://doi.org/10.1038/s41366-020-0642-3; html:https://europepmc.org/articles/PMC7577847; pdf:https://europepmc.org/articles/PMC7577847?pdf=render
 33341984,https://doi.org/10.1111/tme.12750,Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): A diagnostic accuracy study.,"Bell S, Sweeting M, Ramond A, Chung R, Kaptoge S, Walker M, Bolton T, Sambrook J, Moore C, McMahon A, Fahle S, Cullen D, Mehenny S, Wood AM, Armitage J, Ouwehand WH, Miflin G, Roberts DJ, Danesh J, Di Angelantonio E, COMPARE Study Group.",,"Transfusion medicine (Oxford, England)",2021,2020-12-20,Y,Hemocue; Gravimetry; Whole Blood Donor; Non-invasive Haemoglobin Measurement; Inappropriate Deferral; Haemoglobin Screening; Inappropriate Bleeding,,,"<h4>Objective</h4>To compare four haemoglobin measurement methods in whole blood donors.<h4>Background</h4>To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant's (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT's customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold).<h4>Methods</h4>We compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN-2000 haematology analyser, the reference standard: (1) NHSBT's customary method; (2) ""post donation"" approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor's most recent prior donation; (3) ""portable haemoglobinometry"" (using capillary HemoCue); (4) non-invasive spectrometry (using MBR Haemospect or Orsense NMB200). We assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation (""deferred"") incorrectly; and test preference.<h4>Results</h4>Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT's customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT's customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT's customary method to 20.3% in women for OrSense. Most donors preferred non-invasive spectrometry.<h4>Conclusion</h4>In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHSBT's customary method with portable haemoglobinometry.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/315673/1/tme.12750.pdf; doi:https://doi.org/10.1111/tme.12750; html:https://europepmc.org/articles/PMC8048787; pdf:https://europepmc.org/articles/PMC8048787?pdf=render
 36084617,https://doi.org/10.1016/j.ebiom.2022.104243,Machine learning integration of multimodal data identifies key features of blood pressure regulation.,"Louca P, Tran TQB, Toit CD, Christofidou P, Spector TD, Mangino M, Suhre K, Padmanabhan S, Menni C.",,EBioMedicine,2022,2022-09-06,Y,Diet; Blood pressure; Genomics; Metabolomics; Machine Learning,,,"<h4>Background</h4>Association studies have identified several biomarkers for blood pressure and hypertension, but a thorough understanding of their mutual dependencies is lacking. By integrating two different high-throughput datasets, biochemical and dietary data, we aim to understand the multifactorial contributors of blood pressure (BP).<h4>Methods</h4>We included 4,863 participants from TwinsUK with concurrent BP, metabolomics, genomics, biochemical measures, and dietary data. We used 5-fold cross-validation with the machine learning XGBoost algorithm to identify features of importance in context of one another in TwinsUK (80% training, 20% test). The features tested in TwinsUK were then probed using the same algorithm in an independent dataset of 2,807 individuals from the Qatari Biobank (QBB).<h4>Findings</h4>Our model explained 39·2% [4·5%, MAE:11·32 mmHg (95%CI, +/- 0·65)] of the variance in systolic BP (SBP) in TwinsUK. Of the top 50 features, the most influential non-demographic variables were dihomo-linolenate, cis-4-decenoyl carnitine, lactate, chloride, urate, and creatinine along with dietary intakes of total, trans and saturated fat. We also highlight the incremental value of each included dimension. Furthermore, we replicated our model in the QBB [SBP variance explained = 45·2% (13·39%)] cohort and 30 of the top 50 features overlapped between cohorts.<h4>Interpretation</h4>We show that an integrated analysis of omics, biochemical and dietary data improves our understanding of their in-between relationships and expands the range of potential biomarkers for blood pressure. Our results point to potentially key biological pathways to be prioritised for mechanistic studies.<h4>Funding</h4>Chronic Disease Research Foundation, Medical Research Council, Wellcome Trust, Qatar Foundation.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463529; doi:https://doi.org/10.1016/j.ebiom.2022.104243; html:https://europepmc.org/articles/PMC9463529; pdf:https://europepmc.org/articles/PMC9463529?pdf=render
@@ -1826,10 +1826,10 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 32303767,https://doi.org/10.1093/schbul/sbaa040,Real-World Clinical Outcomes Two Years After Transition to Psychosis in Individuals at Clinical High Risk: Electronic Health Record Cohort Study. ,"Fusar-Poli P, De Micheli A, Patel R, Signorini L, Miah S, Spencer T, McGuire P.",,Schizophrenia bulletin,2020,2020-04-18,N,,,,"The objective of this study is to describe the 2-year real-world clinical outcomes after transition to psychosis in patients at clinical high-risk. The study used the clinical electronic health record cohort study including all patients receiving a first index primary diagnosis of nonorganic International Classification of Diseases (ICD)-10 psychotic disorder within the early psychosis pathway in the South London and Maudsley (SLaM) National Health Service (NHS) Trust from 2001 to 2017. Outcomes encompassed: cumulative probability (at 3, 6, 12, and 24 months) of receiving a first (1) treatment with antipsychotic, (2) informal admission, (3) compulsory admission, and (4) treatment with clozapine and (5) numbers of days spent in hospital (at 12 and 24 months) in patients transitioning to psychosis from clinical high-risk services (Outreach and Support in south London; OASIS) compared to other first-episode groups. Analyses included logistic and 0-inflated negative binomial regressions. In the study, 1561 patients were included; those who had initially been managed by OASIS and had subsequently transitioned to a first episode of psychosis (n = 130) were more likely to receive antipsychotic medication (at 3, 6, and 24 months; all P < .023), to be admitted informally (at all timepoints, all P < .004) and on a compulsory basis (at all timepoints, all P < .013), and to have spent more time in hospital (all timepoints, all P < .007) than first-episode patients who were already psychotic when seen by the OASIS service (n = 310), or presented to early intervention services (n = 1121). The likelihood of receiving clozapine was similar across all groups (at 12/24 months, all P < .101). Transition to psychosis from a clinical high-risk state is associated with severe real-world clinical outcomes. Prevention of transition to psychosis should remain a core target of future research. The study protocol was registered on www.researchregistry.com; researchregistry5039).",,pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/46/5/1114/33777256/sbaa040.pdf; doi:https://doi.org/10.1093/schbul/sbaa040; html:https://europepmc.org/articles/PMC7505186; pdf:https://europepmc.org/articles/PMC7505186?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa040
 32724101,https://doi.org/10.1038/s41467-020-17477-x,Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk.,"Huang QQ, Tang HHF, Teo SM, Mok D, Ritchie SC, Nath AP, Brozynska M, Salim A, Bakshi A, Holt BJ, Khor CC, Sly PD, Holt PG, Holt KE, Inouye M.",,Nature communications,2020,2020-07-28,Y,,,,"Chronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we map expression quantitative trait loci (eQTLs) in resting myeloid cells and CD4<sup>+</sup> T cells from cord blood samples, as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively. Cis-eQTLs are largely specific to cell type or stimulation, and 31% and 52% of genes with cis-eQTLs have response eQTLs (reQTLs) in myeloid cells and T cells, respectively. We identified cis regulatory factors acting as mediators of trans effects. There is extensive colocalisation between condition-specific neonatal cis-eQTLs and variants associated with immune-mediated diseases, in particular CTSH had widespread colocalisation across diseases. Mendelian randomisation shows causal neonatal gene expression effects on disease risk for BTN3A2, HLA-C and others. Our study elucidates the genetics of gene expression in neonatal immune cells, and aetiological origins of autoimmune and allergic diseases.",,pdf:https://www.nature.com/articles/s41467-020-17477-x.pdf; doi:https://doi.org/10.1038/s41467-020-17477-x; html:https://europepmc.org/articles/PMC7387553; pdf:https://europepmc.org/articles/PMC7387553?pdf=render
 34167318,https://doi.org/10.1161/circulationaha.121.054302,Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction.,"Wereski R, Kimenai DM, Taggart C, Doudesis D, Lee KK, Lowry MTH, Bularga A, Lowe DJ, Fujisawa T, Apple FS, Collinson PO, Anand A, Chapman AR, Mills NL.",,Circulation,2021,2021-06-25,Y,Kinetics; Troponin; Myocardial infarction; Predictive Value Of Tests,,,"<h4>Background</h4>Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice.<h4>Methods</h4>In a secondary analysis of a multicenter randomized controlled trial, we identified 46 092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction.<h4>Results</h4>Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (<i>P</i><0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]).<h4>Conclusions</h4>Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054302; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.054302; html:https://europepmc.org/articles/PMC8360674; pdf:https://europepmc.org/articles/PMC8360674?pdf=render
-36647047,https://doi.org/10.1186/s12916-022-02722-5,"Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.","Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMC medicine,2023,2023-01-16,Y,Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions,,,"<h4>Background</h4>The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.<h4>Methods</h4>A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.<h4>Results</h4>During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.<h4>Conclusions</h4>The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render
 32548911,https://doi.org/10.1002/ehf2.12779,A registry-based algorithm to predict ejection fraction in patients with heart failure.,"Uijl A, Lund LH, Vaartjes I, Brugts JJ, Linssen GC, Asselbergs FW, Hoes AW, Dahlström U, Koudstaal S, Savarese G.",,ESC heart failure,2020,2020-06-17,Y,Prediction; Ejection fraction; Heart Failure; Electronic Health Records; Hfpef; Hfref; Hfmref,,,"<h4>Aims</h4>Left ventricular ejection fraction (EF) is required to categorize heart failure (HF) [i.e. HF with preserved (HFpEF), mid-range (HFmrEF), and reduced (HFrEF) EF] but is often not captured in population-based cohorts or non-HF registries. The aim was to create an algorithm that identifies EF subphenotypes for research purposes.<h4>Methods and results</h4>We included 42 061 HF patients from the Swedish Heart Failure Registry. As primary analysis, we performed two logistic regression models including 22 variables to predict (i) EF≥ vs. <50% and (ii) EF≥ vs. <40%. In the secondary analysis, we performed a multivariable multinomial analysis with 22 variables to create a model for all three separate EF subphenotypes: HFrEF vs. HFmrEF vs. HFpEF. The models were validated in the database from the CHECK-HF study, a cross-sectional survey of 10 627 patients from the Netherlands. The C-statistic (discrimination) was 0.78 [95% confidence interval (CI) 0.77-0.78] for EF ≥50% and 0.76 (95% CI 0.75-0.76) for EF ≥40%. Similar results were achieved for HFrEF and HFpEF in the multinomial model, but the C-statistic for HFmrEF was lower: 0.63 (95% CI 0.63-0.64). The external validation showed similar discriminative ability to the development cohort.<h4>Conclusions</h4>Routine clinical characteristics could potentially be used to identify different EF subphenotypes in databases where EF is not readily available. Accuracy was good for the prediction of HFpEF and HFrEF but lower for HFmrEF. The proposed algorithm enables more effective research on HF in the big data setting.",,doi:https://doi.org/10.1002/ehf2.12779; doi:https://doi.org/10.1002/ehf2.12779; html:https://europepmc.org/articles/PMC7524089; pdf:https://europepmc.org/articles/PMC7524089?pdf=render
-37338017,https://doi.org/10.1111/jvh.13863,Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies.,"Trickey A, Ingle SM, Boyd A, Gill MJ, Grabar S, Jarrin I, Obel N, Touloumi G, Zangerle R, Rauch A, Rentsch CT, Satre DD, Silverberg MJ, Bonnet F, Guest J, Burkholder G, Crane H, Teira R, Berenguer J, Wyen C, Abgrall S, Hessamfar M, Reiss P, d'Arminio Monforte A, McGinnis KA, Sterne JAC, Wittkop L, Antiretroviral Therapy Cohort Collaboration.",,Journal of viral hepatitis,2023,2023-06-20,N,Mortality; Alcohol; Hepatitis C virus; HIV; Cohort; Cause-specific,,,"Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1-20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0 g/day and 1.84 (1.62-2.09) for >20.0 g/day compared with 0.1-20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0 g/day and 1.64 (1.33-2.02) for >20.0 g/day compared with 0.1-20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863; doi:https://doi.org/10.1111/jvh.13863
+36647047,https://doi.org/10.1186/s12916-022-02722-5,"Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.","Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMC medicine,2023,2023-01-16,Y,Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions,,,"<h4>Background</h4>The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.<h4>Methods</h4>A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.<h4>Results</h4>During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.<h4>Conclusions</h4>The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render
 35255491,https://doi.org/10.1038/s41586-022-04569-5,SARS-CoV-2 is associated with changes in brain structure in UK Biobank.,"Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JLR, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM.",,Nature,2022,2022-03-07,Y,,,,"There is strong evidence of brain-related abnormalities in COVID-19<sup>1-13</sup>. However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51-81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans-with 141 days on average separating their diagnosis and the second scan-as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.",,pdf:https://www.nature.com/articles/s41586-022-04569-5.pdf; doi:https://doi.org/10.1038/s41586-022-04569-5; html:https://europepmc.org/articles/PMC9046077; pdf:https://europepmc.org/articles/PMC9046077?pdf=render
+37338017,https://doi.org/10.1111/jvh.13863,Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies.,"Trickey A, Ingle SM, Boyd A, Gill MJ, Grabar S, Jarrin I, Obel N, Touloumi G, Zangerle R, Rauch A, Rentsch CT, Satre DD, Silverberg MJ, Bonnet F, Guest J, Burkholder G, Crane H, Teira R, Berenguer J, Wyen C, Abgrall S, Hessamfar M, Reiss P, d'Arminio Monforte A, McGinnis KA, Sterne JAC, Wittkop L, Antiretroviral Therapy Cohort Collaboration.",,Journal of viral hepatitis,2023,2023-06-20,N,Mortality; Alcohol; Hepatitis C virus; HIV; Cohort; Cause-specific,,,"Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1-20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0 g/day and 1.84 (1.62-2.09) for >20.0 g/day compared with 0.1-20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0 g/day and 1.64 (1.33-2.02) for >20.0 g/day compared with 0.1-20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863; doi:https://doi.org/10.1111/jvh.13863
 37128097,https://doi.org/10.1038/s43016-020-0092-z,RETRACTED ARTICLE: Dietary metabotype modelling predicts individual responses to dietary interventions.,"Garcia-Perez I, Posma JM, Chambers ES, Mathers JC, Draper J, Beckmann M, Nicholson JK, Holmes E, Frost G.",,Nature food,2020,2020-06-17,N,,,,"Habitual consumption of poor quality diets is linked directly to risk factors for many non-communicable diseases. This has resulted in the vast majority of countries and the World Health Organization developing policies for healthy eating to reduce the prevalence of non-communicable diseases in the population. However, there is mounting evidence of variability in individual metabolic responses to any dietary intervention. We have developed a method for applying a pipeline for understanding interindividual differences in response to diet, based on coupling data from highly controlled dietary studies with deep metabolic phenotyping. In this feasibility study, we create an individual Dietary Metabotype Score (DMS) that embodies interindividual variability in dietary response and captures consequent dynamic changes in concentrations of urinary metabolites. We find an inverse relationship between the DMS and blood glucose concentration. There is also a relationship between the DMS and urinary metabolic energy loss. Furthermore, we use a metabolic entropy approach to visualize individual and collective responses to dietary interventions. Potentially, the DMS offers a method to target and to enhance dietary response at the individual level, thereby reducing the burden of non-communicable diseases at the population level.",,html:http://hdl.handle.net/10044/1/80100; doi:https://doi.org/10.1038/s43016-020-0092-z
 33201485,https://doi.org/10.1007/s12471-020-01517-8,ONCOR: design of the Dutch cardio-oncology registry.,"Kamphuis JAM, Linschoten M, Cramer MJ, Alsemgeest F, van Kessel DJW, Urgel K, Post MC, Manintveld OC, Hassing HC, Liesting C, Wardeh AJ, Olde Bijvank EGM, Schaap J, Stevense-den Boer AM, Doevendans PA, Asselbergs FW, Teske AJ.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2021,2020-11-17,Y,Research Design; Registries; Cardio-oncology,,,"<h4>Background</h4>The relative new subspecialty 'cardio-oncology' was established to meet the growing demand for an interdisciplinary approach to the management of cancer therapy-related cardiovascular adverse events. In recent years, specialised cardio-oncology services have been implemented worldwide, which all strive to improve the cardiovascular health of cancer patients. However, limited data are currently available on the outcomes and experiences of these specialised services, and optimal strategies for cardio-oncological care have not been established.<h4>Aim</h4>The ONCOR registry has been created for prospective data collection and evaluation of cardio-oncological care in daily practice.<h4>Methods</h4>Dutch hospitals using a standardised cardio-oncology care pathway are included in this national, multicentre, observational cohort study. All patients visiting these cardio-oncology services are eligible for study inclusion. Data collection at baseline consists of the (planned) cancer treatment and the cardiovascular risk profile, which are used to estimate the cardiotoxic risk. Information regarding invasive and noninvasive tests is collected during the time patients receive cardio-oncological care. Outcome data consist of the incidence of cardiovascular complications and major adverse cardiac events, and the impact of these events on the oncological treatment.<h4>Discussion</h4>Outcomes of the ONCOR registry may aid in gaining more insight into the incidence of cancer therapy-related cardiovascular complications. The registry facilitates research on mechanisms of cardiovascular complications and on diagnostic, prognostic and therapeutic strategies. In addition, it provides a platform for future (interventional) studies. Centres with cardio-oncology services that are interested in contributing to the ONCOR registry are hereby invited to participate.",,pdf:https://link.springer.com/content/pdf/10.1007/s12471-020-01517-8.pdf; doi:https://doi.org/10.1007/s12471-020-01517-8; html:https://europepmc.org/articles/PMC8062648; pdf:https://europepmc.org/articles/PMC8062648?pdf=render
 36245269,https://doi.org/10.15252/embj.2022111857,Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.,"Yu X, Ni T, Munson G, Zhang P, Gilbert RJC.",,The EMBO journal,2022,2022-10-17,Y,Cryo-electron Tomography; Cryo-em; Subtomogram Averaging; Pore-forming Protein; Perforin-2,,,"Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 β-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2022111857; doi:https://doi.org/10.15252/embj.2022111857; html:https://europepmc.org/articles/PMC9713709; pdf:https://europepmc.org/articles/PMC9713709?pdf=render
@@ -1870,8 +1870,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 37188768,https://doi.org/10.1038/s42003-023-04836-9,Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.,"Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.",,Communications biology,2023,2023-05-15,Y,,,,"There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, D<sub>f</sub>, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of D<sub>f</sub> is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of D<sub>f</sub> and analyse its relationship with CAD. We replicated 5 D<sub>f</sub> loci and found 4 additional loci with suggestive significance (P < 1e-05) to contribute to D<sub>f</sub> variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between D<sub>f</sub> and CAD, and between D<sub>f</sub> and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of D<sub>f</sub> loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, D<sub>f</sub>, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that D<sub>f</sub> provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of D<sub>f</sub>, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.",,doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render
 37130615,https://doi.org/10.3399/bjgp.2022.0389,Predicting the risk of acute kidney injury in primary care: derivation and validation of STRATIFY-AKI.,"Koshiaris C, Archer L, Lay-Flurrie S, Snell KI, Riley RD, Stevens R, Banerjee A, Usher-Smith JA, Clegg A, Payne RA, Ogden M, Hobbs FR, McManus RJ, Sheppard JP.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-07-27,Y,Blood pressure; Vascular diseases; epidemiology; Primary Health Care; Electronic Health Records; Drug-related Side Effects And Adverse Reactions,,,"<h4>Background</h4>Antihypertensives reduce the risk of cardiovascular disease but are also associated with harms including acute kidney injury (AKI). Few data exist to guide clinical decision making regarding these risks.<h4>Aim</h4>To develop a prediction model estimating the risk of AKI in people potentially indicated for antihypertensive treatment.<h4>Design and setting</h4>Observational cohort study using routine primary care data from the Clinical Practice Research Datalink (CPRD) in England.<h4>Method</h4>People aged ≥40 years, with at least one blood pressure measurement between 130 mmHg and 179 mmHg were included. Outcomes were admission to hospital or death with AKI within 1, 5, and 10 years. The model was derived with data from CPRD GOLD (<i>n</i> = 1 772 618), using a Fine-Gray competing risks approach, with subsequent recalibration using pseudo-values. External validation used data from CPRD Aurum (<i>n</i> = 3 805 322).<h4>Results</h4>The mean age of participants was 59.4 years and 52% were female. The final model consisted of 27 predictors and showed good discrimination at 1, 5, and 10 years (C-statistic for 10-year risk 0.821, 95% confidence interval [CI] = 0.818 to 0.823). There was some overprediction at the highest predicted probabilities (ratio of observed to expected event probability for 10-year risk 0.633, 95% CI = 0.621 to 0.645), affecting patients with the highest risk. Most patients (>95%) had a low 1- to 5-year risk of AKI, and at 10 years only 0.1% of the population had a high AKI and low CVD risk.<h4>Conclusion</h4>This clinical prediction model enables GPs to accurately identify patients at high risk of AKI, which will aid treatment decisions. As the vast majority of patients were at low risk, such a model may provide useful reassurance that most antihypertensive treatment is safe and appropriate while flagging the few for whom this is not the case.",,pdf:https://bjgp.org/content/bjgp/early/2023/01/31/BJGP.2022.0389.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0389; html:https://europepmc.org/articles/PMC10170524; pdf:https://europepmc.org/articles/PMC10170524?pdf=render
 36474045,https://doi.org/10.1038/s41588-022-01233-6,Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.,"Aragam KG, Jiang T, Goel A, Kanoni S, Wolford BN, Atri DS, Weeks EM, Wang M, Hindy G, Zhou W, Grace C, Roselli C, Marston NA, Kamanu FK, Surakka I, Venegas LM, Sherliker P, Koyama S, Ishigaki K, Åsvold BO, Brown MR, Brumpton B, de Vries PS, Giannakopoulou O, Giardoglou P, Gudbjartsson DF, Güldener U, Haider SMI, Helgadottir A, Ibrahim M, Kastrati A, Kessler T, Kyriakou T, Konopka T, Li L, Ma L, Meitinger T, Mucha S, Munz M, Murgia F, Nielsen JB, Nöthen MM, Pang S, Reinberger T, Schnitzler G, Smedley D, Thorleifsson G, von Scheidt M, Ulirsch JC, Biobank Japan, EPIC-CVD, Arnar DO, Burtt NP, Costanzo MC, Flannick J, Ito K, Jang DK, Kamatani Y, Khera AV, Komuro I, Kullo IJ, Lotta LA, Nelson CP, Roberts R, Thorgeirsson G, Thorsteinsdottir U, Webb TR, Baras A, Björkegren JLM, Boerwinkle E, Dedoussis G, Holm H, Hveem K, Melander O, Morrison AC, Orho-Melander M, Rallidis LS, Ruusalepp A, Sabatine MS, Stefansson K, Zalloua P, Ellinor PT, Farrall M, Danesh J, Ruff CT, Finucane HK, Hopewell JC, Clarke R, Gupta RM, Erdmann J, Samani NJ, Schunkert H, Watkins H, Willer CJ, Deloukas P, Kathiresan S, Butterworth AS, CARDIoGRAMplusC4D Consortium.",,Nature genetics,2022,2022-12-06,Y,,,,"The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR-Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.",,pdf:https://www.nature.com/articles/s41588-022-01233-6.pdf; doi:https://doi.org/10.1038/s41588-022-01233-6; html:https://europepmc.org/articles/PMC9729111; pdf:https://europepmc.org/articles/PMC9729111?pdf=render
-37538507,https://doi.org/10.1016/j.rpth.2023.100175,<i>PIK3R3</i> is a candidate regulator of platelet count in people of Bangladeshi ancestry.,"Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.",,Research and practice in thrombosis and haemostasis,2023,2023-05-14,Y,Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases,,,"<h4>Background</h4>Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.<h4>Objectives</h4>To reveal new regulatory genes for platelet count (PLT).<h4>Methods</h4>Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.<h4>Results</h4>Of 1588 significantly associated variants (<i>P</i> < 5 × 10<sup>-8</sup>) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (<i>r</i><sup>2</sup> ≥ 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be <i>PIK3R3</i> encoding a regulator of phosphoinositol 3-kinase (PI3K).<h4>Conclusion</h4>Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between <i>PIK3R3</i> and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.",,doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render
 32340307,https://doi.org/10.3390/genes11040460,An Improved Phenotype-Driven Tool for Rare Mendelian Variant Prioritization: Benchmarking Exomiser on Real Patient Whole-Exome Data.,"Cipriani V, Pontikos N, Arno G, Sergouniotis PI, Lenassi E, Thawong P, Danis D, Michaelides M, Webster AR, Moore AT, Robinson PN, Jacobsen JOB, Smedley D.",,Genes,2020,2020-04-23,Y,Bioinformatics; Whole-exome Sequencing; Rare Disease; Whole-genome Sequencing; Human Phenotype Ontology; Variant Prioritization; Phenotypic Similarity; Inherited Retinal Disease,,,"Next-generation sequencing has revolutionized rare disease diagnostics, but many patients remain without a molecular diagnosis, particularly because many candidate variants usually survive despite strict filtering. Exomiser was launched in 2014 as a Java tool that performs an integrative analysis of patients' sequencing data and their phenotypes encoded with Human Phenotype Ontology (HPO) terms. It prioritizes variants by leveraging information on variant frequency, predicted pathogenicity, and gene-phenotype associations derived from human diseases, model organisms, and protein-protein interactions. Early published releases of Exomiser were able to prioritize disease-causative variants as top candidates in up to 97% of simulated whole-exomes. The size of the tested real patient datasets published so far are very limited. Here, we present the latest Exomiser version 12.0.1 with many new features. We assessed the performance using a set of 134 whole-exomes from patients with a range of rare retinal diseases and known molecular diagnosis. Using default settings, Exomiser ranked the correct diagnosed variants as the top candidate in 74% of the dataset and top 5 in 94%; not using the patients' HPO profiles (i.e., variant-only analysis) decreased the performance to 3% and 27%, respectively. In conclusion, Exomiser is an effective support tool for rare Mendelian phenotype-driven variant prioritization.",,pdf:https://www.mdpi.com/2073-4425/11/4/460/pdf?version=1587647599; doi:https://doi.org/10.3390/genes11040460; html:https://europepmc.org/articles/PMC7230372; pdf:https://europepmc.org/articles/PMC7230372?pdf=render
+37538507,https://doi.org/10.1016/j.rpth.2023.100175,<i>PIK3R3</i> is a candidate regulator of platelet count in people of Bangladeshi ancestry.,"Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.",,Research and practice in thrombosis and haemostasis,2023,2023-05-14,Y,Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases,,,"<h4>Background</h4>Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.<h4>Objectives</h4>To reveal new regulatory genes for platelet count (PLT).<h4>Methods</h4>Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.<h4>Results</h4>Of 1588 significantly associated variants (<i>P</i> < 5 × 10<sup>-8</sup>) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (<i>r</i><sup>2</sup> ≥ 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be <i>PIK3R3</i> encoding a regulator of phosphoinositol 3-kinase (PI3K).<h4>Conclusion</h4>Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between <i>PIK3R3</i> and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.",,doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render
 34455223,https://doi.org/10.1016/j.media.2021.102213,Medical image segmentation automatic quality control: A multi-dimensional approach.,"Fournel J, Bartoli A, Bendahan D, Guye M, Bernard M, Rauseo E, Khanji MY, Petersen SE, Jacquier A, Ghattas B.",,Medical image analysis,2021,2021-08-12,N,Deep Learning; Cmr Image Segmentation; Medical Image Segmentation Automatic Quality Control; Multi-dimensional Quality Control,,,"In clinical applications, using erroneous segmentations of medical images can have dramatic consequences. Current approaches dedicated to medical image segmentation automatic quality control do not predict segmentation quality at slice-level (2D), resulting in sub-optimal evaluations. Our 2D-based deep learning method simultaneously performs quality control at 2D-level and 3D-level for cardiovascular MR image segmentations. We compared it with 3D approaches by training both on 36,540 (2D) / 3842 (3D) samples to predict Dice Similarity Coefficients (DSC) for 4 different structures from the left ventricle, i.e., trabeculations (LVT), myocardium (LVM), papillary muscles (LVPM) and blood (LVC). The 2D-based method outperformed the 3D method. At the 2D-level, the mean absolute errors (MAEs) of the DSC predictions for 3823 samples, were 0.02, 0.02, 0.05 and 0.02 for LVM, LVC, LVT and LVPM, respectively. At the 3D-level, for 402 samples, the corresponding MAEs were 0.02, 0.01, 0.02 and 0.04. The method was validated in a clinical practice evaluation against semi-qualitative scores provided by expert cardiologists for 1016 subjects of the UK BioBank. Finally, we provided evidence that a multi-level QC could be used to enhance clinical measurements derived from image segmentations.",,pdf:http://manuscript.elsevier.com/S1361841521002589/pdf/S1361841521002589.pdf; doi:https://doi.org/10.1016/j.media.2021.102213
 32108548,https://doi.org/10.1177/0269881120907973,Synthetic cannabinoid use in psychiatric patients and relationship to hospitalisation: A retrospective electronic case register study.,"Hobbs M, Patel R, Morrison PD, Kalk N, Stone JM.",,"Journal of psychopharmacology (Oxford, England)",2020,2020-02-28,Y,Cannabis; Psychosis; Hospitalisation; Synthetic Cannabinoids,,,"<h4>Introduction and objectives</h4>Cannabis use has been associated with psychosis and with poor outcome in patients with mental illness. Synthetic cannabinoids (SCs) have been suggested to pose an even greater risk to mental health, but the effect on clinical outcome has not been directly measured. In this study, we aimed to investigate the demographics and hospitalisation of psychiatric patients who were SC users.<h4>Methods</h4>We searched the Biomedical Research Centre Clinical Record Interactive Search register for SC users and age- and sex-matched SC non-users who had been psychiatric patients under the South London and Maudsley NHS Trust. We recorded diagnosis, homelessness, cannabis use and the total number of days admitted as an inpatient to secondary and tertiary mental-health services.<h4>Results</h4>We identified 635 SC users and 635 age- and sex-matched SC non-users. SC users were significantly more likely to be homeless (χ<sup>2</sup>=138.0; <i>p</i><0.0001) and to use cannabis (χ<sup>2</sup>=257.3; <i>p</i><0.0001) than SC non-users. SC users had significantly more inpatient days after their first recorded use of SCs than controls (<i>M</i> (<i>SD</i>)=85.5 (199.7) vs. 25.4 (92.32); <i>p</i><0.0001). Post hoc tests revealed that SC non-users who used cannabis had fewer inpatient days than SC users (<i>p</i><0.0001), and that non-users of both SC and cannabis had fewer inpatient days than SC non-using cannabis users (<i>p</i>=0.02).<h4>Conclusions</h4>SC use may lead to an increase in the number of days spent in hospital in patients with psychiatric illness. This highlights the need for clinicians to ask specifically about SC use.",,pdf:https://europepmc.org/articles/pmc7249610?pdf=render; doi:https://doi.org/10.1177/0269881120907973; html:https://europepmc.org/articles/PMC7249610; pdf:https://europepmc.org/articles/PMC7249610?pdf=render
 34371093,https://doi.org/10.1016/j.jaad.2021.07.066,The impact of psoriasis and sexual orientation on mental and physical health among adults in the United States.,"Mansh MD, Mulick A, Langan SM.",,Journal of the American Academy of Dermatology,2022,2021-08-08,Y,,,,,,doi:https://doi.org/10.1016/j.jaad.2021.07.066; doi:https://doi.org/10.1016/j.jaad.2021.07.066; html:https://europepmc.org/articles/PMC7612892; pdf:https://europepmc.org/articles/PMC7612892?pdf=render
@@ -1885,8 +1885,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 31782492,https://doi.org/10.1093/ajcn/nqz293,The association of fish consumption and its urinary metabolites with cardiovascular risk factors: the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP).,"Gibson R, Lau CE, Loo RL, Ebbels TMD, Chekmeneva E, Dyer AR, Miura K, Ueshima H, Zhao L, Daviglus ML, Stamler J, Van Horn L, Elliott P, Holmes E, Chan Q.",,The American journal of clinical nutrition,2020,2020-02-01,Y,Hypertension; Blood pressure; FISH; Shellfish; Biomarkers; body mass index; Seafood; Metabonomics; Homarine; Intermap Metabolomics,Improving Public Health,,"<h4>Background</h4>Results from observational studies regarding associations between fish (including shellfish) intake and cardiovascular disease risk factors, including blood pressure (BP) and BMI, are inconsistent.<h4>Objective</h4>To investigate associations of fish consumption and associated urinary metabolites with BP and BMI in free-living populations.<h4>Methods</h4>We used cross-sectional data from the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP), including 4680 men and women (40-59 y) from Japan, China, the United Kingdom, and United States. Dietary intakes were assessed by four 24-h dietary recalls and BP from 8 measurements. Urinary metabolites (2 timed 24-h urinary samples) associated with fish intake acquired from NMR spectroscopy were identified. Linear models were used to estimate BP and BMI differences across categories of intake and per 2 SD higher intake of fish and its biomarkers.<h4>Results</h4>No significant associations were observed between fish intake and BP. There was a direct association with fish intake and BMI in the Japanese population sample (P trend = 0.03; fully adjusted model). In Japan, trimethylamine-N-oxide (TMAO) and taurine, respectively, demonstrated area under the receiver operating characteristic curve (AUC) values of 0.81 and 0.78 in discriminating high against low fish intake, whereas homarine (a metabolite found in shellfish muscle) demonstrated an AUC of 0.80 for high/nonshellfish intake. Direct associations were observed between urinary TMAO and BMI for all regions except Japan (P < 0.0001) and in Western populations between TMAO and BP (diastolic blood pressure: mean difference 1.28; 95% CI: 0.55, 2.02 mmHg; P = 0.0006, systolic blood pressure: mean difference 1.67; 95% CI: 0.60, 2.73 mmHg; P = 0.002).<h4>Conclusions</h4>Urinary TMAO showed a stronger association with fish intake in the Japanese compared with the Western population sample. Urinary TMAO was directly associated with BP in the Western but not the Japanese population sample. Associations between fish intake and its biomarkers and downstream associations with BP/BMI appear to be context specific. INTERMAP is registered at www.clinicaltrials.gov as NCT00005271.",Gibson et al.’s study investigates whether having fish in diet will have an effect on urinary metabolism. They’ve assessed dietary and BP measurement across Asian and Westerns and shown that the relationship was stronger in Japanese population compared to Western population and is highly context dependant. ,doi:https://doi.org/10.1093/ajcn/nqz293; doi:https://doi.org/10.1093/ajcn/nqz293; html:https://europepmc.org/articles/PMC6997096; pdf:https://europepmc.org/articles/PMC6997096?pdf=render
 35605170,https://doi.org/10.2196/37668,Differences in Clinical Presentation With Long COVID After Community and Hospital Infection and Associations With All-Cause Mortality: English Sentinel Network Database Study.,"Meza-Torres B, Delanerolle G, Okusi C, Mayor N, Anand S, Macartney J, Gatenby P, Glampson B, Chapman M, Curcin V, Mayer E, Joy M, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-16,Y,Phenotype; Hospitalization; Social Class; General Practitioners; Ethnicity; Medical Record Systems; Systematized Nomenclature Of Medicine; Computerized; Biomedical Ontologies; Data Accuracy; Covid-19; Sars-cov-2; Long Covid; Post–covid-19 Syndrome; Post–acute Covid-19 Syndrome; Data Extracts,,,"<h4>Background</h4>Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records.<h4>Objective</h4>We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates.<h4>Methods</h4>We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs.<h4>Results</h4>In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001).<h4>Conclusions</h4>The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.",,pdf:https://publichealth.jmir.org/2022/8/e37668/PDF; doi:https://doi.org/10.2196/37668; html:https://europepmc.org/articles/PMC9384859
 34244281,https://doi.org/10.1136/bmjopen-2021-049611,"Ethnicity and COVID-19 outcomes among healthcare workers in the UK: UK-REACH ethico-legal research, qualitative research on healthcare workers' experiences and stakeholder engagement protocol.","Gogoi M, Reed-Berendt R, Al-Oraibi A, Hassan O, Wobi F, Gupta A, Abubakar I, Dove E, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,BMJ open,2021,2021-07-09,Y,Medical Ethics; Qualitative Research; Medical Law; Covid-19,,,"<h4>Introduction</h4>As the world continues to grapple with the COVID-19 pandemic, emerging evidence suggests that individuals from ethnic minority backgrounds may be disproportionately affected. The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) project has been initiated to generate rapid evidence on whether and why ethnicity affects COVID-19 diagnosis and clinical outcomes in healthcare workers (HCWs) in the UK, through five interlinked work packages/work streams, three of which form the basis of this protocol. The ethico-legal work (Work Package 3) aims to understand and address legal, ethical and acceptability issues around big data research; the HCWs' experiences study (Work Package 4) explores their work and personal experiences, perceptions of risk, support and coping mechanisms; the stakeholder engagement work (Work Package 5) aims to provide feedback and support with the formulation and dissemination of the project recommendations.<h4>Methods and analysis</h4>Work Package 3 has two different research strands: (A) desk-based doctrinal research; and (B) empirical qualitative research with key opinion leaders. For the empirical research, in-depth interviews will be conducted digitally and recorded with participants' permission. Recordings will be transcribed, coded and analysed using thematic analysis. In Work Package 4, online in-depth interviews and focus groups will be conducted with approximately 150 HCWs, from across the UK, and these will be recorded with participants' consent. The recordings will be transcribed and coded and data will be analysed using thematic analysis. Work Package 5 will achieve its objectives through regular group meetings and in-group discussions.<h4>Ethics and dissemination</h4>Ethical approval has been received from the London-Brighton & Sussex Research Ethics Committee of the Health Research Authority (Ref No 20/HRA/4718). Results of the study will be published in open-access journals, and disseminated through conference presentations, project website, stakeholder organisations, media and scientific advisory groups.<h4>Trial registration number</h4>ISRCTN11811602.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e049611.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049611; html:https://europepmc.org/articles/PMC8275361; pdf:https://europepmc.org/articles/PMC8275361?pdf=render
-36244350,https://doi.org/10.1016/s2468-2667(22)00225-0,The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.,European Antimicrobial Resistance Collaborators.,,The Lancet. Public health,2022,2022-10-14,Y,,,,"<h4>Background</h4>Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.<h4>Methods</h4>We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.<h4>Findings</h4>We estimated 541 000 deaths (95% UI 370 000-763 000) associated with bacterial AMR and 133 000 deaths (90 100-188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000-333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900-185 000]) and respiratory infections (120 000 deaths [94 500-154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.<h4>Interpretation</h4>The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.<h4>Funding</h4>Bill &amp; Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.",,pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf; doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253
 34216337,https://doi.org/10.1007/s10552-021-01466-6,"Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank.","Watts EL, Perez-Cornago A, Doherty A, Allen NE, Fensom GK, Tin Tin S, Key TJ, Travis RC.",,Cancer causes & control : CCC,2021,2021-07-03,Y,Testosterone; IGF-I; Physical Activity; Accelerometer; Shbg; Uk Biobank,,,"<h4>Purpose</h4>Physical activity may reduce the risk of some types of cancer in men. Biological mechanisms may involve changes in hormone concentrations; however, this relationship is not well established. Therefore, we aimed to investigate the associations of physical activity with circulating insulin-like growth factor-I (IGF-I), sex hormone-binding globulin (SHBG, which modifies sex hormone activity), and total and free testosterone concentrations, and the extent these associations might be mediated by body mass index (BMI).<h4>Methods</h4>Circulating concentrations of these hormones and anthropometric measurements and self-reported physical activity data were available for 117,100 healthy male UK Biobank participants at recruitment. Objectively measured accelerometer physical activity levels were also collected on average 5.7 years after recruitment in 28,000 men. Geometric means of hormone concentrations were estimated using multivariable-adjusted analysis of variance, with and without adjustment for BMI.<h4>Results</h4>The associations between physical activity and hormones were modest and similar for objectively measured (accelerometer) and self-reported physical activity. Compared to men with the lowest objectively measured physical activity, men with high physical activity levels had 14% and 8% higher concentrations of SHBG and total testosterone, respectively, and these differences were attenuated to 6% and 3% following adjustment for BMI.<h4>Conclusion</h4>Our results suggest that the associations of physical activity with the hormones investigated are, at most, modest; and following adjustment for BMI, the small associations with SHBG and total testosterone were largely attenuated. Therefore, it is unlikely that changes in these circulating hormones explain the associations of physical activity with risk of cancer either independently or via BMI.",,pdf:https://link.springer.com/content/pdf/10.1007/s10552-021-01466-6.pdf; doi:https://doi.org/10.1007/s10552-021-01466-6; html:https://europepmc.org/articles/PMC8492588; pdf:https://europepmc.org/articles/PMC8492588?pdf=render
+36244350,https://doi.org/10.1016/s2468-2667(22)00225-0,The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.,European Antimicrobial Resistance Collaborators.,,The Lancet. Public health,2022,2022-10-14,Y,,,,"<h4>Background</h4>Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.<h4>Methods</h4>We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.<h4>Findings</h4>We estimated 541 000 deaths (95% UI 370 000-763 000) associated with bacterial AMR and 133 000 deaths (90 100-188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000-333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900-185 000]) and respiratory infections (120 000 deaths [94 500-154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.<h4>Interpretation</h4>The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.<h4>Funding</h4>Bill &amp; Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.",,pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf; doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253
 35948708,https://doi.org/10.1038/s41586-022-05023-2,Spatially resolved clonal copy number alterations in benign and malignant tissue.,"Erickson A, He M, Berglund E, Marklund M, Mirzazadeh R, Schultz N, Kvastad L, Andersson A, Bergenstråhle L, Bergenstråhle J, Larsson L, Alonso Galicia L, Shamikh A, Basmaci E, Díaz De Ståhl T, Rajakumar T, Doultsinos D, Thrane K, Ji AL, Khavari PA, Tarish F, Tanoglidi A, Maaskola J, Colling R, Mirtti T, Hamdy FC, Woodcock DJ, Helleday T, Mills IG, Lamb AD, Lundeberg J.",,Nature,2022,2022-08-10,Y,,,,"Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer<sup>1</sup>. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics<sup>2</sup> to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.",,pdf:https://www.nature.com/articles/s41586-022-05023-2.pdf; doi:https://doi.org/10.1038/s41586-022-05023-2; html:https://europepmc.org/articles/PMC9365699; pdf:https://europepmc.org/articles/PMC9365699?pdf=render
 31950891,https://doi.org/10.1192/bjo.2019.96,Predicting high-cost care in a mental health setting.,"Colling C, Khondoker M, Patel R, Fok M, Harland R, Broadbent M, McCrone P, Stewart R.",,BJPsych open,2020,2020-01-17,Y,Prediction; Natural Language Processing; Mental Health Service; Digital Health Records,,,"<h4>Background</h4>The density of information in digital health records offers new potential opportunities for automated prediction of cost-relevant outcomes.<h4>Aims</h4>We investigated the extent to which routinely recorded data held in the electronic health record (EHR) predict priority service outcomes and whether natural language processing tools enhance the predictions. We evaluated three high priority outcomes: in-patient duration, readmission following in-patient care and high service cost after first presentation.<h4>Method</h4>We used data obtained from a clinical database derived from the EHR of a large mental healthcare provider within the UK. We combined structured data with text-derived data relating to diagnosis statements, medication and psychiatric symptomatology. Predictors of the three different clinical outcomes were modelled using logistic regression with performance evaluated against a validation set to derive areas under receiver operating characteristic curves.<h4>Results</h4>In validation samples, the full models (using all available data) achieved areas under receiver operating characteristic curves between 0.59 and 0.85 (in-patient duration 0.63, readmission 0.59, high service use 0.85). Adding natural language processing-derived data to the models increased the variance explained across all clinical scenarios (observed increase in r2 = 12-46%).<h4>Conclusions</h4>EHR data offer the potential to improve routine clinical predictions by utilising previously inaccessible data. Of our scenarios, prediction of high service use after initial presentation achieved the highest performance.","This study uses data from a mental healthcare provider to predict 3 things: 1) extended duration of stay in a hospital, 2) the likelihood of needing to be admitted to hospital again after discharge, and 3) likehood of needing 'high intesity service' (high cost services). The authors developed a natural language processing model (a computer system than aims to interpret text and draw out useful information) to review the text, diagnoses, medications and the patient symptoms to work out which patients would fall within those 3 categories. They conclude that their model could be used to improve services through predicting users who will require the most intense and costly care.",pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/6EF9FC74DC5A744C9D841DD649992ABE/S2056472419000966a.pdf/div-class-title-predicting-high-cost-care-in-a-mental-health-setting-div.pdf; doi:https://doi.org/10.1192/bjo.2019.96; html:https://europepmc.org/articles/PMC7001466; pdf:https://europepmc.org/articles/PMC7001466?pdf=render
 35584845,https://doi.org/10.1136/bmj-2022-070904,Reporting guideline for the early stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,BMJ (Clinical research ed.),2022,2022-05-18,Y,,,,,,pdf:https://www.bmj.com/content/bmj/377/bmj-2022-070904.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070904; html:https://europepmc.org/articles/PMC9116198
@@ -1899,9 +1899,9 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33024096,https://doi.org/10.1038/s41467-020-18783-0,Changing travel patterns in China during the early stages of the COVID-19 pandemic.,"Gibbs H, Liu Y, Pearson CAB, Jarvis CI, Grundy C, Quilty BJ, Diamond C, LSHTM CMMID COVID-19 working group, Eggo RM.",,Nature communications,2020,2020-10-06,Y,,,,"Understanding changes in human mobility in the early stages of the COVID-19 pandemic is crucial for assessing the impacts of travel restrictions designed to reduce disease spread. Here, relying on data from mainland China, we investigate the spatio-temporal characteristics of human mobility between 1st January and 1st March 2020, and discuss their public health implications. An outbound travel surge from Wuhan before travel restrictions were implemented was also observed across China due to the Lunar New Year, indicating that holiday travel may have played a larger role in mobility changes compared to impending travel restrictions. Holiday travel also shifted healthcare pressure related to COVID-19 towards locations with lower healthcare capacity. Network analyses showed no sign of major changes in the transportation network after Lunar New Year. Changes observed were temporary and did not lead to structural reorganisation of the transportation network during the study period.",,pdf:https://www.nature.com/articles/s41467-020-18783-0.pdf; doi:https://doi.org/10.1038/s41467-020-18783-0; html:https://europepmc.org/articles/PMC7538915; pdf:https://europepmc.org/articles/PMC7538915?pdf=render
 30928767,https://doi.org/10.1016/j.evalprogplan.2019.03.002,Understanding the factors that influence health promotion evaluation: The development and validation of the evaluation practice analysis survey.,"Schwarzman J, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Evaluation and program planning,2019,2019-03-22,N,Measurement; Validity; reliability; Health Promotion; Evaluation Capacity Building; Evaluation Practice,,,"The demand for improved quality of health promotion evaluation and greater capacity to undertake evaluation is growing, yet evidence of the challenges and facilitators to evaluation practice within the health promotion field is lacking. A limited number of evaluation capacity measurement instruments have been validated in government or non-government organisations (NGO), however there is no instrument designed for health promotion organisations. This study aimed to develop and validate an Evaluation Practice Analysis Survey (EPAS) to examine evaluation practices in health promotion organisations. Qualitative interviews, existing frameworks and instruments informed the survey development. Health promotion practitioners from government agencies and NGOs completed the survey (n = 169). Principal components analysis was used to determine scale structure and Cronbach's α used to estimate internal reliability. Logistic regression was conducted to assess predictive validity of selected EPAS scale. The final survey instrument included 25 scales (125 items). The EPAS demonstrated good internal reliability (α > 0.7) for 23 scales. Dedicated resources and time for evaluation, leadership, organisational culture and internal support for evaluation showed promising predictive validity. The EPAS can be used to describe elements of evaluation capacity at the individual, organisational and system levels and to guide initiatives to improve evaluation practice in health promotion organisations.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa49960/Download/0049960-14052019134527.pdf; doi:https://doi.org/10.1016/j.evalprogplan.2019.03.002
 35879886,https://doi.org/10.1017/s0033291722002501,"Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.","Young KS, Purves KL, Hübel C, Davies MR, Thompson KN, Bristow S, Krebs G, Danese A, Hirsch C, Parsons CE, Vassos E, Adey BN, Bright S, Hegemann L, Lee YT, Kalsi G, Monssen D, Mundy J, Peel AJ, Rayner C, Rogers HC, Ter Kuile A, Ward C, York K, Lin Y, Palmos AB, Schmidt U, Veale D, Nicholson TR, Pollak TA, Stevelink SAM, Moukhtarian T, Martineau AR, Holt H, Maughan B, Al-Chalabi A, Chaudhuri KR, Richardson MP, Bradley JR, Chinnery PF, Kingston N, Papadia S, Stirrups KE, Linger R, Hotopf M, Eley TC, Breen G.",,Psychological medicine,2023,2022-07-26,Y,Depression; Anxiety; Ptsd; Covid-19,,,"<h4>Background</h4>The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.<h4>Method</h4>Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (<i>n</i> = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.<h4>Results</h4>Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.<h4>Conclusions</h4>We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8C3760ED596F1ED8B80F729AC5E47B9B/S0033291722002501a.pdf/div-class-title-depression-anxiety-and-ptsd-symptoms-before-and-during-the-covid-19-pandemic-in-the-uk-div.pdf; doi:https://doi.org/10.1017/S0033291722002501; html:https://europepmc.org/articles/PMC10482709; pdf:https://europepmc.org/articles/PMC10482709?pdf=render
-37247330,https://doi.org/10.1093/eurheartj/ehad260,SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.,SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.,,European heart journal,2023,2023-07-01,Y,Cardiovascular diseases; Prediction model; Diabetes,,,"<h4>Aims</h4>To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.<h4>Methods and results</h4>SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.<h4>Conclusion</h4>SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.",,doi:https://doi.org/10.1093/eurheartj/ehad260; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render
 32576090,https://doi.org/10.1161/strokeaha.120.029042,Telemedicine Cognitive Behavioral Therapy for Anxiety After Stroke: Proof-of-Concept Randomized Controlled Trial.,"Chun HY, Carson AJ, Tsanas A, Dennis MS, Mead GE, Calabria C, Whiteley WN.",,Stroke,2020,2020-06-24,Y,Stroke; Anxiety; Workflow; Telemedicine; psychotherapy,,,"<h4>Background and purpose</h4>Disabling anxiety affects a quarter of stroke survivors but access to treatment is poor. We developed a telemedicine model for delivering guided self-help cognitive behavioral therapy (CBT) for anxiety after stroke (TASK-CBT). We aimed to evaluate the feasibility of TASK-CBT in a randomized controlled trial workflow that enabled all trial procedures to be carried out remotely. In addition, we explored the feasibility of wrist-worn actigraphy sensor as a way of measuring objective outcomes in this clinical trial.<h4>Methods</h4>We recruited adult community-based stroke patients (n=27) and randomly allocated them to TASK-CBT (n=14) or relaxation therapy (TASK-Relax), an active comparator (n=13).<h4>Results</h4>In our sample (mean age 65 [±10]; 56% men; 63% stroke, 37% transient ischemic attacks), remote self-enrolment, electronic signature, intervention delivery, and automated follow-up were feasible. All participants completed all TASK-CBT sessions (14/14). Lower levels of anxiety were observed in TASK-CBT when compared with TASK-Relax at both weeks 6 and 20. Mean actigraphy sensor wearing-time was 33 days (±15).<h4>Conclusions</h4>Our preliminary feasibility data from the current study support a larger definitive clinical trial and the use of wrist-worn actigraphy sensor in anxious stroke survivors. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03439813.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.029042; doi:https://doi.org/10.1161/STROKEAHA.120.029042; html:https://europepmc.org/articles/PMC7382539; pdf:https://europepmc.org/articles/PMC7382539?pdf=render
 35861824,https://doi.org/10.1161/jaha.121.025935,Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.,"Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.",,Journal of the American Heart Association,2022,2022-07-13,Y,Biomarkers; Childhood Cancer Survivors; Cardio‐oncology; Chemokine Ligands; Cancer Therapy–related Cardiac Dysfunction; Anthracycline‐related Cardiomyopathy,,,"Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction ≥53% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; <i>P</i>=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; <i>P</i>=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.",,doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935
+37247330,https://doi.org/10.1093/eurheartj/ehad260,SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.,SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.,,European heart journal,2023,2023-07-01,Y,Cardiovascular diseases; Prediction model; Diabetes,,,"<h4>Aims</h4>To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.<h4>Methods and results</h4>SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.<h4>Conclusion</h4>SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.",,doi:https://doi.org/10.1093/eurheartj/ehad260; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render
 35545669,https://doi.org/10.1038/s41586-022-04712-2,Genetic and chemotherapeutic influences on germline hypermutation.,"Kaplanis J, Ide B, Sanghvi R, Neville M, Danecek P, Coorens T, Prigmore E, Short P, Gallone G, McRae J, Genomics England Research Consortium, Carmichael J, Barnicoat A, Firth H, O'Brien P, Rahbari R, Hurles M.",,Nature,2022,2022-05-11,Y,,,,"Mutations in the germline generates all evolutionary genetic variation and is a cause of genetic disease. Parental age is the primary determinant of the number of new germline mutations in an individual's genome<sup>1,2</sup>. Here we analysed the genome-wide sequences of 21,879 families with rare genetic diseases and identified 12 individuals with a hypermutated genome with between two and seven times more de novo single-nucleotide variants than expected. In most families (9 out of 12), the excess mutations came from the father. Two families had genetic drivers of germline hypermutation, with fathers carrying damaging genetic variation in DNA-repair genes. For five of the families, paternal exposure to chemotherapeutic agents before conception was probably a key driver of hypermutation. Our results suggest that the germline is well protected from mutagenic effects, hypermutation is rare, the number of excess mutations is relatively modest and most individuals with a hypermutated genome will not have a genetic disease.",,pdf:https://www.nature.com/articles/s41586-022-04712-2.pdf; doi:https://doi.org/10.1038/s41586-022-04712-2; html:https://europepmc.org/articles/PMC9117138; pdf:https://europepmc.org/articles/PMC9117138?pdf=render
 37565978,https://doi.org/10.1016/j.jchf.2023.07.007,Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.,"Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.",,JACC. Heart failure,2023,2023-08-09,N,Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7,,,"<h4>Background</h4>MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.<h4>Objectives</h4>This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.<h4>Methods</h4>In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.<h4>Results</h4>In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001).<h4>Conclusions</h4>MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.",,doi:https://doi.org/10.1016/j.jchf.2023.07.007
 36865374,https://doi.org/10.12688/wellcomeopenres.18175.1,GroundsWell: Community-engaged and data-informed systems transformation of Urban Green and Blue Space for population health - a new initiative.,"Hunter RF, Rodgers SE, Hilton J, Clarke M, Garcia L, Ward Thompson C, Geary R, Green MA, O'Neill C, Longo A, Lovell R, Nurse A, Wheeler BW, Clement S, Porroche-Escudero A, Mitchell R, Barr B, Barry J, Bell S, Bryan D, Buchan I, Butters O, Clemens T, Clewley N, Corcoran R, Elliott L, Ellis G, Guell C, Jurek-Loughrey A, Kee F, Maguire A, Maskell S, Murtagh B, Smith G, Taylor T, Jepson R, GroundsWell Consortium.",,Wellcome open research,2022,2022-09-20,Y,Public Health; Non-Communicable Disease; Green And Blue Space; Complex Systems; Data Science; Citizen Science; Interdisciplinary; Health Inequalities,,,"Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and <i>whole society</i> processes <i>,</i> with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, <i>GroundsWell</i>, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.",,doi:https://doi.org/10.12688/wellcomeopenres.18175.1; doi:https://doi.org/10.12688/wellcomeopenres.18175.1; html:https://europepmc.org/articles/PMC9971655; pdf:https://europepmc.org/articles/PMC9971655?pdf=render
@@ -1928,8 +1928,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 31073125,https://doi.org/10.1038/s41533-019-0132-z,Systematic review of clinical prediction models to support the diagnosis of asthma in primary care.,"Daines L, McLean S, Buelo A, Lewis S, Sheikh A, Pinnock H.",,NPJ primary care respiratory medicine,2019,2019-05-09,Y,,The Human Phenome,,"Diagnosing asthma is challenging. Misdiagnosis can lead to untreated symptoms, incorrect treatment and avoidable deaths. The best combination of clinical features and tests to achieve a diagnosis of asthma is unclear. As asthma is usually diagnosed in non-specialist settings, a clinical prediction model to aid the assessment of the probability of asthma in primary care may improve diagnostic accuracy. We aimed to identify and describe existing prediction models to support the diagnosis of asthma in children and adults in primary care. We searched Medline, Embase, CINAHL, TRIP and US National Guidelines Clearinghouse databases from 1 January 1990 to 23 November 17. We included prediction models designed for use in primary care or equivalent settings to aid the diagnostic decision-making of clinicians assessing patients with symptoms suggesting asthma. Two reviewers independently screened titles, abstracts and full texts for eligibility, extracted data and assessed risk of bias. From 13,798 records, 53 full-text articles were reviewed. We included seven modelling studies; all were at high risk of bias. Model performance varied, and the area under the receiving operating characteristic curve ranged from 0.61 to 0.82. Patient-reported wheeze, symptom variability and history of allergy or allergic rhinitis were associated with asthma. In conclusion, clinical prediction models may support the diagnosis of asthma in primary care, but existing models are at high risk of bias and thus unreliable for informing practice. Future studies should adhere to recognised standards, conduct model validation and include a broader range of clinical data to derive a prediction model of value for clinicians.",,pdf:https://www.nature.com/articles/s41533-019-0132-z.pdf; doi:https://doi.org/10.1038/s41533-019-0132-z; html:https://europepmc.org/articles/PMC6509212; pdf:https://europepmc.org/articles/PMC6509212?pdf=render
 32987048,https://doi.org/10.1016/j.ijcard.2020.09.053,Predicting 10-year risk of recurrent cardiovascular events andcardiovascular interventions in patients with established cardiovascular disease: results from UCC-SMART and REACH.,"Klooster CCV', Bhatt DL, Steg PG, Massaro JM, Dorresteijn JAN, Westerink J, Ruigrok YM, de Borst GJ, Asselbergs FW, van der Graaf Y, Visseren FLJ, UCC-SMART study group.",,International journal of cardiology,2021,2020-09-25,N,Risk Prediction; Cardiovascular Interventions; Major Cardiovascular Events; Patients With Established Cardiovascular Disease,,,"<h4>Background</h4>Existing cardiovascular risk scores for patients with established cardiovascular disease (CVD) estimate residual risk of recurrent major cardiovascular events (MACE). The aim of the current study is to develop and externally validate a prediction model to estimate the 10-year combined risk of recurrent MACE and cardiovascular interventions (MACE+) in patients with established CVD.<h4>Methods</h4>Data of patients with established CVD from the UCC-SMART cohort (N = 8421) were used for model development, and patient data from REACH Western Europe (N = 14,528) and REACH North America (N = 19,495) for model validation. Predictors were selected based on the existing SMART risk score. A Fine and Gray competing risk-adjusted 10-year risk model was developed for the combined outcome MACE+. The model was validated in all patients and in strata of coronary heart disease (CHD), cerebrovascular disease (CeVD), peripheral artery disease (PAD).<h4>Results</h4>External calibration for 2-year risk in REACH Western Europe and REACH North America was good, c-statistics were moderate: 0.60 and 0.58, respectively. In strata of CVD at baseline good external calibration was observed in patients with CHD and CeVD, however, poor calibration was seen in patients with PAD. C-statistics for patients with CHD were 0.60 and 0.57, for patients with CeVD 0.62 and 0.61, and for patients with PAD 0.53 and 0.54 in REACH Western Europe and REACH North America, respectively.<h4>Conclusions</h4>The 10-year combined risk of recurrent MACE and cardiovascular interventions can be estimated in patients with established CHD or CeVD. However, cardiovascular interventions in patients with PAD could not be predicted reliably.",,pdf:http://www.internationaljournalofcardiology.com/article/S0167527320338341/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.09.053
 32032817,https://doi.org/10.1016/j.nicl.2020.102172,Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study.,"Grist JT, Withey S, MacPherson L, Oates A, Powell S, Novak J, Abernethy L, Pizer B, Grundy R, Bailey S, Mitra D, Arvanitis TN, Auer DP, Avula S, Peet AC.",,NeuroImage. Clinical,2020,2020-01-23,Y,Diffusion; Perfusion; Machine Learning,Understanding the Causes of Disease,cancer and neoplasms,"The imaging and subsequent accurate diagnosis of paediatric brain tumours presents a radiological challenge, with magnetic resonance imaging playing a key role in providing tumour specific imaging information. Diffusion weighted and perfusion imaging are commonly used to aid the non-invasive diagnosis of children's brain tumours, but are usually evaluated by expert qualitative review. Quantitative studies are mainly single centre and single modality. The aim of this work was to combine multi-centre diffusion and perfusion imaging, with machine learning, to develop machine learning based classifiers to discriminate between three common paediatric tumour types. The results show that diffusion and perfusion weighted imaging of both the tumour and whole brain provide significant features which differ between tumour types, and that combining these features gives the optimal machine learning classifier with >80% predictive precision. This work represents a step forward to aid in the non-invasive diagnosis of paediatric brain tumours, using advanced clinical imaging.",Grist et al. team trained computers to analyse brain images from children for identification of tumours. They’ve shown that applying analytical methods to enable machine distinguishes between the entire brain area and the tumour area in the images more than 80% improves how machine analyses the image to identify exact tumour area. ,doi:https://doi.org/10.1016/j.nicl.2020.102172; doi:https://doi.org/10.1016/j.nicl.2020.102172; html:https://europepmc.org/articles/PMC7005468; pdf:https://europepmc.org/articles/PMC7005468?pdf=render
-35017564,https://doi.org/10.1038/s41467-021-27950-w,Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies.,"Keown JR, Zhu Z, Carrique L, Fan H, Walker AP, Serna Martin I, Pardon E, Steyaert J, Fodor E, Grimes JM.",,Nature communications,2022,2022-01-11,Y,,,,"Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.",,pdf:https://www.nature.com/articles/s41467-021-27950-w.pdf; doi:https://doi.org/10.1038/s41467-021-27950-w; html:https://europepmc.org/articles/PMC8752864; pdf:https://europepmc.org/articles/PMC8752864?pdf=render
 32360702,https://doi.org/10.1016/j.ijcard.2020.04.068,Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design.,"Savarese G, Settergren C, Schrage B, Thorvaldsen T, Löfman I, Sartipy U, Mellbin L, Meyers A, Farsani SF, Brueckmann M, Brodovicz KG, Vedin O, Asselbergs FW, Dahlström U, Cosentino F, Lund LH.",,International journal of cardiology,2020,2020-04-30,N,Type 2 diabetes mellitus; Atrial fibrillation; Ejection fraction; Heart Failure; Chronic Kidney Disease; Trial Design,,,"<h4>Background</h4>Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.<h4>Methods and results</h4>Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.<h4>Conclusion</h4>HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.",,pdf:http://www.internationaljournalofcardiology.com/article/S016752732031679X/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.04.068
+35017564,https://doi.org/10.1038/s41467-021-27950-w,Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies.,"Keown JR, Zhu Z, Carrique L, Fan H, Walker AP, Serna Martin I, Pardon E, Steyaert J, Fodor E, Grimes JM.",,Nature communications,2022,2022-01-11,Y,,,,"Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.",,pdf:https://www.nature.com/articles/s41467-021-27950-w.pdf; doi:https://doi.org/10.1038/s41467-021-27950-w; html:https://europepmc.org/articles/PMC8752864; pdf:https://europepmc.org/articles/PMC8752864?pdf=render
 33714592,https://doi.org/10.1016/j.mayocp.2021.02.007,"Place and Underlying Cause of Death During the COVID-19 Pandemic: Retrospective Cohort Study of 3.5 Million Deaths in England and Wales, 2014 to 2020.","Wu J, Mafham M, Mamas MA, Rashid M, Kontopantelis E, Deanfield JE, de Belder MA, Gale CP.",,Mayo Clinic proceedings,2021,2021-02-16,Y,,,,"<h4>Objective</h4>To describe the place and cause of death during the coronavirus disease 2019 (COVID-19) pandemic to assess its impact on excess mortality.<h4>Methods</h4>This national death registry included all adult (aged ≥18 years) deaths in England and Wales between January 1, 2014, and June 30, 2020. Daily deaths during the COVID-19 pandemic were compared against the expected daily deaths, estimated with use of the Farrington surveillance algorithm for daily historical data between 2014 and 2020 by place and cause of death.<h4>Results</h4>Between March 2 and June 30, 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (87%) were COVID-19 related. At home, only 14% (2267) of the 16,190 excess deaths were related to COVID-19, with 5963 deaths due to cancer and 2485 deaths due to cardiac disease, few of which involved COVID-19. In care homes or hospices, 61% (15,623) of the 25,611 excess deaths were related to COVID-19, 5539 of which were due to respiratory disease, and most of these (4315 deaths) involved COVID-19. In the hospital, there were 16,174 fewer deaths than expected that did not involve COVID-19, with 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.<h4>Conclusion</h4>The COVID-19 pandemic has resulted in a large excess of deaths in care homes that were poorly characterized and likely to be the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, suggesting public avoidance of hospital care for non-COVID-19 conditions.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885692; doi:https://doi.org/10.1016/j.mayocp.2021.02.007; html:https://europepmc.org/articles/PMC7885692; pdf:https://europepmc.org/articles/PMC7885692?pdf=render
 33531015,https://doi.org/10.1186/s12916-021-01906-9,The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya.,"Mburu CN, Ojal J, Chebet R, Akech D, Karia B, Tuju J, Sigilai A, Abbas K, Jit M, Funk S, Smits G, van Gageldonk PGM, van der Klis FRM, Tabu C, Nokes DJ, LSHTM CMMID COVID-19 Working Group, Scott J, Flasche S, Adetifa I.",,BMC medicine,2021,2021-02-03,Y,outbreak; Measles; Vaccination Coverage; Supplementary Immunisation Activities; Covid-19,,,"<h4>Background</h4>The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region.<h4>Methods</h4>Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020.<h4>Results</h4>In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 34% (8-54). As the COVID-19 contact restrictions are nearly fully eased, from December 2020, the probability of a large measles outbreak will increase to 38% (19-54), 46% (30-59), and 54% (43-64) assuming a 15%, 50%, and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 43% (25-56), 54% (43-63), and 67% (59-72) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of all restrictions can be overcome by conducting a SIA with ≥ 95% coverage in under-fives.<h4>Conclusion</h4>While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once these restrictions are lifted. Implementing delayed SIAs will be critical for prevention of measles outbreaks given the roll-back of contact restrictions in Kenya.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-01906-9; doi:https://doi.org/10.1186/s12916-021-01906-9; html:https://europepmc.org/articles/PMC7854026; pdf:https://europepmc.org/articles/PMC7854026?pdf=render
 33628949,https://doi.org/10.12688/wellcomeopenres.16020.1,The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture April-May 2020. ,"Northstone K, Howarth S, Smith D, Bowring C, Wells N, Timpson NJ.",,Wellcome open research,2020,2020-06-10,Y,,,,"The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992. The resource provides an informative and efficient setting for collecting data on the current coronavirus 2019 (COVID-19) pandemic. In early March 2020, a questionnaire was developed in collaboration with other longitudinal population studies to ensure cross-cohort comparability. It targeted retrospective and current COVID-19 infection information (exposure assessment, symptom tracking and reported clinical outcomes) and the impact of both disease and mitigating measures implemented to manage the COVID-19 crisis more broadly. Data were collected on symptoms of COVID-19 and seasonal flu, travel prior to the pandemic, mental health and social, behavioural and lifestyle factors. The online questionnaire was deployed across the parent and offspring generations between the 9 th April and 15 th May 2020. 6807 participants completed the questionnaire (2706 original mothers, 1014 original fathers/partners, 2973 offspring (mean age ~28 years) and 114 partners of offspring). Eight (0.01%) participants (4 G0 and 4 G1) reported a positive test for COVID-19, 77 (1.13%; 28 G0 and 49 G1) reported that they had been told by a doctor they likely had COVID-19 and 865 (12.7%; 426 G0 and 439 G1) suspected that they have had COVID-19.  Using algorithmically defined cases, we estimate that the predicted proportion of COVID-19 cases fell between 1.03% - 4.19% depending on timing of measurement during the period of reporting. Data from this first questionnaire will be complemented with at least two more follow-up questionnaires, linkage to health records and results of biological testing as they become available. Data has been released as: 1) a standard dataset containing all participant responses with key sociodemographic factors and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study.",,doi:https://doi.org/10.12688/wellcomeopenres.16020.1; html:https://europepmc.org/articles/PMC7883314; pdf:https://europepmc.org/articles/PMC7883314?pdf=render
@@ -1938,8 +1938,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34600625,https://doi.org/10.1016/s0140-6736(21)01609-3,"Fatal police violence by race and state in the USA, 1980-2019: a network meta-regression.",GBD 2019 Police Violence US Subnational Collaborators.,,"Lancet (London, England)",2021,2021-10-01,Y,,,,"<h4>Background</h4>The burden of fatal police violence is an urgent public health crisis in the USA. Mounting evidence shows that deaths at the hands of the police disproportionately impact people of certain races and ethnicities, pointing to systemic racism in policing. Recent high-profile killings by police in the USA have prompted calls for more extensive and public data reporting on police violence. This study examines the presence and extent of under-reporting of police violence in US Government-run vital registration data, offers a method for correcting under-reporting in these datasets, and presents revised estimates of deaths due to police violence in the USA.<h4>Methods</h4>We compared data from the USA National Vital Statistics System (NVSS) to three non-governmental, open-source databases on police violence: Fatal Encounters, Mapping Police Violence, and The Counted. We extracted and standardised the age, sex, US state of death registration, year of death, and race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic of other races, and Hispanic of any race) of each decedent for all data sources and used a network meta-regression to quantify the rate of under-reporting within the NVSS. Using these rates to inform correction factors, we provide adjusted estimates of deaths due to police violence for all states, ages, sexes, and racial and ethnic groups from 1980 to 2019 across the USA.<h4>Findings</h4>Across all races and states in the USA, we estimate 30 800 deaths (95% uncertainty interval [UI] 30 300-31 300) from police violence between 1980 and 2018; this represents 17 100 more deaths (16 600-17 600) than reported by the NVSS. Over this time period, the age-standardised mortality rate due to police violence was highest in non-Hispanic Black people (0·69 [95% UI 0·67-0·71] per 100 000), followed by Hispanic people of any race (0·35 [0·34-0·36]), non-Hispanic White people (0·20 [0·19-0·20]), and non-Hispanic people of other races (0·15 [0·14- 0·16]). This variation is further affected by the decedent's sex and shows large discrepancies between states. Between 1980 and 2018, the NVSS did not report 55·5% (54·8-56·2) of all deaths attributable to police violence. When aggregating all races, the age-standardised mortality rate due to police violence was 0·25 (0·24-0·26) per 100 000 in the 1980s and 0·34 (0·34-0·35) per 100 000 in the 2010s, an increase of 38·4% (32·4-45·1) over the period of study.<h4>Interpretation</h4>We found that more than half of all deaths due to police violence that we estimated in the USA from 1980 to 2018 were unreported in the NVSS. Compounding this, we found substantial differences in the age-standardised mortality rate due to police violence over time and by racial and ethnic groups within the USA. Proven public health intervention strategies are needed to address these systematic biases. State-level estimates allow for appropriate targeting of these strategies to address police violence and improve its reporting.<h4>Funding</h4>Bill & Melinda Gates Foundation, National Institute on Minority Health and Health Disparities, and National Heart, Lung, and Blood Institute.",,pdf:http://www.thelancet.com/article/S0140673621016093/pdf; doi:https://doi.org/10.1016/S0140-6736(21)01609-3; html:https://europepmc.org/articles/PMC8485022; pdf:https://europepmc.org/articles/PMC8485022?pdf=render
 32814899,https://doi.org/10.1038/s41586-020-2635-8,Genetic and functional insights into the fractal structure of the heart.,"Meyer HV, Dawes TJW, Serrani M, Bai W, Tokarczuk P, Cai J, de Marvao A, Henry A, Lumbers RT, Gierten J, Thumberger T, Wittbrodt J, Ware JS, Rueckert D, Matthews PM, Prasad SK, Costantino ML, Cook SA, Birney E, O'Regan DP.",,Nature,2020,2020-08-19,N,,,,"The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a remnant of embryonic development<sup>1,2</sup>. The function of these trabeculae in adults and their genetic architecture are unknown. Here we performed a genome-wide association study to investigate image-derived phenotypes of trabeculae using the fractal analysis of trabecular morphology in 18,096 participants of the UK Biobank. We identified 16 significant loci that contain genes associated with haemodynamic phenotypes and regulation of cytoskeletal arborization<sup>3,4</sup>. Using biomechanical simulations and observational data from human participants, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Through genetic association studies with cardiac disease phenotypes and Mendelian randomization, we find a causal relationship between trabecular morphology and risk of cardiovascular disease. These findings suggest a previously unknown role for myocardial trabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity and reveal the influence of the myocardial trabeculae on susceptibility to cardiovascular disease.",,pdf:https://discovery.ucl.ac.uk/10110799/1/Meyer_accepted_version.pdf; doi:https://doi.org/10.1038/s41586-020-2635-8; html:https://europepmc.org/articles/PMC7116759; pdf:https://europepmc.org/articles/PMC7116759?pdf=render; doi:https://doi.org/10.1038/s41586-020-2635-8
 35231023,https://doi.org/10.1371/journal.pmed.1003907,Changes in social contacts in England during the COVID-19 pandemic between March 2020 and March 2021 as measured by the CoMix survey: A repeated cross-sectional study.,"Gimma A, Munday JD, Wong KLM, Coletti P, van Zandvoort K, Prem K, CMMID COVID-19 working group, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI.",,PLoS medicine,2022,2022-03-01,Y,,,,"<h4>Background</h4>During the Coronavirus Disease 2019 (COVID-19) pandemic, the United Kingdom government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We conducted a repeated cross-sectional study to measure contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering 3 national lockdowns interspersed by periods of less restrictive policies.<h4>Methods and findings</h4>The repeated cross-sectional survey data were collected using online surveys of representative samples of the UK population by age and gender. Survey participants were recruited by the online market research company Ipsos MORI through internet-based banner and social media ads and email campaigns. The participant data used for this analysis are restricted to those who reported living in England. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor. To put the findings in perspective, we discuss contact rates recorded throughout the year in terms of previously recorded rates from the POLYMOD study social contact study. The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. We observed changes in social contact patterns in England over time and by participants' age, personal risk factors, and perception of risk. The mean reported contacts for adults 18 to 59 years old ranged between 2.39 (95% confidence interval [CI] 2.20 to 2.60) contacts and 4.93 (95% CI 4.65 to 5.19) contacts during the study period. The mean contacts for school-age children (5 to 17 years old) ranged from 3.07 (95% CI 2.89 to 3.27) to 15.11 (95% CI 13.87 to 16.41). This demonstrates a sustained decrease in social contacts compared to a mean of 11.08 (95% CI 10.54 to 11.57) contacts per participant in all age groups combined as measured by the POLYMOD social contact study in 2005 to 2006. Contacts measured during periods of lockdowns were lower than in periods of eased social restrictions. The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. The main limitations of this analysis are the potential for selection bias, as participants are recruited through internet-based campaigns, and recall bias, in which participants may under- or overreport the number of contacts they have made.<h4>Conclusions</h4>In this study, we observed that recorded contacts reduced dramatically compared to prepandemic levels (as measured in the POLYMOD study), with changes in reported contacts correlated with government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, the mean number of reported contacts only returned to about half of that observed prepandemic at its highest recorded level. The CoMix survey provides a unique repeated cross-sectional data set for a full year in England, from the first day of the first lockdown, for use in statistical analyses and mathematical modelling of COVID-19 and other diseases.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render
-33430602,https://doi.org/10.1161/circheartfailure.120.007022,Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.,"Schuldt M, Pei J, Harakalova M, Dorsch LM, Schlossarek S, Mokry M, Knol JC, Pham TV, Schelfhorst T, Piersma SR, Dos Remedios C, Dalinghaus M, Michels M, Asselbergs FW, Moutin MJ, Carrier L, Jimenez CR, van der Velden J, Kuster DWD.",,Circulation. Heart failure,2021,2021-01-12,Y,Mutation; Genotype; Tubulin; Heart diseases; Proteomics; Treatment; Cardiomyopathies,,,"<h4>Background</h4>Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCM<sub>SMP</sub>), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCM<sub>SMN</sub>). Genotype-specific differences have been reported in cardiac function. Moreover, HCM<sub>SMN</sub> patients have later disease onset and a better prognosis than HCM<sub>SMP</sub> patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group.<h4>Methods</h4>A proteomics screen was performed in cardiac tissue from 39 HCM<sub>SMP</sub> patients, 11HCM<sub>SMN</sub> patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel <i>MYBPC3</i><sub>2373insG</sub> mouse model was used to confirm functional relevance of our proteomic findings.<h4>Results</h4>In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated α-tubulin were markedly higher in HCM<sub>SMP</sub> than in HCM<sub>SMN</sub> and controls. Higher tubulin detyrosination was also found in 2 unrelated <i>MYBPC3</i> mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes.<h4>Conclusions</h4>Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCM<sub>SMP</sub>. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCM<sub>SMP</sub>, whereas a beneficial effect may be limited in patients with HCM<sub>SMN</sub>.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.120.007022; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render
 30981377,https://doi.org/10.1016/j.aap.2019.03.007,How much space do drivers provide when passing cyclists? Understanding the impact of motor vehicle and infrastructure characteristics on passing distance.,"Beck B, Chong D, Olivier J, Perkins M, Tsay A, Rushford A, Li L, Cameron P, Fry R, Johnson M.",,Accident; analysis and prevention,2019,2019-04-10,N,Road Infrastructure; Overtaking; Cyclist Safety; Passing Distance,,,"<h4>Background</h4>Understanding factors that influence the distance that drivers provide when passing cyclists is critical to reducing subjective risk and improving cycling participation. This study aimed to quantify passing distance and assess the impact of motor vehicle and road infrastructure characteristics on passing distance.<h4>Methods</h4>An on-road observational study was conducted in Victoria, Australia. Participants had a custom device installed on their bicycle and rode as per their usual cycling for one to two weeks. A hierarchical linear model was used to investigate the relationship between motor vehicle and infrastructure characteristics (location, presence of on-road marked bicycle lane and the presence of parked cars on the kerbside) and passing distance (defined as the lateral distance between the end of the bicycle handlebars and the passing motor vehicle).<h4>Results</h4>Sixty cyclists recorded 18,527 passing events over 422 trips. The median passing distance was 173 cm (Q1: 137 cm, Q3: 224 cm) and 1085 (5.9%) passing events were less than 100 cm. Relative to sedans, 4WDs had a reduced mean passing distance of 15 cm (Q1: 12 cm, Q3: 17 cm) and buses had a reduced mean passing distance of 28 cm (Q1: 16 cm, Q3: 40 cm). Relative to passing events that occurred on roads without a marked bicycle lane and without parked cars, passing events on roads with a bike lane with no parked cars had a reduced mean passing distance of 27 cm (Q1: 25 cm, Q3: 29 cm), and passing events on roads with a bike lane and parked cars had a mean lower passing distance of 40 cm (Q1: 37 cm, Q3: 43 cm).<h4>Conclusions</h4>One in every 17 passing events was a close (<100 cm) passing event. We identified that on-road bicycle lanes and parked cars reduced passing distance. These data can be used to inform the selection and design of cycling-related infrastructure and road use with the aim of improving safety for cyclists.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa50030/Download/0050030-20052019102229.pdf; doi:https://doi.org/10.1016/j.aap.2019.03.007
+33430602,https://doi.org/10.1161/circheartfailure.120.007022,Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.,"Schuldt M, Pei J, Harakalova M, Dorsch LM, Schlossarek S, Mokry M, Knol JC, Pham TV, Schelfhorst T, Piersma SR, Dos Remedios C, Dalinghaus M, Michels M, Asselbergs FW, Moutin MJ, Carrier L, Jimenez CR, van der Velden J, Kuster DWD.",,Circulation. Heart failure,2021,2021-01-12,Y,Mutation; Genotype; Tubulin; Heart diseases; Proteomics; Treatment; Cardiomyopathies,,,"<h4>Background</h4>Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCM<sub>SMP</sub>), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCM<sub>SMN</sub>). Genotype-specific differences have been reported in cardiac function. Moreover, HCM<sub>SMN</sub> patients have later disease onset and a better prognosis than HCM<sub>SMP</sub> patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group.<h4>Methods</h4>A proteomics screen was performed in cardiac tissue from 39 HCM<sub>SMP</sub> patients, 11HCM<sub>SMN</sub> patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel <i>MYBPC3</i><sub>2373insG</sub> mouse model was used to confirm functional relevance of our proteomic findings.<h4>Results</h4>In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated α-tubulin were markedly higher in HCM<sub>SMP</sub> than in HCM<sub>SMN</sub> and controls. Higher tubulin detyrosination was also found in 2 unrelated <i>MYBPC3</i> mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes.<h4>Conclusions</h4>Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCM<sub>SMP</sub>. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCM<sub>SMP</sub>, whereas a beneficial effect may be limited in patients with HCM<sub>SMN</sub>.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.120.007022; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render
 31196905,https://doi.org/10.1136/bmjopen-2019-028929,Recorded poor insight as a predictor of service use outcomes: cohort study of patients with first-episode psychosis in a large mental healthcare database.,"Ramu N, Kolliakou A, Sanyal J, Patel R, Stewart R.",,BMJ open,2019,2019-06-12,Y,Insight; Psychosis; Natural Language Processing; Mental Health Outcomes; Cris; Service Use Outcomes,Applied Analytics,,"<h4>Objectives</h4>To investigate recorded poor insight in relation to mental health and service use outcomes in a cohort with first-episode psychosis.<h4>Design</h4>We developed a natural language processing algorithm to ascertain statements of poor or diminished insight and tested this in a cohort of patients with first-episode psychosis.<h4>Setting</h4>The clinical record text at the South London and Maudsley National Health Service Trust in the UK was used.<h4>Participants</h4>We applied the algorithm to characterise a cohort of 2026 patients with first-episode psychosis attending an early intervention service.<h4>Primary and secondary outcome measures</h4>Recorded poor insight within 1 month of registration was investigated in relation to (1) incidence of psychiatric hospitalisation, (2) odds of legally enforced hospitalisation, (3) number of days spent as a mental health inpatient and (4) number of different antipsychotic agents prescribed; outcomes were measured over varying follow-up periods from 12 months to 60 months, adjusting for a range of sociodemographic and clinical covariates.<h4>Results</h4>Recorded poor insight, present in 48.9% of the sample, was positively associated with youngest and oldest age groups, unemployment and schizophrenia (compared with bipolar disorder) and was negatively associated with Asian ethnicity, married status, home ownership and recorded cannabis use. It was significantly associated with higher levels of all four outcomes over the succeeding 12 months. Associations with hospitalisation incidence and number of antipsychotics remained independently significant when measured over 60 and 48 months, respectively.<h4>Conclusions</h4>Recorded poor insight in people with recent onset psychosis predicted higher subsequent inpatient mental healthcare use. Improving insight might benefit patients' course of illness as well as reduce mental health service use.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/6/e028929.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-028929; html:https://europepmc.org/articles/PMC6577359; pdf:https://europepmc.org/articles/PMC6577359?pdf=render
 37034358,https://doi.org/10.1016/j.eclinm.2023.101932,Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.,"Voss EA, Shoaibi A, Yin Hui Lai L, Blacketer C, Alshammari T, Makadia R, Haynes K, Sena AG, Rao G, van Sandijk S, Fraboulet C, Boyer L, Le Carrour T, Horban S, Morales DR, Martínez Roldán J, Ramírez-Anguita JM, Mayer MA, de Wilde M, John LH, Duarte-Salles T, Roel E, Pistillo A, Kolde R, Maljković F, Denaxas S, Papez V, Kahn MG, Natarajan K, Reich C, Secora A, Minty EP, Shah NH, Posada JD, Garcia Morales MT, Bosca D, Cadenas Juanino H, Diaz Holgado A, Pedrera Jiménez M, Serrano Balazote P, García Barrio N, Şen S, Üresin AY, Erdogan B, Belmans L, Byttebier G, Malbrain MLNG, Dedman DJ, Cuccu Z, Vashisht R, Butte AJ, Patel A, Dahm L, Han C, Bu F, Arshad F, Ostropolets A, Nyberg F, Hripcsak G, Suchard MA, Prieto-Alhambra D, Rijnbeek PR, Schuemie MJ, Ryan PB.",,EClinicalMedicine,2023,2023-04-04,Y,Observational Research; Omop Cdm; Covid-19; Adverse Events Of Special Interest,,,"<h4>Background</h4>Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population.<h4>Methods</h4>A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases.<h4>Findings</h4>Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism.<h4>Interpretation</h4>Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term.<h4>Funding</h4>None.",,doi:https://doi.org/10.1016/j.eclinm.2023.101932; doi:https://doi.org/10.1016/j.eclinm.2023.101932; html:https://europepmc.org/articles/PMC10072853; pdf:https://europepmc.org/articles/PMC10072853?pdf=render
 32305733,https://doi.org/10.1016/j.atherosclerosis.2020.03.022,The relation between healthy lifestyle changes and decrease in systemic inflammation in patients with stable cardiovascular disease.,"van 't Klooster CC, van der Graaf Y, Ridker PM, Westerink J, Hjortnaes J, Sluijs I, Asselbergs FW, Bots ML, Kappelle LJ, Visseren FLJ, UCC-SMART study group.",,Atherosclerosis,2020,2020-04-06,N,C-reactive Protein; Lifestyle Changes; Low-grade Inflammation; Patients With Stable Cardiovascular Disease,,,"<h4>Background and aims</h4>Pharmacological lowering of inflammation has proven effective in reducing recurrent cardiovascular event rates. Aim of the current study is to evaluate lifestyle changes (smoking cessation, weight loss, physical activity level increase, alcohol moderation, and a summary lifestyle improvement score) in relation to change in plasma C-reactive protein (CRP) concentration in patients with established cardiovascular disease.<h4>Methods</h4>In total, 1794 patients from the UCC-SMART cohort with stable cardiovascular disease and CRP levels ≤10 mg/L, who returned for a follow-up study visit after median 9.9 years (IQR 5.4-10.8), were included. The relation between changes in smoking status, weight, physical activity, alcohol consumption, a summary lifestyle improvement score and change in plasma CRP concentration was evaluated with linear regression analyses.<h4>Results</h4>Smoking cessation was related to a 0.40 mg/L decline in CRP concentration (β-coefficient -0.40; 95%CI -0.73,-0.07). Weight loss (per 1SD = 6.4 kg) and increase in physical activity (per 1 SD = 48 MET hours per week) were related to a decrease in CRP concentration (β-coefficients -0.25; 95%CI -0.33,-0.16 and -0.09; 95%CI -0.17,-0.01 per SD). Change in alcohol consumption was not related to CRP difference. Every point higher in the summary lifestyle improvement score was related to a decrease in CRP concentration of 0.17 mg/L (β-coefficient -0.17; 95%CI -0.26,-0.07).<h4>Conclusions</h4>Smoking cessation, increase in physical activity, and weight loss are related to a decrease in CRP concentration in patients with stable cardiovascular disease. Patients with the highest summary lifestyle improvement score have the most decrease in CRP concentration. These results may indicate that healthy lifestyle changes contribute to lowering systemic inflammation, potentially leading to a lower cardiovascular risk in patients with established cardiovascular disease.",,pdf:http://www.atherosclerosis-journal.com/article/S0021915020301763/pdf; doi:https://doi.org/10.1016/j.atherosclerosis.2020.03.022
@@ -1966,16 +1966,16 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34796246,https://doi.org/10.1093/ofid/ofab496,"Acceptability, Usability, and Performance of Lateral Flow Immunoassay Tests for Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies: REACT-2 Study of Self-Testing in Nonhealthcare Key Workers.","Davies B, Araghi M, Moshe M, Gao H, Bennet K, Jenkins J, Atchison C, Darzi A, Ashby D, Riley S, Barclay W, Elliott P, Ward H, Cooke G.",,Open forum infectious diseases,2021,2021-10-04,Y,Sensitivity and specificity; Antibody testing; Sars-cov-2; Covid-19 Diagnostic Testing,,,"<h4>Background</h4>Seroprevalence studies are essential to understand the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.<h4>Methods</h4>In June 2020, current and former members of the United Kingdom police forces and fire service performed a self-test lateral flow immunoassay (LFIA), had a nurse-performed LFIA, and provided a venous blood sample for enzyme-linked immunosorbent assay (ELISA). We present the prevalence of antibodies to SARS-CoV-2 and the acceptability and usability of self-test LFIAs, and we determine the sensitivity and specificity of LFIAs compared with laboratory ELISA.<h4>Results</h4>In this cohort of 5189 current and former members of the police service and 263 members of the fire service, 7.4% (396 of 5348; 95% confidence interval [CI], 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (95% CI, 6.9-11.4) in those under 40 years, 11.5% (95% CI, 8.8-15.0) in those of nonwhite ethnicity, and 7.8% (95% CI, 7.1-8.7) in those currently working. Self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 95% CI, 0.77-0.83). The LFIAs had a similar performance: compared with ELISA, sensitivity was 82.1% (95% CI, 77.7-86.0) self-test and 76.4% (95% CI, 71.9-80.5) nurse-performed with specificity of 97.8% (95% CI, 97.3-98.2) and 98.5% (95% CI, 98.1-98.8), respectively.<h4>Conclusions</h4>A greater proportion of this nonhealthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (95% CI, 5.8-6.1) after the first wave in England. The high acceptability and usability reported by participants and similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home testing in occupational and community prevalence studies.",,pdf:https://academic.oup.com/ofid/article-pdf/8/11/ofab496/41174715/ofab496.pdf; doi:https://doi.org/10.1093/ofid/ofab496; html:https://europepmc.org/articles/PMC8522420; pdf:https://europepmc.org/articles/PMC8522420?pdf=render
 34330923,https://doi.org/10.1038/s41467-021-24930-y,Toxin import through the antibiotic efflux channel TolC.,"Housden NG, Webby MN, Lowe ED, El-Baba TJ, Kaminska R, Redfield C, Robinson CV, Kleanthous C.",,Nature communications,2021,2021-07-30,Y,,,,"Bacteria often secrete diffusible protein toxins (bacteriocins) to kill bystander cells during interbacterial competition. Here, we use biochemical, biophysical and structural analyses to show how a bacteriocin exploits TolC, a major outer-membrane antibiotic efflux channel in Gram-negative bacteria, to transport itself across the outer membrane of target cells. Klebicin C (KlebC), a rRNase toxin produced by Klebsiella pneumoniae, binds TolC of a related species (K. quasipneumoniae) with high affinity through an N-terminal, elongated helical hairpin domain common amongst bacteriocins. The KlebC helical hairpin opens like a switchblade to bind TolC. A cryo-EM structure of this partially translocated state, at 3.1 Å resolution, reveals that KlebC associates along the length of the TolC channel. Thereafter, the unstructured N-terminus of KlebC protrudes beyond the TolC iris, presenting a TonB-box sequence to the periplasm. Association with proton-motive force-linked TonB in the inner membrane drives toxin import through the channel. Finally, we demonstrate that KlebC binding to TolC blocks drug efflux from bacteria. Our results indicate that TolC, in addition to its known role in antibiotic export, can function as a protein import channel for bacteriocins.",,pdf:https://www.nature.com/articles/s41467-021-24930-y.pdf; doi:https://doi.org/10.1038/s41467-021-24930-y; html:https://europepmc.org/articles/PMC8324772; pdf:https://europepmc.org/articles/PMC8324772?pdf=render
 32895551,https://doi.org/10.1038/s41588-020-0682-6,Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases.,"Zheng J, Haberland V, Baird D, Walker V, Haycock PC, Hurle MR, Gutteridge A, Erola P, Liu Y, Luo S, Robinson J, Richardson TG, Staley JR, Elsworth B, Burgess S, Sun BB, Danesh J, Runz H, Maranville JC, Martin HM, Yarmolinsky J, Laurin C, Holmes MV, Liu JZ, Estrada K, Santos R, McCarthy L, Waterworth D, Nelson MR, Smith GD, Butterworth AS, Hemani G, Scott RA, Gaunt TR.",,Nature genetics,2020,2020-09-07,Y,,,,"The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here we estimated the effects of 1,002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130 (31.5%) were not supported by results of colocalization analyses, suggesting that genetic confounding due to linkage disequilibrium is widespread in naïve phenome-wide association studies of proteins. Combining MR and colocalization evidence in cis-only analyses, we identified 111 putatively causal effects between 65 proteins and 52 disease-related phenotypes ( https://www.epigraphdb.org/pqtl/ ). Evaluation of data from historic drug development programs showed that target-indication pairs with MR and colocalization support were more likely to be approved, evidencing the value of this approach in identifying and prioritizing potential therapeutic targets.",,pdf:https://ueaeprints.uea.ac.uk/id/eprint/76368/1/Zheng_et_al_final_manuscript.pdf; doi:https://doi.org/10.1038/s41588-020-0682-6; html:https://europepmc.org/articles/PMC7610464; pdf:https://europepmc.org/articles/PMC7610464?pdf=render
-35103486,https://doi.org/10.1128/msystems.01132-21,Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.,"Shenhav L, Azad MB.",,mSystems,2022,2022-02-01,Y,Lactation; Human Milk; Breastfeeding; Chronobiology; Computational Methods; System Biology; Human Microbiome; Community Ecology Theory,,,"Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, ""our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation"" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant ""triad"" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a ""system within a system.""",,doi:https://doi.org/10.1128/msystems.01132-21; doi:https://doi.org/10.1128/msystems.01132-21; html:https://europepmc.org/articles/PMC8805635; pdf:https://europepmc.org/articles/PMC8805635?pdf=render
-32546850,https://doi.org/10.1038/s41598-020-66737-9,Genetic aetiology of self-harm ideation and behaviour.,"Campos AI, Verweij KJH, Statham DJ, Madden PAF, Maciejewski DF, Davis KAS, John A, Hotopf M, Heath AC, Martin NG, Rentería ME.",,Scientific reports,2020,2020-06-16,Y,,,,"Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (h<sub>snp</sub><sup>2</sup>) estimates were ~10%, and both traits were highly genetically correlated (LDSC r<sub>g</sub> > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant.",,pdf:https://www.nature.com/articles/s41598-020-66737-9.pdf; doi:https://doi.org/10.1038/s41598-020-66737-9; html:https://europepmc.org/articles/PMC7297971; pdf:https://europepmc.org/articles/PMC7297971?pdf=render
 31666364,https://doi.org/10.1128/jcm.00963-19,Metagenomic Nanopore Sequencing of Influenza Virus Direct from Clinical Respiratory Samples.,"Lewandowski K, Xu Y, Pullan ST, Lumley SF, Foster D, Sanderson N, Vaughan A, Morgan M, Bright N, Kavanagh J, Vipond R, Carroll M, Marriott AC, Gooch KE, Andersson M, Jeffery K, Peto TEA, Crook DW, Walker AS, Matthews PC.",,Journal of clinical microbiology,2019,2019-12-23,Y,DNA sequencing; Sequencing; Influenza; Diagnosis; Molecular epidemiology; epidemiology; Diagnostics; Metagenomics; Nanopore; Metagenomic,Understanding the Causes of Disease,,"Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential for a diagnostic test for influenza virus which also provides insights on transmission, evolution, and drug resistance and simultaneously detects other viruses. We therefore set out to apply the Oxford Nanopore Technologies sequencing method to metagenomic sequencing of respiratory samples. We generated influenza virus reads down to a limit of detection of 10<sup>2</sup> to 10<sup>3</sup> genome copies/ml in pooled samples, observing a strong relationship between the viral titer and the proportion of influenza virus reads (<i>P</i> = 4.7 × 10<sup>-5</sup>). Applying our methods to clinical throat swabs, we generated influenza virus reads for 27/27 samples with mid-to-high viral titers (cycle threshold [<i>C<sub>T</sub></i> ] values, <30) and 6/13 samples with low viral titers (<i>C<sub>T</sub></i> values, 30 to 40). No false-positive reads were generated from 10 influenza virus-negative samples. Thus, Nanopore sequencing operated with 83% sensitivity (95% confidence interval [CI], 67 to 93%) and 100% specificity (95% CI, 69 to 100%) compared to the current diagnostic standard. Coverage of full-length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza virus titers, we were able to reconstruct >99% complete sequences for all eight gene segments. We also detected a human coronavirus coinfection in one clinical sample. While further optimization is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza virus and other respiratory viruses.",,doi:https://doi.org/10.1128/jcm.00963-19; doi:https://doi.org/10.1128/JCM.00963-19; html:https://europepmc.org/articles/PMC6935926; pdf:https://europepmc.org/articles/PMC6935926?pdf=render
+32546850,https://doi.org/10.1038/s41598-020-66737-9,Genetic aetiology of self-harm ideation and behaviour.,"Campos AI, Verweij KJH, Statham DJ, Madden PAF, Maciejewski DF, Davis KAS, John A, Hotopf M, Heath AC, Martin NG, Rentería ME.",,Scientific reports,2020,2020-06-16,Y,,,,"Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (h<sub>snp</sub><sup>2</sup>) estimates were ~10%, and both traits were highly genetically correlated (LDSC r<sub>g</sub> > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant.",,pdf:https://www.nature.com/articles/s41598-020-66737-9.pdf; doi:https://doi.org/10.1038/s41598-020-66737-9; html:https://europepmc.org/articles/PMC7297971; pdf:https://europepmc.org/articles/PMC7297971?pdf=render
+35103486,https://doi.org/10.1128/msystems.01132-21,Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.,"Shenhav L, Azad MB.",,mSystems,2022,2022-02-01,Y,Lactation; Human Milk; Breastfeeding; Chronobiology; Computational Methods; System Biology; Human Microbiome; Community Ecology Theory,,,"Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, ""our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation"" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant ""triad"" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a ""system within a system.""",,doi:https://doi.org/10.1128/msystems.01132-21; doi:https://doi.org/10.1128/msystems.01132-21; html:https://europepmc.org/articles/PMC8805635; pdf:https://europepmc.org/articles/PMC8805635?pdf=render
 30609404,https://doi.org/10.1016/j.ajhg.2018.11.014,Integrating Genomics into Healthcare: A Global Responsibility.,"Stark Z, Dolman L, Manolio TA, Ozenberger B, Hill SL, Caulfied MJ, Levy Y, Glazer D, Wilson J, Lawler M, Boughtwood T, Braithwaite J, Goodhand P, Birney E, North KN.",,American journal of human genetics,2019,2019-01-01,N,,Understanding the Causes of Disease,,"Genomic sequencing is rapidly transitioning into clinical practice, and implementation into healthcare systems has been supported by substantial government investment, totaling over US$4 billion, in at least 14 countries. These national genomic-medicine initiatives are driving transformative change under real-life conditions while simultaneously addressing barriers to implementation and gathering evidence for wider adoption. We review the diversity of approaches and current progress made by national genomic-medicine initiatives in the UK, France, Australia, and US and provide a roadmap for sharing strategies, standards, and data internationally to accelerate implementation.",,pdf:http://www.cell.com/article/S0002929718304221/pdf; doi:https://doi.org/10.1016/j.ajhg.2018.11.014; html:https://europepmc.org/articles/PMC6323624; pdf:https://europepmc.org/articles/PMC6323624?pdf=render; doi:https://doi.org/10.1016/j.ajhg.2018.11.014
-37743838,https://doi.org/10.1017/s0033291722003671,The association between persistent cognitive difficulties and depression and functional outcomes in people with major depressive disorder.,"Matcham F, Simblett SK, Leightley D, Dalby M, Siddi S, Haro JM, Lamers F, Penninx BWHJ, Bruce S, Nica R, Zormpas S, Gilpin G, White KM, Oetzmann C, Annas P, Brasen JC, Narayan VA, Hotopf M, Wykes T, RADAR-CNS consortium.",,Psychological medicine,2023,2022-12-13,Y,Cognitive function; epidemiology; Longitudinal; Major Depressive Disorder; Predictive; Remote Measurement,,,"<h4>Background</h4>Cognitive symptoms are common during and following episodes of depression. Little is known about the persistence of self-reported and performance-based cognition with depression and functional outcomes.<h4>Methods</h4>This is a secondary analysis of a prospective naturalistic observational clinical cohort study of individuals with recurrent major depressive disorder (MDD; <i>N</i> = 623). Participants completed app-based self-reported and performance-based cognitive function assessments alongside validated measures of depression, functional disability, and self-esteem every 3 months. Participants were followed-up for a maximum of 2-years. Multilevel hierarchically nested modelling was employed to explore between- and within-participant variation over time to identify whether persistent cognitive difficulties are related to levels of depression and functional impairment during follow-up.<h4>Results</h4>508 individuals (81.5%) provided data (mean age: 46.6, s.d.: 15.6; 76.2% female). Increasing persistence of self-reported cognitive difficulty was associated with higher levels of depression and functional impairment throughout the follow-up. In comparison to low persistence of objective cognitive difficulty (<25% of timepoints), those with high persistence (>75% of timepoints) reported significantly higher levels of depression (<i>B</i> = 5.17, s.e. = 2.21, <i>p</i> = 0.019) and functional impairment (<i>B</i> = 4.82, s.e. = 1.79, <i>p</i> = 0.002) over time. Examination of the individual cognitive modules shows that persistently impaired executive function is associated with worse functioning, and poor processing speed is particularly important for worsened depressive symptoms.<h4>Conclusions</h4>We replicated previous findings of greater persistence of cognitive difficulty with increasing severity of depression and further demonstrate that these cognitive difficulties are associated with pervasive functional disability. Difficulties with cognition may be an indicator and target for further treatment input.",,doi:https://doi.org/10.1017/S0033291722003671; html:https://europepmc.org/articles/PMC10520589; pdf:https://europepmc.org/articles/PMC10520589?pdf=render
 33220850,https://doi.org/10.1016/s0140-6736(20)32465-x,Urgent actions and policies needed to address COVID-19 among UK ethnic minorities.,"Mathur R, Bear L, Khunti K, Eggo RM.",,"Lancet (London, England)",2020,2020-11-19,Y,,,,,,pdf:http://www.thelancet.com/article/S014067362032465X/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32465-X; html:https://europepmc.org/articles/PMC7831890; pdf:https://europepmc.org/articles/PMC7831890?pdf=render
+37743838,https://doi.org/10.1017/s0033291722003671,The association between persistent cognitive difficulties and depression and functional outcomes in people with major depressive disorder.,"Matcham F, Simblett SK, Leightley D, Dalby M, Siddi S, Haro JM, Lamers F, Penninx BWHJ, Bruce S, Nica R, Zormpas S, Gilpin G, White KM, Oetzmann C, Annas P, Brasen JC, Narayan VA, Hotopf M, Wykes T, RADAR-CNS consortium.",,Psychological medicine,2023,2022-12-13,Y,Cognitive function; epidemiology; Longitudinal; Major Depressive Disorder; Predictive; Remote Measurement,,,"<h4>Background</h4>Cognitive symptoms are common during and following episodes of depression. Little is known about the persistence of self-reported and performance-based cognition with depression and functional outcomes.<h4>Methods</h4>This is a secondary analysis of a prospective naturalistic observational clinical cohort study of individuals with recurrent major depressive disorder (MDD; <i>N</i> = 623). Participants completed app-based self-reported and performance-based cognitive function assessments alongside validated measures of depression, functional disability, and self-esteem every 3 months. Participants were followed-up for a maximum of 2-years. Multilevel hierarchically nested modelling was employed to explore between- and within-participant variation over time to identify whether persistent cognitive difficulties are related to levels of depression and functional impairment during follow-up.<h4>Results</h4>508 individuals (81.5%) provided data (mean age: 46.6, s.d.: 15.6; 76.2% female). Increasing persistence of self-reported cognitive difficulty was associated with higher levels of depression and functional impairment throughout the follow-up. In comparison to low persistence of objective cognitive difficulty (<25% of timepoints), those with high persistence (>75% of timepoints) reported significantly higher levels of depression (<i>B</i> = 5.17, s.e. = 2.21, <i>p</i> = 0.019) and functional impairment (<i>B</i> = 4.82, s.e. = 1.79, <i>p</i> = 0.002) over time. Examination of the individual cognitive modules shows that persistently impaired executive function is associated with worse functioning, and poor processing speed is particularly important for worsened depressive symptoms.<h4>Conclusions</h4>We replicated previous findings of greater persistence of cognitive difficulty with increasing severity of depression and further demonstrate that these cognitive difficulties are associated with pervasive functional disability. Difficulties with cognition may be an indicator and target for further treatment input.",,doi:https://doi.org/10.1017/S0033291722003671; html:https://europepmc.org/articles/PMC10520589; pdf:https://europepmc.org/articles/PMC10520589?pdf=render
 31862893,https://doi.org/10.1038/s41467-019-13848-1,Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.,"Abraham G, Malik R, Yonova-Doing E, Salim A, Wang T, Danesh J, Butterworth AS, Howson JMM, Inouye M, Dichgans M.",,Nature communications,2019,2019-12-20,Y,,,,"Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n = 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22-1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset of individuals at monogenic levels of risk: the top 0.25% of metaGRS have three-fold risk of IS. The metaGRS is similarly or more predictive compared to several risk factors, such as family history, blood pressure, body mass index, and smoking. We estimate the reductions needed in modifiable risk factors for individuals with different levels of genomic risk and suggest that, for individuals with high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk.",,pdf:https://www.nature.com/articles/s41467-019-13848-1.pdf; doi:https://doi.org/10.1038/s41467-019-13848-1; html:https://europepmc.org/articles/PMC6925280; pdf:https://europepmc.org/articles/PMC6925280?pdf=render
 37067557,https://doi.org/10.1007/s00134-023-07039-2,Variants of concern and clinical outcomes in critically ill COVID-19 patients.,DP-EFFECT-BRAZIL investigators.,,Intensive care medicine,2023,2023-04-17,Y,,,,,,pdf:https://link.springer.com/content/pdf/10.1007/s00134-023-07039-2.pdf; doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render
-34039579,https://doi.org/10.1136/bmjopen-2021-049721,Changes in daily mental health service use and mortality at the commencement and lifting of COVID-19 'lockdown' policy in 10 UK sites: a regression discontinuity in time design.,"Bakolis I, Stewart R, Baldwin D, Beenstock J, Bibby P, Broadbent M, Cardinal R, Chen S, Chinnasamy K, Cipriani A, Douglas S, Horner P, Jackson CA, John A, Joyce DW, Lee SC, Lewis J, McIntosh A, Nixon N, Osborn D, Phiri P, Rathod S, Smith T, Sokal R, Waller R, Landau S.",,BMJ open,2021,2021-05-26,Y,Mental health; Adult Psychiatry; Old Age Psychiatry; Organisation Of Health Services; Covid-19,,,"<h4>Objectives</h4>To investigate changes in daily mental health (MH) service use and mortality in response to the introduction and the lifting of the COVID-19 'lockdown' policy in Spring 2020.<h4>Design</h4>A regression discontinuity in time (RDiT) analysis of daily service-level activity.<h4>Setting and participants</h4>Mental healthcare data were extracted from 10 UK providers.<h4>Outcome measures</h4>Daily (weekly for one site) deaths from all causes, referrals and discharges, inpatient care (admissions, discharges, caseloads) and community services (face-to-face (f2f)/non-f2f contacts, caseloads): Adult, older adult and child/adolescent mental health; early intervention in psychosis; home treatment teams and liaison/Accident and Emergency (A&E). Data were extracted from 1 Jan 2019 to 31 May 2020 for all sites, supplemented to 31 July 2020 for four sites. Changes around the commencement and lifting of COVID-19 'lockdown' policy (23 March and 10 May, respectively) were estimated using a RDiT design with a difference-in-difference approach generating incidence rate ratios (IRRs), meta-analysed across sites.<h4>Results</h4>Pooled estimates for the lockdown transition showed increased daily deaths (IRR 2.31, 95% CI 1.86 to 2.87), reduced referrals (IRR 0.62, 95% CI 0.55 to 0.70) and reduced inpatient admissions (IRR 0.75, 95% CI 0.67 to 0.83) and caseloads (IRR 0.85, 95% CI 0.79 to 0.91) compared with the pre lockdown period. All community services saw shifts from f2f to non-f2f contacts, but varied in caseload changes. Lift of lockdown was associated with reduced deaths (IRR 0.42, 95% CI 0.27 to 0.66), increased referrals (IRR 1.36, 95% CI 1.15 to 1.60) and increased inpatient admissions (IRR 1.21, 95% CI 1.04 to 1.42) and caseloads (IRR 1.06, 95% CI 1.00 to 1.12) compared with the lockdown period. Site-wide activity, inpatient care and community services did not return to pre lockdown levels after lift of lockdown, while number of deaths did. Between-site heterogeneity most often indicated variation in size rather than direction of effect.<h4>Conclusions</h4>MH service delivery underwent sizeable changes during the first national lockdown, with as-yet unknown and unevaluated consequences.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049721.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049721; html:https://europepmc.org/articles/PMC8159668; pdf:https://europepmc.org/articles/PMC8159668?pdf=render
 32724860,https://doi.org/10.12688/wellcomeopenres.15651.2,Using a knowledge exchange event to assess study participants' attitudes to research in a rapidly evolving research context.,"Beange I, Kirkham EJ, Fletcher-Watson S, Iveson MH, Lawrie SM, Batty GD, Boardman JP, Deary IJ, Black C, Porteous DJ, McIntosh AM.",,Wellcome open research,2020,2020-08-28,Y,Health; Cohort; Scotland; Data Linkage; Public Engagement; Opinion; Knowledge Exchange; Big Data; Data Science; Guthrie,,,"<b>Background:</b> The UK hosts some of the world's longest-running longitudinal cohort studies, which make repeated observations of their participants and use these data to explore health outcomes. An alternative method for data collection is record linkage; the linking together of electronic health and administrative records. Applied nationally, this could provide unrivalled opportunities to follow a large number of people in perpetuity. However, public attitudes to the use of data in research are currently unclear. Here we report on an event where we collected attitudes towards recent opportunities and controversies within health data science. <b>Methods:</b> The event was attended by ~250 individuals (cohort members and their guests), who had been invited through the offices of their participating cohort studies. There were a series of presentations describing key research results and the audience participated in 15 multiple-choice questions using interactive voting pads. <b>Results:</b> Our participants showed a high level of trust in researchers (87% scoring them 4/5 or 5/5) and doctors (81%); but less trust in commercial companies (35%). They supported the idea of researchers using information from both neonatal blood spots (Guthrie spots) (97% yes) and from electronic health records (95% yes). Our respondents were willing to wear devices like a 'Fit-bit' (88% agreed) or take a brain scan that might predict later mental illness (73%). However, they were less willing to take a new drug for research purposes (45%). They were keen to encourage others to take part in research; whether that be offering the opportunity to pregnant mothers (97% agreed) or extending invitations to their own children and grandchildren (98%). <b>Conclusions:</b> Our participants were broadly supportive of research access to data, albeit less supportive when commercial interests were involved. Public engagement events that facilitate two-way interactions can influence and support future research and public engagement efforts.",,pdf:https://wellcomeopenresearch.org/articles/5-24/v2/pdf; doi:https://doi.org/10.12688/wellcomeopenres.15651.2; html:https://europepmc.org/articles/PMC7361507; pdf:https://europepmc.org/articles/PMC7361507?pdf=render
+34039579,https://doi.org/10.1136/bmjopen-2021-049721,Changes in daily mental health service use and mortality at the commencement and lifting of COVID-19 'lockdown' policy in 10 UK sites: a regression discontinuity in time design.,"Bakolis I, Stewart R, Baldwin D, Beenstock J, Bibby P, Broadbent M, Cardinal R, Chen S, Chinnasamy K, Cipriani A, Douglas S, Horner P, Jackson CA, John A, Joyce DW, Lee SC, Lewis J, McIntosh A, Nixon N, Osborn D, Phiri P, Rathod S, Smith T, Sokal R, Waller R, Landau S.",,BMJ open,2021,2021-05-26,Y,Mental health; Adult Psychiatry; Old Age Psychiatry; Organisation Of Health Services; Covid-19,,,"<h4>Objectives</h4>To investigate changes in daily mental health (MH) service use and mortality in response to the introduction and the lifting of the COVID-19 'lockdown' policy in Spring 2020.<h4>Design</h4>A regression discontinuity in time (RDiT) analysis of daily service-level activity.<h4>Setting and participants</h4>Mental healthcare data were extracted from 10 UK providers.<h4>Outcome measures</h4>Daily (weekly for one site) deaths from all causes, referrals and discharges, inpatient care (admissions, discharges, caseloads) and community services (face-to-face (f2f)/non-f2f contacts, caseloads): Adult, older adult and child/adolescent mental health; early intervention in psychosis; home treatment teams and liaison/Accident and Emergency (A&E). Data were extracted from 1 Jan 2019 to 31 May 2020 for all sites, supplemented to 31 July 2020 for four sites. Changes around the commencement and lifting of COVID-19 'lockdown' policy (23 March and 10 May, respectively) were estimated using a RDiT design with a difference-in-difference approach generating incidence rate ratios (IRRs), meta-analysed across sites.<h4>Results</h4>Pooled estimates for the lockdown transition showed increased daily deaths (IRR 2.31, 95% CI 1.86 to 2.87), reduced referrals (IRR 0.62, 95% CI 0.55 to 0.70) and reduced inpatient admissions (IRR 0.75, 95% CI 0.67 to 0.83) and caseloads (IRR 0.85, 95% CI 0.79 to 0.91) compared with the pre lockdown period. All community services saw shifts from f2f to non-f2f contacts, but varied in caseload changes. Lift of lockdown was associated with reduced deaths (IRR 0.42, 95% CI 0.27 to 0.66), increased referrals (IRR 1.36, 95% CI 1.15 to 1.60) and increased inpatient admissions (IRR 1.21, 95% CI 1.04 to 1.42) and caseloads (IRR 1.06, 95% CI 1.00 to 1.12) compared with the lockdown period. Site-wide activity, inpatient care and community services did not return to pre lockdown levels after lift of lockdown, while number of deaths did. Between-site heterogeneity most often indicated variation in size rather than direction of effect.<h4>Conclusions</h4>MH service delivery underwent sizeable changes during the first national lockdown, with as-yet unknown and unevaluated consequences.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049721.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049721; html:https://europepmc.org/articles/PMC8159668; pdf:https://europepmc.org/articles/PMC8159668?pdf=render
 32505923,https://doi.org/10.1016/j.ebiom.2020.102818,"Children first, or last?",Modi N.,,EBioMedicine,2020,2020-06-04,Y,,,,,,pdf:http://www.thelancet.com/article/S2352396420301936/pdf; doi:https://doi.org/10.1016/j.ebiom.2020.102818; html:https://europepmc.org/articles/PMC7276509; pdf:https://europepmc.org/articles/PMC7276509?pdf=render
 33623826,https://doi.org/10.12688/wellcomeopenres.16164.2,"The effectiveness of social bubbles as part of a Covid-19 lockdown exit strategy, a modelling study.","Leng T, White C, Hilton J, Kucharski A, Pellis L, Stage H, Davies NG, Centre for Mathematical Modelling of Infectious Disease 2019 nCoV Working Group, Keeling MJ, Flasche S.",,Wellcome open research,2020,2020-01-01,Y,Exit Strategy; Covid-19; Contact Clustering; Social Bubble,,,"<b>Background:</b> <i>​</i> During the coronavirus disease 2019 (COVID-19) lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study. <b>Methods:</b> <i>​</i> We used an individual based model for a synthetic population similar to the UK, stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate social bubble strategies (where two households form an exclusive pair) for households including children, for single occupancy households, and for all households. We test the sensitivity of results to a range of alternative model assumptions and parameters. <b>Results:</b>  Clustering contacts outside the household into exclusive bubbles is an effective strategy of increasing contacts while limiting the associated increase in epidemic risk. In the base case, social bubbles reduced fatalities by 42% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to above the epidemic threshold of R=1. Strategies allowing households with young children or single occupancy households to form social bubbles increased the reproduction number by less than 11%. The corresponding increase in mortality is proportional to the increase in the epidemic risk but is focussed in older adults irrespective of inclusion in social bubbles. <b>Conclusions: ​</b> If managed appropriately, social bubbles can be an effective way of extending contacts beyond the household while limiting the increase in epidemic risk.",,doi:https://doi.org/10.12688/wellcomeopenres.16164.2; doi:https://doi.org/10.12688/wellcomeopenres.16164.2; html:https://europepmc.org/articles/PMC7871360; pdf:https://europepmc.org/articles/PMC7871360?pdf=render
 33087179,https://doi.org/10.1186/s12916-020-01790-9,Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections.,"Russell TW, Golding N, Hellewell J, Abbott S, Wright L, Pearson CAB, van Zandvoort K, Jarvis CI, Gibbs H, Liu Y, Eggo RM, Edmunds WJ, Kucharski AJ, CMMID COVID-19 working group.",,BMC medicine,2020,2020-10-22,Y,Surveillance; Situational Awareness; Under-reporting; Case Ascertainment; Outbreak Analysis; Covid-19; Sars-cov-2,,,"<h4>Background</h4>Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures.<h4>Methods</h4>Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever ≥ 37.5 °C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment.<h4>Results</h4>Based on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6 July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of 7 June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI 5.6-24%) (Belgium).<h4>Conclusions</h4>We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country's population infected with SARS-CoV-2 worldwide is generally low.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01790-9; doi:https://doi.org/10.1186/s12916-020-01790-9; html:https://europepmc.org/articles/PMC7577796; pdf:https://europepmc.org/articles/PMC7577796?pdf=render
@@ -1985,8 +1985,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 36436752,https://doi.org/10.1016/j.ijid.2022.11.024,"Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa.","Davies MA, Morden E, Rousseau P, Arendse J, Bam JL, Boloko L, Cloete K, Cohen C, Chetty N, Dane P, Heekes A, Hsiao NY, Hunter M, Hussey H, Jacobs T, Jassat W, Kariem S, Kassanjee R, Laenen I, Roux SL, Lessells R, Mahomed H, Maughan D, Meintjes G, Mendelson M, Mnguni A, Moodley M, Murie K, Naude J, Ntusi NAB, Paleker M, Parker A, Pienaar D, Preiser W, Prozesky H, Raubenheimer P, Rossouw L, Schrueder N, Smith B, Smith M, Solomon W, Symons G, Taljaard J, Wasserman S, Wilkinson RJ, Wolmarans M, Wolter N, Boulle A.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2023,2022-11-24,Y,"Covid-19; Omicron; Ba.4; Ba.5; Death, Severe Hospitalization",,,"<h4>Objectives</h4>We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.<h4>Methods</h4>We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection.<h4>Results</h4>Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective.<h4>Conclusion</h4>Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective.",,doi:https://doi.org/10.1016/j.ijid.2022.11.024; doi:https://doi.org/10.1016/j.ijid.2022.11.024; html:https://europepmc.org/articles/PMC9686046; pdf:https://europepmc.org/articles/PMC9686046?pdf=render
 31792462,https://doi.org/10.1038/s41591-019-0665-2,Plasma protein patterns as comprehensive indicators of health.,"Williams SA, Kivimaki M, Langenberg C, Hingorani AD, Casas JP, Bouchard C, Jonasson C, Sarzynski MA, Shipley MJ, Alexander L, Ash J, Bauer T, Chadwick J, Datta G, DeLisle RK, Hagar Y, Hinterberg M, Ostroff R, Weiss S, Ganz P, Wareham NJ.",,Nature medicine,2019,2019-12-02,N,,,,"Proteins are effector molecules that mediate the functions of genes<sup>1,2</sup> and modulate comorbidities<sup>3-10</sup>, behaviors and drug treatments<sup>11</sup>. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning<sup>12-16</sup> coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.",,pdf:https://europepmc.org/articles/pmc6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2; html:https://europepmc.org/articles/PMC6922049; pdf:https://europepmc.org/articles/PMC6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2
 34609275,https://doi.org/10.1099/mgen.0.000630,"A genomic epidemiological study shows that prevalence of antimicrobial resistance in <i>Enterobacterales</i> is associated with the livestock host, as well as antimicrobial usage.","AbuOun M, Jones H, Stubberfield E, Gilson D, Shaw LP, Hubbard ATM, Chau KK, Sebra R, Peto TEA, Crook DW, Read DS, Gweon HS, Walker AS, Stoesser N, Smith RP, Anjum MF, On Behalf Of The Rehab Consortium.",,Microbial genomics,2021,2021-10-01,Y,Plasmid; Livestock; Antimicrobial resistance; Antimicrobial Usage,,,,,doi:https://doi.org/10.1099/mgen.0.000630; doi:https://doi.org/10.1099/mgen.0.000630; html:https://europepmc.org/articles/PMC8627209; pdf:https://europepmc.org/articles/PMC8627209?pdf=render
-36568709,https://doi.org/10.1136/bmjmed-2022-000215,Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.,"Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.",,BMJ medicine,2022,2022-09-28,Y,"Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities",,,"<h4>Objective</h4>To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.<h4>Design</h4>Cohort study.<h4>Setting</h4>Patients registered at primary care practices in England.<h4>Participants</h4>106 789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.<h4>Main outcome measures</h4>In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.<h4>Results</h4>680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.<h4>Conclusions</h4>Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render
 34321180,https://doi.org/10.1016/j.aucc.2021.05.013,The impact of distance on post-ICU disability.,"D'Arcy J, Haines K, Paul E, Doherty Z, Goodwin A, Bailey M, Barrett J, Bellomo R, Bucknall T, Gabbe BJ, Higgins AM, Iwashyna TJ, Murray LJ, Myles PS, Ponsford J, Pilcher D, Udy AA, Walker C, Young M, Cooper DJJ, Hodgson CL, ICU-Recovery Investigators.",,Australian critical care : official journal of the Confederation of Australian Critical Care Nurses,2022,2021-07-25,N,Quality of life; Mechanical ventilation; Distance; Disability; Intensive Care,,,"<h4>Background</h4>Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness.<h4>Objectives</h4>The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km.<h4>Methods</h4>This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received >24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU: <50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p < 0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable.<h4>Results</h4>A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living <50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health.",,doi:https://doi.org/10.1016/j.aucc.2021.05.013
+36568709,https://doi.org/10.1136/bmjmed-2022-000215,Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.,"Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.",,BMJ medicine,2022,2022-09-28,Y,"Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities",,,"<h4>Objective</h4>To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.<h4>Design</h4>Cohort study.<h4>Setting</h4>Patients registered at primary care practices in England.<h4>Participants</h4>106 789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.<h4>Main outcome measures</h4>In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.<h4>Results</h4>680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.<h4>Conclusions</h4>Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render
 37173061,https://doi.org/10.1016/j.ajcnut.2022.12.021,"Evidence for human milk as a biological system and recommendations for study design-a report from ""Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)"" Working Group 4.","Donovan SM, Aghaeepour N, Andres A, Azad MB, Becker M, Carlson SE, Järvinen KM, Lin W, Lönnerdal B, Slupsky CM, Steiber AL, Raiten DJ.",,The American journal of clinical nutrition,2023,2023-04-01,Y,Immune; systems biology; Human Milk; Microbiome; Infant Development,,,"Human milk contains all of the essential nutrients required by the infant within a complex matrix that enhances the bioavailability of many of those nutrients. In addition, human milk is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Our ability to fully appreciate the importance of this matrix relies on the recognition of short- and long-term health benefits and, as highlighted in previous sections of this supplement, its ecology (i.e., interactions among the lactating parent and breastfed infant as well as within the context of the human milk matrix itself). Designing and interpreting studies to address this complexity depends on the availability of new tools and technologies that account for such complexity. Past efforts have often compared human milk to infant formula, which has provided some insight into the bioactivity of human milk, as a whole, or of individual milk components supplemented with formula. However, this experimental approach cannot capture the contributions of the individual components to the human milk ecology, the interaction between these components within the human milk matrix, or the significance of the matrix itself to enhance human milk bioactivity on outcomes of interest. This paper presents approaches to explore human milk as a biological system and the functional implications of that system and its components. Specifically, we discuss study design and data collection considerations and how emerging analytical technologies, bioinformatics, and systems biology approaches could be applied to advance our understanding of this critical aspect of human biology.",,doi:https://doi.org/10.1016/j.ajcnut.2022.12.021; html:https://europepmc.org/articles/PMC10356565; pdf:https://europepmc.org/articles/PMC10356565?pdf=render
 36029521,https://doi.org/10.1093/ije/dyac171,Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH). ,"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.",,International journal of epidemiology,2023,2023-02-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render
 36697134,https://doi.org/10.1016/j.jacc.2022.10.034,Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.,"Ćorović A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jørgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM.",,Journal of the American College of Cardiology,2023,2023-01-01,Y,Atherosclerosis; Inflammation; Molecular Imaging; Giant Cell Arteritis; Takayasu Arteritis; Somatostatin Receptor,,,"<h4>Background</h4>Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures.<h4>Objectives</h4>We aimed to investigate somatostatin receptor 2 (SST<sub>2</sub>) as a novel inflammation-specific molecular imaging target in LVV.<h4>Methods</h4>In a prospective, observational cohort study, in vivo arterial SST<sub>2</sub> expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using <sup>68</sup>Ga-DOTATATE and <sup>18</sup>F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing.<h4>Results</h4>Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST<sub>2</sub> maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST<sub>2</sub> signal was not elevated in any of the control subjects. SST<sub>2</sub> PET/MRI was generally consistent with <sup>18</sup>F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST<sub>2</sub> maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST<sub>2</sub> expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers.<h4>Conclusions</h4>SST<sub>2</sub> PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).",,doi:https://doi.org/10.1016/j.jacc.2022.10.034; doi:https://doi.org/10.1016/j.jacc.2022.10.034; html:https://europepmc.org/articles/PMC9883634; pdf:https://europepmc.org/articles/PMC9883634?pdf=render
@@ -2000,8 +2000,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 35523486,https://doi.org/10.1136/bmjopen-2021-059258,Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study.,"de Angel V, Lewis S, Munir S, Matcham F, Dobson R, Hotopf M.",,BMJ open,2022,2022-05-06,Y,Mental health; Anxiety Disorders; Health Informatics; Depression & Mood Disorders,,,"<h4>Introduction</h4>Digital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field, most studies are small and based on student populations outside of a clinical setting. The current study aims to determine the feasibility and acceptability of using smartphones and wearable devices to collect behavioural and clinical data in people undergoing therapy for depressive disorders and establish the extent to which they can be potentially useful biomarkers of depression and recovery after treatment.<h4>Methods and analysis</h4>This is an observational, prospective cohort study of 65 people attending psychological therapy for depression in multiple London-based sites. It will collect continuous passive data from smartphone sensors and a Fitbit fitness tracker, and deliver questionnaires, speech tasks and cognitive assessments through smartphone-based apps. Objective data on sleep, physical activity, location, Bluetooth contact, smartphone use and heart rate will be gathered for 7 months, and compared with clinical and contextual data. A mixed methods design, including a qualitative interview of patient experiences, will be used to evaluate key feasibility indicators, digital phenotypes of depression and therapy prognosis. Patient and public involvement was sought for participant-facing documents and the study design of the current research proposal.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the London Westminster Research Ethics Committee, and the Health Research Authority, Integrated Research Application System (project ID: 270918). Privacy and confidentiality will be guaranteed and the procedures for handling, processing, storage and destruction of the data will comply with the General Data Protection Regulation. Findings from this study will form part of a doctoral thesis, will be presented at national and international meetings or academic conferences and will generate manuscripts to be submitted to peer-reviewed journals.<h4>Trial registration number</h4>https://doi.org/10.17605/OSF.IO/PMYTA.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e059258.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render
 36914875,https://doi.org/10.1038/s41588-023-01314-0,Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.,"Shrine N, Izquierdo AG, Chen J, Packer R, Hall RJ, Guyatt AL, Batini C, Thompson RJ, Pavuluri C, Malik V, Hobbs BD, Moll M, Kim W, Tal-Singer R, Bakke P, Fawcett KA, John C, Coley K, Piga NN, Pozarickij A, Lin K, Millwood IY, Chen Z, Li L, China Kadoorie Biobank Collaborative Group, Wijnant SRA, Lahousse L, Brusselle G, Uitterlinden AG, Manichaikul A, Oelsner EC, Rich SS, Barr RG, Kerr SM, Vitart V, Brown MR, Wielscher M, Imboden M, Jeong A, Bartz TM, Gharib SA, Flexeder C, Karrasch S, Gieger C, Peters A, Stubbe B, Hu X, Ortega VE, Meyers DA, Bleecker ER, Gabriel SB, Gupta N, Smith AV, Luan J, Zhao JH, Hansen AF, Langhammer A, Willer C, Bhatta L, Porteous D, Smith BH, Campbell A, Sofer T, Lee J, Daviglus ML, Yu B, Lim E, Xu H, O'Connor GT, Thareja G, Albagha OME, Qatar Genome Program Research (QGPR) Consortium, Suhre K, Granell R, Faquih TO, Hiemstra PS, Slats AM, Mullin BH, Hui J, James A, Beilby J, Patasova K, Hysi P, Koskela JT, Wyss AB, Jin J, Sikdar S, Lee M, May-Wilson S, Pirastu N, Kentistou KA, Joshi PK, Timmers PRHJ, Williams AT, Free RC, Wang X, Morrison JL, Gilliland FD, Chen Z, Wang CA, Foong RE, Harris SE, Taylor A, Redmond P, Cook JP, Mahajan A, Lind L, Palviainen T, Lehtimäki T, Raitakari OT, Kaprio J, Rantanen T, Pietiläinen KH, Cox SR, Pennell CE, Hall GL, Gauderman WJ, Brightling C, Wilson JF, Vasankari T, Laitinen T, Salomaa V, Mook-Kanamori DO, Timpson NJ, Zeggini E, Dupuis J, Hayward C, Brumpton B, Langenberg C, Weiss S, Homuth G, Schmidt CO, Probst-Hensch N, Jarvelin MR, Morrison AC, Polasek O, Rudan I, Lee JH, Sayers I, Rawlins EL, Dudbridge F, Silverman EK, Strachan DP, Walters RG, Morris AP, London SJ, Cho MH, Wain LV, Hall IP, Tobin MD.",,Nature genetics,2023,2023-03-13,Y,,,,"Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.",,pdf:https://www.nature.com/articles/s41588-023-01314-0.pdf; doi:https://doi.org/10.1038/s41588-023-01314-0; html:https://europepmc.org/articles/PMC10011137; pdf:https://europepmc.org/articles/PMC10011137?pdf=render
 32935027,https://doi.org/10.23889/ijpds.v4i1.1093,Health Data Linkage for UK Public Interest Research: Key Obstacles and Solutions.,"Mourby MJ, Doidge J, Jones KH, Aidinlis S, Smith H, Bell J, Gilbert R, Dutey-Magni P, Kaye J.",,International journal of population data science,2019,2019-04-02,Y,,,,"<h4>Introduction</h4>Analysis of linked health data can generate important, even life-saving, insights into population health. Yet obstacles both legal and organisational in nature can impede this work.<h4>Approach</h4>We focus on three UK infrastructures set up to link and share data for research: the Administrative Data Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank. Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges and successes in linking health data for research.<h4>Results</h4>We identify examples of uncertainty surrounding legal powers to share and link data, and around data protection obligations, as well as systemic delays and historic public backlash. These issues require updated official guidance on the relevant law, approaches to linkage which are planned for impact and ongoing utility, greater transparency between data providers and researchers, and engagement with the patient population which is both high-profile and carefully considered.<h4>Conclusions</h4>Health data linkage for research presents varied challenges, to which there can be no single solution. Our recommendations would require action from a number of data providers and regulators to be meaningfully advanced. This illustrates the scale and complexity of the challenge of health data linkage, in the UK and beyond: a challenge which our case studies suggest no single organisation can combat alone. Planned programmes of linkage are critical because they allow time for organisations to address these challenges without adversely affecting the feasibility of individual research projects.",,pdf:https://ijpds.org/article/download/1093/1035; doi:https://doi.org/10.23889/ijpds.v4i1.1093; html:https://europepmc.org/articles/PMC7482514; pdf:https://europepmc.org/articles/PMC7482514?pdf=render
-36527096,https://doi.org/10.1186/s12910-022-00875-9,"""Data makes the story come to life:"" understanding the ethical and legal implications of Big Data research involving ethnic minority healthcare workers in the United Kingdom-a qualitative study.","Dove ES, Reed-Berendt R, Pareek M, UK-REACH Study Collaborative Group.",,BMC medical ethics,2022,2022-12-16,Y,Ethics; Public Health; United Kingdom; Healthcare Workers; Ethnic Minorities; Big Data; Covid-19,,,"The aim of UK-REACH (""The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers"") is to understand if, how, and why healthcare workers (HCWs) in the United Kingdom (UK) from ethnic minority groups are at increased risk of poor outcomes from COVID-19. In this article, we present findings from the ethical and legal stream of the study, which undertook qualitative research seeking to understand and address legal, ethical, and social acceptability issues around data protection, privacy, and information governance associated with the linkage of HCWs' registration data and healthcare data. We interviewed 22 key opinion leaders in healthcare and health research from across the UK in two-to-one semi-structured interviews. Transcripts were coded using qualitative thematic analysis. Participants told us that a significant aspect of Big Data research in public health is varying drivers of mistrust-of the research itself, research staff and funders, and broader concerns of mistrust within participant communities, particularly in the context of COVID-19 and those situated in more marginalised community settings. However, despite the challenges, participants also identified ways in which legally compliant and ethically informed approaches to research can be crafted to mitigate or overcome mistrust and establish greater confidence in Big Data public health research. Overall, our research indicates that a ""Big Data Ethics by Design"" approach to research in this area can help assure (1) that meaningful community and participant engagement is taking place and that extant challenges are addressed, and (2) that any new challenges or hitherto unknown unknowns can be rapidly and properly considered to ensure potential (but material) harms are identified and minimised where necessary. Our findings indicate such an approach, in turn, will help drive better scientific breakthroughs that translate into medical innovations and effective public health interventions, which benefit the publics studied, including those who are often marginalised in research.",,pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?pdf=render
 34252085,https://doi.org/10.1371/journal.pcbi.1009162,Detecting behavioural changes in human movement to inform the spatial scale of interventions against COVID-19.,"Gibbs H, Nightingale E, Liu Y, Cheshire J, Danon L, Smeeth L, Pearson CAB, Grundy C, LSHTM CMMID COVID-19 working group, Kucharski AJ, Eggo RM.",,PLoS computational biology,2021,2021-07-12,Y,,,,"On March 23 2020, the UK enacted an intensive, nationwide lockdown to mitigate transmission of COVID-19. As restrictions began to ease, more localized interventions were used to target resurgences in transmission. Understanding the spatial scale of networks of human interaction, and how these networks change over time, is critical to targeting interventions at the most at-risk areas without unnecessarily restricting areas at low risk of resurgence. We use detailed human mobility data aggregated from Facebook users to determine how the spatially-explicit network of movements changed before and during the lockdown period, in response to the easing of restrictions, and to the introduction of locally-targeted interventions. We also apply community detection techniques to the weighted, directed network of movements to identify geographically-explicit movement communities and measure the evolution of these community structures through time. We found that the mobility network became more sparse and the number of mobility communities decreased under the national lockdown, a change that disproportionately affected long distance connections central to the mobility network. We also found that the community structure of areas in which locally-targeted interventions were implemented following epidemic resurgence did not show reorganization of community structure but did show small decreases in indicators of travel outside of local areas. We propose that communities detected using Facebook or other mobility data be used to assess the impact of spatially-targeted restrictions and may inform policymakers about the spatial extent of human movement patterns in the UK. These data are available in near real-time, allowing quantification of changes in the distribution of the population across the UK, as well as changes in travel patterns to inform our understanding of the impact of geographically-targeted interventions.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009162&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009162; html:https://europepmc.org/articles/PMC8297940; pdf:https://europepmc.org/articles/PMC8297940?pdf=render
+36527096,https://doi.org/10.1186/s12910-022-00875-9,"""Data makes the story come to life:"" understanding the ethical and legal implications of Big Data research involving ethnic minority healthcare workers in the United Kingdom-a qualitative study.","Dove ES, Reed-Berendt R, Pareek M, UK-REACH Study Collaborative Group.",,BMC medical ethics,2022,2022-12-16,Y,Ethics; Public Health; United Kingdom; Healthcare Workers; Ethnic Minorities; Big Data; Covid-19,,,"The aim of UK-REACH (""The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers"") is to understand if, how, and why healthcare workers (HCWs) in the United Kingdom (UK) from ethnic minority groups are at increased risk of poor outcomes from COVID-19. In this article, we present findings from the ethical and legal stream of the study, which undertook qualitative research seeking to understand and address legal, ethical, and social acceptability issues around data protection, privacy, and information governance associated with the linkage of HCWs' registration data and healthcare data. We interviewed 22 key opinion leaders in healthcare and health research from across the UK in two-to-one semi-structured interviews. Transcripts were coded using qualitative thematic analysis. Participants told us that a significant aspect of Big Data research in public health is varying drivers of mistrust-of the research itself, research staff and funders, and broader concerns of mistrust within participant communities, particularly in the context of COVID-19 and those situated in more marginalised community settings. However, despite the challenges, participants also identified ways in which legally compliant and ethically informed approaches to research can be crafted to mitigate or overcome mistrust and establish greater confidence in Big Data public health research. Overall, our research indicates that a ""Big Data Ethics by Design"" approach to research in this area can help assure (1) that meaningful community and participant engagement is taking place and that extant challenges are addressed, and (2) that any new challenges or hitherto unknown unknowns can be rapidly and properly considered to ensure potential (but material) harms are identified and minimised where necessary. Our findings indicate such an approach, in turn, will help drive better scientific breakthroughs that translate into medical innovations and effective public health interventions, which benefit the publics studied, including those who are often marginalised in research.",,pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?pdf=render
 35189575,https://doi.org/10.1016/j.ebiom.2022.103878,The impact of hypoxia on B cells in COVID-19.,"Kotagiri P, Mescia F, Hanson AL, Turner L, Bergamaschi L, Peñalver A, Richoz N, Moore SD, Ortmann BM, Dunmore BJ, Morgan MD, Tuong ZK, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Göttgens B, Toshner M, Hess C, Maxwell PH, Clatworthy MR, Nathan JA, Bradley JR, Lyons PA, Burrows N, Smith KGC.",,EBioMedicine,2022,2022-02-19,Y,Hypoxia; B cells; Lymphopenia; Covid-19,,,"<h4>Background</h4>Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This presentation resembles the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19.<h4>Methods</h4>Detailed B cell phenotyping was undertaken by flow-cytometry on longitudinal samples from patients with COVID-19 across a range of severities (NIHR Cambridge BioResource). The impact of hypoxia on the transcriptome was assessed by single-cell and whole blood RNA sequencing analysis. The direct effect of hypoxia on B cells was determined through immunisation studies in genetically modified and hypoxia-exposed mice.<h4>Findings</h4>We demonstrate the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes also observed in B cell VHL-deficient mice. These findings were associated with hypoxia-related transcriptional changes in COVID-19 patient B cells, and similar B cell abnormalities were seen in mice kept in hypoxic conditions.<h4>Interpretation</h4>Hypoxia may contribute to the pronounced and persistent B cell pathology observed in acute COVID-19 pneumonia. Assessment of the impact of early oxygen therapy on these immune defects should be considered, as their correction could contribute to improved outcomes.<h4>Funding</h4>Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2352396422000627/pdf; doi:https://doi.org/10.1016/j.ebiom.2022.103878; html:https://europepmc.org/articles/PMC8856886; pdf:https://europepmc.org/articles/PMC8856886?pdf=render
 36522333,https://doi.org/10.1038/s41467-022-35454-4,Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.,"Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.",,Nature communications,2022,2022-12-15,Y,,,,"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.",,pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render
 32184442,https://doi.org/10.1038/s42003-020-0857-9,Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank.,"Olafsdottir T, Thorleifsson G, Sulem P, Stefansson OA, Medek H, Olafsson K, Ingthorsson O, Gudmundsson V, Jonsdottir I, Halldorsson GH, Kristjansson RP, Frigge ML, Stefansdottir L, Sigurdsson JK, Oddsson A, Sigurdsson A, Eggertsson HP, Melsted P, Halldorsson BV, Lund SH, Styrkarsdottir U, Steinthorsdottir V, Gudmundsson J, Holm H, Tragante V, Asselbergs FW, Thorsteinsdottir U, Gudbjartsson DF, Jonsdottir K, Rafnar T, Stefansson K.",,Communications biology,2020,2020-03-17,Y,,,,"Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10<sup>-8</sup>); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.",,pdf:https://www.nature.com/articles/s42003-020-0857-9.pdf; doi:https://doi.org/10.1038/s42003-020-0857-9; html:https://europepmc.org/articles/PMC7078216; pdf:https://europepmc.org/articles/PMC7078216?pdf=render
@@ -2013,15 +2013,15 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33995410,https://doi.org/10.3389/fimmu.2021.671052,Plasma Lectin Pathway Complement Proteins in Patients With COVID-19 and Renal Disease.,"Medjeral-Thomas NR, Troldborg A, Hansen AG, Gisby J, Clarke CL, Prendecki M, McAdoo SP, Sandhu E, Lightstone L, Thomas DC, Willicombe M, Botto M, Peters JE, Pickering MC, Thiel S.",,Frontiers in immunology,2021,2021-04-29,Y,Complement; Lectin; Coronavirus; Chronic Kidney Disease; Covid-19,,,"We do not understand why non-white ethnicity and chronic kidney disease increase susceptibility to COVID-19. The lectin pathway of complement activation is a key contributor to innate immunity and inflammation. Concentrations of plasma lectin pathway proteins influence pathway activity and vary with ethnicity. We measured circulating lectin proteins in a multi-ethnic cohort of chronic kidney disease patients with and without COVID19 infection to determine if lectin pathway activation was contributing to COVID19 severity. We measured 11 lectin proteins in serial samples from a cohort of 33 patients with chronic kidney impairment and COVID19. Controls were single plasma samples from 32 patients on dialysis and 32 healthy individuals. We demonstrated multiple associations between recognition molecules and associated proteases of the lectin pathway and COVID-19, including COVID-19 severity. Some of these associations were unique to patients of Asian and White ethnicity. Our novel findings demonstrate that COVID19 infection alters the concentration of plasma lectin proteins and some of these changes were linked to ethnicity. This suggests a role for the lectin pathway in the host response to COVID-19 and suggest that variability within this pathway may contribute to ethnicity-associated differences in susceptibility to severe COVID-19.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2021.671052/pdf; doi:https://doi.org/10.3389/fimmu.2021.671052; html:https://europepmc.org/articles/PMC8118695; pdf:https://europepmc.org/articles/PMC8118695?pdf=render
 33203906,https://doi.org/10.1038/s41598-020-76518-z,Accelerated MRI-predicted brain ageing and its associations with cardiometabolic and brain disorders.,"Kolbeinsson A, Filippi S, Panagakis Y, Matthews PM, Elliott P, Dehghan A, Tzoulaki I.",,Scientific reports,2020,2020-11-17,Y,,,,"Brain structure in later life reflects both influences of intrinsic aging and those of lifestyle, environment and disease. We developed a deep neural network model trained on brain MRI scans of healthy people to predict ""healthy"" brain age. Brain regions most informative for the prediction included the cerebellum, hippocampus, amygdala and insular cortex. We then applied this model to data from an independent group of people not stratified for health. A phenome-wide association analysis of over 1,410 traits in the UK Biobank with differences between the predicted and chronological ages for the second group identified significant associations with over 40 traits including diseases (e.g., type I and type II diabetes), disease risk factors (e.g., increased diastolic blood pressure and body mass index), and poorer cognitive function. These observations highlight relationships between brain and systemic health and have implications for understanding contributions of the latter to late life dementia risk.",,pdf:https://www.nature.com/articles/s41598-020-76518-z.pdf; doi:https://doi.org/10.1038/s41598-020-76518-z; html:https://europepmc.org/articles/PMC7672070; pdf:https://europepmc.org/articles/PMC7672070?pdf=render
 33932483,https://doi.org/10.1016/j.jclinepi.2021.04.015,Probabilistic linkage without personal information successfully linked national clinical datasets.,"Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K.",,Journal of clinical epidemiology,2021,2021-04-28,Y,Electronic Health Records; Record Linkage; Personal Information; Probabilistic Linkage; National Clinical Datasets; Patient Identifiers,,,"<h4>Background</h4>Probabilistic linkage can link patients from different clinical databases without the need for personal information. If accurate linkage can be achieved, it would accelerate the use of linked datasets to address important clinical and public health questions.<h4>Objective</h4>We developed a step-by-step process for probabilistic linkage of national clinical and administrative datasets without personal information, and validated it against deterministic linkage using patient identifiers.<h4>Study design and setting</h4>We used electronic health records from the National Bowel Cancer Audit and Hospital Episode Statistics databases for 10,566 bowel cancer patients undergoing emergency surgery in the English National Health Service.<h4>Results</h4>Probabilistic linkage linked 81.4% of National Bowel Cancer Audit records to Hospital Episode Statistics, vs. 82.8% using deterministic linkage. No systematic differences were seen between patients that were and were not linked, and regression models for mortality and length of hospital stay according to patient and tumour characteristics were not sensitive to the linkage approach.<h4>Conclusion</h4>Probabilistic linkage was successful in linking national clinical and administrative datasets for patients undergoing a major surgical procedure. It allows analysts outside highly secure data environments to undertake linkage while minimizing costs and delays, protecting data security, and maintaining linkage quality.",,pdf:http://www.jclinepi.com/article/S0895435621001384/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.04.015; html:https://europepmc.org/articles/PMC8443839
-35296488,https://doi.org/10.1136/bmjopen-2021-058552,"AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353 157 patients in London, UK.","Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.",,BMJ open,2022,2022-03-16,Y,Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology,,,"<h4>Purpose</h4>Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.<h4>Participants</h4>Between 1 January 2008 and 1 April 2018, 353 157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.<h4>Findings to date</h4>Among the 353 157 individuals, 186 651 had a total of 1 337 711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12 022 patients with myocardial infarction, 11 735 with all-cause stroke and 13 363 with all-cause dementia. A total of 6 261 931 retinal images of seven different modalities and across three manufacturers were acquired from 1 54 830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).<h4>Future plans</h4>AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/3/e058552.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render
 34036180,https://doi.org/10.23889/ijpds.v5i2.1385,Linking data on women in public family law court proceedings concerning their children to mental health service records in South London.,"Pearson RJ, Jewell A, Wijlaars L, Bedston S, Finch E, Broadhurst K, Downs J, Gilbert R.",,International journal of population data science,2021,2021-02-24,Y,,,,"<h4>Introduction</h4>Maternal mental health problems and substance misuse are key risk factors for child neglect or abuse and court-mandated placement into care. Linkage between mental health records and family court data could raise awareness about parent mental health needs and inform approaches to address them.<h4>Objectives</h4>To evaluate data linkage between administrative family court data and electronic mental health records for a population-based mental health service for 1.3 million people in South London.<h4>Methods</h4>We deterministically linked administrative family court data for women (n=5463) involved in care proceedings in South London with service user records from the South London and Maudsley NHS Mental Health Trust (SLaM). We restricted the cohort to women involved in proceedings between 2007 and 2019, in local authorities where SLaM solely provides secondary/tertiary mental health services and the Improving Access to Psychological Therapies (IAPT) (n=3226). We analysed the associations between match status and sociodemographic/case characteristics using multivariable logistic regression.<h4>Results</h4>Two-thirds (2317/3226; 66%) of women linked to a SLaM service user record at some point; most (91%) who linked accessed secondary/tertiary mental health services, indicating serious mental illness. Accounting for possible missed matches, we estimated that 70-83% of women accessed SLaM services at some point. Older women at index proceedings (>35yrs OR: 0.69, 95%CI: 0.54-0.88vs <25yrs) and Black women or women from other ethnic groups (Black ethnic groups 0.65, 0.50-0.83; other ethnicity 0.59, 0.43-0.81 vs White ethnic groups) had lower odds of linking. Odds of linking were higher for women with an infant in proceedings (1.42, 1.18-1.71), or with curtailed/terminated parental responsibility (1.44, 1.20-1.73).<h4>Conclusion</h4>Our linkage supports growing evidence of a high burden of mental health problems and substance misuse among women whose children enter care in England, compared to the general population. Research using this linkage should inform strategies to address the considerable mental health needs of vulnerable women and their children.",,doi:https://doi.org/10.23889/ijpds.v5i2.1385; html:https://europepmc.org/articles/PMC8133060; pdf:https://europepmc.org/articles/PMC8133060?pdf=render
+35296488,https://doi.org/10.1136/bmjopen-2021-058552,"AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353 157 patients in London, UK.","Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.",,BMJ open,2022,2022-03-16,Y,Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology,,,"<h4>Purpose</h4>Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.<h4>Participants</h4>Between 1 January 2008 and 1 April 2018, 353 157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.<h4>Findings to date</h4>Among the 353 157 individuals, 186 651 had a total of 1 337 711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12 022 patients with myocardial infarction, 11 735 with all-cause stroke and 13 363 with all-cause dementia. A total of 6 261 931 retinal images of seven different modalities and across three manufacturers were acquired from 1 54 830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).<h4>Future plans</h4>AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/3/e058552.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render
 35585198,https://doi.org/10.1038/s41591-022-01772-9,Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,Nature medicine,2022,2022-05-18,N,,,,"A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system's actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use and pave the way to further large-scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multi-stakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two-round, modified Delphi process to collect and analyze expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 pre-defined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. In total, 123 experts participated in the first round of Delphi, 138 in the second round, 16 in the consensus meeting and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI-specific reporting items (made of 28 subitems) and ten generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we developed a guideline comprising key items that should be reported in early-stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings.",,pdf:https://www.nature.com/articles/s41591-022-01772-9.pdf; doi:https://doi.org/10.1038/s41591-022-01772-9
 30772400,https://doi.org/10.1016/j.neuroimage.2019.02.028,Hierarchical complexity of the adult human structural connectome.,"Smith K, Bastin ME, Cox SR, Valdés Hernández MC, Wiseman S, Escudero J, Sudlow C.",,NeuroImage,2019,2019-02-14,Y,MRI; Brain Networks; Hierarchical Complexity; Human Structural Connectome,The Human Phenome,,"The structural network of the human brain has a rich topology which many have sought to characterise using standard network science measures and concepts. However, this characterisation remains incomplete and the non-obvious features of this topology have largely confounded attempts towards comprehensive constructive modelling. This calls for new perspectives. Hierarchical complexity is an emerging paradigm of complex network topology based on the observation that complex systems are composed of hierarchies within which the roles of hierarchically equivalent nodes display highly variable connectivity patterns. Here we test the hierarchical complexity of the human structural connectomes of a group of seventy-nine healthy adults. Binary connectomes are found to be more hierarchically complex than three benchmark random network models. This provides a new key description of brain structure, revealing a rich diversity of connectivity patterns within hierarchically equivalent nodes. Dividing the connectomes into four tiers based on degree magnitudes indicates that the most complex nodes are neither those with the highest nor lowest degrees but are instead found in the middle tiers. Spatial mapping of the brain regions in each hierarchical tier reveals consistency with the current anatomical, functional and neuropsychological knowledge of the human brain. The most complex tier (Tier 3) involves regions believed to bridge high-order cognitive (Tier 1) and low-order sensorimotor processing (Tier 2). We then show that such diversity of connectivity patterns aligns with the diversity of functional roles played out across the brain, demonstrating that hierarchical complexity can characterise functional diversity strictly from the network topology.",,doi:https://doi.org/10.1016/j.neuroimage.2019.02.028; doi:https://doi.org/10.1016/j.neuroimage.2019.02.028; html:https://europepmc.org/articles/PMC6503942
 30681347,https://doi.org/10.1161/circgen.118.002328,Integrative Functional Annotation of 52 Genetic Loci Influencing Myocardial Mass Identifies Candidate Regulatory Variants and Target Genes.,"Hemerich D, Pei J, Harakalova M, van Setten J, Boymans S, Boukens BJ, Efimov IR, Michels M, van der Velden J, Vink A, Cheng C, van der Harst P, Moore JH, Mokry M, Tragante V, Asselbergs FW.",,Circulation. Genomic and precision medicine,2019,2019-02-01,N,Genetics; Electrocardiography; Acetylation; Heart Failure; Cardiomyopathies,The Human Phenome,,"BACKGROUND:Regulatory elements may be involved in the mechanisms by which 52 loci influence myocardial mass, reflected by abnormal amplitude and duration of the QRS complex on the ECG. Functional annotation thus far did not take into account how these elements are affected in disease context. METHODS:We generated maps of regulatory elements on hypertrophic cardiomyopathy patients (ChIP-seq N=14 and RNA-seq N=11) and nondiseased hearts (ChIP-seq N=4 and RNA-seq N=11). We tested enrichment of QRS-associated loci on elements differentially acetylated and directly regulating differentially expressed genes between hypertrophic cardiomyopathy patients and controls. We further performed functional annotation on QRS-associated loci using these maps of differentially active regulatory elements. RESULTS:Regions differentially affected in disease showed a stronger enrichment ( P=8.6×10-5) for QRS-associated variants than those not showing differential activity ( P=0.01). Promoters of genes differentially regulated between hypertrophic cardiomyopathy patients and controls showed more enrichment ( P=0.001) than differentially acetylated enhancers ( P=0.8) and super-enhancers ( P=0.025). We also identified 74 potential causal variants overlapping these differential regulatory elements. Eighteen of the genes mapped confirmed previous findings, now also pinpointing the potentially affected regulatory elements and candidate causal variants. Fourteen new genes were also mapped. CONCLUSIONS:Our results suggest differentially active regulatory elements between hypertrophic cardiomyopathy patients and controls can offer more insights into the mechanisms of QRS-associated loci than elements not affected by disease.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002328; doi:https://doi.org/10.1161/CIRCGEN.118.002328; html:https://europepmc.org/articles/PMC6380958; pdf:https://europepmc.org/articles/PMC6380958?pdf=render; doi:https://doi.org/10.1161/circgen.118.002328
 36895957,https://doi.org/10.1093/braincomms/fcad037,Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.,"Themistocleous AC, Baskozos G, Blesneac I, Comini M, Megy K, Chong S, Deevi SVV, Ginsberg L, Gosal D, Hadden RDM, Horvath R, Mahdi-Rogers M, Manzur A, Mapeta R, Marshall A, Matthews E, McCarthy MI, Reilly MM, Renton T, Rice ASC, Vale TA, van Zuydam N, Walker SM, Woods CG, Bennett DLH.",,Brain communications,2023,2023-02-20,Y,Sodium channels; Neuropathic pain; Peripheral Neuropathy; Whole Genome Sequencing,,,"The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes was completed. Association testing for genes carrying rare variants was completed using the gene-wise approach of the combined burden and variance-component test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants: <i>SCN9A(ENST00000409672.1):</i> c.2544T>C, p.Ile848Thr that causes inherited erythromelalgia, and <i>SPTLC1(ENST00000262554.2):</i>c.340T>G, p.Cys133Tr variant that causes hereditary sensory neuropathy type-1. (ii) Clinically relevant variants were most common in voltage-gated sodium channels (Na<sub>v</sub>). (iii) <i>SCN9A(ENST00000409672.1):</i>c.554G>A, pArg185His variant was more common in non-freezing cold injury participants than controls and causes a gain of function of Na<sub>V</sub>1.7 after cooling (the environmental trigger for non-freezing cold injury). (iv) Rare variant association testing showed a significant difference in distribution for genes NGF, <i>KIF1A</i>, <i>SCN8A</i>, <i>TRPM8</i>, <i>KIF1A</i>, <i>TRPA1</i> and the regulatory regions of genes <i>SCN11A</i>, <i>FLVCR1</i>, <i>KIF1A</i> and <i>SCN9A</i> between European participants with neuropathic pain and controls. (v) The <i>TRPA1(ENST00000262209.4):c.515C>T,</i> p.Ala172Val variant identified in participants with episodic somatic pain disorder demonstrated gain-of-channel function to agonist stimulation. Whole genome sequencing identified clinically relevant variants in over 10% of participants with extreme neuropathic pain phenotypes. The majority of these variants were found in ion channels. Combining genetic analysis with functional validation can lead to a better understanding as to how rare variants in ion channels lead to sensory neuron hyper-excitability, and how cold, as an environmental trigger, interacts with the gain-of-function Na<sub>V</sub>1.7 p.Arg185His variant. Our findings highlight the role of ion channel variants in the pathogenesis of extreme neuropathic pain disorders, likely mediated through changes in sensory neuron excitability and interaction with environmental triggers.",,pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad037/49446967/fcad037.pdf; doi:https://doi.org/10.1093/braincomms/fcad037; html:https://europepmc.org/articles/PMC9991512; pdf:https://europepmc.org/articles/PMC9991512?pdf=render
 35587468,https://doi.org/10.1371/journal.pmed.1003981,Integrating polygenic risk scores in the prediction of type 2 diabetes risk and subtypes in British Pakistanis and Bangladeshis: A population-based cohort study.,"Hodgson S, Huang QQ, Sallah N, Genes & Health Research Team, Griffiths CJ, Newman WG, Trembath RC, Wright J, Lumbers RT, Kuchenbaecker K, van Heel DA, Mathur R, Martin HC, Finer S.",,PLoS medicine,2022,2022-05-19,Y,,,,"<h4>Background</h4>Type 2 diabetes (T2D) is highly prevalent in British South Asians, yet they are underrepresented in research. Genes & Health (G&H) is a large, population study of British Pakistanis and Bangladeshis (BPB) comprising genomic and routine health data. We assessed the extent to which genetic risk for T2D is shared between BPB and European populations (EUR). We then investigated whether the integration of a polygenic risk score (PRS) for T2D with an existing risk tool (QDiabetes) could improve prediction of incident disease and the characterisation of disease subtypes.<h4>Methods and findings</h4>In this observational cohort study, we assessed whether common genetic loci associated with T2D in EUR individuals were replicated in 22,490 BPB individuals in G&H. We replicated fewer loci in G&H (n = 76/338, 22%) than would be expected given power if all EUR-ascertained loci were transferable (n = 101, 30%; p = 0.001). Of the 27 transferable loci that were powered to interrogate this, only 9 showed evidence of shared causal variants. We constructed a T2D PRS and combined it with a clinical risk instrument (QDiabetes) in a novel, integrated risk tool (IRT) to assess risk of incident diabetes. To assess model performance, we compared categorical net reclassification index (NRI) versus QDiabetes alone. In 13,648 patients free from T2D followed up for 10 years, NRI was 3.2% for IRT versus QDiabetes (95% confidence interval (CI): 2.0% to 4.4%). IRT performed best in reclassification of individuals aged less than 40 years deemed low risk by QDiabetes alone (NRI 5.6%, 95% CI 3.6% to 7.6%), who tended to be free from comorbidities and slim. After adjustment for QDiabetes score, PRS was independently associated with progression to T2D after gestational diabetes (hazard ratio (HR) per SD of PRS 1.23, 95% CI 1.05 to 1.42, p = 0.028). Using cluster analysis of clinical features at diabetes diagnosis, we replicated previously reported disease subgroups, including Mild Age-Related, Mild Obesity-related, and Insulin-Resistant Diabetes, and showed that PRS distribution differs between subgroups (p = 0.002). Integrating PRS in this cluster analysis revealed a Probable Severe Insulin Deficient Diabetes (pSIDD) subgroup, despite the absence of clinical measures of insulin secretion or resistance. We also observed differences in rates of progression to micro- and macrovascular complications between subgroups after adjustment for confounders. Study limitations include the absence of an external replication cohort and the potential biases arising from missing or incorrect routine health data.<h4>Conclusions</h4>Our analysis of the transferability of T2D loci between EUR and BPB indicates the need for larger, multiancestry studies to better characterise the genetic contribution to disease and its varied aetiology. We show that a T2D PRS optimised for this high-risk BPB population has potential clinical application in BPB, improving the identification of T2D risk (especially in the young) on top of an established clinical risk algorithm and aiding identification of subgroups at diagnosis, which may help future efforts to stratify care and treatment of the disease.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003981&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003981; html:https://europepmc.org/articles/PMC9119501; pdf:https://europepmc.org/articles/PMC9119501?pdf=render
-33972514,https://doi.org/10.1038/s41467-021-22338-2,Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.,"Pazoki R, Vujkovic M, Elliott J, Evangelou E, Gill D, Ghanbari M, van der Most PJ, Pinto RC, Wielscher M, Farlik M, Zuber V, de Knegt RJ, Snieder H, Uitterlinden AG, Lifelines Cohort Study, Lynch JA, Jiang X, Said S, Kaplan DE, Lee KM, Serper M, Carr RM, Tsao PS, Atkinson SR, Dehghan A, Tzoulaki I, Ikram MA, Herzig KH, Järvelin MR, Alizadeh BZ, O'Donnell CJ, Saleheen D, Voight BF, Chang KM, Thursz MR, Elliott P, VA Million Veteran Program.",,Nature communications,2021,2021-05-10,Y,,,,"Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.",,pdf:https://www.nature.com/articles/s41467-021-22338-2.pdf; doi:https://doi.org/10.1038/s41467-021-22338-2; html:https://europepmc.org/articles/PMC8110798; pdf:https://europepmc.org/articles/PMC8110798?pdf=render
 31382511,https://doi.org/10.3390/toxins11080454,Indoxyl Sulfate Stimulates Angiogenesis by Regulating Reactive Oxygen Species Production via CYP1B1.,"Pei J, Juni R, Harakalova M, Duncker DJ, Asselbergs FW, Koolwijk P, Hinsbergh VV, Verhaar MC, Mokry M, Cheng C.",,Toxins,2019,2019-08-02,Y,Reactive oxygen species; Angiogenesis; Chronic Kidney Disease; Cyp1b1; Indoxyl Sulfate,Understanding the Causes of Disease,,"Indoxyl sulfate (IS) is an accumulative protein-bound uremic toxin found in patients with kidney disease. It is reported that IS impairs the vascular endothelium, but a comprehensive overview of all mechanisms active in IS-injury currently remains lacking. Here we performed RNA sequencing in human umbilical vein endothelial cells (HUVECs) after IS or control medium treatment and identified 1293 genes that were affected in a IS-induced response. Gene enrichment analysis highlighted pathways involved in altered vascular formation and cell metabolism. We confirmed these transcriptome profiles at the functional level by demonstrating decreased viability and increased cell senescence in response to IS treatment. In line with the additional pathways highlighted by the transcriptome analysis, we further could demonstrate that IS exposure of HUVECs promoted tubule formation as shown by the increase in total tubule length in a 3D HUVECs/pericytes co-culture assay. Notably, the pro-angiogenic response of IS and increased ROS production were abolished when <i>CYP1B1</i>, one of the main target genes that was highly upregulated by IS, was silenced. This observation indicates IS-induced ROS in endothelial cells is <i>CYP1B1</i>-dependent. Taken together, our findings demonstrate that IS promotes angiogenesis and <i>CYP1B1</i> is an important factor in IS-activated angiogenic response.",,pdf:https://www.mdpi.com/2072-6651/11/8/454/pdf?version=1565690179; doi:https://doi.org/10.3390/toxins11080454; html:https://europepmc.org/articles/PMC6723868; pdf:https://europepmc.org/articles/PMC6723868?pdf=render
+33972514,https://doi.org/10.1038/s41467-021-22338-2,Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.,"Pazoki R, Vujkovic M, Elliott J, Evangelou E, Gill D, Ghanbari M, van der Most PJ, Pinto RC, Wielscher M, Farlik M, Zuber V, de Knegt RJ, Snieder H, Uitterlinden AG, Lifelines Cohort Study, Lynch JA, Jiang X, Said S, Kaplan DE, Lee KM, Serper M, Carr RM, Tsao PS, Atkinson SR, Dehghan A, Tzoulaki I, Ikram MA, Herzig KH, Järvelin MR, Alizadeh BZ, O'Donnell CJ, Saleheen D, Voight BF, Chang KM, Thursz MR, Elliott P, VA Million Veteran Program.",,Nature communications,2021,2021-05-10,Y,,,,"Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.",,pdf:https://www.nature.com/articles/s41467-021-22338-2.pdf; doi:https://doi.org/10.1038/s41467-021-22338-2; html:https://europepmc.org/articles/PMC8110798; pdf:https://europepmc.org/articles/PMC8110798?pdf=render
 35042708,https://doi.org/10.1136/bmjopen-2021-055572,Use of the kidney failure risk equation to inform clinical care of patients with chronic kidney disease: a mixed-methods systematic review.,"Bhachu HK, Fenton A, Cockwell P, Aiyegbusi O, Kyte D, Calvert M.",,BMJ open,2022,2022-01-18,Y,Dialysis; Renal transplantation; Chronic Renal Failure; End Stage Renal Failure,,,"<h4>Rationale and objective</h4>The Kidney Failure Risk Equation (KFRE) predicts the risk of end-stage kidney disease in patients with chronic kidney disease (CKD). This study aimed to evaluate the impact of the utility of KFRE in clinical practice.<h4>Study design</h4>Systematic review.<h4>Setting and study populations</h4>Adult patients with CKD but not receiving renal replacement therapy enrolled in studies where KFRE was used in clinical care pathways.<h4>Selection criteria for studies</h4>All studies published from April 2011 to October 2021 identified from Medline, Cumulative Index to Nursing and Allied Health Literature, Embase and reference and citation searches of included studies.<h4>Data extraction</h4>Relevant data were extracted, and two reviewers independently assessed study quality using appropriate appraisal tools.<h4>Analytical approach</h4>Findings reported as a narrative synthesis due to heterogeneity of the included studies.<h4>Results</h4>Of 1635 studies identified, 440 duplicates were removed. The remaining 1195 titles and abstracts were screened. All five studies for full-text review were included in the analysis. Three uses of KFRE were assessed: (1) primary to specialty care interface; (2) general nephrology to multidisciplinary care transition; and (3) treatment planning. Evidence of impact on number of patient referrals into nephrology care was conflicting. However, wait times improved in one study. Although KFRE identified high-risk patients for increased multidisciplinary support, there was concern patients stepped down, no longer meeting eligibility criteria, may lack access to services.<h4>Conclusions</h4>This is the first systematic review of studies that have assessed the actual impact of KFRE in clinical practice with five studies of varying quality reported to date. Trials are in progress assessing the impact on clinical outcomes of using KFRE in clinical practice, and KFRE is being incorporated into guidelines for CKD management. Further studies are needed to assess the impact of KFRE on clinical care.<h4>Trial registration number</h4>Protocol registered on PROSPERO before initiation of the study (Ref: CRD42020219926).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e055572.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055572; html:https://europepmc.org/articles/PMC8768913; pdf:https://europepmc.org/articles/PMC8768913?pdf=render
 33293538,https://doi.org/10.1038/s41467-020-20096-1,Patient and public perspectives on cell and gene therapies: a systematic review.,"Aiyegbusi OL, Macpherson K, Elston L, Myles S, Washington J, Sungum N, Briggs M, Newsome PN, Calvert MJ.",,Nature communications,2020,2020-12-08,Y,,,,"Cell and gene therapies offer opportunities for treating disease with potential to restore function, and cure disease. However, they are not without risk and pose complex logistical, economic, ethical and social challenges for health systems. Here we report our systematic review of the current evidence on patient and public knowledge and perspectives of cell and gene therapies, to inform future research, education and awareness raising activities. We screened 10,735 titles and abstracts, and evaluated the full texts of 151 publications. The final selection was 35 publications. Four themes were generated from the narrative synthesis of the study findings namely: (1) Knowledge and understanding of cell and gene therapies, (2) Acceptance of cell and gene therapies (3) Understanding of risk and benefits of therapy, and (4) Information needs and current sources of information. As potential funders or future recipients, it is important that the public and patients are aware of these therapies, understand the issues involved, and can contribute to the debate. This review highlights the need for appropriate patient and public education on the various aspects of cell and gene therapies. High quality studies exploring patient and public opinions and experiences of cell and gene therapy are required. Patient and public perceptions of these therapies, alongside evidence of clinical and cost-effectiveness, will be central to their uptake and use.",,pdf:https://www.nature.com/articles/s41467-020-20096-1.pdf; doi:https://doi.org/10.1038/s41467-020-20096-1; html:https://europepmc.org/articles/PMC7722871; pdf:https://europepmc.org/articles/PMC7722871?pdf=render
 32336304,https://doi.org/10.1192/j.eurpsy.2020.39,Prevalence and incidence of clinical outcomes in patients presenting to secondary mental health care with mood instability and sleep disturbance.,"McDonald K, Smith T, Broadbent M, Patel R, Geddes JR, Saunders KEA.",,European psychiatry : the journal of the Association of European Psychiatrists,2020,2020-04-27,Y,Sleep; Psychiatry; epidemiology; Mood; Electronic Health Records,,,"<h4>Background</h4>Mood instability and sleep disturbance are common symptoms in people with mental illness. Both features are clinically important and associated with poorer illness trajectories. We compared clinical outcomes in people presenting to secondary mental health care with mood instability and/or sleep disturbance with outcomes in people without either mood instability or sleep disturbance.<h4>Methods</h4>Data were from electronic health records of 31,391 patients ages 16-65 years presenting to secondary mental health services between 2008 and 2016. Mood instability and sleep disturbance were identified using natural language processing. Prevalence of mood instability and sleep disturbance were estimated at baseline. Incidence rate ratios were estimates for clinical outcomes including psychiatric diagnoses, prescribed medication, and hospitalization within 2-years of presentation in persons with mood instability and/or sleep disturbance compared to individuals without either symptom.<h4>Results</h4>Mood instability was present in 9.58%, and sleep disturbance in 26.26% of patients within 1-month of presenting to secondary mental health services. Compared with individuals without either symptom, those with mood instability and sleep disturbance showed significantly increased incidence of prescription of any psychotropic medication (incidence rate ratios [IRR] = 7.04, 95% confidence intervals [CI] 6.53-7.59), and hospitalization (IRR = 5.32, 95% CI 5.32, 4.67-6.07) within 2-years of presentation. Incidence rates of most clinical outcomes were considerably increased among persons with both mood instability and sleep disturbance, relative to persons with only one symptom.<h4>Conclusions</h4>Mood instability and sleep disturbance are present in a wide range of mental disorders, beyond those in which they are conventionally considered to be symptoms. They are associated with poor outcomes, particularly when they occur together. The poor prognosis associated with mood instability and sleep disorder may be, in part, because they are often treated as secondary symptoms. Mood instability and sleep disturbance need better recognition as clinical targets for treatment in their own right.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A209144AEF3BF1C7774F5FE041090CA8/S0924933820000395a.pdf/div-class-title-prevalence-and-incidence-of-clinical-outcomes-in-patients-presenting-to-secondary-mental-health-care-with-mood-instability-and-sleep-disturbance-div.pdf; doi:https://doi.org/10.1192/j.eurpsy.2020.39; html:https://europepmc.org/articles/PMC7355164; pdf:https://europepmc.org/articles/PMC7355164?pdf=render
@@ -2064,8 +2064,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 35294976,https://doi.org/10.1007/s00127-022-02221-1,Mental health service use among mothers involved in public family law proceedings: linked data cohort study in South London 2007-2019.,"Pearson RJ, Grant C, Wijlaars L, Finch E, Bedston S, Broadhurst K, Gilbert R.",,Social psychiatry and psychiatric epidemiology,2022,2022-03-16,Y,Substance Misuse; Child Protection; Record Linkage; Maternal Mental Health; Family Court,,,"<h4>Purpose</h4>Mental health problems and substance misuse are common among the mothers of children who experience court-mandated placement into care in England, yet there is limited research characterising these health needs to inform evidence-based policy. In this descriptive study, we aimed to generate evidence about the type, severity, and timing of mental health and substance misuse needs among women involved in public family law proceedings concerning child placement into care ('care proceedings').<h4>Methods</h4>This is a retrospective, matched cohort study using linked family court and mental health service records for 2137 (66%) of the 3226 women involved in care proceedings between 2007 and 2019 in the South London and Maudsley NHS Mental Health Trust (SLaM) catchment area. We compared mental health service use and risk of dying with 17,096 female-matched controls who accessed SLaM between 2007 and 2019, aged 16-55 years, and were not involved in care proceedings.<h4>Results</h4>Most women (79%) were known to SLaM before care proceedings began. Women had higher rates of schizophrenia spectrum disorders (19% vs 11% matched controls), personality disorders (21% vs 11%), and substance misuse (33% vs 12%). They were more likely to have a SLaM inpatient admission (27% vs 14%) or to be sectioned (19% vs 8%). Women had a 2.15 (95% CI 1.68-2.74) times greater hazard of dying, compared to matched controls, adjusted for age.<h4>Conclusion</h4>Women involved in care proceedings experience a particularly high burden of severe and complex mental health and substance misuse need. Women's increased risk of mortality following proceedings highlights that interventions responding to maternal mental health and substance misuse within family courts should offer continued, long-term support.",,pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02221-1.pdf; doi:https://doi.org/10.1007/s00127-022-02221-1; html:https://europepmc.org/articles/PMC9477900; pdf:https://europepmc.org/articles/PMC9477900?pdf=render
 33328634,https://doi.org/10.1038/s41586-020-03043-4,Mapping routine measles vaccination in low- and middle-income countries.,Local Burden of Disease Vaccine Coverage Collaborators.,,Nature,2021,2020-12-16,Y,,,,"The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)<sup>1-4</sup>. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)<sup>5-8</sup>. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km<sup>2</sup> pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.",,pdf:https://www.nature.com/articles/s41586-020-03043-4.pdf; doi:https://doi.org/10.1038/s41586-020-03043-4; html:https://europepmc.org/articles/PMC7739806; pdf:https://europepmc.org/articles/PMC7739806?pdf=render
 31171806,https://doi.org/10.1038/s41598-019-44907-8,On neighbourhood degree sequences of complex networks.,Smith KM.,,Scientific reports,2019,2019-06-06,Y,,Applied Analytics,,"Network topology is a fundamental aspect of network science that allows us to gather insights into the complicated relational architectures of the world we inhabit. We provide a first specific study of neighbourhood degree sequences in complex networks. We consider how to explicitly characterise important physical concepts such as similarity, heterogeneity and organization in these sequences, as well as updating the notion of hierarchical complexity to reflect previously unnoticed organizational principles. We also point out that neighbourhood degree sequences are related to a powerful subtree kernel for unlabeled graph classification. We study these newly defined sequence properties in a comprehensive array of graph models and over 200 real-world networks. We find that these indices are neither highly correlated with each other nor with classical network indices. Importantly, the sequences of a wide variety of real world networks are found to have greater similarity and organisation than is expected for networks of their given degree distributions. Notably, while biological, social and technological networks all showed consistently large neighbourhood similarity and organisation, hierarchical complexity was not a consistent feature of real world networks. Neighbourhood degree sequences are an interesting tool for describing unique and important characteristics of complex networks.",,pdf:https://www.nature.com/articles/s41598-019-44907-8.pdf; doi:https://doi.org/10.1038/s41598-019-44907-8; html:https://europepmc.org/articles/PMC6554413; pdf:https://europepmc.org/articles/PMC6554413?pdf=render
-37414900,https://doi.org/10.1038/s41591-023-02429-x,A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.,"Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, Genes & Health Research Team; the Million Veteran Program, Tsao PS, Sun YV, Cho K, Wilson PWF, Assimes TL, van Heel DA, Butterworth AS, Aragam KG, Natarajan P, Khera AV.",,Nature medicine,2023,2023-07-06,Y,,,,"Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPS<sub>Mult</sub>, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPS<sub>Mult</sub> strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P < 0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPS<sub>Mult</sub> was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P < 0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPS<sub>Mult</sub> demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPS<sub>Mult</sub> for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.",,pdf:https://www.nature.com/articles/s41591-023-02429-x.pdf; doi:https://doi.org/10.1038/s41591-023-02429-x; html:https://europepmc.org/articles/PMC10353935; pdf:https://europepmc.org/articles/PMC10353935?pdf=render
 34972825,https://doi.org/10.1038/s41564-021-01029-0,Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.,"Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.",,Nature microbiology,2022,2021-12-31,Y,,,,"Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, R<sub>t</sub>, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and R<sub>t</sub>. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of R<sub>t</sub> are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and R<sub>t</sub> that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.",,pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render
+37414900,https://doi.org/10.1038/s41591-023-02429-x,A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.,"Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, Genes & Health Research Team; the Million Veteran Program, Tsao PS, Sun YV, Cho K, Wilson PWF, Assimes TL, van Heel DA, Butterworth AS, Aragam KG, Natarajan P, Khera AV.",,Nature medicine,2023,2023-07-06,Y,,,,"Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPS<sub>Mult</sub>, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPS<sub>Mult</sub> strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P < 0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPS<sub>Mult</sub> was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P < 0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPS<sub>Mult</sub> demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPS<sub>Mult</sub> for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.",,pdf:https://www.nature.com/articles/s41591-023-02429-x.pdf; doi:https://doi.org/10.1038/s41591-023-02429-x; html:https://europepmc.org/articles/PMC10353935; pdf:https://europepmc.org/articles/PMC10353935?pdf=render
 32127008,https://doi.org/10.1186/s13059-020-01969-6,Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS.,"Liu Y, Cheng J, Siejka-Zielińska P, Weldon C, Roberts H, Lopopolo M, Magri A, D'Arienzo V, Harris JM, McKeating JA, Song CX.",,Genome biology,2020,2020-03-03,Y,DNA methylation; 5-methylcytosine; Long-read Sequencing; Bisulfite-free; Epigenetic Phasing,Understanding the Causes of Disease,infection,"We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range epigenetic phasing. We applied lrTAPS to sequence difficult-to-map regions in mouse embryonic stem cells and to identify distinct methylation events in the integrated hepatitis B virus genome.",,pdf:https://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-020-01969-6; doi:https://doi.org/10.1186/s13059-020-01969-6; html:https://europepmc.org/articles/PMC7053107; pdf:https://europepmc.org/articles/PMC7053107?pdf=render
 32423943,https://doi.org/10.1136/bmjopen-2020-038974,Study protocol for a multicentre longitudinal mixed methods study to explore the Outcomes of ChildrEn and fAmilies in the first year after paediatric Intensive Care: the OCEANIC study.,"Manning JC, Latour JM, Curley MAQ, Draper ES, Jilani T, Quinlan PR, Watson RS, Rennick JE, Colville G, Pinto N, Latif A, Popejoy E, Coad J, OCEANIC Study Investigators.",,BMJ open,2020,2020-05-17,Y,Qualitative Research; Statistics & Research Methods; Paediatric Intensive & Critical Care,,,"<h4>Introduction</h4>Annually in the UK, 20 000 children become very ill or injured and need specialist care within a paediatric intensive care unit (PICU). Most children survive. However, some children and their families may experience problems after they have left the PICU including physical, functional and/or emotional problems. It is unknown which children and families experience such problems, when these occur or what causes them. The aim of this mixed-method longitudinal cohort study is to understand the physical, functional, emotional and social impact of children surviving PICU (aged: 1 month-17 years), their parents and siblings, during the first year after a PICU admission.<h4>Methods and analysis</h4>A quantitative study involving 300 child survivors of PICU; 300 parents; and 150-300 siblings will collect data (using self-completion questionnaires) at baseline, PICU discharge, 1, 3, 6 and 12 months post-PICU discharge. Questionnaires will comprise validated and reliable instruments. Demographic data, PICU admission and treatment data, health-related quality of life, functional status, strengths and difficulties behaviour and post-traumatic stress symptoms will be collected from the child. Parent and sibling data will be collected on the impact of paediatric health conditions on the family's functioning capabilities, levels of anxiety and social impact of the child's PICU admission. Data will be analysed using descriptive and inferential statistics. Concurrently, an embedded qualitative study involving semistructured interviews with 24 enrolled families at 3 months and 9 months post-PICU discharge will be undertaken. Framework analysis will be used to analyse the qualitative data.<h4>Ethics and dissemination</h4>The study has received ethical approval from the National Health Services Research Ethics Committee (Ref: 19/WM/0290) and full governance clearance. This will be the first UK study to comprehensively investigate physical, functional, emotional and social consequences of PICU survival in the first-year postdischarge.Clinical Trials Registration Number: ISRCTN28072812 [Pre-results].",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/5/e038974.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038974; html:https://europepmc.org/articles/PMC7239532; pdf:https://europepmc.org/articles/PMC7239532?pdf=render
 35537820,https://doi.org/10.1136/thoraxjnl-2021-217993,Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease.,"Guyatt A, John C, Williams AT, Shrine N, Reeve NF, SpiroMeta consortium, Sayers I, Hall I, Wain LV, Sheehan N, Dudbridge F, Tobin MD.",,Thorax,2023,2022-05-10,Y,respiratory infection; Copd Epidemiology; Eosinophil Biology; Asthma Mechanisms; Asthma Epidemiology; Asthma Genetics; Copd Exacerbations Mechanisms,,,"<h4>Rationale</h4>Eosinophils are associated with airway inflammation in respiratory disease. Eosinophil production and survival is controlled partly by interleukin-5: anti-interleukin-5 agents reduce asthma and response correlates with baseline eosinophil counts. However, whether raised eosinophils are causally related to chronic obstructive pulmonary disease (COPD) and other respiratory phenotypes is not well understood.<h4>Objectives</h4>We investigated causality between eosinophils and: lung function, acute exacerbations of COPD, asthma-COPD overlap (ACO), moderate-to-severe asthma and respiratory infections.<h4>Methods</h4>We performed Mendelian randomisation (MR) using 151 variants from genome-wide association studies of blood eosinophils in UK Biobank/INTERVAL, and respiratory traits in UK Biobank/SpiroMeta, using methods relying on different assumptions for validity. We performed multivariable analyses using eight cell types where there was possible evidence of causation by eosinophils.<h4>Measurements and main results</h4>Causal estimates derived from individual variants were highly heterogeneous, which may arise from pleiotropy. The average effect of raising eosinophils was to increase risk of ACO (weighted median OR per SD eosinophils, 1.44 (95%CI 1.19 to 1.74)), and moderate-severe asthma (weighted median OR 1.50 (95%CI 1.23 to 1.83)), and to reduce forced expiratory volume in 1 s (FEV<sub>1</sub>)/forced vital capacity (FVC) and FEV<sub>1</sub> (weighted median estimator, SD FEV<sub>1</sub>/FVC: -0.054 (95% CI -0.078 to -0.029), effect only prominent in individuals with asthma).<h4>Conclusions</h4>Broad consistency across MR methods may suggest causation by eosinophils (although of uncertain magnitude), yet heterogeneity necessitates caution: other important mechanisms may be responsible for the impairment of respiratory health by these eosinophil-raising variants. These results could suggest that anti-IL5 agents (designed to lower eosinophils) may be valuable in treating other respiratory conditions, including people with overlapping features of asthma and COPD.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/05/10/thoraxjnl-2021-217993.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217993; html:https://europepmc.org/articles/PMC10176352; pdf:https://europepmc.org/articles/PMC10176352?pdf=render
@@ -2081,8 +2081,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 37343968,https://doi.org/10.1136/bmj-2022-072976,Risk prediction of covid-19 related death or hospital admission in adults testing positive for SARS-CoV-2 infection during the omicron wave in England (QCOVID4): cohort study.,"Hippisley-Cox J, Khunti K, Sheikh A, Nguyen-Van-Tam JS, Coupland CAC.",,BMJ (Clinical research ed.),2023,2023-06-21,Y,,,,"<h4>Objectives</h4>To derive and validate risk prediction algorithms (QCOVID4) to estimate the risk of covid-19 related death and hospital admission in people with a positive SARS-CoV-2 test result during the period when the omicron variant of the virus was predominant in England, and to evaluate performance compared with a high risk cohort from NHS Digital.<h4>Design</h4>Cohort study.<h4>Setting</h4>QResearch database linked to English national data on covid-19 vaccinations, SARS-CoV-2 test results, hospital admissions, and cancer and mortality data, 11 December 2021 to 31 March 2022, with follow-up to 30 June 2022.<h4>Participants</h4>1.3 million adults in the derivation cohort and 0.15 million adults in the validation cohort, aged 18-100 years, with a positive test result for SARS-CoV-2 infection.<h4>Main outcome measures</h4>Primary outcome was covid-19 related death and secondary outcome was hospital admission for covid-19. Risk equations with predictor variables were derived from models fitted in the derivation cohort. Performance was evaluated in a separate validation cohort.<h4>Results</h4>Of 1 297 922 people with a positive test result for SARS-CoV-2 infection in the derivation cohort, 18 756 (1.5%) had a covid-19 related hospital admission and 3878 (0.3%) had a covid-19 related death during follow-up. The final QCOVID4 models included age, deprivation score and a range of health and sociodemographic factors, number of covid-19 vaccinations, and previous SARS-CoV-2 infection. The risk of death related to covid-19 was lower among those who had received a covid-19 vaccine, with evidence of a dose-response relation (42% risk reduction associated with one vaccine dose and 92% reduction with four or more doses in men). Previous SARS-CoV-2 infection was associated with a reduction in the risk of covid-19 related death (49% reduction in men). The QCOVID4 algorithm for covid-19 explained 76.0% (95% confidence interval 73.9% to 78.2%) of the variation in time to covid-19 related death in men with a D statistic of 3.65 (3.43 to 3.86) and Harrell's C statistic of 0.970 (0.962 to 0.979). Results were similar for women. QCOVID4 was well calibrated. QCOVID4 was substantially more efficient than the NHS Digital algorithm for correctly identifying patients at high risk of covid-19 related death. Of the 461 covid-19 related deaths in the validation cohort, 333 (72.2%) were in the QCOVID4 high risk group and 95 (20.6%) in the NHS Digital high risk group.<h4>Conclusion</h4>The QCOVID4 risk algorithm, modelled from data during the period when the omicron variant of the SARS-CoV-2 virus was predominant in England, now includes vaccination dose and previous SARS-CoV-2 infection, and predicted covid-19 related death among people with a positive test result. QCOVID4 more accurately identified individuals at the highest levels of absolute risk for targeted interventions than the approach adopted by NHS Digital. QCOVID4 performed well and could be used for targeting treatments for covid-19 disease.",,pdf:https://www.bmj.com/content/bmj/381/bmj-2022-072976.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072976; html:https://europepmc.org/articles/PMC10282241; pdf:https://europepmc.org/articles/PMC10282241?pdf=render
 31331193,https://doi.org/10.1161/circulationaha.119.041546,Impact of <i>ADCY9</i> Genotype on Response to Anacetrapib.,"Hopewell JC, Ibrahim M, Hill M, Shaw PM, Braunwald E, Blaustein RO, Bowman L, Landray MJ, Sabatine MS, Collins R, HPS3/TIMI55–REVEAL Collaborative Group.",,Circulation,2019,2019-07-23,Y,Randomized controlled trial; Pharmacogenetics; Anacetrapib; Cholesterol Ester Transfer Protein; Adenylate Cyclase 9,"Better, Faster and More Efficient Clinical Trials",,"<h4>Background</h4>Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to cholesteryl ester transfer protein (CETP) inhibitor therapy differs by <i>ADCY9</i> genotype, prompting the ongoing dal-GenE trial in individuals with a particular genetic profile. The randomized placebo-controlled REVEAL trial (Randomized Evaluation of the Effects of Anacetrapib through Lipid-Modification) demonstrated the clinical efficacy of the CETP inhibitor anacetrapib among patients with preexisting atherosclerotic vascular disease. In the present study, we examined the impact of <i>ADCY9</i> genotype on response to anacetrapib in the REVEAL trial.<h4>Methods</h4>Individuals with stable atherosclerotic vascular disease who were treated with intensive atorvastatin therapy received either anacetrapib 100 mg daily or matching placebo. Cox proportional hazards models, adjusted for the first 5 principal components of ancestry, were used to estimate the effects of allocation to anacetrapib on major vascular events (a composite of coronary death, myocardial infarction, coronary revascularization, or presumed ischemic stroke) and the interaction with <i>ADCY9</i> rs1967309 genotype.<h4>Results</h4>Among 19 210 genotyped individuals of European ancestry, 2504 (13.0%) had a first major vascular event during 4 years median follow-up: 1216 (12.6%) among anacetrapib-allocated participants and 1288 (13.4%) among placebo-allocated participants. Proportional reductions in the risk of major vascular events with anacetrapib did not differ significantly by <i>ADCY9</i> genotype: hazard ratio (HR) = 0.92 (95% CI, 0.81-1.05) for GG; HR = 0.94 (95% CI, 0.84-1.06) for AG; and HR = 0.93 (95% CI, 0.76-1.13) for AA genotype carriers, respectively; genotypic <i>P</i> for interaction = 0.96. Furthermore, there were no associations between <i>ADCY9</i> genotype and the proportional reductions in the separate components of major vascular events or meaningful differences in lipid response to anacetrapib.<h4>Conclusions</h4>The REVEAL trial is the single largest study to date evaluating the <i>ADCY9</i> pharmacogenetic interaction. It provides no support for the hypothesis that <i>ADCY9</i> genotype is materially relevant to the clinical effects of the CETP inhibitor anacetrapib. The ongoing dal-GenE study will provide direct evidence as to whether there is any specific pharmacogenetic interaction with dalcetrapib.<h4>Clinical trial registration</h4>URL: https://www.<h4>Clinicaltrials</h4>gov. Unique identifier: NCT01252953. URL: http://www.isrctn.com. Unique identifier: ISRCTN48678192. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,doi:https://doi.org/10.1161/circulationaha.119.041546; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041546; html:https://europepmc.org/articles/PMC6749971; pdf:https://europepmc.org/articles/PMC6749971?pdf=render
 32880390,https://doi.org/10.1210/clinem/dgaa627,"Systemic Corticosteroids and Mortality in Severe and Critical COVID-19 Patients in Wuhan, China. ","Wu J, Huang J, Zhu G, Liu Y, Xiao H, Zhou Q, Si X, Yi H, Wang C, Yang D, Chen S, Liu X, Liu Z, Wang Q, Lv Q, Huang Y, Yu Y, Guan X, Li Y, Nirantharakumar K, Cheng K, Peng S, Xiao H.",,The Journal of clinical endocrinology and metabolism,2020,2020-12-01,Y,,,,"Systemic corticosteroids are now recommended in many treatment guidelines, although supporting evidence is limited to 1 randomized controlled clinical trial (RECOVERY). To identify whether corticosteroids were beneficial to COVID-19 patients. A total of 1514 severe and 249 critical hospitalized COVID-19 patients from 2 medical centers in Wuhan, China. Multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting [IPTW] and propensity score matching [PSM]) were used to estimate the association of corticosteroid use with risk of in-hospital mortality in severe and critical cases. Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to the non-corticosteroid group, systemic corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality in either severe cases (HR = 1.77; 95% CI, 1.08-2.89; P = 0.023), or critical cases (HR = 2.07; 95% CI, 1.08-3.98; P = 0.028). Findings were similar in time-varying Cox analysis. For patients with severe COVID-19 at admission, corticosteroid use was not associated with improved or harmful outcome in either PSM or IPTW analysis. For critical COVID-19 patients at admission, results were consistent with multivariable Cox model analysis. Corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality for severe or critical cases in Wuhan. Absence of the beneficial effect in our study in contrast to that observed in the RECOVERY clinical trial may be due to biases in observational data, in particular prescription by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, timing of initiation of treatment, and duration of treatment.",,pdf:https://academic.oup.com/jcem/article-pdf/105/12/e4230/41829325/dgaa627.pdf; doi:https://doi.org/10.1210/clinem/dgaa627; html:https://europepmc.org/articles/PMC7499588; pdf:https://europepmc.org/articles/PMC7499588?pdf=render
-37757828,https://doi.org/10.1016/j.cell.2023.08.028,Influence of autozygosity on common disease risk across the phenotypic spectrum.,"Malawsky DS, van Walree E, Jacobs BM, Heng TH, Huang QQ, Sabir AH, Rahman S, Sharif SM, Khan A, Mirkov MU, 23andMe Research Team, Genes & Health Research Team, Kuwahara H, Gao X, Alkuraya FS, Posthuma D, Newman WG, Griffiths CJ, Mathur R, van Heel DA, Finer S, O'Connell J, Martin HC.",,Cell,2023,2023-09-26,Y,Consanguinity; Medical genetics; Recessive; Autozygosity; Common Diseases; Diverse Cohorts,,,"Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F<sub>ROH</sub>) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F<sub>ROH</sub>. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F<sub>ROH</sub> and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.",,doi:https://doi.org/10.1016/j.cell.2023.08.028; html:https://europepmc.org/articles/PMC10580289; pdf:https://europepmc.org/articles/PMC10580289?pdf=render
 33174830,https://doi.org/10.1099/mgen.0.000453,Optimized use of Oxford Nanopore flowcells for hybrid assemblies.,"Lipworth S, Pickford H, Sanderson N, Chau KK, Kavanagh J, Barker L, Vaughan A, Swann J, Andersson M, Jeffery K, Morgan M, Peto TEA, Crook DW, Stoesser N, Walker AS.",,Microbial genomics,2020,2020-11-01,Y,Enterobacteriaceae; Hybrid Assembly; Nanopore Sequencing; Bacterial Genomics; Long-read Assembly,,,"Hybrid assemblies are highly valuable for studies of <i>Enterobacteriaceae</i> due to their ability to fully resolve the structure of mobile genetic elements, such as plasmids, which are involved in the carriage of clinically important genes (e.g. those involved in antimicrobial resistance/virulence). The widespread application of this technique is currently primarily limited by cost. Recent data have suggested that non-inferior, and even superior, hybrid assemblies can be produced using a fraction of the total output from a multiplexed nanopore [Oxford Nanopore Technologies (ONT)] flowcell run. In this study we sought to determine the optimal minimal running time for flowcells when acquiring reads for hybrid assembly. We then evaluated whether the ONT wash kit might allow users to exploit shorter running times by sequencing multiple libraries per flowcell. After 24 h of sequencing, most chromosomes and plasmids had circularized and there was no benefit associated with longer running times. Quality was similar at 12 h, suggesting that shorter running times are likely to be acceptable for certain applications (e.g. plasmid genomics). The ONT wash kit was highly effective in removing DNA between libraries. Contamination between libraries did not appear to affect subsequent hybrid assemblies, even when the same barcodes were used successively on a single flowcell. Utilizing shorter run times in combination with between-library nuclease washes allows at least 36 <i>Enterobacteriaceae</i> isolates to be sequenced per flowcell, significantly reducing the per-isolate sequencing cost. Ultimately this will facilitate large-scale studies utilizing hybrid assembly, advancing our understanding of the genomics of key human pathogens.",,doi:https://doi.org/10.1099/mgen.0.000453; doi:https://doi.org/10.1099/mgen.0.000453; html:https://europepmc.org/articles/PMC7725331; pdf:https://europepmc.org/articles/PMC7725331?pdf=render
+37757828,https://doi.org/10.1016/j.cell.2023.08.028,Influence of autozygosity on common disease risk across the phenotypic spectrum.,"Malawsky DS, van Walree E, Jacobs BM, Heng TH, Huang QQ, Sabir AH, Rahman S, Sharif SM, Khan A, Mirkov MU, 23andMe Research Team, Genes & Health Research Team, Kuwahara H, Gao X, Alkuraya FS, Posthuma D, Newman WG, Griffiths CJ, Mathur R, van Heel DA, Finer S, O'Connell J, Martin HC.",,Cell,2023,2023-09-26,Y,Consanguinity; Medical genetics; Recessive; Autozygosity; Common Diseases; Diverse Cohorts,,,"Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F<sub>ROH</sub>) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F<sub>ROH</sub>. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F<sub>ROH</sub> and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.",,doi:https://doi.org/10.1016/j.cell.2023.08.028; html:https://europepmc.org/articles/PMC10580289; pdf:https://europepmc.org/articles/PMC10580289?pdf=render
 37316763,https://doi.org/10.1007/s10875-023-01530-7,Autosomal Dominant STAT6 Gain of Function Causes Severe Atopy Associated with Lymphoma.,"Minskaia E, Maimaris J, Jenkins P, Albuquerque AS, Hong Y, Eleftheriou D, Gilmour KC, Grace R, Moreira F, Grimbacher B, NIHR Bioresource-Rare Diseases Consortium, Morris EC, Burns SO.",,Journal of clinical immunology,2023,2023-06-14,Y,Lymphoma; STAT6; Atopy; Gain-of-function,,,"The transcription factor STAT6 (Signal Transducer and Activator of Transcription 6) is a key regulator of Th2 (T-helper 2) mediated allergic inflammation via the IL-4 (interleukin-4) JAK (Janus kinase)/STAT signalling pathway. We identified a novel heterozygous germline mutation STAT6 c.1255G > C, p.D419H leading to overactivity of IL-4 JAK/STAT signalling pathway, in a kindred affected by early-onset atopic dermatitis, food allergy, eosinophilic asthma, anaphylaxis and follicular lymphoma. STAT6 D419H expression and functional activity were compared with wild type STAT6 in transduced HEK293T cells and to healthy control primary skin fibroblasts and peripheral blood mononuclear cells (PBMC). We observed consistently higher STAT6 levels at baseline and higher STAT6 and phosphorylated STAT6 following IL-4 stimulation in D419H cell lines and primary cells compared to wild type controls. The pSTAT6/STAT6 ratios were unchanged between D419H and control cells suggesting that elevated pSTAT6 levels resulted from higher total basal STAT6 expression. The selective JAK1/JAK2 inhibitor ruxolitinib reduced pSTAT6 levels in D419H HEK293T cells and patient PBMC. Nuclear staining demonstrated increased STAT6 in patient fibroblasts at baseline and both STAT6 and pSTAT6 after IL-4 stimulation. We also observed higher transcriptional upregulation of downstream genes (XBP1 and EPAS1) in patient PBMC. Our study confirms STAT6 gain of function (GOF) as a novel monogenetic cause of early onset atopic disease. The clinical association of lymphoma in our kindred, along with previous data linking somatic STAT6 D419H mutations to follicular lymphoma suggest that patients with STAT6 GOF disease may be at higher risk of lymphomagenesis.245 words.",,pdf:https://link.springer.com/content/pdf/10.1007/s10875-023-01530-7.pdf; doi:https://doi.org/10.1007/s10875-023-01530-7; html:https://europepmc.org/articles/PMC10499697; pdf:https://europepmc.org/articles/PMC10499697?pdf=render
 34151270,https://doi.org/10.1136/bmjno-2021-000133,"Variation in waiting times by diagnostic category: an observational study of 1,951 referrals to a neurology outpatient clinic.","Biggin F, Howcroft T, Davies Q, Knight J, Emsley HCA.",,BMJ neurology open,2021,2021-06-03,Y,Neurology; Outpatient; Observational Study; Waiting Times; Routinely Collected Data,,,"<h4>Objective</h4>To investigate the frequency of diagnoses seen among new referrals to neurology outpatient services; to understand how these services are used through exploratory analysis of diagnostic tests and follow-up appointments; and to examine the waiting times between referral and appointment.<h4>Methods</h4>Routine data from new National Health Service appointments at a single consultant-delivered clinic between September 2016 and January 2019 were collected. These clinical data were then linked to hospital administrative data. The combined data were assigned diagnostic categories based on working diagnoses to allow further analysis using descriptive statistics.<h4>Results</h4>Five diagnostic categories accounted for 62% of all patients seen within the study period, the most common of which was headache disorders. Following a first appointment, 50% of all patients were offered at least one diagnostic test, and 35% were offered a follow-up appointment, with variation in both measures by diagnostic category. Waiting times from referral to appointment also varied by diagnostic category. 65% of patients with a seizure/epilepsy disorder were seen within the 18-week referral to treatment target, compared with 38% of patients with a movement disorder.<h4>Conclusions</h4>A small number of diagnostic categories account for a large proportion of new patients. This information could be used in policy decision-making to describe a minimum subset of categories for diagnostic coding. We found significant differences in waiting times by diagnostic category, as well as tests ordered, and follow-up offered; further investigation could address causes of variation.",,pdf:https://neurologyopen.bmj.com/content/bmjno/3/1/e000133.full.pdf; doi:https://doi.org/10.1136/bmjno-2021-000133; html:https://europepmc.org/articles/PMC8183200; pdf:https://europepmc.org/articles/PMC8183200?pdf=render
 35143473,https://doi.org/10.1371/journal.pbio.3001531,SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.,"Finch E, Lowe R, Fischinger S, de St Aubin M, Siddiqui SM, Dayal D, Loesche MA, Rhee J, Beger S, Hu Y, Gluck MJ, Mormann B, Hasdianda MA, Musk ER, Alter G, Menon AS, Nilles EJ, Kucharski AJ, CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative.",,PLoS biology,2022,2022-02-10,Y,,,,"Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.",,pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001531&type=printable; doi:https://doi.org/10.1371/journal.pbio.3001531; html:https://europepmc.org/articles/PMC8865659; pdf:https://europepmc.org/articles/PMC8865659?pdf=render
@@ -2119,8 +2119,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 32709645,https://doi.org/10.1136/bmjopen-2019-035968,Infant formula composition and educational performance: a protocol to extend follow-up for a set of randomised controlled trials using linked administrative education records.,"Verfürden M, Harron K, Jerrim J, Fewtrell M, Gilbert R.",,BMJ open,2020,2020-07-23,Y,Public Health; Clinical Trials; Paediatric Neurology; Nutrition & Dietetics,,,"<h4>Introduction</h4>The effect of infant nutrition on long-term cognition is important for parents and policy makers. However, most clinical trials typically have short follow-up periods, when measures of cognition are poorly predictive of later function. The few trials with longer-term follow-up have high levels of attrition, which can lead to selection bias, and in turn to erroneous interpretation of long-term harms and benefits of infant nutrition. We address the need for unbiased, long-term follow-up, by linking measures of educational performance from administrative education records. Educational performance is a meaningful marker of cognitive function in children and it is strongly correlated with IQ. We aim to evaluate educational performance for children who, as infants, were part of a series of trials that randomised participants to either nutritionally modified infant formula or standard formula. Most trialists anticipated positive effects of these interventions on later cognitive function.<h4>Methods and analysis</h4>Using data from 1923 participants of seven randomised infant formula trials linked to the English National Pupil Database (NPD), this study will provide new insights into the effect of nutrient intake in infancy on school achievement. Our primary outcome will be the mean differences in z-scores between intervention and control groups for a compulsory Mathematics exam sat at age 16. Secondary outcomes will be z-scores for a compulsory English exam at age 16 and z-scores for compulsory Mathematics and English exams at age 11. We will also evaluate intervention effects on the likelihood of receiving special educational needs (SEN) support. All analyses will be performed separately by trial.<h4>Ethics and dissemination</h4>Research ethics approval, and approval from the Health Research Authority Confidentiality Advisory Group, has been obtained for this study. The results of this study will be disseminated to scientific, practitioner, and lay audiences, submitted for publication in peer-reviewed journals, and will contribute towards a PhD dissertation.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/7/e035968.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-035968; html:https://europepmc.org/articles/PMC7380883; pdf:https://europepmc.org/articles/PMC7380883?pdf=render
 33208942,https://doi.org/10.1038/s41586-020-2927-z,Host ANP32A mediates the assembly of the influenza virus replicase.,"Carrique L, Fan H, Walker AP, Keown JR, Sharps J, Staller E, Barclay WS, Fodor E, Grimes JM.",,Nature,2020,2020-11-18,Y,,,,"Aquatic birds represent a vast reservoir from which new pandemic influenza A viruses can emerge<sup>1</sup>. Influenza viruses contain a negative-sense segmented RNA genome that is transcribed and replicated by the viral heterotrimeric RNA polymerase (FluPol) in the context of viral ribonucleoprotein complexes<sup>2,3</sup>. RNA polymerases of avian influenza A viruses (FluPolA) replicate viral RNA inefficiently in human cells because of species-specific differences in acidic nuclear phosphoprotein 32 (ANP32), a family of essential host proteins for FluPol activity<sup>4</sup>. Host-adaptive mutations, particularly a glutamic-acid-to-lysine mutation at amino acid residue 627 (E627K) in the 627 domain of the PB2 subunit, enable avian FluPolA to overcome this restriction and efficiently replicate viral RNA in the presence of human ANP32 proteins. However, the molecular mechanisms of genome replication and the interplay with ANP32 proteins remain largely unknown. Here we report cryo-electron microscopy structures of influenza C virus polymerase (FluPolC) in complex with human and chicken ANP32A. In both structures, two FluPolC molecules form an asymmetric dimer bridged by the N-terminal leucine-rich repeat domain of ANP32A. The C-terminal low-complexity acidic region of ANP32A inserts between the two juxtaposed PB2 627 domains of the asymmetric FluPolA dimer, suggesting a mechanism for how the adaptive PB2(E627K) mutation enables the replication of viral RNA in mammalian hosts. We propose that this complex represents a replication platform for the viral RNA genome, in which one of the FluPol molecules acts as a replicase while the other initiates the assembly of the nascent replication product into a viral ribonucleoprotein complex.",,pdf:https://www.nature.com/articles/s41586-020-2927-z.pdf; doi:https://doi.org/10.1038/s41586-020-2927-z; html:https://europepmc.org/articles/PMC7116770; pdf:https://europepmc.org/articles/PMC7116770?pdf=render
 35151371,https://doi.org/10.1016/j.immuni.2022.01.017,Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease.,"Vijayakumar B, Boustani K, Ogger PP, Papadaki A, Tonkin J, Orton CM, Ghai P, Suveizdyte K, Hewitt RJ, Desai SR, Devaraj A, Snelgrove RJ, Molyneaux PL, Garner JL, Peters JE, Shah PL, Lloyd CM, Harker JA.",,Immunity,2022,2022-01-26,Y,T cells; Proteomics; Respiratory Tract; Airways; Respiratory Viral Infection; Tissue-resident Memory; Covid-19; Sars-cov-2; Long Covid,,,"Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells.",,pdf:http://www.cell.com/article/S1074761322000462/pdf; doi:https://doi.org/10.1016/j.immuni.2022.01.017; html:https://europepmc.org/articles/PMC8789571; pdf:https://europepmc.org/articles/PMC8789571?pdf=render
-35608616,https://doi.org/10.1007/s00125-022-05714-5,Risk of incident obstructive sleep apnoea in patients with type 1 diabetes: a population-based retrospective cohort study.,"Alshehri Z, Subramanian A, Adderley NJ, Gokhale KM, Karamat MA, Ray CJ, Kumar P, Nirantharakumar K, Tahrani AA.",,Diabetologia,2022,2022-05-24,Y,Obesity; Depression; type 1 diabetes; Sleep Apnoea,,,"<h4>Aims/hypothesis</h4>People with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes.<h4>Methods</h4>We used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis.<h4>Results</h4>In total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43 years ((IQR 2.19-10.11), and the mean BMI was 25.82 kg/m<sup>2</sup> (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p<0.001). Predictors of incident obstructive sleep apnoea in patients with type 1 diabetes were older age, male sex, obesity, being prescribed antihypertensive or lipid-lowering drugs, atrial fibrillation and depression.<h4>Conclusions/interpretation</h4>Individuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs.",,pdf:https://link.springer.com/content/pdf/10.1007/s00125-022-05714-5.pdf; doi:https://doi.org/10.1007/s00125-022-05714-5; html:https://europepmc.org/articles/PMC9283161; pdf:https://europepmc.org/articles/PMC9283161?pdf=render
 32095773,https://doi.org/10.1159/000503957,Advancing the Use of Mobile Technologies in Clinical Trials: Recommendations from the Clinical Trials Transformation Initiative.,"Coran P, Goldsack JC, Grandinetti CA, Bakker JP, Bolognese M, Dorsey ER, Vasisht K, Amdur A, Dell C, Helfgott J, Kirchoff M, Miller CJ, Narayan A, Patel D, Peterson B, Ramirez E, Schiller D, Switzer T, Wing L, Forrest A, Doherty A.",,Digital biomarkers,2019,2019-09-01,N,Clinical Trials; Regulatory Approval; Wearable Sensors; Mobile Technologies,"Better, Faster and More Efficient Clinical Trials",,"Mobile technologies offer the potential to reduce the costs of conducting clinical trials by collecting high-quality information on health outcomes in real-world settings that are relevant to patients and clinicians. However, widespread use of mobile technologies in clinical trials has been impeded by their perceived challenges. To advance solutions to these challenges, the Clinical Trials Transformation Initiative (CTTI) has issued best practices and realistic approaches that clinical trial sponsors can now use. These include CTTI recommendations on technology selection; data collection, analysis, and interpretation; data management; protocol design and execution; and US Food and Drug Administration submission and inspection. The scientific principles underpinning the clinical trials enterprise continue to apply to studies using mobile technologies. These recommendations provide a framework for including mobile technologies in clinical trials that can lead to more efficient assessment of new therapies for patients.","The authors of this publication have developed a set of guidelines for planning, running and writing up research that uses mobile technologies in clinical trials. The guidelines they have put together should make it easer for patient experience to be recorded in clinical trials.",pdf:https://www.karger.com/Article/Pdf/503957; doi:https://doi.org/10.1159/000503957; html:https://europepmc.org/articles/PMC7011727; pdf:https://europepmc.org/articles/PMC7011727?pdf=render; doi:https://doi.org/10.1159/000503957
+35608616,https://doi.org/10.1007/s00125-022-05714-5,Risk of incident obstructive sleep apnoea in patients with type 1 diabetes: a population-based retrospective cohort study.,"Alshehri Z, Subramanian A, Adderley NJ, Gokhale KM, Karamat MA, Ray CJ, Kumar P, Nirantharakumar K, Tahrani AA.",,Diabetologia,2022,2022-05-24,Y,Obesity; Depression; type 1 diabetes; Sleep Apnoea,,,"<h4>Aims/hypothesis</h4>People with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes.<h4>Methods</h4>We used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis.<h4>Results</h4>In total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43 years ((IQR 2.19-10.11), and the mean BMI was 25.82 kg/m<sup>2</sup> (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p<0.001). Predictors of incident obstructive sleep apnoea in patients with type 1 diabetes were older age, male sex, obesity, being prescribed antihypertensive or lipid-lowering drugs, atrial fibrillation and depression.<h4>Conclusions/interpretation</h4>Individuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs.",,pdf:https://link.springer.com/content/pdf/10.1007/s00125-022-05714-5.pdf; doi:https://doi.org/10.1007/s00125-022-05714-5; html:https://europepmc.org/articles/PMC9283161; pdf:https://europepmc.org/articles/PMC9283161?pdf=render
 37645200,https://doi.org/10.12688/openreseurope.13860.2,An agenda-setting paper on data sharing platforms: euCanSHare workshop.,"Devriendt T, Ammann C, W Asselbergs F, Bernier A, Costas R, Friedrich MG, Gelpi JL, Jarvelin MR, Kuulasmaa K, Lekadir K, Mayrhofer MT, Papez V, Pasterkamp G, Petersen SE, Schmidt CO, Schulz-Menger J, Söderberg S, Shabani M, Veronesi G, Viezzer DS, Borry P.",,Open research Europe,2021,2021-11-23,Y,data sharing; Incentives; Science Policy; Open Science; Data Infrastructure,,,"Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.",,doi:https://doi.org/10.12688/openreseurope.13860.2; html:https://europepmc.org/articles/PMC10445835; pdf:https://europepmc.org/articles/PMC10445835?pdf=render
 32597303,https://doi.org/10.1080/15476286.2020.1777768,Targeted RNA sequencing enhances gene expression profiling of ultra-low input samples.,"Curion F, Handel AE, Attar M, Gallone G, Bowden R, Cader MZ, Clark MB.",,RNA biology,2020,2020-06-28,Y,Method; Gene Expression; Rna-seq; Targeted Rna Sequencing; Low-input Sequencing; Stem-cell-derived Neurons; Captureseq,,,"RNA-seq is the standard method for profiling gene expression in many biological systems. Due to the wide dynamic range and complex nature of the transcriptome, RNA-seq provides an incomplete characterization, especially of lowly expressed genes and transcripts. Targeted RNA sequencing (RNA CaptureSeq) focuses sequencing on genes of interest, providing exquisite sensitivity for transcript detection and quantification. However, uses of CaptureSeq have focused on bulk samples and its performance on very small populations of cells is unknown. Here we show CaptureSeq greatly enhances transcriptomic profiling of target genes in ultra-low-input samples and provides equivalent performance to that on bulk samples. We validate the performance of CaptureSeq using multiple probe sets on samples of iPSC-derived cortical neurons. We demonstrate up to 275-fold enrichment for target genes, the detection of 10% additional genes and a greater than 5-fold increase in identified gene isoforms. Analysis of spike-in controls demonstrated CaptureSeq improved both detection sensitivity and expression quantification. Comparison to the CORTECON database of cerebral cortex development revealed CaptureSeq enhanced the identification of sample differentiation stage. CaptureSeq provides sensitive, reliable and quantitative expression measurements on hundreds-to-thousands of target genes from ultra-low-input samples and has the potential to greatly enhance transcriptomic profiling when samples are limiting.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/15476286.2020.1777768?needAccess=true; doi:https://doi.org/10.1080/15476286.2020.1777768; html:https://europepmc.org/articles/PMC7746246; pdf:https://europepmc.org/articles/PMC7746246?pdf=render
 31350032,https://doi.org/10.1016/j.burns.2019.07.003,"Epidemiology of burn-related fatalities in Australia and New Zealand, 2009-2015.","McInnes JA, Cleland HJ, Cameron PA, Darton A, Tracy LM, Wood FM, Singer Y, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2019,2019-07-24,N,Burns; Mortality; Australia; New Zealand; epidemiology; Fatality,,,"<h4>Background</h4>Knowledge of the epidemiology of burn-related fatalities is limited, with most previous studies based on hospital and burn centre data only.<h4>Aims</h4>To describe the epidemiological characteristics of all burn-related fatalities in Australia and New Zealand, and to identify any trends in burn-related fatality incidence over the study period.<h4>Methods</h4>Data from the National Coronial Information System, including data for pre-hospital and in-hospital burn-related fatality cases, was used to examine the characteristics of burn-related fatalities occurring in Australia and New Zealand from 2009 to 2015. Burn-related fatality rates per 100,000 population were estimated, and incidence trends assessed using Poisson regression analysis.<h4>Results</h4>Of the 310 burn-related fatalities that occurred in Australia and New Zealand, 2009-2015, 41% occurred in a pre-hospital setting. Overall, most burn-related fatality cases were fire related, occurred at home, and were of people aged 41-80 years. One quarter of all burn-related fatalities were a result of intentional self-harm. The population incidence of all burn-related fatalities combined, and for NSW, decreased over the study period.<h4>Conclusions</h4>This study has identified the importance of examining all burn-related fatalities. If this is not done, vulnerable population subgroups will be missed and prevention efforts poorly targeted.",,doi:https://doi.org/10.1016/j.burns.2019.07.003
@@ -2130,21 +2130,21 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 34812717,https://doi.org/10.1099/mgen.0.000700,Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study. ,"Young BC, Wu CH, Charlesworth J, Earle S, Price JR, Gordon NC, Cole K, Dunn L, Liu E, Oakley S, Godwin H, Fung R, Miller R, Knox K, Votintseva A, Quan TP, Tilley R, Scarborough M, Crook DW, Peto TE, Walker AS, Llewelyn MJ, Wilson DJ.",,Microbial genomics,2021,2021-11-01,Y,,,,"Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.",,doi:https://doi.org/10.1099/mgen.0.000700; doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render
 34561430,https://doi.org/10.1038/s41467-021-25703-3,Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease.,"Schmidt AF, Hunt NB, Gordillo-Marañón M, Charoen P, Drenos F, Kivimaki M, Lawlor DA, Giambartolomei C, Papacosta O, Chaturvedi N, Bis JC, O'Donnell CJ, Wannamethee G, Wong A, Price JF, Hughes AD, Gaunt TR, Franceschini N, Mook-Kanamori DO, Zwierzyna M, Sofat R, Hingorani AD, Finan C.",,Nature communications,2021,2021-09-24,Y,,,,"Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disease, multiple sclerosis, and stroke, while potentially increasing the risk of Alzheimer's disease and asthma. Due to distinct effects on lipoprotein metabolite profiles, joint inhibition of CETP and PCSK9 may provide added benefit. In conclusion, we provide genetic evidence that CETP is an effective target for CHD prevention but with a potential on-target adverse effect on age-related macular degeneration.",,pdf:https://www.nature.com/articles/s41467-021-25703-3.pdf; doi:https://doi.org/10.1038/s41467-021-25703-3; html:https://europepmc.org/articles/PMC8463530; pdf:https://europepmc.org/articles/PMC8463530?pdf=render
 37043172,https://doi.org/10.1007/s12325-023-02511-3,Commentary: Patient Perspectives on Artificial Intelligence; What have We Learned and How Should We Move Forward?,"Camaradou JCL, Hogg HDJ.",,Advances in therapy,2023,2023-04-12,Y,Development; Artificial intelligence; Technology; Product; Clinical; Innovation; Patient; Perspectives; Engagement; Involvement; Acceptability; Public; Multi-stakeholder; Start-ups; Small Medium-sized Enterprises,,,"Artificial intelligence (AI) in healthcare has now begun to make its contributions to real-world patient care with varying degrees of both public and clinical acceptability around it. The heavy investment from governments, industry and academia needed to reach this point has helped to surface different perspectives on AI. As clinical AI applications become a reality, however, there is an increasing need to harness and integrate patient perspectives, which address the distinct needs of different populations, healthcare systems and clinical problems more closely. Despite this need, patient perspectives on AI implementation have little presence in academic literature and within implementation science and are not sufficiently considered throughout the MedTech and eHealthtech product development cycle, which brings its own challenges and opportunities. This joint patient expert/clinician commentary aims to briefly summarise views on AI. It reflects upon recommendations on how stakeholders such as clinicians and Health & MedTech small and medium-sized enterprises (SMEs) can make practical usage of these views. The recommendations of the authors centre around how to work better with patients to enable both product centric and patient centric innovation and person-centred care.",,pdf:https://link.springer.com/content/pdf/10.1007/s12325-023-02511-3.pdf; doi:https://doi.org/10.1007/s12325-023-02511-3; html:https://europepmc.org/articles/PMC10092909; pdf:https://europepmc.org/articles/PMC10092909?pdf=render
-37794492,https://doi.org/10.1186/s13073-023-01233-z,Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.,"Neumann A, Ohlei O, Küçükali F, Bos IJ, Timsina J, Vos S, Prokopenko D, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Scheltens P, Teunissen CE, Engelborghs S, Frisoni GB, Blin O, Richardson JC, Bordet R, Lleó A, Alcolea D, Popp J, Marsh TW, Gorijala P, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Van Broeckhoven C, Tanzi RE, Ten Kate M, Lill CM, Barkhof F, Cruchaga C, Lovestone S, Streffer J, Zetterberg H, Visser PJ, Sleegers K, Bertram L, EMIF-AD & ADNI study group.",,Genome medicine,2023,2023-10-04,Y,Principal component analysis; Biomarkers; Alzheimer’s disease; Dementia; Cerebrospinal fluid (CSF); multivariate analysis; Structural Equation Modeling; Mediation; Genome-wide Association Study (Gwas),,,"<h4>Background</h4>Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.<h4>Methods</h4>We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.<h4>Results</h4>Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.<h4>Conclusions</h4>These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01233-z; doi:https://doi.org/10.1186/s13073-023-01233-z; html:https://europepmc.org/articles/PMC10548686; pdf:https://europepmc.org/articles/PMC10548686?pdf=render
 31408153,https://doi.org/10.1093/europace/euz220,"Subtypes of atrial fibrillation with concomitant valvular heart disease derived from electronic health records: phenotypes, population prevalence, trends and prognosis.","Banerjee A, Allan V, Denaxas S, Shah A, Kotecha D, Lambiase PD, Joseph J, Lund LH, Hemingway H.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2019,2019-12-01,Y,Mortality; Atrial fibrillation; Stroke; Valvular Heart Disease; Electronic Health Records; Systemic Embolism,The Human Phenome,,"<h4>Aims</h4>To evaluate population-based electronic health record (EHR) definitions of atrial fibrillation (AF) and valvular heart disease (VHD) subtypes, time trends in prevalence and prognosis.<h4>Methods and results</h4>A total of 76 019 individuals with AF were identified in England in 1998-2010 in the CALIBER resource, linking primary and secondary care EHR. An algorithm was created, implemented, and refined to identify 18 VHD subtypes using 406 diagnosis, procedure, and prescription codes. Cox models were used to investigate associations with a composite endpoint of incident stroke (ischaemic, haemorrhagic, and unspecified), systemic embolism (SSE), and all-cause mortality. Among individuals with AF, the prevalence of AF with concomitant VHD increased from 11.4% (527/4613) in 1998 to 17.6% (7014/39 868) in 2010 and also in individuals aged over 65 years. Those with mechanical valves, mitral stenosis (MS), or aortic stenosis had highest risk of clinical events compared to AF patients with no VHD, in relative [hazard ratio (95% confidence interval): 1.13 (1.02-1.24), 1.20 (1.05-1.36), and 1.27 (1.19-1.37), respectively] and absolute (excess risk: 2.04, 4.20, and 6.37 per 100 person-years, respectively) terms. Of the 95.2% of individuals with indication for warfarin (men and women with CHA2DS2-VASc ≥1 and ≥2, respectively), only 21.8% had a prescription 90 days prior to the study.<h4>Conclusion</h4>Prevalence of VHD among individuals with AF increased from 1998 to 2010. Atrial fibrillation associated with aortic stenosis, MS, or mechanical valves (compared to AF without VHD) was associated with an excess absolute risk of stroke, SSE, and mortality, but anticoagulation was underused in the pre-direct oral anticoagulant (DOAC) era, highlighting need for urgent clarity regarding DOACs in AF and concomitant VHD.","This study identified EHR records of AF and vavular heard disease in over 70k UK individuals and looked for associations with stroke, systemic embolism and mortality. They used CALIBER - a data source connecting office of national statistics, CPRD and HES data from over 10 years. They reported clear methodology on how the EHR was used to classify disease, showed overall prevalence change in different AF related diseases over time, and were able to provide insights at a more granular level - for example, valvular heart disease subtypes in AF than previous studies. The full code list (EHR codes) is provided in supplement, so methods are theoretically reproducible. Immediate impact to patient is less strong and there is wasn't much emphasis on diversity and inclusion.",pdf:https://academic.oup.com/europace/article-pdf/21/12/1776/31175830/euz220.pdf; doi:https://doi.org/10.1093/europace/euz220; html:https://europepmc.org/articles/PMC6888023; pdf:https://europepmc.org/articles/PMC6888023?pdf=render
+37794492,https://doi.org/10.1186/s13073-023-01233-z,Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.,"Neumann A, Ohlei O, Küçükali F, Bos IJ, Timsina J, Vos S, Prokopenko D, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Scheltens P, Teunissen CE, Engelborghs S, Frisoni GB, Blin O, Richardson JC, Bordet R, Lleó A, Alcolea D, Popp J, Marsh TW, Gorijala P, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Van Broeckhoven C, Tanzi RE, Ten Kate M, Lill CM, Barkhof F, Cruchaga C, Lovestone S, Streffer J, Zetterberg H, Visser PJ, Sleegers K, Bertram L, EMIF-AD & ADNI study group.",,Genome medicine,2023,2023-10-04,Y,Principal component analysis; Biomarkers; Alzheimer’s disease; Dementia; Cerebrospinal fluid (CSF); multivariate analysis; Structural Equation Modeling; Mediation; Genome-wide Association Study (Gwas),,,"<h4>Background</h4>Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.<h4>Methods</h4>We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.<h4>Results</h4>Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.<h4>Conclusions</h4>These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01233-z; doi:https://doi.org/10.1186/s13073-023-01233-z; html:https://europepmc.org/articles/PMC10548686; pdf:https://europepmc.org/articles/PMC10548686?pdf=render
 31978332,https://doi.org/10.1016/j.ajhg.2020.01.003,A Multi-tissue Transcriptome Analysis of Human Metabolites Guides Interpretability of Associations Based on Multi-SNP Models for Gene Expression.,"Ndungu A, Payne A, Torres JM, van de Bunt M, McCarthy MI.",,American journal of human genetics,2020,2020-01-23,Y,Metabolites; Gene regulation; colocalization; Gene Expression; Gwas; Eqtls; Twas; S-predixcan; Multi-tissue Gtex; Transcriptome Wide Association Studies,,,"There is particular interest in transcriptome-wide association studies (TWAS) gene-level tests based on multi-SNP predictive models of gene expression-for identifying causal genes at loci associated with complex traits. However, interpretation of TWAS associations may be complicated by divergent effects of model SNPs on phenotype and gene expression. We developed an iterative modeling scheme for obtaining multi-SNP models of gene expression and applied this framework to generate expression models for 43 human tissues from the Genotype-Tissue Expression (GTEx) Project. We characterized the performance of single- and multi-SNP models for identifying causal genes in GWAS data for 46 circulating metabolites. We show that: (A) multi-SNP models captured more variation in expression than did the top cis-eQTL (median 2-fold improvement); (B) predicted expression based on multi-SNP models was associated (false discovery rate < 0.01) with metabolite levels for 826 unique gene-metabolite pairs, but, after stepwise conditional analyses, 90% were dominated by a single eQTL SNP; (C) among the 35% of associations where a SNP in the expression model was a significant cis-eQTL and metabolomic-QTL (met-QTL), 92% demonstrated colocalization between these signals, but interpretation was often complicated by incomplete overlap of QTLs in multi-SNP models; and (D) using a ""truth"" set of causal genes at 61 met-QTLs, the sensitivity was high (67%), but the positive predictive value was low, as only 8% of TWAS associations (19% when restricted to colocalized associations at met-QTLs) involved true causal genes. These results guide the interpretation of TWAS and highlight the need for corroborative data to provide confident assignment of causality.", ,pdf:http://www.cell.com/article/S0002929720300033/pdf; doi:https://doi.org/10.1016/j.ajhg.2020.01.003; html:https://europepmc.org/articles/PMC7010967; pdf:https://europepmc.org/articles/PMC7010967?pdf=render
 31678029,https://doi.org/10.1016/s1473-3099(19)30401-3,Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years: an analysis of the Global Burden of Disease Study 2017.,GBD 2017 Diarrhoeal Disease Collaborators.,,The Lancet. Infectious diseases,2020,2019-10-31,Y,,,,"<h4>Background</h4>Many countries have shown marked declines in diarrhoeal disease mortality among children younger than 5 years. With this analysis, we provide updated results on diarrhoeal disease mortality among children younger than 5 years from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) and use the study's comparative risk assessment to quantify trends and effects of risk factors, interventions, and broader sociodemographic development on mortality changes in 195 countries and territories from 1990 to 2017.<h4>Methods</h4>This analysis for GBD 2017 had three main components. Diarrhoea mortality was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive, Bayesian, ensemble modelling tool; and the attribution of risk factors and interventions for diarrhoea were modelled in a counterfactual framework that combines modelled population-level prevalence of the exposure to each risk or intervention with the relative risk of diarrhoea given exposure to that factor. We assessed the relative and absolute change in diarrhoea mortality rate between 1990 and 2017, and used the change in risk factor exposure and sociodemographic status to explain differences in the trends of diarrhoea mortality among children younger than 5 years.<h4>Findings</h4>Diarrhoea was responsible for an estimated 533 768 deaths (95% uncertainty interval 477 162-593 145) among children younger than 5 years globally in 2017, a rate of 78·4 deaths (70·1-87·1) per 100 000 children. The diarrhoea mortality rate ranged between countries by over 685 deaths per 100 000 children. Diarrhoea mortality per 100 000 globally decreased by 69·6% (63·1-74·6) between 1990 and 2017. Among the risk factors considered in this study, those responsible for the largest declines in the diarrhoea mortality rate were reduction in exposure to unsafe sanitation (13·3% decrease, 11·2-15·5), childhood wasting (9·9% decrease, 9·6-10·2), and low use of oral rehydration solution (6·9% decrease, 4·8-8·4).<h4>Interpretation</h4>Diarrhoea mortality has declined substantially since 1990, although there are variations by country. Improvements in sociodemographic indicators might explain some of these trends, but changes in exposure to risk factors-particularly unsafe sanitation, childhood growth failure, and low use of oral rehydration solution-appear to be related to the relative and absolute rates of decline in diarrhoea mortality. Although the most effective interventions might vary by country or region, identifying and scaling up the interventions aimed at preventing and protecting against diarrhoea that have already reduced diarrhoea mortality could further avert many thousands of deaths due to this illness.<h4>Funding</h4>Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S1473309919304013/pdf; doi:https://doi.org/10.1016/S1473-3099(19)30401-3; html:https://europepmc.org/articles/PMC7340495
 34662334,https://doi.org/10.1371/journal.pgen.1009436,Machine learning to predict the source of campylobacteriosis using whole genome data.,"Arning N, Sheppard SK, Bayliss S, Clifton DA, Wilson DJ.",,PLoS genetics,2021,2021-10-18,Y,,,,"Campylobacteriosis is among the world's most common foodborne illnesses, caused predominantly by the bacterium Campylobacter jejuni. Effective interventions require determination of the infection source which is challenging as transmission occurs via multiple sources such as contaminated meat, poultry, and drinking water. Strain variation has allowed source tracking based upon allelic variation in multi-locus sequence typing (MLST) genes allowing isolates from infected individuals to be attributed to specific animal or environmental reservoirs. However, the accuracy of probabilistic attribution models has been limited by the ability to differentiate isolates based upon just 7 MLST genes. Here, we broaden the input data spectrum to include core genome MLST (cgMLST) and whole genome sequences (WGS), and implement multiple machine learning algorithms, allowing more accurate source attribution. We increase attribution accuracy from 64% using the standard iSource population genetic approach to 71% for MLST, 85% for cgMLST and 78% for kmerized WGS data using the classifier we named aiSource. To gain insight beyond the source model prediction, we use Bayesian inference to analyse the relative affinity of C. jejuni strains to infect humans and identified potential differences, in source-human transmission ability among clonally related isolates in the most common disease causing lineage (ST-21 clonal complex). Providing generalizable computationally efficient methods, based upon machine learning and population genetics, we provide a scalable approach to global disease surveillance that can continuously incorporate novel samples for source attribution and identify fine-scale variation in transmission potential.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009436&type=printable; doi:https://doi.org/10.1371/journal.pgen.1009436; html:https://europepmc.org/articles/PMC8553134; pdf:https://europepmc.org/articles/PMC8553134?pdf=render
 35484151,https://doi.org/10.1038/s41467-022-29932-y,Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach.,"Richardson TG, Crouch DJM, Power GM, Morales-Berstein F, Hazelwood E, Fang S, Cho Y, Inshaw JRJ, Robertson CC, Sidore C, Cucca F, Rich SS, Todd JA, Davey Smith G.",,Nature communications,2022,2022-04-28,Y,,,,"The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR = 2.05 per change in body size category, 95% CI = 1.20 to 3.50, P = 0.008), which remains after accounting for body size at birth and during adulthood using multivariable MR (OR = 2.32, 95% CI = 1.21 to 4.42, P = 0.013). We validate this direct effect of childhood body size using data from a large-scale T1D meta-analysis based on n = 15,573 cases and n = 158,408 controls (OR = 1.94, 95% CI = 1.21 to 3.12, P = 0.006). We also provide evidence that childhood body size influences risk of asthma, eczema and hypothyroidism, although multivariable MR suggested that these effects are mediated by body size in later life. Our findings support a causal role for higher childhood body size on risk of being diagnosed with T1D, whereas its influence on the other immune-associated diseases is likely explained by a long-term effect of remaining overweight for many years over the lifecourse.",,pdf:https://www.nature.com/articles/s41467-022-29932-y.pdf; doi:https://doi.org/10.1038/s41467-022-29932-y; html:https://europepmc.org/articles/PMC9051135; pdf:https://europepmc.org/articles/PMC9051135?pdf=render
 31182084,https://doi.org/10.1186/s12911-019-0824-x,The effect of computerized decision support systems on cardiovascular risk factors: a systematic review and meta-analysis.,"Groenhof TKJ, Asselbergs FW, Groenwold RHH, Grobbee DE, Visseren FLJ, Bots ML, UCC-SMART study group.",,BMC medical informatics and decision making,2019,2019-06-10,Y,Cdss; Computerized Decision Support; Cardiovascular Risk Management,,,"<h4>Background</h4>Cardiovascular risk management (CVRM) is notoriously difficult because of multi-morbidity and the different phenotypes and severities of cardiovascular disease. Computerized decision support systems (CDSS) enable the clinician to integrate the latest scientific evidence and patient information into tailored strategies. The effect on cardiovascular risk factor management is yet to be confirmed.<h4>Methods</h4>We performed a systematic review and meta-analysis evaluating the effects of CDSS on CVRM, defined as the change in absolute values and attainment of treatment goals of systolic blood pressure (SBP), low density lipoprotein cholesterol (LDL-c) and HbA1c. Also, CDSS characteristics related to more effective CVRM were identified. Eligible articles were methodologically appraised using the Cochrane risk of bias tool. We calculated mean differences, relative risks, and if appropriate (I<sup>2</sup> < 70%), pooled the results using a random-effects model.<h4>Results</h4>Of the 14,335 studies identified, 22 were included. Four studies reported on SBP, 3 on LDL-c, 10 on CVRM in patients with type II diabetes and 5 on guideline adherence. The CDSSs varied considerably in technical performance and content. Heterogeneity of results was such that quantitative pooling was often not appropriate. Among CVRM patients, the results tended towards a beneficial effect of CDSS, but only LDL-c target attainment in diabetes patients reached statistical significance. Prompting, integration into the electronical health record, patient empowerment, and medication support were related to more effective CVRM.<h4>Conclusion</h4>We did not find a clear clinical benefit from CDSS in cardiovascular risk factor levels and target attainment. Some features of CDSS seem more promising than others. However, the variability in CDSS characteristics and heterogeneity of the results - emphasizing the immaturity of this research area - limit stronger conclusions. Clinical relevance of CDSS in CVRM might additionally be sought in the improvement of shared decision making and patient empowerment.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0824-x; doi:https://doi.org/10.1186/s12911-019-0824-x; html:https://europepmc.org/articles/PMC6558725; pdf:https://europepmc.org/articles/PMC6558725?pdf=render
 31289267,https://doi.org/10.1038/s41467-019-10724-w,Mapping the drivers of within-host pathogen evolution using massive data sets.,"Palmer DS, Turner I, Fidler S, Frater J, Goedhals D, Goulder P, Huang KG, Oxenius A, Phillips R, Shapiro R, Vuuren CV, McLean AR, McVean G.",,Nature communications,2019,2019-07-09,Y,,Applied Analytics,,"Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Genetic association studies can potentially identify such interactions. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. We present a Bayesian approach for detecting host influences on pathogen evolution that exploits vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Our simulations and empirical analysis of drug-induced selection on the HIV-1 genome show that the method recovers known associations and has superior precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.",,pdf:https://www.nature.com/articles/s41467-019-10724-w.pdf; doi:https://doi.org/10.1038/s41467-019-10724-w; html:https://europepmc.org/articles/PMC6616926; pdf:https://europepmc.org/articles/PMC6616926?pdf=render
-36315390,https://doi.org/10.1002/eat.23834,"Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.","Davies HL, Hübel C, Herle M, Kakar S, Mundy J, Peel AJ, Ter Kuile AR, Zvrskovec J, Monssen D, Lim KX, Davies MR, Palmos AB, Lin Y, Kalsi G, Rogers HC, Bristow S, Glen K, Malouf CM, Kelly EJ, Purves KL, Young KS, Hotopf M, Armour C, McIntosh AM, Eley TC, Treasure J, Breen G.",,The International journal of eating disorders,2023,2022-10-31,Y,Mental health; Psychiatric disorders; Eating Disorders; Comorbidity; Suicidal Ideation,,,"<h4>Objective</h4>The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic.<h4>Method</h4>Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self-harm ideation (n = 18,040), and self-harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes.<h4>Results</h4>Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation.<h4>Discussion</h4>Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics.<h4>Public significance</h4>In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eat.23834; doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?pdf=render
 31641117,https://doi.org/10.1038/s41467-019-12682-9,Sequence variants with large effects on cardiac electrophysiology and disease.,"Norland K, Sveinbjornsson G, Thorolfsdottir RB, Davidsson OB, Tragante V, Rajamani S, Helgadottir A, Gretarsdottir S, van Setten J, Asselbergs FW, Sverrisson JT, Stephensen SS, Oskarsson G, Sigurdsson EL, Andersen K, Danielsen R, Thorgeirsson G, Thorsteinsdottir U, Arnar DO, Sulem P, Holm H, Gudbjartsson DF, Stefansson K.",,Nature communications,2019,2019-10-22,Y,,,,"Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease.",,pdf:https://www.nature.com/articles/s41467-019-12682-9.pdf; doi:https://doi.org/10.1038/s41467-019-12682-9; html:https://europepmc.org/articles/PMC6805929; pdf:https://europepmc.org/articles/PMC6805929?pdf=render
+36315390,https://doi.org/10.1002/eat.23834,"Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.","Davies HL, Hübel C, Herle M, Kakar S, Mundy J, Peel AJ, Ter Kuile AR, Zvrskovec J, Monssen D, Lim KX, Davies MR, Palmos AB, Lin Y, Kalsi G, Rogers HC, Bristow S, Glen K, Malouf CM, Kelly EJ, Purves KL, Young KS, Hotopf M, Armour C, McIntosh AM, Eley TC, Treasure J, Breen G.",,The International journal of eating disorders,2023,2022-10-31,Y,Mental health; Psychiatric disorders; Eating Disorders; Comorbidity; Suicidal Ideation,,,"<h4>Objective</h4>The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic.<h4>Method</h4>Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self-harm ideation (n = 18,040), and self-harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes.<h4>Results</h4>Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation.<h4>Discussion</h4>Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics.<h4>Public significance</h4>In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eat.23834; doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?pdf=render
 31822727,https://doi.org/10.1038/s41598-019-55098-7,Co-incidence of RCC-susceptibility polymorphisms with HIF cis-acting sequences supports a pathway tuning model of cancer.,"Schmid V, Lafleur VN, Lombardi O, Li R, Salama R, Colli L, Choudhry H, Chanock S, Ratcliffe PJ, Mole DR.",,Scientific reports,2019,2019-12-10,Y,,Understanding the Causes of Disease,,"Emerging evidence suggests that dysregulation of oncogenic pathways requires precise tuning in order for cancer to develop. To test this, we examined the overlap between cis-acting elements of the hypoxia-inducible factor (HIF) pathway and cancer-susceptibility polymorphisms as defined in genome-wide association studies (GWAS). In renal cancer, where HIF is constitutively and un-physiologically activated by mutation of the von Hippel-Lindau tumour suppressor, we observed marked excess overlap, which extended to potential susceptibility polymorphisms that are below the conventional threshold applied in GWAS. In contrast, in other cancers where HIF is upregulated by different mechanisms, including micro-environmental hypoxia, we observed no excess in overlap. Our findings support a 'pathway tuning' model of cancer, whereby precise modulation of multiple outputs of specific, activated pathways is important in oncogenesis. This implies that selective pressures to modulate such pathways operate during cancer development and should focus attempts to identify their nature and consequences.",This study investigated the association between proteins responsible for DNA replication the susceptibility to cancer using GWAS. ,pdf:https://www.nature.com/articles/s41598-019-55098-7.pdf; doi:https://doi.org/10.1038/s41598-019-55098-7; html:https://europepmc.org/articles/PMC6904466; pdf:https://europepmc.org/articles/PMC6904466?pdf=render
 34552082,https://doi.org/10.1038/s41467-021-25833-8,Modelling the persistence and control of Rift Valley fever virus in a spatially heterogeneous landscape.,"Tennant WSD, Cardinale E, Cêtre-Sossah C, Moutroifi Y, Le Godais G, Colombi D, Spencer SEF, Tildesley MJ, Keeling MJ, Charafouddine O, Colizza V, Edmunds WJ, Métras R.",,Nature communications,2021,2021-09-22,Y,,,,"The persistence mechanisms of Rift Valley fever (RVF), a zoonotic arboviral haemorrhagic fever, at both local and broader geographical scales have yet to be fully understood and rigorously quantified. We developed a mathematical metapopulation model describing RVF virus transmission in livestock across the four islands of the Comoros archipelago, accounting for island-specific environments and inter-island animal movements. By fitting our model in a Bayesian framework to 2004-2015 surveillance data, we estimated the importance of environmental drivers and animal movements on disease persistence, and tested the impact of different control scenarios on reducing disease burden throughout the archipelago. Here we report that (i) the archipelago network was able to sustain viral transmission in the absence of explicit disease introduction events after early 2007, (ii) repeated outbreaks during 2004-2020 may have gone under-detected by local surveillance, and (iii) co-ordinated within-island control measures are more effective than between-island animal movement restrictions.",,pdf:https://www.nature.com/articles/s41467-021-25833-8.pdf; doi:https://doi.org/10.1038/s41467-021-25833-8; html:https://europepmc.org/articles/PMC8458460; pdf:https://europepmc.org/articles/PMC8458460?pdf=render
 31477933,https://doi.org/10.1038/s41588-019-0484-x,A method for genome-wide genealogy estimation for thousands of samples.,"Speidel L, Forest M, Shi S, Myers SR.",,Nature genetics,2019,2019-09-02,N,,,,"Knowledge of genome-wide genealogies for thousands of individuals would simplify most evolutionary analyses for humans and other species, but has remained computationally infeasible. We have developed a method, Relate, scaling to >10,000 sequences while simultaneously estimating branch lengths, mutational ages and variable historical population sizes, as well as allowing for data errors. Application to 1,000 Genomes Project haplotypes produces joint genealogical histories for 26 human populations. Highly diverged lineages are present in all groups, but most frequent in Africa. Outside Africa, these mainly reflect ancient introgression from groups related to Neanderthals and Denisovans, while African signals instead reflect unknown events unique to that continent. Our approach allows more powerful inferences of natural selection than has previously been possible. We identify multiple regions under strong positive selection, and multi-allelic traits including hair color, body mass index and blood pressure, showing strong evidence of directional selection, varying among human groups.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610517; doi:https://doi.org/10.1038/s41588-019-0484-x; html:https://europepmc.org/articles/PMC7610517; pdf:https://europepmc.org/articles/PMC7610517?pdf=render; doi:https://doi.org/10.1038/s41588-019-0484-x
-36258219,https://doi.org/10.1186/s13063-022-06824-6,"Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.","Sandercock PAG, Darbyshire J, DeMets D, Fowler R, Lalloo DG, Munavvar M, Staplin N, Warris A, Wittes J, Emberson JR.",,Trials,2022,2022-10-18,Y,,,,"<h4>Aim</h4>To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.<h4>Methods and findings</h4>During the first 24 months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving > 45,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively 'competing' for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab + imdevimab, and tocilizumab.<h4>Conclusions</h4>RECOVERY's streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial's efficiency, without compromising the DMC's ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06824-6; doi:https://doi.org/10.1186/s13063-022-06824-6; html:https://europepmc.org/articles/PMC9579551; pdf:https://europepmc.org/articles/PMC9579551?pdf=render
 31539079,https://doi.org/10.1001/jamanetworkopen.2019.11970,Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China.,"Seow WJ, Shu XO, Nicholson JK, Holmes E, Walker DI, Hu W, Cai Q, Gao YT, Xiang YB, Moore SC, Bassig BA, Wong JYY, Zhang J, Ji BT, Boulangé CL, Kaluarachchi M, Wijeyesekera A, Zheng W, Elliott P, Rothman N, Lan Q.",,JAMA network open,2019,2019-09-04,Y,,Understanding the Causes of Disease,,"<h4>Importance</h4>Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood.<h4>Objective</h4>To assess the association between metabolomics and lung cancer risk among never-smoking women.<h4>Design, setting, and participants</h4>This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018.<h4>Exposures</h4>Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured.<h4>Main outcomes and measures</h4>Incident lung cancer.<h4>Results</h4>Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odds ratio for second tertile, 0.52 [95% CI, 0.34-0.80]; and odds ratio for third tertile, 0.46 [95% CI, 0.30-0.70]), and the association was consistent across different histological subtypes and follow-up times. Additionally, metabolic pathway analysis found several systemic biological alterations that were associated with lung cancer risk, including 1-carbon metabolism, nucleotide metabolism, oxidative stress, and inflammation.<h4>Conclusions and relevance</h4>This prospective study of the untargeted urinary metabolome and lung cancer among never-smoking women in China provides support for the hypothesis that soy-based metabolites are associated with lower lung cancer risk in never-smoking women and suggests that biological processes linked to air pollution may be associated with higher lung cancer risk in this population.",,pdf:https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2751559/seow_2019_oi_190459.pdf; doi:https://doi.org/10.1001/jamanetworkopen.2019.11970; html:https://europepmc.org/articles/PMC6755532
+36258219,https://doi.org/10.1186/s13063-022-06824-6,"Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.","Sandercock PAG, Darbyshire J, DeMets D, Fowler R, Lalloo DG, Munavvar M, Staplin N, Warris A, Wittes J, Emberson JR.",,Trials,2022,2022-10-18,Y,,,,"<h4>Aim</h4>To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.<h4>Methods and findings</h4>During the first 24 months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving > 45,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively 'competing' for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab + imdevimab, and tocilizumab.<h4>Conclusions</h4>RECOVERY's streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial's efficiency, without compromising the DMC's ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06824-6; doi:https://doi.org/10.1186/s13063-022-06824-6; html:https://europepmc.org/articles/PMC9579551; pdf:https://europepmc.org/articles/PMC9579551?pdf=render
 33770123,https://doi.org/10.1371/journal.pone.0249189,Association of genetic liability for psychiatric disorders with accelerometer-assessed physical activity in the UK Biobank.,"Dennison CA, Legge SE, Bracher-Smith M, Menzies G, Escott-Price V, Smith DJ, Doherty AR, Owen MJ, O'Donovan MC, Walters JTR.",,PloS one,2021,2021-03-26,Y,,,,"Levels of activity are often affected in psychiatric disorders and can be core symptoms of illness. Advances in technology now allow the accurate assessment of activity levels but it remains unclear whether alterations in activity arise from shared risk factors for developing psychiatric disorders, such as genetics, or are better explained as consequences of the disorders and their associated factors. We aimed to examine objectively-measured physical activity in individuals with psychiatric disorders, and assess the role of genetic liability for psychiatric disorders on physical activity. Accelerometer data were available on 95,529 UK Biobank participants, including measures of overall mean activity and minutes per day of moderate activity, walking, sedentary activity, and sleep. Linear regressions measured associations between psychiatric diagnosis and activity levels, and polygenic risk scores (PRS) for psychiatric disorders and activity levels. Genetic correlations were calculated between psychiatric disorders and different types of activity. Having a diagnosis of schizophrenia, bipolar disorder, depression, or autism spectrum disorders (ASD) was associated with reduced overall activity compared to unaffected controls. In individuals without a psychiatric disorder, reduced overall activity levels were associated with PRS for schizophrenia, depression, and ASD. ADHD PRS was associated with increased overall activity. Genetic correlations were consistent with PRS findings. Variation in physical activity is an important feature across psychiatric disorders. Whilst levels of activity are associated with genetic liability to psychiatric disorders to a very limited extent, the substantial differences in activity levels in those with psychiatric disorders most likely arise as a consequences of disorder-related factors.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0249189&type=printable; doi:https://doi.org/10.1371/journal.pone.0249189; html:https://europepmc.org/articles/PMC8508577; pdf:https://europepmc.org/articles/PMC8508577?pdf=render
 35460409,https://doi.org/10.1093/ageing/afac090,New horizons in evidence-based care for older people: individual participant data meta-analysis.,"Clegg A, Bandeen-Roche K, Farrin A, Forster A, Gill TM, Gladman J, Kerse N, Lindley R, McManus RJ, Melis R, Mujica-Mota R, Raina P, Rockwood K, Teh R, van der Windt D, Witham M.",,Age and ageing,2022,2022-04-01,Y,Ageing; Meta-analysis; Frailty; Older People; Stratified Care; Individual Participant Data,,,"Evidence-based decisions on clinical and cost-effectiveness of interventions are ideally informed by meta-analyses of intervention trial data. However, when undertaken, such meta-analyses in ageing research have typically been conducted using standard methods whereby summary (aggregate) data are extracted from published trial reports. Although meta-analysis of aggregate data can provide useful insights into the average effect of interventions within a selected trial population, it has limitations regarding robust conclusions on which subgroups of people stand to gain the greatest benefit from an intervention or are at risk of experiencing harm. Future evidence synthesis using individual participant data from ageing research trials for meta-analysis could transform understanding of the effectiveness of interventions for older people, supporting evidence-based and sustainable commissioning. A major advantage of individual participant data meta-analysis (IPDMA) is that it enables examination of characteristics that predict treatment effects, such as frailty, disability, cognitive impairment, ethnicity, gender and other wider determinants of health. Key challenges of IPDMA relate to the complexity and resources needed for obtaining, managing and preparing datasets, requiring a meticulous approach involving experienced researchers, frequently with expertise in designing and analysing clinical trials. In anticipation of future IPDMA work in ageing research, we are establishing an international Ageing Research Trialists collective, to bring together trialists with a common focus on transforming care for older people as a shared ambition across nations.",,pdf:https://academic.oup.com/ageing/article-pdf/51/4/afac090/43408856/afac090.pdf; doi:https://doi.org/10.1093/ageing/afac090; html:https://europepmc.org/articles/PMC9034697; pdf:https://europepmc.org/articles/PMC9034697?pdf=render
 34155378,https://doi.org/10.1038/s41588-021-00887-y,The HIF complex recruits the histone methyltransferase SET1B to activate specific hypoxia-inducible genes.,"Ortmann BM, Burrows N, Lobb IT, Arnaiz E, Wit N, Bailey PSJ, Jordon LH, Lombardi O, Peñalver A, McCaffrey J, Seear R, Mole DR, Ratcliffe PJ, Maxwell PH, Nathan JA.",,Nature genetics,2021,2021-06-21,Y,,,,"Hypoxia-inducible transcription factors (HIFs) are fundamental to cellular adaptation to low oxygen levels, but it is unclear how they interact with chromatin and activate their target genes. Here, we use genome-wide mutagenesis to identify genes involved in HIF transcriptional activity, and define a requirement for the histone H3 lysine 4 (H3K4) methyltransferase SET1B. SET1B loss leads to a selective reduction in transcriptional activation of HIF target genes, resulting in impaired cell growth, angiogenesis and tumor establishment in SET1B-deficient xenografts. Mechanistically, we show that SET1B accumulates on chromatin in hypoxia, and is recruited to HIF target genes by the HIF complex. The selective induction of H3K4 trimethylation at HIF target loci is both HIF- and SET1B-dependent and, when impaired, correlates with decreased promoter acetylation and gene expression. Together, these findings show SET1B as a determinant of site-specific histone methylation and provide insight into how HIF target genes are differentially regulated.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611696; doi:https://doi.org/10.1038/s41588-021-00887-y; html:https://europepmc.org/articles/PMC7611696; pdf:https://europepmc.org/articles/PMC7611696?pdf=render
@@ -2156,8 +2156,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 35820692,https://doi.org/10.1136/bmj-2021-069881,Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis.,"de Jong VMT, Rousset RZ, Antonio-Villa NE, Buenen AG, Van Calster B, Bello-Chavolla OY, Brunskill NJ, Curcin V, Damen JAA, Fermín-Martínez CA, Fernández-Chirino L, Ferrari D, Free RC, Gupta RK, Haldar P, Hedberg P, Korang SK, Kurstjens S, Kusters R, Major RW, Maxwell L, Nair R, Naucler P, Nguyen TL, Noursadeghi M, Rosa R, Soares F, Takada T, van Royen FS, van Smeden M, Wynants L, Modrák M, CovidRetro collaboration, Asselbergs FW, Linschoten M, CAPACITY-COVID consortium, Moons KGM, Debray TPA.",,BMJ (Clinical research ed.),2022,2022-07-12,Y,,,,"<h4>Objective</h4>To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19.<h4>Design</h4>Two stage individual participant data meta-analysis.<h4>Setting</h4>Secondary and tertiary care.<h4>Participants</h4>46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021.<h4>Data sources</h4>Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in <i>The BMJ</i>, and through PROSPERO, reference checking, and expert knowledge.<h4>Model selection and eligibility criteria</h4>Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor.<h4>Methods</h4>Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters.<h4>Main outcome measures</h4>30 day mortality or in-hospital mortality.<h4>Results</h4>Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al's model (0.96, 0.59 to 1.55, 0.21 to 4.28).<h4>Conclusion</h4>The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.",,pdf:https://www.bmj.com/content/bmj/378/bmj-2021-069881.full.pdf; doi:https://doi.org/10.1136/bmj-2021-069881; html:https://europepmc.org/articles/PMC9273913; pdf:https://europepmc.org/articles/PMC9273913?pdf=render
 31317072,https://doi.org/10.1002/lrh2.10191,"Our data, our society, our health: A vision for inclusive and transparent health data science in the United Kingdom and beyond.","Ford E, Boyd A, Bowles JKF, Havard A, Aldridge RW, Curcin V, Greiver M, Harron K, Katikireddi V, Rodgers SE, Sperrin M.",,Learning health systems,2019,2019-03-25,Y,Transparency; Health Systems; Stakeholder Involvement; Data Flows; Health Data Science; Citizen‐driven Science,,,"The last 6 years have seen sustained investment in health data science in the United Kingdom and beyond, which should result in a data science community that is inclusive of all stakeholders, working together to use data to benefit society through the improvement of public health and well-being. However, opportunities made possible through the innovative use of data are still not being fully realised, resulting in research inefficiencies and avoidable health harms. In this paper, we identify the most important barriers to achieving higher productivity in health data science. We then draw on previous research, domain expertise, and theory to outline how to go about overcoming these barriers, applying our core values of inclusivity and transparency. We believe a step change can be achieved through meaningful stakeholder involvement at every stage of research planning, design, and execution and team-based data science, as well as harnessing novel and secure data technologies. Applying these values to health data science will safeguard a social licence for health data research and ensure transparent and secure data usage for public benefit.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10191; doi:https://doi.org/10.1002/lrh2.10191; html:https://europepmc.org/articles/PMC6628981; pdf:https://europepmc.org/articles/PMC6628981?pdf=render
 32936291,https://doi.org/10.1001/jamadermatol.2020.3275,Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis.,"Benzian-Olsson N, Dand N, Chaloner C, Bata-Csorgo Z, Borroni R, Burden AD, Cooper HL, Cornelius V, Cro S, Dasandi T, Griffiths CEM, Kingo K, Koks S, Lachmann H, McAteer H, Meynell F, Mrowietz U, Parslew R, Patel P, Pink AE, Reynolds NJ, Tanew A, Torz K, Trattner H, Wahie S, Warren RB, Wright A, Barker JN, Navarini AA, Smith CH, Capon F, ERASPEN consortium and the APRICOT and PLUM study team.",,JAMA dermatology,2020,2020-11-01,Y,,,,"<h4>Importance</h4>Although palmoplantar pustulosis (PPP) can significantly impact quality of life, the factors underlying disease severity have not been studied.<h4>Objective</h4>To examine the factors associated with PPP severity.<h4>Design, setting, and participants</h4>An observational, cross-sectional study of 2 cohorts was conducted. A UK data set including 203 patients was obtained through the Anakinra in Pustular Psoriasis, Response in a Controlled Trial (2016-2019) and its sister research study Pustular Psoriasis, Elucidating Underlying Mechanisms (2016-2020). A Northern European cohort including 193 patients was independently ascertained by the European Rare and Severe Psoriasis Expert Network (2014-2017). Patients had been recruited in secondary or tertiary dermatology referral centers. All patients were of European descent. The PPP diagnosis was established by dermatologists, based on clinical examination and/or published consensus criteria. The present study was conducted from October 1, 2014, to March 15, 2020.<h4>Main outcomes and measures</h4>Demographic characteristics, comorbidities, smoking status, Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI), measuring severity from 0 (no sign of disease) to 72 (very severe disease), or Physician Global Assessment (PGA), measuring severity as 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe).<h4>Results</h4>Among the 203 UK patients (43 men [21%], 160 women [79%]; median age at onset, 48 [interquartile range (IQR), 38-59] years), the PPPASI was inversely correlated with age of onset (r = -0.18, P = .01). Similarly, in the 159 Northern European patients who were eligible for inclusion in this analysis (25 men [16%], 134 women [84%]; median age at onset, 45 [IQR, 34-53.3] years), the median age at onset was lower in individuals with a moderate to severe PGA score (41 years [IQR, 30.5-52 years]) compared with those with a clear to mild PGA score (46.5 years [IQR, 35-55 years]) (P = .04). In the UK sample, the median PPPASI score was higher in women (9.6 [IQR, 3.0-16.2]) vs men (4.0 [IQR, 1.0-11.7]) (P = .01). Likewise, moderate to severe PPP was more prevalent among Northern European women (57 of 134 [43%]) compared with men (5 of 25 [20%]) (P = .03). In the UK cohort, the median PPPASI score was increased in current smokers (10.7 [IQR, 4.2-17.5]) compared with former smokers (7 [IQR, 2.0-14.4]) and nonsmokers (2.2 [IQR, 1-6]) (P = .003). Comparable differences were observed in the Northern European data set, as the prevalence of moderate to severe PPP was higher in former and current smokers (51 of 130 [39%]) compared with nonsmokers (6 of 24 [25%]) (P = .14).<h4>Conclusions and relevance</h4>The findings of this study suggest that PPP severity is associated with early-onset disease, female sex, and smoking status. Thus, smoking cessation intervention might be beneficial.",,pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2770779/jamadermatology_benzianolsson_2020_oi_200054_1604610894.93046.pdf; doi:https://doi.org/10.1001/jamadermatol.2020.3275; html:https://europepmc.org/articles/PMC7495329
-36589292,https://doi.org/10.3389/fncel.2022.1050596,Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data.,"Al Khleifat A, Iacoangeli A, Jones AR, van Vugt JJFA, Moisse M, Shatunov A, Zwamborn RAJ, van der Spek RAA, Cooper-Knock J, Topp S, van Rheenen W, Kenna B, Van Eijk KR, Kenna K, Byrne R, López V, Opie-Martin S, Vural A, Campos Y, Weber M, Smith B, Fogh I, Silani V, Morrison KE, Dobson R, van Es MA, McLaughlin RL, Vourc'h P, Chio A, Corcia P, de Carvalho M, Gotkine M, Panades MP, Mora JS, Shaw PJ, Landers JE, Glass JD, Shaw CE, Basak N, Hardiman O, Robberecht W, Van Damme P, van den Berg LH, Veldink JH, Al-Chalabi A.",,Frontiers in cellular neuroscience,2022,2022-12-15,Y,Genomics; Amyotrophic Lateral Sclerosis (Als); Bigdata; Whole Genome Sequence (Wgs); Telomere–Genetics; Mnd–Motor Neuron Disorders,,,"<h4>Background</h4>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS.<h4>Methods</h4>Samples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression.<h4>Results</h4>There were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 × 10<sup>-12</sup>), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0×10<sup>-7</sup>). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded <i>C9orf72</i> repeats was shorter than in those without expanded <i>C9orf72</i> repeats (p = 5.0×10<sup>-4</sup>).<h4>Discussion</h4>Although telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS.",,pdf:https://www.frontiersin.org/articles/10.3389/fncel.2022.1050596/pdf; doi:https://doi.org/10.3389/fncel.2022.1050596; html:https://europepmc.org/articles/PMC9799999; pdf:https://europepmc.org/articles/PMC9799999?pdf=render
 33623019,https://doi.org/10.1038/s41467-021-21505-9,Flavivirus maturation leads to the formation of an occupied lipid pocket in the surface glycoproteins.,"Renner M, Dejnirattisai W, Carrique L, Martin IS, Karia D, Ilca SL, Ho SF, Kotecha A, Keown JR, Mongkolsapaya J, Screaton GR, Grimes JM.",,Nature communications,2021,2021-02-23,Y,,,,"Flaviviruses such as Dengue (DENV) or Zika virus (ZIKV) assemble into an immature form within the endoplasmatic reticulum (ER), and are then processed by furin protease in the trans-Golgi. To better grasp maturation, we carry out cryo-EM reconstructions of immature Spondweni virus (SPOV), a human flavivirus of the same serogroup as ZIKV. By employing asymmetric localised reconstruction we push the resolution to 3.8 Å, enabling us to refine an atomic model which includes the crucial furin protease recognition site and a conserved Histidine pH-sensor. For direct comparison, we also solve structures of the mature forms of SPONV and DENV to 2.6 Å and 3.1 Å, respectively. We identify an ordered lipid that is present in only the mature forms of ZIKV, SPOV, and DENV and can bind as a consequence of rearranging amphipathic stem-helices of E during maturation. We propose a structural role for the pocket and suggest it stabilizes mature E.",,pdf:https://www.nature.com/articles/s41467-021-21505-9.pdf; doi:https://doi.org/10.1038/s41467-021-21505-9; html:https://europepmc.org/articles/PMC7902656; pdf:https://europepmc.org/articles/PMC7902656?pdf=render
+36589292,https://doi.org/10.3389/fncel.2022.1050596,Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data.,"Al Khleifat A, Iacoangeli A, Jones AR, van Vugt JJFA, Moisse M, Shatunov A, Zwamborn RAJ, van der Spek RAA, Cooper-Knock J, Topp S, van Rheenen W, Kenna B, Van Eijk KR, Kenna K, Byrne R, López V, Opie-Martin S, Vural A, Campos Y, Weber M, Smith B, Fogh I, Silani V, Morrison KE, Dobson R, van Es MA, McLaughlin RL, Vourc'h P, Chio A, Corcia P, de Carvalho M, Gotkine M, Panades MP, Mora JS, Shaw PJ, Landers JE, Glass JD, Shaw CE, Basak N, Hardiman O, Robberecht W, Van Damme P, van den Berg LH, Veldink JH, Al-Chalabi A.",,Frontiers in cellular neuroscience,2022,2022-12-15,Y,Genomics; Amyotrophic Lateral Sclerosis (Als); Bigdata; Whole Genome Sequence (Wgs); Telomere–Genetics; Mnd–Motor Neuron Disorders,,,"<h4>Background</h4>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS.<h4>Methods</h4>Samples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression.<h4>Results</h4>There were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 × 10<sup>-12</sup>), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0×10<sup>-7</sup>). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded <i>C9orf72</i> repeats was shorter than in those without expanded <i>C9orf72</i> repeats (p = 5.0×10<sup>-4</sup>).<h4>Discussion</h4>Although telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS.",,pdf:https://www.frontiersin.org/articles/10.3389/fncel.2022.1050596/pdf; doi:https://doi.org/10.3389/fncel.2022.1050596; html:https://europepmc.org/articles/PMC9799999; pdf:https://europepmc.org/articles/PMC9799999?pdf=render
 34767815,https://doi.org/10.1016/j.jid.2021.08.446,"Differences in Clinical Features and Comorbid Burden between HLA-C∗06:02 Carrier Groups in >9,000 People with Psoriasis.","Douroudis K, Ramessur R, Barbosa IA, Baudry D, Duckworth M, Angit C, Capon F, Chung R, Curtis CJ, Di Meglio P, Goulding JMR, Griffiths CEM, Lee SH, Mahil SK, Parslew R, Reynolds NJ, Shipman AR, Warren RB, Yiu ZZN, Simpson MA, Barker JN, Dand N, Smith CH, BADBIR, BSTOP Study Groups.",,The Journal of investigative dermatology,2022,2021-11-10,N,,,,"The identification of robust endotypes-disease subgroups of clinical relevance-is fundamental to stratified medicine. We hypothesized that HLA-C∗06:02 status, the major genetic determinant of psoriasis, defines a psoriasis endotype of clinical relevance. Using two United Kingdom-based cross-sectional datasets-an observational severe-psoriasis study (Biomarkers of Systemic Treatment Outcomes in Psoriasis; n = 3,767) and a large population-based bioresource (UK Biobank, including n = 5,519 individuals with psoriasis)-we compared demographic, environmental, and clinical variables of interest in HLA-C∗06:02-positive (one or two copies of the HLA-C∗06:02 allele) with those in HLA-C∗06:02‒negative (no copies) individuals of European ancestry. We used multivariable regression analyses to account for mediation effects established a priori. We confirm previous observations that HLA-C∗06:02-positive status is associated with earlier age of psoriasis onset and extend findings to reveal an association with disease expressivity in females (Biomarkers of Systemic Treatment Outcomes in Psoriasis: P = 2.7 × 10<sup>-14</sup>, UK Biobank: P = 1.0 × 10<sup>-8</sup>). We also show HLA-C∗06:02-negative status to be associated with characteristic clinical features (large plaque disease, OR for HLA-C∗06:02 = 0.73, P = 7.4 × 10<sup>-4</sup>; nail involvement, OR = 0.70, P = 2.4 × 10<sup>-6</sup>); higher central adiposity (Biomarkers of Systemic Treatment Outcomes in Psoriasis: waist circumference difference of 2.0 cm, P = 8.4 × 10<sup>-4</sup>; UK Biobank: waist circumference difference of 1.4 cm, P = 1.5 × 10<sup>-4</sup>), especially in women; and a higher prevalence of other cardiometabolic comorbidities. These findings extend the clinical phenotype delineated by HLA-C∗06:02 and highlight its potential as an important biomarker to consider in future multimarker stratified medicine approaches.",,pdf:http://www.jidonline.org/article/S0022202X21024738/pdf; doi:https://doi.org/10.1016/j.jid.2021.08.446
 37248441,https://doi.org/10.1038/s41588-023-01410-1,Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation.,"Adlam D, Berrandou TE, Georges A, Nelson CP, Giannoulatou E, Henry J, Ma L, Blencowe M, Turley TN, Yang ML, Chopade S, Finan C, Braund PS, Sadeg-Sayoud I, Iismaa SE, Kosel ML, Zhou X, Hamby SE, Cheng J, Liu L, Tarr I, Muller DWM, d'Escamard V, King A, Brunham LR, Baranowska-Clarke AA, Debette S, Amouyel P, Olin JW, Patil S, Hesselson SE, Junday K, Kanoni S, Aragam KG, Butterworth AS, CARDIoGRAMPlusC4D, MEGASTROKE, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, Tweet MS, Gulati R, Combaret N, DISCO register, Kadian-Dodov D, Kalman JM, Fatkin D, Hingorani AD, Saw J, Webb TR, Hayes SN, Yang X, Ganesh SK, Olson TM, Kovacic JC, Graham RM, Samani NJ, Bouatia-Naji N.",,Nature genetics,2023,2023-05-29,Y,,,,"Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.",,doi:https://doi.org/10.1038/s41588-023-01410-1; doi:https://doi.org/10.1038/s41588-023-01410-1; html:https://europepmc.org/articles/PMC10260398; pdf:https://europepmc.org/articles/PMC10260398?pdf=render
 31801372,https://doi.org/10.1161/atvbaha.119.313226,"Carotid Intima-Media Thickness: Novel Loci, Sex-Specific Effects, and Genetic Correlations With Obesity and Glucometabolic Traits in UK Biobank.","Strawbridge RJ, Ward J, Bailey MES, Cullen B, Ferguson A, Graham N, Johnston KJA, Lyall LM, Pearsall R, Pell J, Shaw RJ, Tank R, Lyall DM, Smith DJ.",,"Arteriosclerosis, thrombosis, and vascular biology",2020,2019-12-05,Y,"Atherosclerosis; Obesity; Intima-media thickness; coronary artery disease; carotid artery; Genetics, Association Studies; Diabetes, Type 2",Understanding the Causes of Disease,,"<h4>Objective</h4>Atherosclerosis is the underlying cause of most cardiovascular disease, but mechanisms underlying atherosclerosis are incompletely understood. Ultrasound measurement of the carotid intima-media thickness (cIMT) can be used to measure vascular remodeling, which is indicative of atherosclerosis. Genome-wide association studies have identified many genetic loci associated with cIMT, but heterogeneity of measurements collected by many small cohorts have been a major limitation in these efforts. Here, we conducted genome-wide association analyses in UKB (UK Biobank; N=22 179), the largest single study with consistent cIMT measurements. Approach and Results: We used BOLT-LMM software to run linear regression of cIMT in UKB, adjusted for age, sex, and genotyping chip. In white British participants, we identified 5 novel loci associated with cIMT and replicated most previously reported loci. In the first sex-specific analyses of cIMT, we identified a locus on chromosome 5, associated with cIMT in women only and highlight <i>VCAN</i> as a good candidate gene at this locus. Genetic correlations with body mass index and glucometabolic traits were also observed. Two loci influenced risk of ischemic heart disease.<h4>Conclusions</h4>These findings replicate previously reported associations, highlight novel biology, and provide new directions for investigating the sex differences observed in cardiovascular disease presentation and progression.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.119.313226; doi:https://doi.org/10.1161/ATVBAHA.119.313226; html:https://europepmc.org/articles/PMC6975521; pdf:https://europepmc.org/articles/PMC6975521?pdf=render
@@ -2208,8 +2208,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 32139493,https://doi.org/10.1136/bmjopen-2019-035121,Community treatment orders and associations with readmission rates and duration of psychiatric hospital admission: a controlled electronic case register study.,"Barkhuizen W, Cullen AE, Shetty H, Pritchard M, Stewart R, McGuire P, Patel R.",,BMJ open,2020,2020-03-05,Y,Psychiatry; Mental health; epidemiology; Health Policy; Health Informatics; Medical Law,,,"<h4>Objectives</h4>Limited evidence is available regarding the effect of community treatment orders (CTOs) on mortality and readmission to psychiatric hospital. We compared clinical outcomes between patients placed on CTOs to a control group of patients discharged to voluntary community mental healthcare.<h4>Design and setting</h4>An observational study using deidentified electronic health record data from inpatients receiving mental healthcare in South London using the Clinical Record Interactive Search (CRIS) system. Data from patients discharged between November 2008 and May 2014 from compulsory inpatient treatment under the Mental Health Act were analysed.<h4>Participants</h4>830 participants discharged on a CTO (mean age 40 years; 63% male) and 3659 control participants discharged without a CTO (mean age 42 years; 53% male).<h4>Outcome measures</h4>The number of days spent in the community until readmission, the number of days spent in inpatient care in the 2 years prior to and the 2 years following the index admission and mortality.<h4>Results</h4>The mean duration of a CTO was 3.2 years. Patients receiving care from forensic psychiatry services were five times more likely and patients receiving a long-acting injectable antipsychotic were twice as likely to be placed on a CTO. There was a significant association between CTO receipt and readmission in adjusted models (HR: 1.60, 95% CI 1.42 to 1.80, p<0.001). Compared with controls, patients on a CTO spent 17.3 additional days (95% CI 4.0 to 30.6, p=0.011) in a psychiatric hospital in the 2 years following index admission and had a lower mortality rate (HR: 0.66, 95% CI 0.50 to 0.88, p=0.004).<h4>Conclusions</h4>Many patients spent longer on CTOs than initially anticipated by policymakers. Those on CTOs are readmitted sooner, spend more time in hospital and have a lower mortality rate. These findings merit consideration in future amendments to the UK Mental Health Act.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/3/e035121.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-035121; html:https://europepmc.org/articles/PMC7059496; pdf:https://europepmc.org/articles/PMC7059496?pdf=render
 33444330,https://doi.org/10.1371/journal.pmed.1003498,Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses.,"Sun L, Pennells L, Kaptoge S, Nelson CP, Ritchie SC, Abraham G, Arnold M, Bell S, Bolton T, Burgess S, Dudbridge F, Guo Q, Sofianopoulou E, Stevens D, Thompson JR, Butterworth AS, Wood A, Danesh J, Samani NJ, Inouye M, Di Angelantonio E.",,PLoS medicine,2021,2021-01-14,Y,,,,"<h4>Background</h4>Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD.<h4>Methods and findings</h4>Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703-0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009-0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40-75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation.<h4>Conclusions</h4>Our results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003498&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003498; html:https://europepmc.org/articles/PMC7808664; pdf:https://europepmc.org/articles/PMC7808664?pdf=render
 33442528,https://doi.org/10.1140/epjds/s13688-020-00257-4,Privacy preserving data visualizations.,"Avraam D, Wilson R, Butters O, Burton T, Nicolaides C, Jones E, Boyd A, Burton P.",,EPJ data science,2021,2021-01-07,Y,Privacy Protection; Anonymization; Sensitive Data; Data Visualizations; Disclosure Control,,,"Data visualizations are a valuable tool used during both statistical analysis and the interpretation of results as they graphically reveal useful information about the structure, properties and relationships between variables, which may otherwise be concealed in tabulated data. In disciplines like medicine and the social sciences, where collected data include sensitive information about study participants, the sharing and publication of individual-level records is controlled by data protection laws and ethico-legal norms. Thus, as data visualizations - such as graphs and plots - may be linked to other released information and used to identify study participants and their personal attributes, their creation is often prohibited by the terms of data use. These restrictions are enforced to reduce the risk of breaching data subject confidentiality, however they limit analysts from displaying useful descriptive plots for their research features and findings. Here we propose the use of anonymization techniques to generate privacy-preserving visualizations that retain the statistical properties of the underlying data while still adhering to strict data disclosure rules. We demonstrate the use of (i) the well-known <i>k</i>-anonymization process which preserves privacy by reducing the granularity of the data using suppression and generalization, (ii) a novel deterministic approach that replaces individual-level observations with the centroids of each <i>k</i> nearest neighbours, and (iii) a probabilistic procedure that perturbs individual attributes with the addition of random stochastic noise. We apply the proposed methods to generate privacy-preserving data visualizations for exploratory data analysis and inferential regression plot diagnostics, and we discuss their strengths and limitations.",,pdf:https://epjdatascience.springeropen.com/track/pdf/10.1140/epjds/s13688-020-00257-4; doi:https://doi.org/10.1140/epjds/s13688-020-00257-4; html:https://europepmc.org/articles/PMC7790778; pdf:https://europepmc.org/articles/PMC7790778?pdf=render
-36215124,https://doi.org/10.1161/circgen.121.003598,Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.,"Khera AV, Wang M, Chaffin M, Emdin CA, Samani NJ, Schunkert H, Watkins H, McPherson R, Erdmann J, Elosua R, Boerwinkle E, Ardissino D, Butterworth AS, Di Angelantonio E, Naheed A, Danesh J, Chowdhury R, Krumholz HM, Sheu WH, Rich SS, Rotter JI, Chen YI, Gabriel S, Lander ES, Saleheen D, Kathiresan S.",,Circulation. Genomic and precision medicine,2022,2022-10-10,N,Atherosclerosis; coronary artery disease; Genetic Association Studies; Nitric Oxide Synthase Type Iii; Precision Medicine,,,"<h4>Background</h4>A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (<i>LDLR</i>) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.<h4>Methods</h4>To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.<h4>Results</h4>Rare variants in <i>LDLR</i> were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (<i>NOS3</i>), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in <i>NOS3</i> was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; <i>P</i>=5.50×10<sup>-9</sup>). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; <i>P</i>=5.00×10<sup>-6</sup>) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; <i>P</i>=2.00×10<sup>-4</sup>) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk.<h4>Conclusions</h4>Beyond <i>LDLR</i>, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the <i>NOS3</i> gene.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.121.003598; doi:https://doi.org/10.1161/CIRCGEN.121.003598
 29743285,https://doi.org/10.1136/bmj.k1717,Risk of stroke and transient ischaemic attack in patients with a diagnosis of resolved atrial fibrillation: retrospective cohort studies.,"Adderley NJ, Nirantharakumar K, Marshall T.",,BMJ (Clinical research ed.),2018,2018-05-09,Y,,Understanding the Causes of Disease,,"<h4>Objectives</h4>To determine rates of stroke or transient ischaemic attack (TIA) and all cause mortality in patients with a diagnosis of ""resolved"" atrial fibrillation compared to patients with unresolved atrial fibrillation and without atrial fibrillation.<h4>Design</h4>Two retrospective cohort studies.<h4>Setting</h4>General practices contributing to The Health Improvement Network, 1 January 2000 to 15 May 2016.<h4>Participants</h4>Adults aged 18 years or more with no previous stroke or TIA: 11 159 with resolved atrial fibrillation, 15 059 controls with atrial fibrillation, and 22 266 controls without atrial fibrillation.<h4>Main outcome measures</h4>Primary outcome was incidence of stroke or TIA. Secondary outcome was all cause mortality.<h4>Results</h4>Adjusted incidence rate ratios for stroke or TIA in patients with resolved atrial fibrillation were 0.76 (95% confidence interval 0.67 to 0.85, P<0.001) versus controls with atrial fibrillation and 1.63 (1.46 to 1.83, P<0.001) versus controls without atrial fibrillation. Adjusted incidence rate ratios for mortality in patients with resolved atrial fibrillation were 0.60 (0.56 to 0.65, P<0.001) versus controls with atrial fibrillation and 1.13 (1.06 to 1.21, P<0.001) versus controls without atrial fibrillation. When patients with resolved atrial fibrillation and documented recurrent atrial fibrillation were excluded the adjusted incidence rate ratio for stroke or TIA was 1.45 (1.26 to 1.67, P<0.001) versus controls without atrial fibrillation.<h4>Conclusion</h4>Patients with resolved atrial fibrillation remain at higher risk of stroke or TIA than patients without atrial fibrillation. The risk is increased even in those in whom recurrent atrial fibrillation is not documented. Guidelines should be updated to advocate continued use of anticoagulants in patients with resolved atrial fibrillation.",,pdf:https://www.bmj.com/content/bmj/361/bmj.k1717.full.pdf; doi:https://doi.org/10.1136/bmj.k1717; html:https://europepmc.org/articles/PMC5942157
+36215124,https://doi.org/10.1161/circgen.121.003598,Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.,"Khera AV, Wang M, Chaffin M, Emdin CA, Samani NJ, Schunkert H, Watkins H, McPherson R, Erdmann J, Elosua R, Boerwinkle E, Ardissino D, Butterworth AS, Di Angelantonio E, Naheed A, Danesh J, Chowdhury R, Krumholz HM, Sheu WH, Rich SS, Rotter JI, Chen YI, Gabriel S, Lander ES, Saleheen D, Kathiresan S.",,Circulation. Genomic and precision medicine,2022,2022-10-10,N,Atherosclerosis; coronary artery disease; Genetic Association Studies; Nitric Oxide Synthase Type Iii; Precision Medicine,,,"<h4>Background</h4>A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (<i>LDLR</i>) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.<h4>Methods</h4>To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.<h4>Results</h4>Rare variants in <i>LDLR</i> were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (<i>NOS3</i>), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in <i>NOS3</i> was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; <i>P</i>=5.50×10<sup>-9</sup>). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; <i>P</i>=5.00×10<sup>-6</sup>) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; <i>P</i>=2.00×10<sup>-4</sup>) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk.<h4>Conclusions</h4>Beyond <i>LDLR</i>, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the <i>NOS3</i> gene.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.121.003598; doi:https://doi.org/10.1161/CIRCGEN.121.003598
 36113526,https://doi.org/10.1016/s2214-109x(22)00332-1,"Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18: a geospatial modelling study.",Local Burden of Disease Household Air Pollution Collaborators.,,The Lancet. Global health,2022,2022-10-01,Y,,,,"<h4>Background</h4>More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels.<h4>Methods</h4>We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution.<h4>Findings</h4>Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000-257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution.<h4>Interpretation</h4>Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution.<h4>Funding</h4>Bill & Melinda Gates Foundation.",,pdf:https://repository.kaust.edu.sa/bitstream/10754/686177/1/1-s2.0-S2214109X22003321-main.pdf; doi:https://doi.org/10.1016/S2214-109X(22)00332-1; html:https://europepmc.org/articles/PMC9638039
 37221040,https://doi.org/10.1136/oemed-2022-108700,"Coverage, completion and outcomes of COVID-19 risk assessments in a multi-ethnic nationwide cohort of UK healthcare workers: a cross-sectional analysis from the UK-REACH Study.","Martin CA, Woolf K, Bryant L, Goss C, Gogoi M, Lagrata S, Papineni P, Qureshi I, Wobi F, Nellums L, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,Occupational and environmental medicine,2023,2023-05-23,Y,Ethnic Groups; risk assessment; Health Personnel; Covid-19,,,"<h4>Introduction</h4>There are limited data on the outcomes of COVID-19 risk assessment in healthcare workers (HCWs) or the association of ethnicity, other sociodemographic and occupational factors with risk assessment outcomes.<h4>Methods</h4>We used questionnaire data from UK-REACH (UK Research study into Ethnicity And COVID-19 outcomes in Healthcare workers), an ethnically diverse, nationwide cohort of UK HCWs. We derived four binary outcomes: (1) offered a risk assessment; (2) completed a risk assessment; (3) working practices changed as a result of the risk assessment; (4) wanted changes to working practices after risk assessment but working practices did not change.We examined the association of ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk variables on our outcomes using multivariable logistic regression.<h4>Results</h4>8649 HCWs were included in total. HCWs from ethnic minority groups were more likely to report being offered a risk assessment than white HCWs, and those from Asian and black ethnic groups were more likely to report having completed an assessment if offered. Ethnic minority HCWs had lower odds of reporting having their work change as a result of risk assessment. Those from Asian and black ethnic groups were more likely to report no changes to their working practices despite wanting them.Previous SARS-CoV-2 infection was associated with lower odds of being offered a risk assessment and having adjustments made to working practices.<h4>Discussion</h4>We found differences in risk assessment outcomes by ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk factors. These findings are concerning and warrant further research using actual (rather than reported) risk assessment outcomes in an unselected cohort.",,pdf:https://oem.bmj.com/content/oemed/80/7/399.full.pdf; doi:https://doi.org/10.1136/oemed-2022-108700; html:https://europepmc.org/articles/PMC10314065; pdf:https://europepmc.org/articles/PMC10314065?pdf=render
 33385551,https://doi.org/10.1016/j.neuroimage.2020.117689,Deep learning-based unlearning of dataset bias for MRI harmonisation and confound removal.,"Dinsdale NK, Jenkinson M, Namburete AIL.",,NeuroImage,2021,2020-12-30,Y,MRI; Harmonization; Joint Domain Adaptation,,,"Increasingly large MRI neuroimaging datasets are becoming available, including many highly multi-site multi-scanner datasets. Combining the data from the different scanners is vital for increased statistical power; however, this leads to an increase in variance due to nonbiological factors such as the differences in acquisition protocols and hardware, which can mask signals of interest. We propose a deep learning based training scheme, inspired by domain adaptation techniques, which uses an iterative update approach to aim to create scanner-invariant features while simultaneously maintaining performance on the main task of interest, thus reducing the influence of scanner on network predictions. We demonstrate the framework for regression, classification and segmentation tasks with two different network architectures. We show that not only can the framework harmonise many-site datasets but it can also adapt to many data scenarios, including biased datasets and limited training labels. Finally, we show that the framework can be extended for the removal of other known confounds in addition to scanner. The overall framework is therefore flexible and should be applicable to a wide range of neuroimaging studies.",,doi:https://doi.org/10.1016/j.neuroimage.2020.117689; doi:https://doi.org/10.1016/j.neuroimage.2020.117689; html:https://europepmc.org/articles/PMC7903160; pdf:https://europepmc.org/articles/PMC7903160?pdf=render
@@ -2253,8 +2253,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm
 33203707,https://doi.org/10.2337/dc20-1328,Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.,"Zheng JS, Luan J, Sofianopoulou E, Imamura F, Stewart ID, Day FR, Pietzner M, Wheeler E, Lotta LA, Gundersen TE, Amiano P, Ardanaz E, Chirlaque MD, Fagherazzi G, Franks PW, Kaaks R, Laouali N, Mancini FR, Nilsson PM, Onland-Moret NC, Olsen A, Overvad K, Panico S, Palli D, Ricceri F, Rolandsson O, Spijkerman AMW, Sánchez MJ, Schulze MB, Sala N, Sieri S, Tjønneland A, Tumino R, van der Schouw YT, Weiderpass E, Riboli E, Danesh J, Butterworth AS, Sharp SJ, Langenberg C, Forouhi NG, Wareham NJ.",,Diabetes care,2021,2020-11-17,Y,,,,"<h4>Objective</h4>Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.<h4>Research design and methods</h4>We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.<h4>Results</h4>We identified 11 genomic regions associated with plasma vitamin C (<i>P</i> < 5 × 10<sup>-8</sup>), with the strongest signal at <i>SLC23A1</i>, and 10 novel genetic loci including <i>SLC23A3</i>, <i>CHPT1</i>, <i>BCAS3</i>, <i>SNRPF</i>, <i>RER1</i>, <i>MAF</i>, <i>GSTA5</i>, <i>RGS14</i>, <i>AKT1</i>, and <i>FADS1</i>. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding <i>FADS1</i> variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).<h4>Conclusions</h4>These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.",,pdf:https://diabetesjournals.org/care/article-pdf/44/1/98/532486/dc201328.pdf; doi:https://doi.org/10.2337/dc20-1328; html:https://europepmc.org/articles/PMC7783939; pdf:https://europepmc.org/articles/PMC7783939?pdf=render
 36240095,https://doi.org/10.1212/wnl.0000000000201006,Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke.,"Jaworek T, Xu H, Gaynor BJ, Cole JW, Rannikmae K, Stanne TM, Tomppo L, Abedi V, Amouyel P, Armstrong ND, Attia J, Bell S, Benavente OR, Boncoraglio GB, Butterworth A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez J, Chen Z, Chong M, Cruchaga C, Cushman M, Danesh J, Debette S, Duggan DJ, Durda JP, Engstrom G, Enzinger C, Faul JD, Fecteau NS, Fernandez-Cadenas I, Gieger C, Giese AK, Grewal RP, Grittner U, Havulinna AS, Heitsch L, Hochberg MC, Holliday E, Hu J, Ilinca A, INVENT Consortium, Irvin MR, Jackson RD, Jacob MA, Janssen RR, Jimenez-Conde J, Johnson JA, Kamatani Y, Kardia SL, Koido M, Kubo M, Lange L, Lee JM, Lemmens R, Levi CR, Li J, Li L, Lin K, Lopez H, Luke S, Maguire J, McArdle PF, McDonough CW, Meschia JF, Metso T, Muller-Nurasyid M, O'Connor TD, O'Donnell M, Peddareddygari LR, Pera J, Perry JA, Peters A, Putaala J, Ray D, Rexrode K, Ribases M, Rosand J, Rothwell PM, Rundek T, Ryan KA, Sacco RL, Salomaa V, Sanchez-Mora C, Schmidt R, Sharma P, Slowik A, Smith JA, Smith NL, Wassertheil-Smoller S, Soederholm M, Stine OC, Strbian D, Sudlow CL, Tatlisumak T, Terao C, Thijs V, Torres-Aguila NP, Tregouet DA, Tuladhar AM, Veldink JH, Walters RG, Weir DR, Woo D, Worrall BB, Hong CC, Ross O, Zand R, Leeuw FE, Lindgren AG, Pare G, Anderson CD, Markus HS, Jern C, Malik R, Dichgans M, Mitchell BD, Kittner SJ, Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC).",,Neurology,2022,2022-08-31,Y,,,,"<h4>Background and objectives</h4>Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke.<h4>Methods</h4>We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS.<h4>Results</h4>We observed genome-wide significant associations of EOS with two variants in <i>ABO</i>, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008).<h4>Discussion</h4>The <i>ABO</i> locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.",,pdf:https://n.neurology.org/content/neurology/99/16/e1738.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000201006; html:https://europepmc.org/articles/PMC9620803; pdf:https://europepmc.org/articles/PMC9620803?pdf=render
 36210437,https://doi.org/10.1186/s12916-022-02588-7,Hesitancy for receiving regular SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis from the UK-REACH study.,"Veli N, Martin CA, Woolf K, Nazareth J, Pan D, Al-Oraibi A, Baggaley RF, Bryant L, Nellums LB, Gray LJ, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,BMC medicine,2022,2022-10-10,Y,Vaccination; Ethnicity; Healthcare; Hesitancy; Covid-19; Sars-cov-2,,,"<h4>Background</h4>Regular vaccination against SARS-CoV-2 may be needed to maintain immunity in 'at-risk' populations, which include healthcare workers (HCWs). However, little is known about the proportion of HCWs who might be hesitant about receiving a hypothetical regular SARS-CoV-2 vaccination or the factors associated with this hesitancy.<h4>Methods</h4>Cross-sectional analysis of questionnaire data collected as part of UK-REACH, a nationwide, longitudinal cohort study of HCWs. The outcome measure was binary, either a participant indicated they would definitely accept regular SARS-CoV-2 vaccination if recommended or they indicated some degree of hesitancy regarding acceptance (probably accept or less likely). We used logistic regression to identify factors associated with hesitancy for receiving regular vaccination.<h4>Results</h4>A total of 5454 HCWs were included in the analysed cohort, 23.5% of whom were hesitant about regular SARS-CoV-2 vaccination. Black HCWs were more likely to be hesitant than White HCWs (aOR 2.60, 95%CI 1.80-3.72) as were those who reported a previous episode of COVID-19 (1.33, 1.13-1.57 [vs those who tested negative]). Those who received influenza vaccination in the previous two seasons were over five times less likely to report hesitancy for regular SARS-CoV-2 vaccination than those not vaccinated against influenza in either season (0.18, 0.14-0.21). HCWs who trusted official sources of vaccine information (such as NHS or government adverts or websites) were less likely to report hesitancy for a regular vaccination programme. Those who had been exposed to information advocating against vaccination from friends and family were more likely to be hesitant.<h4>Conclusions</h4>In this study, nearly a quarter of UK HCWs were hesitant about receiving a regular SARS-CoV-2 vaccination. We have identified key factors associated with hesitancy for regular SARS-CoV-2 vaccination, which can be used to identify groups of HCWs at the highest risk of vaccine hesitancy and tailor interventions accordingly. Family and friends of HCWs may influence decisions about regular vaccination. This implies that working with HCWs and their social networks to allay concerns about SARS-CoV-2 vaccination could improve uptake in a regular vaccination programme.<h4>Trial registration</h4>ISRCTN Registry, ISRCTN11811602.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02588-7; doi:https://doi.org/10.1186/s12916-022-02588-7; html:https://europepmc.org/articles/PMC9548389; pdf:https://europepmc.org/articles/PMC9548389?pdf=render
-35908040,https://doi.org/10.1038/s41597-022-01534-9,"ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.","ISARIC Clinical Characterization Group, Garcia-Gallo E, Merson L, Kennon K, Kelly S, Citarella BW, Fryer DV, Shrapnel S, Lee J, Duque S, Fuentes YV, Balan V, Smith S, Wei J, Gonçalves BP, Russell CD, Sigfrid L, Dagens A, Olliaro PL, Baruch J, Kartsonaki C, Dunning J, Rojek A, Rashan A, Beane A, Murthy S, Reyes LF.",,Scientific data,2022,2022-07-30,Y,,,,"The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.",,pdf:https://www.nature.com/articles/s41597-022-01534-9.pdf; doi:https://doi.org/10.1038/s41597-022-01534-9; html:https://europepmc.org/articles/PMC9339000; pdf:https://europepmc.org/articles/PMC9339000?pdf=render
 32062083,https://doi.org/10.1016/j.neuroimage.2020.116604,Optimising network modelling methods for fMRI.,"Pervaiz U, Vidaurre D, Woolrich MW, Smith SM.",,NeuroImage,2020,2020-02-13,Y,Functional Connectivity; Connectome; Deep Learning; Riemannian Geometry; Convolutional Neural Networks; Netmat,,,"A major goal of neuroimaging studies is to develop predictive models to analyze the relationship between whole brain functional connectivity patterns and behavioural traits. However, there is no single widely-accepted standard pipeline for analyzing functional connectivity. The common procedure for designing functional connectivity based predictive models entails three main steps: parcellating the brain, estimating the interaction between defined parcels, and lastly, using these integrated associations between brain parcels as features fed to a classifier for predicting non-imaging variables e.g., behavioural traits, demographics, emotional measures, etc. There are also additional considerations when using correlation-based measures of functional connectivity, resulting in three supplementary steps: utilising Riemannian geometry tangent space parameterization to preserve the geometry of functional connectivity; penalizing the connectivity estimates with shrinkage approaches to handle challenges related to short time-series (and noisy) data; and removing confounding variables from brain-behaviour data. These six steps are contingent on each-other, and to optimise a general framework one should ideally examine these various methods simultaneously. In this paper, we investigated strengths and short-comings, both independently and jointly, of the following measures: parcellation techniques of four kinds (categorized further depending upon number of parcels), five measures of functional connectivity, the decision of staying in the ambient space of connectivity matrices or in tangent space, the choice of applying shrinkage estimators, six alternative techniques for handling confounds and finally four novel classifiers/predictors. For performance evaluation, we have selected two of the largest datasets, UK Biobank and the Human Connectome Project resting state fMRI data, and have run more than 9000 different pipeline variants on a total of ∼14000 individuals to determine the optimum pipeline. For independent performance validation, we have run some best-performing pipeline variants on ABIDE and ACPI datasets (∼1000 subjects) to evaluate the generalisability of proposed network modelling methods.",,doi:https://doi.org/10.1016/j.neuroimage.2020.116604; doi:https://doi.org/10.1016/j.neuroimage.2020.116604; html:https://europepmc.org/articles/PMC7086233
+35908040,https://doi.org/10.1038/s41597-022-01534-9,"ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.","ISARIC Clinical Characterization Group, Garcia-Gallo E, Merson L, Kennon K, Kelly S, Citarella BW, Fryer DV, Shrapnel S, Lee J, Duque S, Fuentes YV, Balan V, Smith S, Wei J, Gonçalves BP, Russell CD, Sigfrid L, Dagens A, Olliaro PL, Baruch J, Kartsonaki C, Dunning J, Rojek A, Rashan A, Beane A, Murthy S, Reyes LF.",,Scientific data,2022,2022-07-30,Y,,,,"The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.",,pdf:https://www.nature.com/articles/s41597-022-01534-9.pdf; doi:https://doi.org/10.1038/s41597-022-01534-9; html:https://europepmc.org/articles/PMC9339000; pdf:https://europepmc.org/articles/PMC9339000?pdf=render
 31122927,https://doi.org/10.1136/bmj.l1778,Determinants of the decline in mortality from acute stroke in England: linked national database study of 795 869 adults.,"Seminog OO, Scarborough P, Wright FL, Rayner M, Goldacre MJ.",,BMJ (Clinical research ed.),2019,2019-05-22,Y,,Improving Public Health,,"<h4>Objectives</h4>To study trends in stroke mortality rates, event rates, and case fatality, and to explain the extent to which the reduction in stroke mortality rates was influenced by changes in stroke event rates or case fatality.<h4>Design</h4>Population based study.<h4>Setting</h4>Person linked routine hospital and mortality data, England.<h4>Participants</h4>795 869 adults aged 20 and older who were admitted to hospital with acute stroke or died from stroke.<h4>Main outcome measures</h4>Stroke mortality rates, stroke event rates (stroke admission or stroke death without admission), and case fatality within 30 days after stroke.<h4>Results</h4>Between 2001 and 2010 stroke mortality rates decreased by 55%, stroke event rates by 20%, and case fatality by 40%. The study population included 358 599 (45%) men and 437 270 (55%) women. Average annual change in mortality rate was -6.0% (95% confidence interval -6.2% to -5.8%) in men and -6.1% (-6.3% to -6.0%) in women, in stroke event rate was -1.3% (-1.4% to -1.2%) in men and -2.1% (-2.2 to -2.0) in women, and in case fatality was -4.7% (-4.9% to -4.5%) in men and -4.4% (-4.5% to -4.2%) in women. Mortality and case fatality but not event rate declined in all age groups: the stroke event rate decreased in older people but increased by 2% each year in adults aged 35 to 54 years. Of the total decline in mortality rates, 71% was attributed to the decline in case fatality (78% in men and 66% in women) and the remainder to the reduction in stroke event rates. The contribution of the two factors varied between age groups. Whereas the reduction in mortality rates in people younger than 55 years was due to the reduction in case fatality, in the oldest age group (≥85 years) reductions in case fatality and event rates contributed nearly equally.<h4>Conclusions</h4>Declines in case fatality, probably driven by improvements in stroke care, contributed more than declines in event rates to the overall reduction in stroke mortality. Mortality reduction in men and women younger than 55 was solely a result of a decrease in case fatality, whereas stroke event rates increased in the age group 35 to 54 years. The increase in stroke event rates in young adults is a concern. This suggests that stroke prevention needs to be strengthened to reduce the occurrence of stroke in people younger than 55 years.",,pdf:https://www.bmj.com/content/bmj/365/bmj.l1778.full.pdf; doi:https://doi.org/10.1136/bmj.l1778; html:https://europepmc.org/articles/PMC6529851
 32831200,https://doi.org/10.3233/jad-200208,Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.,"Shi L, Winchester LM, Liu BY, Killick R, Ribe EM, Westwood S, Baird AL, Buckley NJ, Hong S, Dobricic V, Kilpert F, Franke A, Kiddle S, Sattlecker M, Dobson R, Cuadrado A, Hye A, Ashton NJ, Morgan AR, Bos I, Vos SJB, Ten Kate M, Scheltens P, Vandenberghe R, Gabel S, Meersmans K, Engelborghs S, De Roeck EE, Sleegers K, Frisoni GB, Blin O, Richardson JC, Bordet R, Molinuevo JL, Rami L, Wallin A, Kettunen P, Tsolaki M, Verhey F, Lleó A, Alcolea D, Popp J, Peyratout G, Martinez-Lage P, Tainta M, Johannsen P, Teunissen CE, Freund-Levi Y, Frölich L, Legido-Quigley C, Barkhof F, Blennow K, Rasmussen KL, Nordestgaard BG, Frikke-Schmidt R, Nielsen SF, Soininen H, Vellas B, Kloszewska I, Mecocci P, Zetterberg H, Morgan BP, Streffer J, Visser PJ, Bertram L, Nevado-Holgado AJ, Lovestone S.",,Journal of Alzheimer's disease : JAD,2020,2020-01-01,Y,Replication; Wnt signaling; Dickkopf-1; Somascan; Atn Framework,,,"<h4>Background</h4>Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.<h4>Objective</h4>We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.<h4>Methods</h4>We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677).<h4>Results</h4>We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts.<h4>Conclusions</h4>Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo.",,pdf:https://ddd.uab.cat/pub/artpub/2020/pmc_32831200/pmc_32831200.pdf; doi:https://doi.org/10.3233/JAD-200208; html:https://europepmc.org/articles/PMC7683080; pdf:https://europepmc.org/articles/PMC7683080?pdf=render
 31005938,https://doi.org/10.1136/bmjopen-2018-027289,"Longitudinal access and exposure to green-blue spaces and individual-level mental health and well-being: protocol for a longitudinal, population-wide record-linked natural experiment.","Mizen A, Song J, Fry R, Akbari A, Berridge D, Parker SC, Johnson R, Lovell R, Lyons RA, Nieuwenhuijsen M, Stratton G, Wheeler BW, White J, White M, Rodgers SE.",,BMJ open,2019,2019-04-20,Y,Geographic information systems; Mental health; Environmental exposure; Longitudinal; Wellbeing; Routine Linked Data,Improving Public Health,,"<h4>Introduction</h4>Studies suggest that access and exposure to green-blue spaces (GBS) have beneficial impacts on mental health. However, the evidence base is limited with respect to longitudinal studies. The main aim of this longitudinal, population-wide, record-linked natural experiment, is to model the daily lived experience by linking GBS accessibility indices, residential GBS exposure and health data; to enable quantification of the impact of GBS on well-being and common mental health disorders, for a national population.<h4>Methods and analysis</h4>This research will estimate the impact of neighbourhood GBS access, GBS exposure and visits to GBS on the risk of common mental health conditions and the opportunity for promoting subjective well-being (SWB); both key priorities for public health. We will use a Geographic Information System (GIS) to create quarterly household GBS accessibility indices and GBS exposure using digital map and satellite data for 1.4 million homes in Wales, UK (2008-2018). We will link the GBS accessibility indices and GBS exposures to individual-level mental health outcomes for 1.7 million people with general practitioner (GP) data and data from the National Survey for Wales (n=~12 000) on well-being in the Secure Anonymised Information Linkage (SAIL) Databank. We will examine if these associations are modified by multiple sociophysical variables, migration and socioeconomic disadvantage. Subgroup analyses will examine associations by different types of GBS. This longitudinal study will be augmented by cross-sectional research using survey data on self-reported visits to GBS and SWB.<h4>Ethics and dissemination</h4>All data will be anonymised and linked within the privacy protecting SAIL Databank. We will be using anonymised data and therefore we are exempt from National Research Ethics Committee (NREC). An Information Governance Review Panel (IGRP) application (Project ID: 0562) to link these data has been approved.The research programme will be undertaken in close collaboration with public/patient involvement groups. A multistrategy programme of dissemination is planned with the academic community, policy-makers, practitioners and the public.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/4/e027289.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-027289; html:https://europepmc.org/articles/PMC6528002; pdf:https://europepmc.org/articles/PMC6528002?pdf=render
diff --git a/data/papers.json b/data/papers.json
index 936bf6ea..43d1ce20 100644
--- a/data/papers.json
+++ b/data/papers.json
@@ -1138,23 +1138,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1097/EDE.0000000000001626"
   },
-  {
-    "id": "37562853",
-    "doi": "https://doi.org/10.1136/bmjment-2023-300842",
-    "title": "Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.",
-    "authorString": "McElroy E, Herrett E, Patel K, Piehlmaier DM, Gessa GD, Huggins C, Green MJ, Kwong ASF, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, OpenSAFELY Collaborative, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson LA, Patalay P, Longitudinal Health and Wellbeing Collaborative.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ mental health",
-    "pubYear": "2023",
-    "date": "2023-08-01",
-    "isOpenAccess": "Y",
-    "keywords": "Psychiatry; Anxiety Disorders; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic.<h4>Objective</h4>To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic.<h4>Methods</h4>Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP.<h4>Findings</h4>In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic.<h4>Conclusions</h4>People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use.<h4>Clinical implications</h4>Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/bmjment-2023-300842; html:https://europepmc.org/articles/PMC10577768; pdf:https://europepmc.org/articles/PMC10577768?pdf=render"
-  },
   {
     "id": "35501391",
     "doi": "https://doi.org/10.1038/s41416-022-01830-6",
@@ -1172,6 +1155,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41416-022-01830-6.pdf; doi:https://doi.org/10.1038/s41416-022-01830-6; html:https://europepmc.org/articles/PMC9060409; pdf:https://europepmc.org/articles/PMC9060409?pdf=render"
   },
+  {
+    "id": "37562853",
+    "doi": "https://doi.org/10.1136/bmjment-2023-300842",
+    "title": "Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.",
+    "authorString": "McElroy E, Herrett E, Patel K, Piehlmaier DM, Gessa GD, Huggins C, Green MJ, Kwong ASF, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, OpenSAFELY Collaborative, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson LA, Patalay P, Longitudinal Health and Wellbeing Collaborative.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ mental health",
+    "pubYear": "2023",
+    "date": "2023-08-01",
+    "isOpenAccess": "Y",
+    "keywords": "Psychiatry; Anxiety Disorders; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic.<h4>Objective</h4>To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic.<h4>Methods</h4>Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP.<h4>Findings</h4>In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic.<h4>Conclusions</h4>People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use.<h4>Clinical implications</h4>Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1136/bmjment-2023-300842; html:https://europepmc.org/articles/PMC10577768; pdf:https://europepmc.org/articles/PMC10577768?pdf=render"
+  },
   {
     "id": "36469089",
     "doi": "https://doi.org/10.1093/ageing/afac250",
@@ -1376,6 +1376,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.compbiomed.2021.104216; doi:https://doi.org/10.1016/j.compbiomed.2021.104216; html:https://europepmc.org/articles/PMC7910278"
   },
+  {
+    "id": "36332519",
+    "doi": "https://doi.org/10.1016/j.ijmedinf.2022.104905",
+    "title": "Creation of a core competency framework for clinical informatics: From genesis to maintaining relevance.",
+    "authorString": "Davies A, Hassey A, Williams J, Moulton G.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of medical informatics",
+    "pubYear": "2022",
+    "date": "2022-10-30",
+    "isOpenAccess": "N",
+    "keywords": "Informatics; Core Competencies; Competency Framework; Healthcare Workforce; Informaticians",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>The United Kingdom's Faculty of Clinical Informatics (FCI) embarked on the creation of a core competency framework in response to the need to provide support to those working in clinical and health and social care that also hold informatics roles.<h4>Methods</h4>The work spanned several phases and utilised a mixed-methods approach consisting of interviews, surveys, job listing analysis, expert discussions and a systematic literature review. The work presented here explores the lessons learnt from the process of creating the framework and the next steps for ensuring its use and continued relevance.<h4>Results</h4>A core competency framework was generated with six domains, 36 sub-domains and 111 individual competency statements. A discussion and eight key recommendations are presented based on the development of this framework.<h4>Conclusion</h4>Definition of the target audience is important to manage scope and define purpose. The use of robust reproducible methods helps to establish a strong evidence base. Competency frameworks should be living documents, ideally presented in an accessible digital form to enable easy use and embedding in other tools (e.g. for accreditation or to search competencies).",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.ijmedinf.2022.104905"
+  },
   {
     "id": "36860174",
     "doi": "https://doi.org/10.1093/ije/dyad022",
@@ -1410,23 +1427,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e070637.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070637; html:https://europepmc.org/articles/PMC10255029; pdf:https://europepmc.org/articles/PMC10255029?pdf=render"
   },
-  {
-    "id": "36332519",
-    "doi": "https://doi.org/10.1016/j.ijmedinf.2022.104905",
-    "title": "Creation of a core competency framework for clinical informatics: From genesis to maintaining relevance.",
-    "authorString": "Davies A, Hassey A, Williams J, Moulton G.",
-    "authorAffiliations": "",
-    "journalTitle": "International journal of medical informatics",
-    "pubYear": "2022",
-    "date": "2022-10-30",
-    "isOpenAccess": "N",
-    "keywords": "Informatics; Core Competencies; Competency Framework; Healthcare Workforce; Informaticians",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>The United Kingdom's Faculty of Clinical Informatics (FCI) embarked on the creation of a core competency framework in response to the need to provide support to those working in clinical and health and social care that also hold informatics roles.<h4>Methods</h4>The work spanned several phases and utilised a mixed-methods approach consisting of interviews, surveys, job listing analysis, expert discussions and a systematic literature review. The work presented here explores the lessons learnt from the process of creating the framework and the next steps for ensuring its use and continued relevance.<h4>Results</h4>A core competency framework was generated with six domains, 36 sub-domains and 111 individual competency statements. A discussion and eight key recommendations are presented based on the development of this framework.<h4>Conclusion</h4>Definition of the target audience is important to manage scope and define purpose. The use of robust reproducible methods helps to establish a strong evidence base. Competency frameworks should be living documents, ideally presented in an accessible digital form to enable easy use and embedding in other tools (e.g. for accreditation or to search competencies).",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.ijmedinf.2022.104905"
-  },
   {
     "id": "35273122",
     "doi": "https://doi.org/10.1136/heartjnl-2021-320325",
@@ -2158,23 +2158,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/s0140-6736(22)01656-7; doi:https://doi.org/10.1016/S0140-6736(22)01656-7; html:https://europepmc.org/articles/PMC9560746; pdf:https://europepmc.org/articles/PMC9560746?pdf=render"
   },
-  {
-    "id": "37368983",
-    "doi": "https://doi.org/10.2337/dc23-0294",
-    "title": "Relationship Among Diabetes, Obesity, and Cardiovascular Disease Phenotypes: A UK Biobank Cohort Study.",
-    "authorString": "Brown OI, Drozd M, McGowan H, Giannoudi M, Conning-Rowland M, Gierula J, Straw S, Wheatcroft SB, Bridge K, Roberts LD, Levelt E, Ajjan R, Griffin KJ, Bailey MA, Kearney MT, Cubbon RM.",
-    "authorAffiliations": "",
-    "journalTitle": "Diabetes care",
-    "pubYear": "2023",
-    "date": "2023-08-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>Obesity and diabetes frequently coexist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events, and mortality in the UK Biobank stratified by BMI and diabetes.<h4>Research design and methods</h4>A total of 451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including carotid intima-media thickness (CIMT), arterial stiffness, left ventricular ejection fraction (LVEF), and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRRs) for myocardial infarction, ischemic stroke, and cardiovascular death, with normal-weight nondiabetes as comparator.<h4>Results</h4>Five percent of participants had diabetes (10% normal weight, 34% overweight, and 55% obese vs. 34%, 43%, and 23%, respectively, without diabetes). In the nondiabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness, and CCI and lower LVEF (P < 0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (P < 0.005), particularly in the normal-weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke, and cardiovascular mortality rose across increasing BMI categories without diabetes (P < 0.005); this was comparable in the diabetes groups (P-interaction > 0.05). Normal-weight diabetes had comparable adjusted cardiovascular mortality to obese nondiabetes (IRR 1.22 [95% CI 0.96-1.56]; P = 0.1).<h4>Conclusions</h4>Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. While adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting that other factors underpin the high cardiovascular risk of normal-weight diabetes.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.2337/dc23-0294; html:https://europepmc.org/articles/PMC10369123; pdf:https://europepmc.org/articles/PMC10369123?pdf=render"
-  },
   {
     "id": "37254630",
     "doi": "https://doi.org/10.1111/acel.13808",
@@ -2192,6 +2175,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1111/acel.13808; doi:https://doi.org/10.1111/acel.13808; html:https://europepmc.org/articles/PMC10352557; pdf:https://europepmc.org/articles/PMC10352557?pdf=render"
   },
+  {
+    "id": "37368983",
+    "doi": "https://doi.org/10.2337/dc23-0294",
+    "title": "Relationship Among Diabetes, Obesity, and Cardiovascular Disease Phenotypes: A UK Biobank Cohort Study.",
+    "authorString": "Brown OI, Drozd M, McGowan H, Giannoudi M, Conning-Rowland M, Gierula J, Straw S, Wheatcroft SB, Bridge K, Roberts LD, Levelt E, Ajjan R, Griffin KJ, Bailey MA, Kearney MT, Cubbon RM.",
+    "authorAffiliations": "",
+    "journalTitle": "Diabetes care",
+    "pubYear": "2023",
+    "date": "2023-08-01",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>Obesity and diabetes frequently coexist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events, and mortality in the UK Biobank stratified by BMI and diabetes.<h4>Research design and methods</h4>A total of 451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including carotid intima-media thickness (CIMT), arterial stiffness, left ventricular ejection fraction (LVEF), and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRRs) for myocardial infarction, ischemic stroke, and cardiovascular death, with normal-weight nondiabetes as comparator.<h4>Results</h4>Five percent of participants had diabetes (10% normal weight, 34% overweight, and 55% obese vs. 34%, 43%, and 23%, respectively, without diabetes). In the nondiabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness, and CCI and lower LVEF (P < 0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (P < 0.005), particularly in the normal-weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke, and cardiovascular mortality rose across increasing BMI categories without diabetes (P < 0.005); this was comparable in the diabetes groups (P-interaction > 0.05). Normal-weight diabetes had comparable adjusted cardiovascular mortality to obese nondiabetes (IRR 1.22 [95% CI 0.96-1.56]; P = 0.1).<h4>Conclusions</h4>Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. While adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting that other factors underpin the high cardiovascular risk of normal-weight diabetes.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.2337/dc23-0294; html:https://europepmc.org/articles/PMC10369123; pdf:https://europepmc.org/articles/PMC10369123?pdf=render"
+  },
   {
     "id": "36638616",
     "doi": "https://doi.org/10.1016/j.compbiomed.2022.106425",
@@ -2226,23 +2226,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264828&type=printable; doi:https://doi.org/10.1371/journal.pone.0264828; html:https://europepmc.org/articles/PMC8982857; pdf:https://europepmc.org/articles/PMC8982857?pdf=render"
   },
-  {
-    "id": "36719907",
-    "doi": "https://doi.org/10.1371/journal.pmed.1004086",
-    "title": "Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study.",
-    "authorString": "Turtle L, Thorpe M, Drake TM, Swets M, Palmieri C, Russell CD, Ho A, Aston S, Wootton DG, Richter A, de Silva TI, Hardwick HE, Leeming G, Law A, Openshaw PJM, Harrison EM, ISARIC4C investigators, Baillie JK, Semple MG, Docherty AB.",
-    "authorAffiliations": "",
-    "journalTitle": "PLoS medicine",
-    "pubYear": "2023",
-    "date": "2023-01-31",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic.<h4>Methods and findings</h4>We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent.<h4>Conclusions</h4>Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group.<h4>Trial registration</h4>ISRCTN 66726260.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004086&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004086; html:https://europepmc.org/articles/PMC9928075; pdf:https://europepmc.org/articles/PMC9928075?pdf=render"
-  },
   {
     "id": "36195871",
     "doi": "https://doi.org/10.1186/s12916-022-02533-8",
@@ -2260,6 +2243,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02533-8; doi:https://doi.org/10.1186/s12916-022-02533-8; html:https://europepmc.org/articles/PMC9533594; pdf:https://europepmc.org/articles/PMC9533594?pdf=render"
   },
+  {
+    "id": "36719907",
+    "doi": "https://doi.org/10.1371/journal.pmed.1004086",
+    "title": "Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study.",
+    "authorString": "Turtle L, Thorpe M, Drake TM, Swets M, Palmieri C, Russell CD, Ho A, Aston S, Wootton DG, Richter A, de Silva TI, Hardwick HE, Leeming G, Law A, Openshaw PJM, Harrison EM, ISARIC4C investigators, Baillie JK, Semple MG, Docherty AB.",
+    "authorAffiliations": "",
+    "journalTitle": "PLoS medicine",
+    "pubYear": "2023",
+    "date": "2023-01-31",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic.<h4>Methods and findings</h4>We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent.<h4>Conclusions</h4>Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group.<h4>Trial registration</h4>ISRCTN 66726260.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004086&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004086; html:https://europepmc.org/articles/PMC9928075; pdf:https://europepmc.org/articles/PMC9928075?pdf=render"
+  },
   {
     "id": "37468507",
     "doi": "https://doi.org/10.1038/s41598-023-37580-5",
@@ -2362,23 +2362,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/9/e042483.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042483; html:https://europepmc.org/articles/PMC8438582; pdf:https://europepmc.org/articles/PMC8438582?pdf=render"
   },
-  {
-    "id": "34799365",
-    "doi": "https://doi.org/10.1136/bmjopen-2021-054861",
-    "title": "Retrospective cohort study to evaluate medication use in patients hospitalised with COVID-19 in Scotland: protocol for a national observational study.",
-    "authorString": "Mueller T, Kerr S, McTaggart S, Kurdi A, Vasileiou E, Docherty A, Fraser K, Shi T, Simpson CR, Bennie M, Sheikh A.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2021",
-    "date": "2021-11-19",
-    "isOpenAccess": "Y",
-    "keywords": "Therapeutics; clinical pharmacology; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>COVID-19 has caused millions of hospitalisations and deaths globally. A range of vaccines have been developed and are being deployed at scale in the UK to prevent SARS-CoV-2 infection, which have reduced risk of infection and severe COVID-19 outcomes. Those with COVID-19 are now being treated with several repurposed drugs based on evidence emerging from recent clinical trials. However, there is currently limited real-world data available related to the use of these drugs in routine clinical practice. The purpose of this study is to address the prevailing knowledge gaps regarding the use of dexamethasone, remdesivir and tocilizumab by conducting an exploratory drug utilisation study, aimed at providing in-depth descriptions of patients receiving these drugs as well as the treatment patterns observed in Scotland.<h4>Methods and analysis</h4>Retrospective cohort study, comprising adult patients admitted to hospital with confirmed or suspected COVID-19 across five Scottish Health Boards using data from in-hospital ePrescribing linked to the Early Estimation of Vaccine and Anti-Viral Effectiveness (EAVE II) COVID-19 surveillance platform. The primary outcome will be exposure to the medicines of interest (dexamethasone, remdesivir, tocilizumab), either alone or in combination; exposure will be described in terms of drug(s) of choice; prescribed and administered dose; treatment duration; and any changes in treatment, for example, dose escalation and/or switching to an alternative drug. Analyses will primarily be descriptive in nature.<h4>Ethics and dissemination</h4>Ethical and information governance approvals have been obtained by the National Research Ethics Service Committee, South East Scotland 02 and the Public Benefit and Privacy Panel for Health and Social Care, respectively. Findings from this study will be presented at academic and clinical conferences, and to the funders and other interested parties as appropriate; study findings will also be published in peer-reviewed journals. Publications will be available on the EAVE II website (https://www.ed.ac.uk/usher/eave-ii/key-outputs/our-publications), alongside lay summaries and infographics aimed at the general public. Press releases will also be considered, if appropriate.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e054861.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054861; html:https://europepmc.org/articles/PMC8609490; pdf:https://europepmc.org/articles/PMC8609490?pdf=render"
-  },
   {
     "id": "32741245",
     "doi": "https://doi.org/10.1177/0954411920946526",
@@ -2396,6 +2379,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/0954411920946526; doi:https://doi.org/10.1177/0954411920946526; html:https://europepmc.org/articles/PMC7675765; pdf:https://europepmc.org/articles/PMC7675765?pdf=render"
   },
+  {
+    "id": "34799365",
+    "doi": "https://doi.org/10.1136/bmjopen-2021-054861",
+    "title": "Retrospective cohort study to evaluate medication use in patients hospitalised with COVID-19 in Scotland: protocol for a national observational study.",
+    "authorString": "Mueller T, Kerr S, McTaggart S, Kurdi A, Vasileiou E, Docherty A, Fraser K, Shi T, Simpson CR, Bennie M, Sheikh A.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2021",
+    "date": "2021-11-19",
+    "isOpenAccess": "Y",
+    "keywords": "Therapeutics; clinical pharmacology; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>COVID-19 has caused millions of hospitalisations and deaths globally. A range of vaccines have been developed and are being deployed at scale in the UK to prevent SARS-CoV-2 infection, which have reduced risk of infection and severe COVID-19 outcomes. Those with COVID-19 are now being treated with several repurposed drugs based on evidence emerging from recent clinical trials. However, there is currently limited real-world data available related to the use of these drugs in routine clinical practice. The purpose of this study is to address the prevailing knowledge gaps regarding the use of dexamethasone, remdesivir and tocilizumab by conducting an exploratory drug utilisation study, aimed at providing in-depth descriptions of patients receiving these drugs as well as the treatment patterns observed in Scotland.<h4>Methods and analysis</h4>Retrospective cohort study, comprising adult patients admitted to hospital with confirmed or suspected COVID-19 across five Scottish Health Boards using data from in-hospital ePrescribing linked to the Early Estimation of Vaccine and Anti-Viral Effectiveness (EAVE II) COVID-19 surveillance platform. The primary outcome will be exposure to the medicines of interest (dexamethasone, remdesivir, tocilizumab), either alone or in combination; exposure will be described in terms of drug(s) of choice; prescribed and administered dose; treatment duration; and any changes in treatment, for example, dose escalation and/or switching to an alternative drug. Analyses will primarily be descriptive in nature.<h4>Ethics and dissemination</h4>Ethical and information governance approvals have been obtained by the National Research Ethics Service Committee, South East Scotland 02 and the Public Benefit and Privacy Panel for Health and Social Care, respectively. Findings from this study will be presented at academic and clinical conferences, and to the funders and other interested parties as appropriate; study findings will also be published in peer-reviewed journals. Publications will be available on the EAVE II website (https://www.ed.ac.uk/usher/eave-ii/key-outputs/our-publications), alongside lay summaries and infographics aimed at the general public. Press releases will also be considered, if appropriate.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e054861.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054861; html:https://europepmc.org/articles/PMC8609490; pdf:https://europepmc.org/articles/PMC8609490?pdf=render"
+  },
   {
     "id": "36000189",
     "doi": "https://doi.org/10.1515/dx-2022-0052",
@@ -2787,23 +2787,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-022-34244-2.pdf; doi:https://doi.org/10.1038/s41467-022-34244-2; html:https://europepmc.org/articles/PMC9651890; pdf:https://europepmc.org/articles/PMC9651890?pdf=render"
   },
-  {
-    "id": "36997856",
-    "doi": "https://doi.org/10.1186/s12882-023-03126-0",
-    "title": "A clinical frailty scale obtained from MDT discussion performs poorly in assessing frailty in haemodialysis recipients.",
-    "authorString": "Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC nephrology",
-    "pubYear": "2023",
-    "date": "2023-03-30",
-    "isOpenAccess": "Y",
-    "keywords": "Mortality; Frailty; Haemodialysis; Hospitalisation; Clinical Frailty Scale",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>The Clinical Frailty Scale (CFS) is a commonly utilised frailty screening tool that has been associated with hospitalisation and mortality in haemodialysis recipients, but is subject to heterogenous methodologies including subjective clinician opinion. The aims of this study were to (i) examine the accuracy of a subjective, multidisciplinary assessment of CFS at haemodialysis Quality Assurance (QA) meetings (CFS-MDT), compared with a standard CFS score via clinical interview, and (ii) ascertain the associations of these scores with hospitalisation and mortality.<h4>Methods</h4>We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalisation. Frailty was assessed using the CFS after structured clinical interview. The CFS-MDT was derived from consensus at haemodialysis QA meetings, involving dialysis nurses, dietitians, and nephrologists.<h4>Results</h4>453 participants were followed-up for a median of 685 days (IQR 544-812), during which there were 96 (21.2%) deaths and 1136 hospitalisations shared between 327 (72.1%) participants. Frailty was identified in 246 (54.3%) participants via CFS, but only 120 (26.5%) via CFS-MDT. There was weak correlation (Spearman Rho 0.485, P\u2009<\u20090.001) on raw frailty scores and minimal agreement (Cohen's \u03ba\u2009=\u20090.274, P\u2009<\u20090.001) on categorisation of frail, vulnerable and robust between the CFS and CFS-MDT. Increasing frailty was associated with higher rates of hospitalisation for the CFS (IRR 1.26, 95% C.I. 1.17-1.36, P\u2009=\u20090.016) and CFS-MDT (IRR 1.10, 1.02-1.19, P\u2009=\u20090.02), but only the CFS-MDT was associated with nights spent in hospital (IRR 1.22, 95% C.I. 1.08-1.38, P\u2009=\u20090.001). Both scores were associated with mortality (CFS HR 1.31, 95% C.I. 1.09-1.57, P\u2009=\u20090.004; CFS-MDT HR 1.36, 95% C.I. 1.16-1.59, P\u2009<\u20090.001).<h4>Conclusions</h4>Assessment of CFS is deeply affected by the underlying methodology, with the potential to profoundly affect decision-making. The CFS-MDT appears to be a weak alternative to conventional CFS. Standardisation of CFS use is of paramount importance in clinical and research practice in haemodialysis.<h4>Trial registration</h4>Clinicaltrials.gov : NCT03071107 registered 06/03/2017.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-023-03126-0; doi:https://doi.org/10.1186/s12882-023-03126-0; html:https://europepmc.org/articles/PMC10062243; pdf:https://europepmc.org/articles/PMC10062243?pdf=render"
-  },
   {
     "id": "36426419",
     "doi": "https://doi.org/10.1111/hsc.14109",
@@ -2821,6 +2804,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/hsc.14109; doi:https://doi.org/10.1111/hsc.14109; html:https://europepmc.org/articles/PMC10100139; pdf:https://europepmc.org/articles/PMC10100139?pdf=render"
   },
+  {
+    "id": "36997856",
+    "doi": "https://doi.org/10.1186/s12882-023-03126-0",
+    "title": "A clinical frailty scale obtained from MDT discussion performs poorly in assessing frailty in haemodialysis recipients.",
+    "authorString": "Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC nephrology",
+    "pubYear": "2023",
+    "date": "2023-03-30",
+    "isOpenAccess": "Y",
+    "keywords": "Mortality; Frailty; Haemodialysis; Hospitalisation; Clinical Frailty Scale",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>The Clinical Frailty Scale (CFS) is a commonly utilised frailty screening tool that has been associated with hospitalisation and mortality in haemodialysis recipients, but is subject to heterogenous methodologies including subjective clinician opinion. The aims of this study were to (i) examine the accuracy of a subjective, multidisciplinary assessment of CFS at haemodialysis Quality Assurance (QA) meetings (CFS-MDT), compared with a standard CFS score via clinical interview, and (ii) ascertain the associations of these scores with hospitalisation and mortality.<h4>Methods</h4>We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalisation. Frailty was assessed using the CFS after structured clinical interview. The CFS-MDT was derived from consensus at haemodialysis QA meetings, involving dialysis nurses, dietitians, and nephrologists.<h4>Results</h4>453 participants were followed-up for a median of 685 days (IQR 544-812), during which there were 96 (21.2%) deaths and 1136 hospitalisations shared between 327 (72.1%) participants. Frailty was identified in 246 (54.3%) participants via CFS, but only 120 (26.5%) via CFS-MDT. There was weak correlation (Spearman Rho 0.485, P\u2009<\u20090.001) on raw frailty scores and minimal agreement (Cohen's \u03ba\u2009=\u20090.274, P\u2009<\u20090.001) on categorisation of frail, vulnerable and robust between the CFS and CFS-MDT. Increasing frailty was associated with higher rates of hospitalisation for the CFS (IRR 1.26, 95% C.I. 1.17-1.36, P\u2009=\u20090.016) and CFS-MDT (IRR 1.10, 1.02-1.19, P\u2009=\u20090.02), but only the CFS-MDT was associated with nights spent in hospital (IRR 1.22, 95% C.I. 1.08-1.38, P\u2009=\u20090.001). Both scores were associated with mortality (CFS HR 1.31, 95% C.I. 1.09-1.57, P\u2009=\u20090.004; CFS-MDT HR 1.36, 95% C.I. 1.16-1.59, P\u2009<\u20090.001).<h4>Conclusions</h4>Assessment of CFS is deeply affected by the underlying methodology, with the potential to profoundly affect decision-making. The CFS-MDT appears to be a weak alternative to conventional CFS. Standardisation of CFS use is of paramount importance in clinical and research practice in haemodialysis.<h4>Trial registration</h4>Clinicaltrials.gov : NCT03071107 registered 06/03/2017.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-023-03126-0; doi:https://doi.org/10.1186/s12882-023-03126-0; html:https://europepmc.org/articles/PMC10062243; pdf:https://europepmc.org/articles/PMC10062243?pdf=render"
+  },
   {
     "id": "35024157",
     "doi": "https://doi.org/10.1177/20552076211059350",
@@ -3093,23 +3093,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1136/openhrt-2023-002378; html:https://europepmc.org/articles/PMC10432634; pdf:https://europepmc.org/articles/PMC10432634?pdf=render"
   },
-  {
-    "id": "36417468",
-    "doi": "https://doi.org/10.1371/journal.pcbi.1010724",
-    "title": "Trends in SARS-CoV-2 infection prevalence during England's roadmap out of lockdown, January to July 2021.",
-    "authorString": "Eales O, Wang H, Haw D, Ainslie KEC, Walters CE, Atchison C, Cooke G, Barclay W, Ward H, Darzi A, Ashby D, Donnelly CA, Elliott P, Riley S.",
-    "authorAffiliations": "",
-    "journalTitle": "PLoS computational biology",
-    "pubYear": "2022",
-    "date": "2022-11-23",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards.<h4>Aim</h4>We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence.<h4>Methods</h4>On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions.<h4>Results</h4>Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was offset by the effects of vaccination and also affected by the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups.<h4>Conclusion</h4>High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was effective at reducing risk of infection with school holidays/closures playing a significant part.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010724&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010724; html:https://europepmc.org/articles/PMC9728904; pdf:https://europepmc.org/articles/PMC9728904?pdf=render"
-  },
   {
     "id": "35155637",
     "doi": "https://doi.org/10.3389/fcvm.2022.822269",
@@ -3128,38 +3111,38 @@
     "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.822269/pdf; doi:https://doi.org/10.3389/fcvm.2022.822269; html:https://europepmc.org/articles/PMC8831539; pdf:https://europepmc.org/articles/PMC8831539?pdf=render"
   },
   {
-    "id": "37120260",
-    "doi": "https://doi.org/10.1016/s2468-2667(23)00079-8",
-    "title": "Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: a retrospective cohort study using the OpenSAFELY platform.",
-    "authorString": "Nab L, Parker EPK, Andrews CD, Hulme WJ, Fisher L, Morley J, Mehrkar A, MacKenna B, Inglesby P, Morton CE, Bacon SCJ, Hickman G, Evans D, Ward T, Smith RM, Davy S, Dillingham I, Maude S, Butler-Cole BFC, O'Dwyer T, Stables CL, Bridges L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Zheng B, Williamson EJ, Eggo RM, Evans SJW, Goldacre B, Tomlinson LA, Walker AJ, OpenSAFELY Collaborative.",
+    "id": "36417468",
+    "doi": "https://doi.org/10.1371/journal.pcbi.1010724",
+    "title": "Trends in SARS-CoV-2 infection prevalence during England's roadmap out of lockdown, January to July 2021.",
+    "authorString": "Eales O, Wang H, Haw D, Ainslie KEC, Walters CE, Atchison C, Cooke G, Barclay W, Ward H, Darzi A, Ashby D, Donnelly CA, Elliott P, Riley S.",
     "authorAffiliations": "",
-    "journalTitle": "The Lancet. Public health",
-    "pubYear": "2023",
-    "date": "2023-05-01",
+    "journalTitle": "PLoS computational biology",
+    "pubYear": "2022",
+    "date": "2022-11-23",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>COVID-19 has been shown to differently affect various demographic and clinical population subgroups. We aimed to describe trends in absolute and relative COVID-19-related mortality risks across clinical and demographic population subgroups during successive SARS-CoV-2 pandemic waves.<h4>Methods</h4>We did a retrospective cohort study in England using the OpenSAFELY platform with the approval of National Health Service England, covering the first five SARS-CoV-2 pandemic waves (wave one [wild-type] from March 23 to May 30, 2020; wave two [alpha (B.1.1.7)] from Sept 7, 2020, to April 24, 2021; wave three [delta (B.1.617.2)] from May 28 to Dec 14, 2021; wave four [omicron (B.1.1.529)] from Dec 15, 2021, to April 29, 2022; and wave five [omicron] from June 24 to Aug 3, 2022). In each wave, we included people aged 18-110 years who were registered with a general practice on the first day of the wave and who had at least 3 months of continuous general practice registration up to this date. We estimated crude and sex-standardised and age-standardised wave-specific COVID-19-related death rates and relative risks of COVID-19-related death in population subgroups.<h4>Findings</h4>18\u2008895\u2008870 adults were included in wave one, 19\u2008014\u2008720 in wave two, 18\u2008932\u2008050 in wave three, 19\u2008097\u2008970 in wave four, and 19\u2008226\u2008475 in wave five. Crude COVID-19-related death rates per 1000 person-years decreased from 4\u00b748 deaths (95% CI 4\u00b741-4\u00b755) in wave one to 2\u00b769 (2\u00b766-2\u00b772) in wave two, 0\u00b764 (0\u00b763-0\u00b766) in wave three, 1\u00b701 (0\u00b799-1\u00b703) in wave four, and 0\u00b767 (0\u00b764-0\u00b771) in wave five. In wave one, the standardised COVID-19-related death rates were highest in people aged 80 years or older, people with chronic kidney disease stage 5 or 4, people receiving dialysis, people with dementia or learning disability, and people who had received a kidney transplant (ranging from 19\u00b785 deaths per 1000 person-years to 44\u00b741 deaths per 1000 person-years, compared with from 0\u00b705 deaths per 1000 person-years to 15\u00b793 deaths per 1000 person-years in other subgroups). In wave two compared with wave one, in a largely unvaccinated population, the decrease in COVID-19-related mortality was evenly distributed across population subgroups. In wave three compared with wave one, larger decreases in COVID-19-related death rates were seen in groups prioritised for primary SARS-CoV-2 vaccination, including people aged 80 years or older and people with neurological disease, learning disability, or severe mental illness (90-91% decrease). Conversely, smaller decreases in COVID-19-related death rates were observed in younger age groups, people who had received organ transplants, and people with chronic kidney disease, haematological malignancies, or immunosuppressive conditions (0-25% decrease). In wave four compared with wave one, the decrease in COVID-19-related death rates was smaller in groups with lower vaccination coverage (including younger age groups) and conditions associated with impaired vaccine response, including people who had received organ transplants and people with immunosuppressive conditions (26-61% decrease).<h4>Interpretation</h4>There was a substantial decrease in absolute COVID-19-related death rates over time in the overall population, but demographic and clinical relative risk profiles persisted and worsened for people with lower vaccination coverage or impaired immune response. Our findings provide an evidence base to inform UK public health policy for protecting these vulnerable population subgroups.<h4>Funding</h4>UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.",
+    "abstract": "<h4>Background</h4>Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards.<h4>Aim</h4>We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence.<h4>Methods</h4>On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions.<h4>Results</h4>Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was offset by the effects of vaccination and also affected by the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups.<h4>Conclusion</h4>High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was effective at reducing risk of infection with school holidays/closures playing a significant part.",
     "laySummary": "",
-    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139026; doi:https://doi.org/10.1016/S2468-2667(23)00079-8; html:https://europepmc.org/articles/PMC10139026; pdf:https://europepmc.org/articles/PMC10139026?pdf=render"
+    "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010724&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010724; html:https://europepmc.org/articles/PMC9728904; pdf:https://europepmc.org/articles/PMC9728904?pdf=render"
   },
   {
-    "id": "37388527",
-    "doi": "https://doi.org/10.1155/2023/4518843",
-    "title": "Somatic Symptoms of Depression Lose Association with Mortality upon Adjustment for Frailty: Analysis from the Fitness Haemodialysis Cohort.",
-    "authorString": "Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",
+    "id": "37120260",
+    "doi": "https://doi.org/10.1016/s2468-2667(23)00079-8",
+    "title": "Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: a retrospective cohort study using the OpenSAFELY platform.",
+    "authorString": "Nab L, Parker EPK, Andrews CD, Hulme WJ, Fisher L, Morley J, Mehrkar A, MacKenna B, Inglesby P, Morton CE, Bacon SCJ, Hickman G, Evans D, Ward T, Smith RM, Davy S, Dillingham I, Maude S, Butler-Cole BFC, O'Dwyer T, Stables CL, Bridges L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Zheng B, Williamson EJ, Eggo RM, Evans SJW, Goldacre B, Tomlinson LA, Walker AJ, OpenSAFELY Collaborative.",
     "authorAffiliations": "",
-    "journalTitle": "International journal of nephrology",
+    "journalTitle": "The Lancet. Public health",
     "pubYear": "2023",
-    "date": "2023-06-21",
+    "date": "2023-05-01",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>The somatic symptom component of depression is associated with increased hospitalisation and mortality and poorer health-related quality of life (HRQOL). However, the relationship of subsets of depression symptoms with frailty and outcomes is not known. This study aimed to (1) explore the relationship between the Clinical Frailty Scale (CFS) and components of depression and (2) their association with mortality, hospitalisation, and HRQOL in haemodialysis recipients.<h4>Methods</h4>We conducted a prospective cohort study of prevalent haemodialysis recipients, with deep bio-clinical phenotyping including CFS and PHQ-9 somatic (fatigue, poor appetite, and poor sleep) and cognitive component scores. EuroQol EQ-5D summary index assessed HRQOL at the baseline. Electronic linkage to English national administration datasets ensured robust follow-up data for hospitalisation and mortality events. <i>Findings</i>. Somatic (<i>\u03b2</i>\u2009=\u20090.067; 95% C.I. 0.029 to 0.104; <i>P</i> < 0.001) and cognitive (<i>\u03b2</i>\u2009=\u20090.062; 95% C.I. 0.034 to 0.089; <i>P</i><0.001) components were associated with increased CFS scores. Both somatic (<i>\u03b2</i>\u2009=\u2009-0.062; 95% C.I. -0.104 to -0.021; <i>P</i><0.001) and cognitive (<i>\u03b2</i>\u2009=\u20090.052; 95% C.I. -0.081 to -0.024; <i>P</i> < 0.001) scores were associated with lower HRQOL. Somatic scores lost mortality association on addition of CFS to the multivariable model (HR1.06; 95% C.I. 0.977 to 1.14; <i>P</i>=0.173). Cognitive symptoms were not associated with mortality. Neither the component score was associated with hospitalisation on multivariable analyses.<h4>Conclusions</h4>Both somatic and cognitive depression symptoms are associated with frailty and poorer HRQOL in haemodialysis recipients but were not associated with mortality or hospitalisation when adjusted for frailty. The risk profile of depression somatic scores may be related to overlap with symptoms of frailty.",
+    "abstract": "<h4>Background</h4>COVID-19 has been shown to differently affect various demographic and clinical population subgroups. We aimed to describe trends in absolute and relative COVID-19-related mortality risks across clinical and demographic population subgroups during successive SARS-CoV-2 pandemic waves.<h4>Methods</h4>We did a retrospective cohort study in England using the OpenSAFELY platform with the approval of National Health Service England, covering the first five SARS-CoV-2 pandemic waves (wave one [wild-type] from March 23 to May 30, 2020; wave two [alpha (B.1.1.7)] from Sept 7, 2020, to April 24, 2021; wave three [delta (B.1.617.2)] from May 28 to Dec 14, 2021; wave four [omicron (B.1.1.529)] from Dec 15, 2021, to April 29, 2022; and wave five [omicron] from June 24 to Aug 3, 2022). In each wave, we included people aged 18-110 years who were registered with a general practice on the first day of the wave and who had at least 3 months of continuous general practice registration up to this date. We estimated crude and sex-standardised and age-standardised wave-specific COVID-19-related death rates and relative risks of COVID-19-related death in population subgroups.<h4>Findings</h4>18\u2008895\u2008870 adults were included in wave one, 19\u2008014\u2008720 in wave two, 18\u2008932\u2008050 in wave three, 19\u2008097\u2008970 in wave four, and 19\u2008226\u2008475 in wave five. Crude COVID-19-related death rates per 1000 person-years decreased from 4\u00b748 deaths (95% CI 4\u00b741-4\u00b755) in wave one to 2\u00b769 (2\u00b766-2\u00b772) in wave two, 0\u00b764 (0\u00b763-0\u00b766) in wave three, 1\u00b701 (0\u00b799-1\u00b703) in wave four, and 0\u00b767 (0\u00b764-0\u00b771) in wave five. In wave one, the standardised COVID-19-related death rates were highest in people aged 80 years or older, people with chronic kidney disease stage 5 or 4, people receiving dialysis, people with dementia or learning disability, and people who had received a kidney transplant (ranging from 19\u00b785 deaths per 1000 person-years to 44\u00b741 deaths per 1000 person-years, compared with from 0\u00b705 deaths per 1000 person-years to 15\u00b793 deaths per 1000 person-years in other subgroups). In wave two compared with wave one, in a largely unvaccinated population, the decrease in COVID-19-related mortality was evenly distributed across population subgroups. In wave three compared with wave one, larger decreases in COVID-19-related death rates were seen in groups prioritised for primary SARS-CoV-2 vaccination, including people aged 80 years or older and people with neurological disease, learning disability, or severe mental illness (90-91% decrease). Conversely, smaller decreases in COVID-19-related death rates were observed in younger age groups, people who had received organ transplants, and people with chronic kidney disease, haematological malignancies, or immunosuppressive conditions (0-25% decrease). In wave four compared with wave one, the decrease in COVID-19-related death rates was smaller in groups with lower vaccination coverage (including younger age groups) and conditions associated with impaired vaccine response, including people who had received organ transplants and people with immunosuppressive conditions (26-61% decrease).<h4>Interpretation</h4>There was a substantial decrease in absolute COVID-19-related death rates over time in the overall population, but demographic and clinical relative risk profiles persisted and worsened for people with lower vaccination coverage or impaired immune response. Our findings provide an evidence base to inform UK public health policy for protecting these vulnerable population subgroups.<h4>Funding</h4>UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1155/2023/4518843; html:https://europepmc.org/articles/PMC10307017; pdf:https://europepmc.org/articles/PMC10307017?pdf=render"
+    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139026; doi:https://doi.org/10.1016/S2468-2667(23)00079-8; html:https://europepmc.org/articles/PMC10139026; pdf:https://europepmc.org/articles/PMC10139026?pdf=render"
   },
   {
     "id": "34217220",
@@ -3178,6 +3161,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-021-02137-9; doi:https://doi.org/10.1186/s12872-021-02137-9; html:https://europepmc.org/articles/PMC8254437; pdf:https://europepmc.org/articles/PMC8254437?pdf=render"
   },
+  {
+    "id": "37388527",
+    "doi": "https://doi.org/10.1155/2023/4518843",
+    "title": "Somatic Symptoms of Depression Lose Association with Mortality upon Adjustment for Frailty: Analysis from the Fitness Haemodialysis Cohort.",
+    "authorString": "Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of nephrology",
+    "pubYear": "2023",
+    "date": "2023-06-21",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>The somatic symptom component of depression is associated with increased hospitalisation and mortality and poorer health-related quality of life (HRQOL). However, the relationship of subsets of depression symptoms with frailty and outcomes is not known. This study aimed to (1) explore the relationship between the Clinical Frailty Scale (CFS) and components of depression and (2) their association with mortality, hospitalisation, and HRQOL in haemodialysis recipients.<h4>Methods</h4>We conducted a prospective cohort study of prevalent haemodialysis recipients, with deep bio-clinical phenotyping including CFS and PHQ-9 somatic (fatigue, poor appetite, and poor sleep) and cognitive component scores. EuroQol EQ-5D summary index assessed HRQOL at the baseline. Electronic linkage to English national administration datasets ensured robust follow-up data for hospitalisation and mortality events. <i>Findings</i>. Somatic (<i>\u03b2</i>\u2009=\u20090.067; 95% C.I. 0.029 to 0.104; <i>P</i> < 0.001) and cognitive (<i>\u03b2</i>\u2009=\u20090.062; 95% C.I. 0.034 to 0.089; <i>P</i><0.001) components were associated with increased CFS scores. Both somatic (<i>\u03b2</i>\u2009=\u2009-0.062; 95% C.I. -0.104 to -0.021; <i>P</i><0.001) and cognitive (<i>\u03b2</i>\u2009=\u20090.052; 95% C.I. -0.081 to -0.024; <i>P</i> < 0.001) scores were associated with lower HRQOL. Somatic scores lost mortality association on addition of CFS to the multivariable model (HR1.06; 95% C.I. 0.977 to 1.14; <i>P</i>=0.173). Cognitive symptoms were not associated with mortality. Neither the component score was associated with hospitalisation on multivariable analyses.<h4>Conclusions</h4>Both somatic and cognitive depression symptoms are associated with frailty and poorer HRQOL in haemodialysis recipients but were not associated with mortality or hospitalisation when adjusted for frailty. The risk profile of depression somatic scores may be related to overlap with symptoms of frailty.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1155/2023/4518843; html:https://europepmc.org/articles/PMC10307017; pdf:https://europepmc.org/articles/PMC10307017?pdf=render"
+  },
   {
     "id": "35027756",
     "doi": "https://doi.org/10.1038/s41591-021-01666-2",
@@ -3416,23 +3416,6 @@
     "laySummary": "Rees et al used a Welsh database to examine inpatient episode/transfer coding coding for psychiatric patients. They identified deficiencies in the existing coding system for psychitatrics transfers and unexplained coding mistakes/problems, then they presesnt several different methods for constructing the inpatient spell to improve coding and avoid misclassification.",
     "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0953-2; doi:https://doi.org/10.1186/s12911-019-0953-2; html:https://europepmc.org/articles/PMC6884917; pdf:https://europepmc.org/articles/PMC6884917?pdf=render"
   },
-  {
-    "id": "37147628",
-    "doi": "https://doi.org/10.1186/s12911-023-02181-9",
-    "title": "Ontology-driven and weakly supervised rare disease identification from clinical notes.",
-    "authorString": "Dong H, Su\u00e1rez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medical informatics and decision making",
-    "pubYear": "2023",
-    "date": "2023-05-05",
-    "isOpenAccess": "Y",
-    "keywords": "Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.<h4>Methods</h4>We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.<h4>Results</h4>The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).<h4>Conclusion</h4>The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02181-9; doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render"
-  },
   {
     "id": "34942103",
     "doi": "https://doi.org/10.1016/s0140-6736(21)02754-9",
@@ -3450,6 +3433,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S0140673621027549/pdf; doi:https://doi.org/10.1016/S0140-6736(21)02754-9; html:https://europepmc.org/articles/PMC8687670"
   },
+  {
+    "id": "37147628",
+    "doi": "https://doi.org/10.1186/s12911-023-02181-9",
+    "title": "Ontology-driven and weakly supervised rare disease identification from clinical notes.",
+    "authorString": "Dong H, Su\u00e1rez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC medical informatics and decision making",
+    "pubYear": "2023",
+    "date": "2023-05-05",
+    "isOpenAccess": "Y",
+    "keywords": "Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.<h4>Methods</h4>We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.<h4>Results</h4>The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).<h4>Conclusion</h4>The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02181-9; doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render"
+  },
   {
     "id": "36174228",
     "doi": "https://doi.org/10.1093/ije/dyac189",
@@ -3705,23 +3705,6 @@
     "laySummary": "",
     "urls": "pdf:https://formative.jmir.org/2023/1/e45849/PDF; doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render"
   },
-  {
-    "id": "37346822",
-    "doi": "https://doi.org/10.12688/wellcomeopenres.18735.2",
-    "title": "First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY.",
-    "authorString": "Hopcroft LE, Curtis HJ, Brown AD, Hulme WJ, Andrews CD, Morton CE, Inglesby P, Morley J, Mehrkar A, Bacon SC, Eggo RM, Mahalingasivam V, Parker EPK, Tomlinson LA, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, Walker AJ, MacKenna B.",
-    "authorAffiliations": "",
-    "journalTitle": "Wellcome open research",
-    "pubYear": "2023",
-    "date": "2023-06-09",
-    "isOpenAccess": "Y",
-    "keywords": "Vaccine; Primary Health Care; Public Health; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<b>Background:</b> The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. <b>Methods:</b> With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,\u00a0 <i>in situ</i>\u00a0and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. <b>Results:</b> Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. <b>Conclusion:</b> First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render"
-  },
   {
     "id": "36369736",
     "doi": "https://doi.org/10.1080/19490976.2022.2139979",
@@ -3739,6 +3722,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1080/19490976.2022.2139979; doi:https://doi.org/10.1080/19490976.2022.2139979; html:https://europepmc.org/articles/PMC9662191; pdf:https://europepmc.org/articles/PMC9662191?pdf=render"
   },
+  {
+    "id": "37346822",
+    "doi": "https://doi.org/10.12688/wellcomeopenres.18735.2",
+    "title": "First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY.",
+    "authorString": "Hopcroft LE, Curtis HJ, Brown AD, Hulme WJ, Andrews CD, Morton CE, Inglesby P, Morley J, Mehrkar A, Bacon SC, Eggo RM, Mahalingasivam V, Parker EPK, Tomlinson LA, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, Walker AJ, MacKenna B.",
+    "authorAffiliations": "",
+    "journalTitle": "Wellcome open research",
+    "pubYear": "2023",
+    "date": "2023-06-09",
+    "isOpenAccess": "Y",
+    "keywords": "Vaccine; Primary Health Care; Public Health; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<b>Background:</b> The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. <b>Methods:</b> With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,\u00a0 <i>in situ</i>\u00a0and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. <b>Results:</b> Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. <b>Conclusion:</b> First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render"
+  },
   {
     "id": "35858698",
     "doi": "https://doi.org/10.1136/bmj-2022-071249",
@@ -4079,23 +4079,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ije/article-pdf/51/5/e245/46495259/dyab243.pdf; doi:https://doi.org/10.1093/ije/dyab243; html:https://europepmc.org/articles/PMC9557859; pdf:https://europepmc.org/articles/PMC9557859?pdf=render"
   },
-  {
-    "id": "37678881",
-    "doi": "https://doi.org/10.1093/ageing/afad157",
-    "title": "Survival and critical care use among people with dementia in a large English cohort.",
-    "authorString": "Yorganci E, Sleeman KE, Sampson EL, Stewart R, EMBED-Care Programme.",
-    "authorAffiliations": "",
-    "journalTitle": "Age and ageing",
-    "pubYear": "2023",
-    "date": "2023-09-01",
-    "isOpenAccess": "Y",
-    "keywords": "Survival; Dementia; Intensive Care; Older People; Critical Care; Routine Data",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England.<h4>Objective</h4>To investigate critical care use and survival among people with dementia in a large London catchment area.<h4>Methods</h4>A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends.<h4>Results</h4>Of 19,787 people diagnosed with dementia, 726 (3.7%) had \u22651 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n\u2009=\u2009345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (\u03b2\u2009=\u2009-0.05; 95% CI = -0.01, -0.0003; P\u2009=\u20090.03), while critical care admissions occurring during the last year of life increased (\u03b2\u2009=\u20090.11, 95% CI = 0.01, 0.20, P\u2009=\u20090.03).<h4>Conclusions</h4>In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?pdf=render"
-  },
   {
     "id": "33228632",
     "doi": "https://doi.org/10.1186/s12920-020-00826-6",
@@ -4113,6 +4096,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedgenomics.biomedcentral.com/track/pdf/10.1186/s12920-020-00826-6; doi:https://doi.org/10.1186/s12920-020-00826-6; html:https://europepmc.org/articles/PMC7685541; pdf:https://europepmc.org/articles/PMC7685541?pdf=render"
   },
+  {
+    "id": "37678881",
+    "doi": "https://doi.org/10.1093/ageing/afad157",
+    "title": "Survival and critical care use among people with dementia in a large English cohort.",
+    "authorString": "Yorganci E, Sleeman KE, Sampson EL, Stewart R, EMBED-Care Programme.",
+    "authorAffiliations": "",
+    "journalTitle": "Age and ageing",
+    "pubYear": "2023",
+    "date": "2023-09-01",
+    "isOpenAccess": "Y",
+    "keywords": "Survival; Dementia; Intensive Care; Older People; Critical Care; Routine Data",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England.<h4>Objective</h4>To investigate critical care use and survival among people with dementia in a large London catchment area.<h4>Methods</h4>A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends.<h4>Results</h4>Of 19,787 people diagnosed with dementia, 726 (3.7%) had \u22651 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n\u2009=\u2009345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (\u03b2\u2009=\u2009-0.05; 95% CI = -0.01, -0.0003; P\u2009=\u20090.03), while critical care admissions occurring during the last year of life increased (\u03b2\u2009=\u20090.11, 95% CI = 0.01, 0.20, P\u2009=\u20090.03).<h4>Conclusions</h4>In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?pdf=render"
+  },
   {
     "id": "37480048",
     "doi": "https://doi.org/10.1186/s12872-023-03394-6",
@@ -4250,21 +4250,21 @@
     "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-021-01693-6; doi:https://doi.org/10.1186/s12911-021-01693-6; html:https://europepmc.org/articles/PMC8653614; pdf:https://europepmc.org/articles/PMC8653614?pdf=render"
   },
   {
-    "id": "37363797",
-    "doi": "https://doi.org/10.1016/j.lanepe.2023.100653",
-    "title": "Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.",
-    "authorString": "Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SC, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",
+    "id": "33683514",
+    "doi": "https://doi.org/10.1007/s10237-021-01437-5",
+    "title": "A framework for incorporating 3D hyperelastic vascular wall models in 1D blood flow simulations.",
+    "authorString": "Coccarelli A, Carson JM, Aggarwal A, Pant S.",
     "authorAffiliations": "",
-    "journalTitle": "The Lancet regional health. Europe",
-    "pubYear": "2023",
-    "date": "2023-05-16",
+    "journalTitle": "Biomechanics and modeling in mechanobiology",
+    "pubYear": "2021",
+    "date": "2021-03-08",
     "isOpenAccess": "Y",
-    "keywords": "Antimicrobial resistance; Primary Care; Broad-spectrum Antibiotics; Covid-19 Pandemic",
+    "keywords": "Pulse wave velocity; Common carotid artery; Hyperelasticity; Tube Law; Axial Stretching; One-dimensional Blood Flow Modelling",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started.<h4>Methods</h4>With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models.<h4>Findings</h4>Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13).<h4>Interpretation</h4>An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation.<h4>Funding</h4>This work was supported by Health Data Research UK and by National Institute for Health Research.",
+    "abstract": "We present a novel framework for investigating the role of vascular structure on arterial haemodynamics in large vessels, with a special focus on the human common carotid artery (CCA). The analysis is carried out by adopting a three-dimensional (3D) derived, fibre-reinforced, hyperelastic structural model, which is coupled with an axisymmetric, reduced order model describing blood flow. The vessel transmural pressure and lumen area are related via a Holzapfel-Ogden type of law, and the residual stresses along the thickness and length of the vessel are also accounted for. After a structural characterization of the adopted hyperelastic model, we investigate the link underlying the vascular wall response and blood-flow dynamics by comparing the proposed framework results against a popular tube law. The comparison shows that the behaviour of the model can be captured by the simpler linear surrogate only if a representative value of compliance is applied. Sobol's multi-variable sensitivity analysis is then carried out in order to identify the extent to which the structural parameters have an impact on the CCA haemodynamics. In this case, the local pulse wave velocity (PWV) is used as index for representing the arterial transmission capacity of blood pressure waveforms. The sensitivity analysis suggests that some geometrical factors, such as the stress-free inner radius and opening angle, play a major role on the system's haemodynamics. Subsequently, we quantified the differences in haemodynamic variables obtained from different virtual CCAs, tube laws and flow conditions. Although each artery presents a distinct vascular response, the differences obtained across different flow regimes are not significant. As expected, the linear tube law is unable to accurately capture all the haemodynamic features characterizing the current model. The findings from the sensitivity analysis are further confirmed by investigating the axial stretching effect on the CCA fluid dynamics. This factor does not seem to alter the pressure and flow waveforms. On the contrary, it is shown that, for an axially stretched vessel, the vascular wall exhibits an attenuation in absolute distension and an increase in circumferential stress, corroborating the findings of previous studies. This analysis shows that the new model offers a good balance between computational complexity and physics captured, making it an ideal framework for studies aiming to investigate the profound link between vascular mechanobiology and blood flow.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100653; doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render"
+    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10237-021-01437-5.pdf; doi:https://doi.org/10.1007/s10237-021-01437-5; html:https://europepmc.org/articles/PMC8298378; pdf:https://europepmc.org/articles/PMC8298378?pdf=render"
   },
   {
     "id": "35910710",
@@ -4284,21 +4284,21 @@
     "urls": "pdf:https://academic.oup.com/rheumap/advance-article-pdf/doi/10.1093/rap/rkac056/45095148/rkac056.pdf; doi:https://doi.org/10.1093/rap/rkac056; html:https://europepmc.org/articles/PMC9336562; pdf:https://europepmc.org/articles/PMC9336562?pdf=render"
   },
   {
-    "id": "33683514",
-    "doi": "https://doi.org/10.1007/s10237-021-01437-5",
-    "title": "A framework for incorporating 3D hyperelastic vascular wall models in 1D blood flow simulations.",
-    "authorString": "Coccarelli A, Carson JM, Aggarwal A, Pant S.",
+    "id": "37363797",
+    "doi": "https://doi.org/10.1016/j.lanepe.2023.100653",
+    "title": "Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.",
+    "authorString": "Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SC, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",
     "authorAffiliations": "",
-    "journalTitle": "Biomechanics and modeling in mechanobiology",
-    "pubYear": "2021",
-    "date": "2021-03-08",
+    "journalTitle": "The Lancet regional health. Europe",
+    "pubYear": "2023",
+    "date": "2023-05-16",
     "isOpenAccess": "Y",
-    "keywords": "Pulse wave velocity; Common carotid artery; Hyperelasticity; Tube Law; Axial Stretching; One-dimensional Blood Flow Modelling",
+    "keywords": "Antimicrobial resistance; Primary Care; Broad-spectrum Antibiotics; Covid-19 Pandemic",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "We present a novel framework for investigating the role of vascular structure on arterial haemodynamics in large vessels, with a special focus on the human common carotid artery (CCA). The analysis is carried out by adopting a three-dimensional (3D) derived, fibre-reinforced, hyperelastic structural model, which is coupled with an axisymmetric, reduced order model describing blood flow. The vessel transmural pressure and lumen area are related via a Holzapfel-Ogden type of law, and the residual stresses along the thickness and length of the vessel are also accounted for. After a structural characterization of the adopted hyperelastic model, we investigate the link underlying the vascular wall response and blood-flow dynamics by comparing the proposed framework results against a popular tube law. The comparison shows that the behaviour of the model can be captured by the simpler linear surrogate only if a representative value of compliance is applied. Sobol's multi-variable sensitivity analysis is then carried out in order to identify the extent to which the structural parameters have an impact on the CCA haemodynamics. In this case, the local pulse wave velocity (PWV) is used as index for representing the arterial transmission capacity of blood pressure waveforms. The sensitivity analysis suggests that some geometrical factors, such as the stress-free inner radius and opening angle, play a major role on the system's haemodynamics. Subsequently, we quantified the differences in haemodynamic variables obtained from different virtual CCAs, tube laws and flow conditions. Although each artery presents a distinct vascular response, the differences obtained across different flow regimes are not significant. As expected, the linear tube law is unable to accurately capture all the haemodynamic features characterizing the current model. The findings from the sensitivity analysis are further confirmed by investigating the axial stretching effect on the CCA fluid dynamics. This factor does not seem to alter the pressure and flow waveforms. On the contrary, it is shown that, for an axially stretched vessel, the vascular wall exhibits an attenuation in absolute distension and an increase in circumferential stress, corroborating the findings of previous studies. This analysis shows that the new model offers a good balance between computational complexity and physics captured, making it an ideal framework for studies aiming to investigate the profound link between vascular mechanobiology and blood flow.",
+    "abstract": "<h4>Background</h4>The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started.<h4>Methods</h4>With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models.<h4>Findings</h4>Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13).<h4>Interpretation</h4>An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation.<h4>Funding</h4>This work was supported by Health Data Research UK and by National Institute for Health Research.",
     "laySummary": "",
-    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10237-021-01437-5.pdf; doi:https://doi.org/10.1007/s10237-021-01437-5; html:https://europepmc.org/articles/PMC8298378; pdf:https://europepmc.org/articles/PMC8298378?pdf=render"
+    "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100653; doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render"
   },
   {
     "id": "34829865",
@@ -4640,23 +4640,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/2079-7737/11/3/365/pdf?version=1645777713; doi:https://doi.org/10.3390/biology11030365; html:https://europepmc.org/articles/PMC8944988; pdf:https://europepmc.org/articles/PMC8944988?pdf=render"
   },
-  {
-    "id": "36944118",
-    "doi": "https://doi.org/10.2337/dc22-1238",
-    "title": "Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.",
-    "authorString": "Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J, Sattar N, MacDonald T, McCrimmon RJ, Morales DR, Pearson ER, Scottish Diabetes Research Network Epidemiology Group.",
-    "authorAffiliations": "",
-    "journalTitle": "Diabetes care",
-    "pubYear": "2023",
-    "date": "2023-05-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.<h4>Research design and methods</h4>A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.<h4>Results</h4>Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17).<h4>Conclusions</h4>Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.",
-    "laySummary": "",
-    "urls": "pdf:https://diabetesjournals.org/care/article-pdf/46/5/967/702262/dc221238.pdf; doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?pdf=render"
-  },
   {
     "id": "32851419",
     "doi": "https://doi.org/10.1007/s00394-020-02372-4",
@@ -4674,6 +4657,23 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02372-4.pdf; doi:https://doi.org/10.1007/s00394-020-02372-4; html:https://europepmc.org/articles/PMC7449523; pdf:https://europepmc.org/articles/PMC7449523?pdf=render"
   },
+  {
+    "id": "36944118",
+    "doi": "https://doi.org/10.2337/dc22-1238",
+    "title": "Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.",
+    "authorString": "Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J, Sattar N, MacDonald T, McCrimmon RJ, Morales DR, Pearson ER, Scottish Diabetes Research Network Epidemiology Group.",
+    "authorAffiliations": "",
+    "journalTitle": "Diabetes care",
+    "pubYear": "2023",
+    "date": "2023-05-01",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.<h4>Research design and methods</h4>A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.<h4>Results</h4>Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17).<h4>Conclusions</h4>Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.",
+    "laySummary": "",
+    "urls": "pdf:https://diabetesjournals.org/care/article-pdf/46/5/967/702262/dc221238.pdf; doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?pdf=render"
+  },
   {
     "id": "37558806",
     "doi": "https://doi.org/10.1038/s41598-023-40215-4",
@@ -4691,6 +4691,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1038/s41598-023-40215-4; html:https://europepmc.org/articles/PMC10412533; pdf:https://europepmc.org/articles/PMC10412533?pdf=render"
   },
+  {
+    "id": "33114263",
+    "doi": "https://doi.org/10.3390/ijms21217886",
+    "title": "Biomarker Prioritisation and Power Estimation Using Ensemble Gene Regulatory Network Inference.",
+    "authorString": "Aziz F, Acharjee A, Williams JA, Russ D, Bravo-Merodio L, Gkoutos GV.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of molecular sciences",
+    "pubYear": "2020",
+    "date": "2020-10-23",
+    "isOpenAccess": "Y",
+    "keywords": "Experimental design; Gene Regulatory Network; Causal Modelling; Omics Integration",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Inferring the topology of a gene regulatory network (GRN) from gene expression data is a challenging but important undertaking for gaining a better understanding of gene regulation. Key challenges include working with noisy data and dealing with a higher number of genes than samples. Although a number of different methods have been proposed to infer the structure of a GRN, there are large discrepancies among the different inference algorithms they adopt, rendering their meaningful comparison challenging. In this study, we used two methods, namely the MIDER (Mutual Information Distance and Entropy Reduction) and the PLSNET (Partial least square based feature selection) methods, to infer the structure of a GRN directly from data and computationally validated our results. Both methods were applied to different gene expression datasets resulting from inflammatory bowel disease (IBD), pancreatic ductal adenocarcinoma (PDAC), and acute myeloid leukaemia (AML) studies. For each case, gene regulators were successfully identified. For example, for the case of the IBD dataset, the <i>UGT1A</i> family genes were identified as key regulators while upon analysing the PDAC dataset, the <i>SULF1</i> and <i>THBS2</i> genes were depicted. We further demonstrate that an ensemble-based approach, that combines the output of the MIDER and PLSNET algorithms, can infer the structure of a GRN from data with higher accuracy. We have also estimated the number of the samples required for potential future validation studies. Here, we presented our proposed analysis framework that caters not only to candidate regulator genes prediction for potential validation experiments but also an estimation of the number of samples required for these experiments.",
+    "laySummary": "",
+    "urls": "pdf:https://www.mdpi.com/1422-0067/21/21/7886/pdf?version=1604329387; doi:https://doi.org/10.3390/ijms21217886; html:https://europepmc.org/articles/PMC7660606; pdf:https://europepmc.org/articles/PMC7660606?pdf=render"
+  },
   {
     "id": "36217535",
     "doi": "https://doi.org/10.1038/s43856-022-00185-6",
@@ -4742,23 +4759,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0280943&type=printable; doi:https://doi.org/10.1371/journal.pone.0280943; html:https://europepmc.org/articles/PMC9879384; pdf:https://europepmc.org/articles/PMC9879384?pdf=render"
   },
-  {
-    "id": "33114263",
-    "doi": "https://doi.org/10.3390/ijms21217886",
-    "title": "Biomarker Prioritisation and Power Estimation Using Ensemble Gene Regulatory Network Inference.",
-    "authorString": "Aziz F, Acharjee A, Williams JA, Russ D, Bravo-Merodio L, Gkoutos GV.",
-    "authorAffiliations": "",
-    "journalTitle": "International journal of molecular sciences",
-    "pubYear": "2020",
-    "date": "2020-10-23",
-    "isOpenAccess": "Y",
-    "keywords": "Experimental design; Gene Regulatory Network; Causal Modelling; Omics Integration",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Inferring the topology of a gene regulatory network (GRN) from gene expression data is a challenging but important undertaking for gaining a better understanding of gene regulation. Key challenges include working with noisy data and dealing with a higher number of genes than samples. Although a number of different methods have been proposed to infer the structure of a GRN, there are large discrepancies among the different inference algorithms they adopt, rendering their meaningful comparison challenging. In this study, we used two methods, namely the MIDER (Mutual Information Distance and Entropy Reduction) and the PLSNET (Partial least square based feature selection) methods, to infer the structure of a GRN directly from data and computationally validated our results. Both methods were applied to different gene expression datasets resulting from inflammatory bowel disease (IBD), pancreatic ductal adenocarcinoma (PDAC), and acute myeloid leukaemia (AML) studies. For each case, gene regulators were successfully identified. For example, for the case of the IBD dataset, the <i>UGT1A</i> family genes were identified as key regulators while upon analysing the PDAC dataset, the <i>SULF1</i> and <i>THBS2</i> genes were depicted. We further demonstrate that an ensemble-based approach, that combines the output of the MIDER and PLSNET algorithms, can infer the structure of a GRN from data with higher accuracy. We have also estimated the number of the samples required for potential future validation studies. Here, we presented our proposed analysis framework that caters not only to candidate regulator genes prediction for potential validation experiments but also an estimation of the number of samples required for these experiments.",
-    "laySummary": "",
-    "urls": "pdf:https://www.mdpi.com/1422-0067/21/21/7886/pdf?version=1604329387; doi:https://doi.org/10.3390/ijms21217886; html:https://europepmc.org/articles/PMC7660606; pdf:https://europepmc.org/articles/PMC7660606?pdf=render"
-  },
   {
     "id": "37798357",
     "doi": "https://doi.org/10.1038/s41598-023-42331-7",
@@ -5116,23 +5116,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/2076-393X/11/3/604/pdf?version=1678670919; doi:https://doi.org/10.3390/vaccines11030604; html:https://europepmc.org/articles/PMC10055803; pdf:https://europepmc.org/articles/PMC10055803?pdf=render"
   },
-  {
-    "id": "37340474",
-    "doi": "https://doi.org/10.1186/s12916-023-02877-9",
-    "title": "Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.",
-    "authorString": "Glebov OO, Mueller C, Stewart R, Aarsland D, Perera G.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medicine",
-    "pubYear": "2023",
-    "date": "2023-06-21",
-    "isOpenAccess": "Y",
-    "keywords": "Antidepressants; Ssri; respiratory infection; Drug Repurposing; Covid-19; Sars-cov-2",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention.<h4>Methods</h4>Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3\u00a0months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure.<h4>Results</h4>AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class.<h4>Conclusions</h4>This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02877-9; doi:https://doi.org/10.1186/s12916-023-02877-9; html:https://europepmc.org/articles/PMC10283271; pdf:https://europepmc.org/articles/PMC10283271?pdf=render"
-  },
   {
     "id": "32565483",
     "doi": "https://doi.org/10.1136/bmjopen-2020-039097",
@@ -5150,6 +5133,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/6/e039097.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-039097; html:https://europepmc.org/articles/PMC7311023; pdf:https://europepmc.org/articles/PMC7311023?pdf=render"
   },
+  {
+    "id": "37340474",
+    "doi": "https://doi.org/10.1186/s12916-023-02877-9",
+    "title": "Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.",
+    "authorString": "Glebov OO, Mueller C, Stewart R, Aarsland D, Perera G.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC medicine",
+    "pubYear": "2023",
+    "date": "2023-06-21",
+    "isOpenAccess": "Y",
+    "keywords": "Antidepressants; Ssri; respiratory infection; Drug Repurposing; Covid-19; Sars-cov-2",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention.<h4>Methods</h4>Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3\u00a0months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure.<h4>Results</h4>AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class.<h4>Conclusions</h4>This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02877-9; doi:https://doi.org/10.1186/s12916-023-02877-9; html:https://europepmc.org/articles/PMC10283271; pdf:https://europepmc.org/articles/PMC10283271?pdf=render"
+  },
   {
     "id": "35567479",
     "doi": "https://doi.org/10.1093/rheumatology/keac283",
@@ -5184,23 +5184,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1007/s40258-022-00777-2; html:https://europepmc.org/articles/PMC9760184; pdf:https://europepmc.org/articles/PMC9760184?pdf=render; pdf:https://link.springer.com/content/pdf/10.1007/s40258-022-00777-2.pdf"
   },
-  {
-    "id": "36857859",
-    "doi": "https://doi.org/10.1016/j.ebiom.2023.104489",
-    "title": "Identifying subtypes of chronic kidney disease with machine learning: development, internal validation and prognostic validation using linked electronic health records in 350,067 individuals.",
-    "authorString": "Dashtban A, Mizani MA, Pasea L, Denaxas S, Corbett R, Mamza JB, Gao H, Morris T, Hemingway H, Banerjee A.",
-    "authorAffiliations": "",
-    "journalTitle": "EBioMedicine",
-    "pubYear": "2023",
-    "date": "2023-02-27",
-    "isOpenAccess": "Y",
-    "keywords": "Cluster analysis; Survival analysis; Machine Learning; Unsupervised Clustering; Ckd Subtype",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Although chronic kidney disease (CKD) is associated with high multimorbidity, polypharmacy, morbidity and mortality, existing classification systems (mild to severe, usually based on estimated glomerular filtration rate, proteinuria or urine albumin-creatinine ratio) and risk prediction models largely ignore the complexity of CKD, its risk factors and its outcomes. Improved subtype definition could improve prediction of outcomes and inform effective interventions.<h4>Methods</h4>We analysed individuals \u226518 years with incident and prevalent CKD (n\u00a0=\u00a0350,067 and 195,422 respectively) from a population-based electronic health record resource (2006-2020; Clinical Practice Research Datalink, CPRD). We included factors (n\u00a0=\u00a0264 with 2670 derived variables), e.g. demography, history, examination, blood laboratory values and medications. Using a published framework, we identified subtypes through seven unsupervised machine learning (ML) methods (K-means, Diana, HC, Fanny, PAM, Clara, Model-based) with 66 (of 2670) variables in each dataset. We evaluated subtypes for: (i) internal validity (within dataset, across methods); (ii) prognostic validity (predictive accuracy for 5-year all-cause mortality and admissions); and (iii) medications (new and existing by British National Formulary chapter).<h4>Findings</h4>After identifying five clusters across seven approaches, we labelled CKD subtypes: 1. Early-onset, 2. Late-onset, 3. Cancer, 4. Metabolic, and 5. Cardiometabolic. Internal validity: We trained a high performing model (using XGBoost) that could predict disease subtypes with 95% accuracy for incident and prevalent CKD (Sensitivity: 0.81-0.98, F1 score:0.84-0.97). Prognostic validity: 5-year all-cause mortality, hospital admissions, and incidence of new chronic diseases differed across CKD subtypes. The 5-year risk of mortality and admissions in the overall incident CKD population were highest in cardiometabolic subtype: 43.3% (42.3-42.8%) and 29.5% (29.1-30.0%), respectively, and lowest in the early-onset subtype: 5.7% (5.5-5.9%) and 18.7% (18.4-19.1%).<h4>Medications</h4>Across CKD subtypes, the distribution of prescription medication classes at baseline varied, with highest medication burden in cardiometabolic and metabolic subtypes, and higher burden in prevalent than incident CKD.<h4>Interpretation</h4>In the largest CKD study using ML, to-date, we identified five distinct subtypes in individuals with incident and prevalent CKD. These subtypes have relevance to study of aetiology, therapeutics and risk prediction.<h4>Funding</h4>AstraZeneca UK Ltd, Health Data Research UK.",
-    "laySummary": "",
-    "urls": "pdf:http://www.thelancet.com/article/S2352396423000543/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104489; html:https://europepmc.org/articles/PMC9989643; pdf:https://europepmc.org/articles/PMC9989643?pdf=render"
-  },
   {
     "id": "35413949",
     "doi": "https://doi.org/10.1038/s41467-022-29521-z",
@@ -5218,6 +5201,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-022-29521-z.pdf; doi:https://doi.org/10.1038/s41467-022-29521-z; html:https://europepmc.org/articles/PMC9005552; pdf:https://europepmc.org/articles/PMC9005552?pdf=render"
   },
+  {
+    "id": "36857859",
+    "doi": "https://doi.org/10.1016/j.ebiom.2023.104489",
+    "title": "Identifying subtypes of chronic kidney disease with machine learning: development, internal validation and prognostic validation using linked electronic health records in 350,067 individuals.",
+    "authorString": "Dashtban A, Mizani MA, Pasea L, Denaxas S, Corbett R, Mamza JB, Gao H, Morris T, Hemingway H, Banerjee A.",
+    "authorAffiliations": "",
+    "journalTitle": "EBioMedicine",
+    "pubYear": "2023",
+    "date": "2023-02-27",
+    "isOpenAccess": "Y",
+    "keywords": "Cluster analysis; Survival analysis; Machine Learning; Unsupervised Clustering; Ckd Subtype",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Although chronic kidney disease (CKD) is associated with high multimorbidity, polypharmacy, morbidity and mortality, existing classification systems (mild to severe, usually based on estimated glomerular filtration rate, proteinuria or urine albumin-creatinine ratio) and risk prediction models largely ignore the complexity of CKD, its risk factors and its outcomes. Improved subtype definition could improve prediction of outcomes and inform effective interventions.<h4>Methods</h4>We analysed individuals \u226518 years with incident and prevalent CKD (n\u00a0=\u00a0350,067 and 195,422 respectively) from a population-based electronic health record resource (2006-2020; Clinical Practice Research Datalink, CPRD). We included factors (n\u00a0=\u00a0264 with 2670 derived variables), e.g. demography, history, examination, blood laboratory values and medications. Using a published framework, we identified subtypes through seven unsupervised machine learning (ML) methods (K-means, Diana, HC, Fanny, PAM, Clara, Model-based) with 66 (of 2670) variables in each dataset. We evaluated subtypes for: (i) internal validity (within dataset, across methods); (ii) prognostic validity (predictive accuracy for 5-year all-cause mortality and admissions); and (iii) medications (new and existing by British National Formulary chapter).<h4>Findings</h4>After identifying five clusters across seven approaches, we labelled CKD subtypes: 1. Early-onset, 2. Late-onset, 3. Cancer, 4. Metabolic, and 5. Cardiometabolic. Internal validity: We trained a high performing model (using XGBoost) that could predict disease subtypes with 95% accuracy for incident and prevalent CKD (Sensitivity: 0.81-0.98, F1 score:0.84-0.97). Prognostic validity: 5-year all-cause mortality, hospital admissions, and incidence of new chronic diseases differed across CKD subtypes. The 5-year risk of mortality and admissions in the overall incident CKD population were highest in cardiometabolic subtype: 43.3% (42.3-42.8%) and 29.5% (29.1-30.0%), respectively, and lowest in the early-onset subtype: 5.7% (5.5-5.9%) and 18.7% (18.4-19.1%).<h4>Medications</h4>Across CKD subtypes, the distribution of prescription medication classes at baseline varied, with highest medication burden in cardiometabolic and metabolic subtypes, and higher burden in prevalent than incident CKD.<h4>Interpretation</h4>In the largest CKD study using ML, to-date, we identified five distinct subtypes in individuals with incident and prevalent CKD. These subtypes have relevance to study of aetiology, therapeutics and risk prediction.<h4>Funding</h4>AstraZeneca UK Ltd, Health Data Research UK.",
+    "laySummary": "",
+    "urls": "pdf:http://www.thelancet.com/article/S2352396423000543/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104489; html:https://europepmc.org/articles/PMC9989643; pdf:https://europepmc.org/articles/PMC9989643?pdf=render"
+  },
   {
     "id": "34598993",
     "doi": "https://doi.org/10.1136/bmjopen-2021-054410",
@@ -5371,23 +5371,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-020-01169-z; doi:https://doi.org/10.1186/s12911-020-01169-z; html:https://europepmc.org/articles/PMC7339522; pdf:https://europepmc.org/articles/PMC7339522?pdf=render"
   },
-  {
-    "id": "37408471",
-    "doi": "https://doi.org/10.1093/eurheartj/ehad424",
-    "title": "The CODE-EHR global framework: lifting the veil on health record data.",
-    "authorString": "Asselbergs FW, Kotecha D.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal",
-    "pubYear": "2023",
-    "date": "2023-09-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad424/50827856/ehad424.pdf; doi:https://doi.org/10.1093/eurheartj/ehad424"
-  },
   {
     "id": "35192611",
     "doi": "https://doi.org/10.1371/journal.pmed.1003916",
@@ -5405,6 +5388,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003916&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003916; html:https://europepmc.org/articles/PMC8863286; pdf:https://europepmc.org/articles/PMC8863286?pdf=render"
   },
+  {
+    "id": "37408471",
+    "doi": "https://doi.org/10.1093/eurheartj/ehad424",
+    "title": "The CODE-EHR global framework: lifting the veil on health record data.",
+    "authorString": "Asselbergs FW, Kotecha D.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal",
+    "pubYear": "2023",
+    "date": "2023-09-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad424/50827856/ehad424.pdf; doi:https://doi.org/10.1093/eurheartj/ehad424"
+  },
   {
     "id": "35289755",
     "doi": "https://doi.org/10.2196/31021",
@@ -6034,23 +6034,6 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1717/3510; doi:https://doi.org/10.23889/ijpds.v7i1.1717; html:https://europepmc.org/articles/PMC9284510; pdf:https://europepmc.org/articles/PMC9284510?pdf=render"
   },
-  {
-    "id": "36863848",
-    "doi": "https://doi.org/10.1136/archdischild-2022-325152",
-    "title": "Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England.",
-    "authorString": "Atchison CJ, Whitaker M, Donnelly CA, Chadeau-Hyam M, Riley S, Darzi A, Ashby D, Barclay W, Cooke GS, Elliott P, Ward H.",
-    "authorAffiliations": "",
-    "journalTitle": "Archives of disease in childhood",
-    "pubYear": "2023",
-    "date": "2023-03-02",
-    "isOpenAccess": "Y",
-    "keywords": "epidemiology; Paediatrics; Adolescent Health; Infectious Disease Medicine; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.<h4>Design</h4>Serial cross-sectional study.<h4>Setting</h4>Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England).<h4>Study population</h4>Children aged 5-17 years in the community.<h4>Predictors</h4>Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset.<h4>Main outcome measures</h4>Prevalence of persistent symptoms, reported as those lasting \u22653 months post-COVID-19.<h4>Results</h4>Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11\u2009year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17\u2009year-olds with prior symptomatic infection reported at least one symptom lasting \u22653 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms.<h4>Conclusions</h4>One in 23 5-11\u2009year-olds and one in eight 12-17\u2009year-olds post-COVID-19 report persistent symptoms lasting \u22653 months, of which one in nine report a large impact on performing day-to-day activities.",
-    "laySummary": "",
-    "urls": "pdf:https://adc.bmj.com/content/archdischild/early/2023/03/01/archdischild-2022-325152.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render"
-  },
   {
     "id": "35361119",
     "doi": "https://doi.org/10.1186/s12859-022-04641-x",
@@ -6068,6 +6051,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-022-04641-x; doi:https://doi.org/10.1186/s12859-022-04641-x; html:https://europepmc.org/articles/PMC8974006; pdf:https://europepmc.org/articles/PMC8974006?pdf=render"
   },
+  {
+    "id": "36863848",
+    "doi": "https://doi.org/10.1136/archdischild-2022-325152",
+    "title": "Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England.",
+    "authorString": "Atchison CJ, Whitaker M, Donnelly CA, Chadeau-Hyam M, Riley S, Darzi A, Ashby D, Barclay W, Cooke GS, Elliott P, Ward H.",
+    "authorAffiliations": "",
+    "journalTitle": "Archives of disease in childhood",
+    "pubYear": "2023",
+    "date": "2023-03-02",
+    "isOpenAccess": "Y",
+    "keywords": "epidemiology; Paediatrics; Adolescent Health; Infectious Disease Medicine; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England.<h4>Design</h4>Serial cross-sectional study.<h4>Setting</h4>Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England).<h4>Study population</h4>Children aged 5-17 years in the community.<h4>Predictors</h4>Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset.<h4>Main outcome measures</h4>Prevalence of persistent symptoms, reported as those lasting \u22653 months post-COVID-19.<h4>Results</h4>Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11\u2009year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17\u2009year-olds with prior symptomatic infection reported at least one symptom lasting \u22653 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms.<h4>Conclusions</h4>One in 23 5-11\u2009year-olds and one in eight 12-17\u2009year-olds post-COVID-19 report persistent symptoms lasting \u22653 months, of which one in nine report a large impact on performing day-to-day activities.",
+    "laySummary": "",
+    "urls": "pdf:https://adc.bmj.com/content/archdischild/early/2023/03/01/archdischild-2022-325152.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-325152; html:https://europepmc.org/articles/PMC10313975; pdf:https://europepmc.org/articles/PMC10313975?pdf=render"
+  },
   {
     "id": "34210356",
     "doi": "https://doi.org/10.1186/s13059-021-02395-y",
@@ -6323,23 +6323,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-021-86324-w.pdf; doi:https://doi.org/10.1038/s41598-021-86324-w; html:https://europepmc.org/articles/PMC8042105; pdf:https://europepmc.org/articles/PMC8042105?pdf=render"
   },
-  {
-    "id": "37634386",
-    "doi": "https://doi.org/10.1016/j.schres.2023.08.014",
-    "title": "Trends in socioeconomic inequalities in incidence of severe mental illness - A population-based linkage study using primary and secondary care routinely collected data between 2000 and 2017.",
-    "authorString": "Lee SC, DelPozo-Banos M, Lloyd K, Jones I, Walters JTR, John A.",
-    "authorAffiliations": "",
-    "journalTitle": "Schizophrenia research",
-    "pubYear": "2023",
-    "date": "2023-08-25",
-    "isOpenAccess": "N",
-    "keywords": "Deprivation; Severe Mental Illness; Inequality; Recession; Urbanicity; Austerity",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>In 2008, the UK entered a period of economic recession followed by sustained austerity measures. We investigate changes in inequalities by area deprivation and urbanicity in incidence of severe mental illness (SMI, including schizophrenia-related disorders and bipolar disorder) between 2000 and 2017.<h4>Methods</h4>We analysed 4.4 million individuals from primary and secondary care routinely collected datasets (2000-2017) in Wales and estimated the incidence of SMI by deprivation and urbanicity measured by the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator respectively. Using linear modelling and joinpoint regression approaches, we examined time trends of the incidence and incidence rate ratios (IRR) of SMI by the WIMD and urban/rural indicator adjusted for available confounders.<h4>Results</h4>We observed a turning point of time trends of incidence of SMI at 2008/2009 where slope changes of time trends were significantly increasing. IRRs by deprivation/urbanicity remained stable or significantly decreased over the study period except for those with bipolar disorder sourced from secondary care settings, with increasing trend of IRRs (increase in IRR by deprivation after 2010: 1.6\u00a0% per year, 95\u00a0% CI: 1.0\u00a0%-2.2\u00a0%; increase in IRR by urbanicity 1.0\u00a0% per year, 95\u00a0% CI: 0.6\u00a0%-1.3\u00a0%).<h4>Conclusions</h4>There was an association between recession/austerity and an increase in the incidence of SMI over time. There were variations in the effects of deprivation/urbanicity on incidence of SMI associated with short- and long-term socioeconomic change. These findings may support targeted interventions and social protection systems to reduce incidence of SMI.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.schres.2023.08.014"
-  },
   {
     "id": "31757986",
     "doi": "https://doi.org/10.1038/s41598-019-53454-1",
@@ -6357,6 +6340,23 @@
     "laySummary": "This study investigated which genes encourage cancer tumors to grow. The study identifies genes and distinguishes their role in different types of cancers. Their method is validated using whole exome and whole genome sequencing",
     "urls": "pdf:https://www.nature.com/articles/s41598-019-53454-1.pdf; doi:https://doi.org/10.1038/s41598-019-53454-1; html:https://europepmc.org/articles/PMC6874647; pdf:https://europepmc.org/articles/PMC6874647?pdf=render"
   },
+  {
+    "id": "37634386",
+    "doi": "https://doi.org/10.1016/j.schres.2023.08.014",
+    "title": "Trends in socioeconomic inequalities in incidence of severe mental illness - A population-based linkage study using primary and secondary care routinely collected data between 2000 and 2017.",
+    "authorString": "Lee SC, DelPozo-Banos M, Lloyd K, Jones I, Walters JTR, John A.",
+    "authorAffiliations": "",
+    "journalTitle": "Schizophrenia research",
+    "pubYear": "2023",
+    "date": "2023-08-25",
+    "isOpenAccess": "N",
+    "keywords": "Deprivation; Severe Mental Illness; Inequality; Recession; Urbanicity; Austerity",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>In 2008, the UK entered a period of economic recession followed by sustained austerity measures. We investigate changes in inequalities by area deprivation and urbanicity in incidence of severe mental illness (SMI, including schizophrenia-related disorders and bipolar disorder) between 2000 and 2017.<h4>Methods</h4>We analysed 4.4 million individuals from primary and secondary care routinely collected datasets (2000-2017) in Wales and estimated the incidence of SMI by deprivation and urbanicity measured by the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator respectively. Using linear modelling and joinpoint regression approaches, we examined time trends of the incidence and incidence rate ratios (IRR) of SMI by the WIMD and urban/rural indicator adjusted for available confounders.<h4>Results</h4>We observed a turning point of time trends of incidence of SMI at 2008/2009 where slope changes of time trends were significantly increasing. IRRs by deprivation/urbanicity remained stable or significantly decreased over the study period except for those with bipolar disorder sourced from secondary care settings, with increasing trend of IRRs (increase in IRR by deprivation after 2010: 1.6\u00a0% per year, 95\u00a0% CI: 1.0\u00a0%-2.2\u00a0%; increase in IRR by urbanicity 1.0\u00a0% per year, 95\u00a0% CI: 0.6\u00a0%-1.3\u00a0%).<h4>Conclusions</h4>There was an association between recession/austerity and an increase in the incidence of SMI over time. There were variations in the effects of deprivation/urbanicity on incidence of SMI associated with short- and long-term socioeconomic change. These findings may support targeted interventions and social protection systems to reduce incidence of SMI.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.schres.2023.08.014"
+  },
   {
     "id": "37159441",
     "doi": "https://doi.org/10.1371/journal.pdig.0000218",
@@ -6391,23 +6391,6 @@
     "laySummary": "",
     "urls": "pdf:https://informatics.bmj.com/content/bmjhci/27/2/e100122.full.pdf; doi:https://doi.org/10.1136/bmjhci-2019-100122; html:https://europepmc.org/articles/PMC7388881; pdf:https://europepmc.org/articles/PMC7388881?pdf=render"
   },
-  {
-    "id": "37185201",
-    "doi": "https://doi.org/10.1136/bmjopen-2022-067337",
-    "title": "Prevalence of HIV in mental health service users: a retrospective cohort study.",
-    "authorString": "Heslin M, Jewell A, Croxford S, Chau C, Smith S, Pittrof R, Covshoff E, Sullivan A, Delpech V, Brown A, King HP, Kakaiya M, Campbell L, Hughes E, Stewart R.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2023",
-    "date": "2023-04-25",
-    "isOpenAccess": "Y",
-    "keywords": "Mental health; Hiv & Aids; Sexual Medicine",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.<h4>Participants</h4>All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.<h4>Primary outcome</h4>Point prevalence of HIV.<h4>Results</h4>There were 181\u2009177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).<h4>Conclusions</h4>The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e067337.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067337; html:https://europepmc.org/articles/PMC10186409; pdf:https://europepmc.org/articles/PMC10186409?pdf=render"
-  },
   {
     "id": "35902613",
     "doi": "https://doi.org/10.1038/s41467-022-32096-4",
@@ -6425,6 +6408,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-022-32096-4.pdf; doi:https://doi.org/10.1038/s41467-022-32096-4; html:https://europepmc.org/articles/PMC9330949; pdf:https://europepmc.org/articles/PMC9330949?pdf=render"
   },
+  {
+    "id": "37185201",
+    "doi": "https://doi.org/10.1136/bmjopen-2022-067337",
+    "title": "Prevalence of HIV in mental health service users: a retrospective cohort study.",
+    "authorString": "Heslin M, Jewell A, Croxford S, Chau C, Smith S, Pittrof R, Covshoff E, Sullivan A, Delpech V, Brown A, King HP, Kakaiya M, Campbell L, Hughes E, Stewart R.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-04-25",
+    "isOpenAccess": "Y",
+    "keywords": "Mental health; Hiv & Aids; Sexual Medicine",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.<h4>Participants</h4>All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.<h4>Primary outcome</h4>Point prevalence of HIV.<h4>Results</h4>There were 181\u2009177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).<h4>Conclusions</h4>The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e067337.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067337; html:https://europepmc.org/articles/PMC10186409; pdf:https://europepmc.org/articles/PMC10186409?pdf=render"
+  },
   {
     "id": "37068951",
     "doi": "https://doi.org/10.1136/thorax-2022-219901",
@@ -6544,23 +6544,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e049441.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049441; html:https://europepmc.org/articles/PMC9013997; pdf:https://europepmc.org/articles/PMC9013997?pdf=render"
   },
-  {
-    "id": "37080124",
-    "doi": "https://doi.org/10.1016/j.seizure.2023.04.006",
-    "title": "COVID-19 vaccination uptake in people with epilepsy in wales.",
-    "authorString": "Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",
-    "authorAffiliations": "",
-    "journalTitle": "Seizure",
-    "pubYear": "2023",
-    "date": "2023-04-06",
-    "isOpenAccess": "Y",
-    "keywords": "Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Purpose</h4>People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.<h4>Methods</h4>We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.<h4>Results</h4>There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.<h4>Conclusions</h4>COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.seizure.2023.04.006; doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render"
-  },
   {
     "id": "34158305",
     "doi": "https://doi.org/10.1136/bmjopen-2020-048333",
@@ -6578,6 +6561,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e048333.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048333; html:https://europepmc.org/articles/PMC8228811; pdf:https://europepmc.org/articles/PMC8228811?pdf=render"
   },
+  {
+    "id": "37080124",
+    "doi": "https://doi.org/10.1016/j.seizure.2023.04.006",
+    "title": "COVID-19 vaccination uptake in people with epilepsy in wales.",
+    "authorString": "Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",
+    "authorAffiliations": "",
+    "journalTitle": "Seizure",
+    "pubYear": "2023",
+    "date": "2023-04-06",
+    "isOpenAccess": "Y",
+    "keywords": "Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Purpose</h4>People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.<h4>Methods</h4>We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.<h4>Results</h4>There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.<h4>Conclusions</h4>COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.seizure.2023.04.006; doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render"
+  },
   {
     "id": "32499256",
     "doi": "https://doi.org/10.1136/bmjopen-2019-033424",
@@ -6850,23 +6850,6 @@
     "laySummary": "",
     "urls": "pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/94586/2/science.abn8347.pdf; doi:https://doi.org/10.1126/science.abn8347; html:https://europepmc.org/articles/PMC8939772; pdf:https://europepmc.org/articles/PMC8939772?pdf=render"
   },
-  {
-    "id": "36936594",
-    "doi": "https://doi.org/10.1136/bmjmed-2022-000247",
-    "title": "Measuring multimorbidity in research: Delphi consensus study.",
-    "authorString": "Ho ISS, Azcoaga-Lorenzo A, Akbari A, Davies J, Khunti K, Kadam UT, Lyons RA, McCowan C, Mercer SW, Nirantharakumar K, Staniszewska S, Guthrie B.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ medicine",
-    "pubYear": "2022",
-    "date": "2022-07-27",
-    "isOpenAccess": "Y",
-    "keywords": "Medicine; epidemiology; Primary Health Care; Public Health; Research Design",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To develop international consensus on the definition and measurement of multimorbidity in research.<h4>Design</h4>Delphi consensus study.<h4>Setting</h4>International consensus; data collected in three online rounds from participants between 30 November 2020 and 18 May 2021.<h4>Participants</h4>Professionals interested in multimorbidity and people with long term conditions were recruited to professional and public panels.<h4>Results</h4>150 professional and 25 public participants completed the first survey round. Response rates for rounds 2/3 were 83%/92% for professionals and 88%/93% in the public panel, respectively. Across both panels, the consensus was that multimorbidity should be defined as two or more long term conditions. Complex multimorbidity was perceived to be a useful concept, but the panels were unable to agree on how to define it. Both panels agreed that conditions should be included in a multimorbidity measure if they were one or more of the following: currently active; permanent in their effects; requiring current treatment, care, or therapy; requiring surveillance; or relapsing-remitting conditions requiring ongoing care. Consensus was reached for 24 conditions to always include in multimorbidity measures, and 35 conditions to usually include unless a good reason not to existed. Simple counts were preferred for estimating prevalence and examining clustering or trajectories, and weighted measures were preferred for risk adjustment and outcome prediction.<h4>Conclusions</h4>Previous multimorbidity research is limited by inconsistent definitions and approaches to measuring multimorbidity. This Delphi study identifies professional and public panel consensus guidance to facilitate consistency of definition and measurement, and to improve study comparability and reproducibility.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000247.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000247; html:https://europepmc.org/articles/PMC9978673; pdf:https://europepmc.org/articles/PMC9978673?pdf=render"
-  },
   {
     "id": "32877922",
     "doi": "https://doi.org/10.1093/gerona/glaa216",
@@ -6884,6 +6867,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/biomedgerontology/article-pdf/75/12/2320/34289886/glaa216.pdf; doi:https://doi.org/10.1093/gerona/glaa216; html:https://europepmc.org/articles/PMC7662170; pdf:https://europepmc.org/articles/PMC7662170?pdf=render"
   },
+  {
+    "id": "36936594",
+    "doi": "https://doi.org/10.1136/bmjmed-2022-000247",
+    "title": "Measuring multimorbidity in research: Delphi consensus study.",
+    "authorString": "Ho ISS, Azcoaga-Lorenzo A, Akbari A, Davies J, Khunti K, Kadam UT, Lyons RA, McCowan C, Mercer SW, Nirantharakumar K, Staniszewska S, Guthrie B.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ medicine",
+    "pubYear": "2022",
+    "date": "2022-07-27",
+    "isOpenAccess": "Y",
+    "keywords": "Medicine; epidemiology; Primary Health Care; Public Health; Research Design",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To develop international consensus on the definition and measurement of multimorbidity in research.<h4>Design</h4>Delphi consensus study.<h4>Setting</h4>International consensus; data collected in three online rounds from participants between 30 November 2020 and 18 May 2021.<h4>Participants</h4>Professionals interested in multimorbidity and people with long term conditions were recruited to professional and public panels.<h4>Results</h4>150 professional and 25 public participants completed the first survey round. Response rates for rounds 2/3 were 83%/92% for professionals and 88%/93% in the public panel, respectively. Across both panels, the consensus was that multimorbidity should be defined as two or more long term conditions. Complex multimorbidity was perceived to be a useful concept, but the panels were unable to agree on how to define it. Both panels agreed that conditions should be included in a multimorbidity measure if they were one or more of the following: currently active; permanent in their effects; requiring current treatment, care, or therapy; requiring surveillance; or relapsing-remitting conditions requiring ongoing care. Consensus was reached for 24 conditions to always include in multimorbidity measures, and 35 conditions to usually include unless a good reason not to existed. Simple counts were preferred for estimating prevalence and examining clustering or trajectories, and weighted measures were preferred for risk adjustment and outcome prediction.<h4>Conclusions</h4>Previous multimorbidity research is limited by inconsistent definitions and approaches to measuring multimorbidity. This Delphi study identifies professional and public panel consensus guidance to facilitate consistency of definition and measurement, and to improve study comparability and reproducibility.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000247.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000247; html:https://europepmc.org/articles/PMC9978673; pdf:https://europepmc.org/articles/PMC9978673?pdf=render"
+  },
   {
     "id": "32704561",
     "doi": "https://doi.org/10.1002/edm2.140",
@@ -7139,23 +7139,6 @@
     "laySummary": "",
     "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/77/5/497.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217580; html:https://europepmc.org/articles/PMC8595052; pdf:https://europepmc.org/articles/PMC8595052?pdf=render"
   },
-  {
-    "id": "35213664",
-    "doi": "https://doi.org/10.1371/journal.pone.0264529",
-    "title": "Achievement of European Society of Cardiology/European Atherosclerosis Society lipid targets in very high-risk patients: Influence of depression and sex.",
-    "authorString": "Ellins EA, Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, John A, Gravenor MB, Halcox JP.",
-    "authorAffiliations": "",
-    "journalTitle": "PloS one",
-    "pubYear": "2022",
-    "date": "2022-02-25",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>To explore differences in the use of lipid lowering therapy and/or achievement of lipid guideline targets in patients with and without prior depression and influence of sex in very high-risk coronary patients.<h4>Methods & findings</h4>A retrospective observational cohort study was conducted using individual-level linked electronic health record data in patients who underwent percutaneous coronary intervention (2012-2017) in Wales. The cohort comprised of 13,781 patients (27.4% female), with 26.1% having prior depression. Lipid levels were recorded in 10,050 patients of whom 25% had depression. History of depression was independently associated with not having lipids checked (OR 0.79 95%CI 0.72-0.87 p<0.001). Patients with prior depression were less likely to achieve targets for low density lipoprotein cholesterol (LDL-C <1.8mmol/l), non-high density lipoprotein cholesterol (non-HDL-C <2.6mmol/l) and triglycerides (<2.3mmol/l) than patients without depression (OR 0.86 95%CI 0.78-0.96 p = 0.007, OR 0.80 95%CI 0.69-0.92 p = 0.003 & OR 0.69 95CI% 0.61-0.79 p<0.001 respectively). Females were less likely to achieve targets for LDL-C and non-HDL-C than males (OR 0.55 95%CI 0.50-0.61 p<0.001 & OR 0.63 95%CI 0.55-0.73 p<0.001). There was an additive effect of depression and sex; females with depression were not only least likely to be tested (OR 0.74 95%CI 0.65-0.84 p<0.001) but also (where levels were known) less likely to achieve LDL-C (OR 0.47 95%CI 0.41-0.55 p<0.001) and non-HDL-C targets (OR 0.50 95%CI 0.41-0.60 p<0.001). It was not possible to look at the influence of medication adherence on achievement of lipid targets due to limitations of the use of anonymised routinely-held clinical care data.<h4>Conclusion</h4>Patients with prior depression were less likely to have their lipids monitored and achieve guideline targets within 1-year. Females with depression are the least likely to be tested and achieve lipid targets, suggesting not only a greater risk of future events, but also an opportunity to improve care.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264529&type=printable; doi:https://doi.org/10.1371/journal.pone.0264529; html:https://europepmc.org/articles/PMC8880762; pdf:https://europepmc.org/articles/PMC8880762?pdf=render"
-  },
   {
     "id": "34693751",
     "doi": "https://doi.org/10.1177/14799731211053332",
@@ -7190,6 +7173,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?pdf=render"
   },
+  {
+    "id": "35213664",
+    "doi": "https://doi.org/10.1371/journal.pone.0264529",
+    "title": "Achievement of European Society of Cardiology/European Atherosclerosis Society lipid targets in very high-risk patients: Influence of depression and sex.",
+    "authorString": "Ellins EA, Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, John A, Gravenor MB, Halcox JP.",
+    "authorAffiliations": "",
+    "journalTitle": "PloS one",
+    "pubYear": "2022",
+    "date": "2022-02-25",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>To explore differences in the use of lipid lowering therapy and/or achievement of lipid guideline targets in patients with and without prior depression and influence of sex in very high-risk coronary patients.<h4>Methods & findings</h4>A retrospective observational cohort study was conducted using individual-level linked electronic health record data in patients who underwent percutaneous coronary intervention (2012-2017) in Wales. The cohort comprised of 13,781 patients (27.4% female), with 26.1% having prior depression. Lipid levels were recorded in 10,050 patients of whom 25% had depression. History of depression was independently associated with not having lipids checked (OR 0.79 95%CI 0.72-0.87 p<0.001). Patients with prior depression were less likely to achieve targets for low density lipoprotein cholesterol (LDL-C <1.8mmol/l), non-high density lipoprotein cholesterol (non-HDL-C <2.6mmol/l) and triglycerides (<2.3mmol/l) than patients without depression (OR 0.86 95%CI 0.78-0.96 p = 0.007, OR 0.80 95%CI 0.69-0.92 p = 0.003 & OR 0.69 95CI% 0.61-0.79 p<0.001 respectively). Females were less likely to achieve targets for LDL-C and non-HDL-C than males (OR 0.55 95%CI 0.50-0.61 p<0.001 & OR 0.63 95%CI 0.55-0.73 p<0.001). There was an additive effect of depression and sex; females with depression were not only least likely to be tested (OR 0.74 95%CI 0.65-0.84 p<0.001) but also (where levels were known) less likely to achieve LDL-C (OR 0.47 95%CI 0.41-0.55 p<0.001) and non-HDL-C targets (OR 0.50 95%CI 0.41-0.60 p<0.001). It was not possible to look at the influence of medication adherence on achievement of lipid targets due to limitations of the use of anonymised routinely-held clinical care data.<h4>Conclusion</h4>Patients with prior depression were less likely to have their lipids monitored and achieve guideline targets within 1-year. Females with depression are the least likely to be tested and achieve lipid targets, suggesting not only a greater risk of future events, but also an opportunity to improve care.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264529&type=printable; doi:https://doi.org/10.1371/journal.pone.0264529; html:https://europepmc.org/articles/PMC8880762; pdf:https://europepmc.org/articles/PMC8880762?pdf=render"
+  },
   {
     "id": "34957254",
     "doi": "https://doi.org/10.3389/fcvm.2021.766287",
@@ -7548,21 +7548,21 @@
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render"
   },
   {
-    "id": "35997000",
-    "doi": "https://doi.org/10.1111/ene.15530",
-    "title": "Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia.",
-    "authorString": "Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",
+    "id": "34145260",
+    "doi": "https://doi.org/10.1038/s41467-021-23935-x",
+    "title": "Community factors and excess mortality in first wave of the COVID-19 pandemic in England.",
+    "authorString": "Davies B, Parkes BL, Bennett J, Fecht D, Blangiardo M, Ezzati M, Elliott P.",
     "authorAffiliations": "",
-    "journalTitle": "European journal of neurology",
-    "pubYear": "2022",
-    "date": "2022-09-11",
+    "journalTitle": "Nature communications",
+    "pubYear": "2021",
+    "date": "2021-06-18",
     "isOpenAccess": "Y",
-    "keywords": "Psychiatric disorders; Movement Disorders; Dystonia; Neurological Disorders",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background and purpose</h4>Although psychiatric diagnoses are recognized in idiopathic dystonia, no previous studies have examined the temporal relationship between idiopathic dystonia and psychiatric diagnoses at scale. Here, we determine rates of psychiatric diagnoses and psychiatric medication prescription in those diagnosed with idiopathic dystsuponia compared to matched controls.<h4>Methods</h4>A longitudinal population-based cohort study using anonymized electronic health care data in Wales (UK) was conducted to identify individuals with idiopathic dystonia and comorbid psychiatric diagnoses/prescriptions between 1 January 1994 and 31 December 2017. Psychiatric diagnoses/prescriptions were identified from primary and secondary health care records.<h4>Results</h4>Individuals with idiopathic dystonia (n\u00a0=\u200952,589) had higher rates of psychiatric diagnosis and psychiatric medication prescription when compared to controls (n\u00a0=\u2009216,754, 43% vs. 31%, p\u00a0&lt;\u20090.001; 45% vs. 37.9%, p\u00a0&lt;\u20090.001, respectively), with depression and anxiety being most common (cases: 31% and 28%). Psychiatric diagnoses predominantly predated dystonia diagnosis, particularly in the 12 months prior to diagnosis (incidence rate ratio [IRR]\u2009=\u20091.98, 95% confidence interval [CI]\u2009=\u20091.9-2.1), with an IRR of 12.4 (95% CI\u00a0=\u00a011.8-13.1) for anxiety disorders. There was, however, an elevated rate of most psychiatric diagnoses throughout the study period, including the 12 months after dystonia diagnosis (IRR\u00a0=\u00a01.96, 95% CI\u00a0=\u00a01.85-2.07).<h4>Conclusions</h4>This study suggests a bidirectional relationship between psychiatric disorders and dystonia, particularly with mood disorders. Psychiatric and motor symptoms in dystonia may have common aetiological mechanisms, with psychiatric disorders potentially forming prodromal symptoms of idiopathic dystonia.",
+    "abstract": "Risk factors for increased risk of death from COVID-19 have been identified, but less is known on characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. We applied a two-stage Bayesian spatial model to quantify inequalities in excess mortality in people aged 40 years and older at the community level during the first wave of the pandemic in England, March-May 2020 compared with 2015-2019. Here we show that communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or with a non-white ethnicity. We found no association between population density or air pollution and excess mortality. Effective and timely public health and healthcare measures that target the communities at greatest risk are urgently needed to avoid further widening of inequalities in mortality patterns as the pandemic progresses.",
     "laySummary": "",
-    "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa62203/Download/62203__26254__0c88bfc9ff7e4fe2acaea5e2a2d74058.pdf; doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41467-021-23935-x.pdf; doi:https://doi.org/10.1038/s41467-021-23935-x; html:https://europepmc.org/articles/PMC8213785; pdf:https://europepmc.org/articles/PMC8213785?pdf=render"
   },
   {
     "id": "35813279",
@@ -7582,21 +7582,21 @@
     "urls": "doi:https://doi.org/10.1016/s2666-7568(22)00147-7; doi:https://doi.org/10.1016/S2666-7568(22)00147-7; html:https://europepmc.org/articles/PMC9252508; pdf:https://europepmc.org/articles/PMC9252508?pdf=render"
   },
   {
-    "id": "34145260",
-    "doi": "https://doi.org/10.1038/s41467-021-23935-x",
-    "title": "Community factors and excess mortality in first wave of the COVID-19 pandemic in England.",
-    "authorString": "Davies B, Parkes BL, Bennett J, Fecht D, Blangiardo M, Ezzati M, Elliott P.",
+    "id": "35997000",
+    "doi": "https://doi.org/10.1111/ene.15530",
+    "title": "Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia.",
+    "authorString": "Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",
     "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2021",
-    "date": "2021-06-18",
+    "journalTitle": "European journal of neurology",
+    "pubYear": "2022",
+    "date": "2022-09-11",
     "isOpenAccess": "Y",
-    "keywords": "",
+    "keywords": "Psychiatric disorders; Movement Disorders; Dystonia; Neurological Disorders",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Risk factors for increased risk of death from COVID-19 have been identified, but less is known on characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. We applied a two-stage Bayesian spatial model to quantify inequalities in excess mortality in people aged 40 years and older at the community level during the first wave of the pandemic in England, March-May 2020 compared with 2015-2019. Here we show that communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or with a non-white ethnicity. We found no association between population density or air pollution and excess mortality. Effective and timely public health and healthcare measures that target the communities at greatest risk are urgently needed to avoid further widening of inequalities in mortality patterns as the pandemic progresses.",
+    "abstract": "<h4>Background and purpose</h4>Although psychiatric diagnoses are recognized in idiopathic dystonia, no previous studies have examined the temporal relationship between idiopathic dystonia and psychiatric diagnoses at scale. Here, we determine rates of psychiatric diagnoses and psychiatric medication prescription in those diagnosed with idiopathic dystsuponia compared to matched controls.<h4>Methods</h4>A longitudinal population-based cohort study using anonymized electronic health care data in Wales (UK) was conducted to identify individuals with idiopathic dystonia and comorbid psychiatric diagnoses/prescriptions between 1 January 1994 and 31 December 2017. Psychiatric diagnoses/prescriptions were identified from primary and secondary health care records.<h4>Results</h4>Individuals with idiopathic dystonia (n\u00a0=\u200952,589) had higher rates of psychiatric diagnosis and psychiatric medication prescription when compared to controls (n\u00a0=\u2009216,754, 43% vs. 31%, p\u00a0&lt;\u20090.001; 45% vs. 37.9%, p\u00a0&lt;\u20090.001, respectively), with depression and anxiety being most common (cases: 31% and 28%). Psychiatric diagnoses predominantly predated dystonia diagnosis, particularly in the 12 months prior to diagnosis (incidence rate ratio [IRR]\u2009=\u20091.98, 95% confidence interval [CI]\u2009=\u20091.9-2.1), with an IRR of 12.4 (95% CI\u00a0=\u00a011.8-13.1) for anxiety disorders. There was, however, an elevated rate of most psychiatric diagnoses throughout the study period, including the 12 months after dystonia diagnosis (IRR\u00a0=\u00a01.96, 95% CI\u00a0=\u00a01.85-2.07).<h4>Conclusions</h4>This study suggests a bidirectional relationship between psychiatric disorders and dystonia, particularly with mood disorders. Psychiatric and motor symptoms in dystonia may have common aetiological mechanisms, with psychiatric disorders potentially forming prodromal symptoms of idiopathic dystonia.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-021-23935-x.pdf; doi:https://doi.org/10.1038/s41467-021-23935-x; html:https://europepmc.org/articles/PMC8213785; pdf:https://europepmc.org/articles/PMC8213785?pdf=render"
+    "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa62203/Download/62203__26254__0c88bfc9ff7e4fe2acaea5e2a2d74058.pdf; doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render"
   },
   {
     "id": "PMC9644982",
@@ -7632,23 +7632,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/2076-393X/11/3/680/pdf?version=1679031223; doi:https://doi.org/10.3390/vaccines11030680; html:https://europepmc.org/articles/PMC10057771; pdf:https://europepmc.org/articles/PMC10057771?pdf=render"
   },
-  {
-    "id": "37663407",
-    "doi": "https://doi.org/10.1093/jamiaopen/ooad072",
-    "title": "Identifying factors associated with user retention and outcomes of a digital intervention for substance use disorder: a retrospective analysis of real-world data.",
-    "authorString": "G\u00fcnther F, Wong D, Elison-Davies S, Yau C.",
-    "authorAffiliations": "",
-    "journalTitle": "JAMIA open",
-    "pubYear": "2023",
-    "date": "2023-09-02",
-    "isOpenAccess": "Y",
-    "keywords": "Substance Use Disorder; Secondary Use; Digital Health Intervention; Real-World Data Exploration; Real-World Uptake",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>Successful delivery of digital health interventions is affected by multiple real-world factors. These factors may be identified in routinely collected, ecologically valid data from these interventions. We propose ideas for exploring these data, focusing on interventions targeting complex, comorbid conditions.<h4>Materials and methods</h4>This study retrospectively explores pre-post data collected between 2016 and 2019 from users of digital cognitive behavioral therapy (CBT)-containing psychoeducation and practical exercises-for substance use disorder (SUD) at UK addiction services. To identify factors associated with heterogenous user responses to the technology, we employed multivariable and multivariate regressions and random forest models of user-reported questionnaire data.<h4>Results</h4>The dataset contained information from 14\u200a078 individuals of which 12\u200a529 reported complete data at baseline and 2925 did so again after engagement with the CBT. Ninety-three percent screened positive for dependence on 1 of 43 substances at baseline, and 73% screened positive for anxiety or depression. Despite pre-post improvements independent of user sociodemographics, women reported more frequent and persistent symptoms of SUD, anxiety, and depression. Retention-minimum 2 use events recorded-was associated more with deployment environment than user characteristics. Prediction accuracy of post-engagement outcomes was acceptable (Area Under Curve [AUC]: 0.74-0.79), depending non-trivially on user characteristics.<h4>Discussion</h4>Traditionally, performance of digital health interventions is determined in controlled trials. Our analysis showcases multivariate models with which real-world data from these interventions can be explored and sources of user heterogeneity in retention and symptom reduction uncovered.<h4>Conclusion</h4>Real-world data from digital health interventions contain information on natural user-technology interactions which could enrich results from controlled trials.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1093/jamiaopen/ooad072; html:https://europepmc.org/articles/PMC10474970; pdf:https://europepmc.org/articles/PMC10474970?pdf=render"
-  },
   {
     "id": "32180562",
     "doi": "https://doi.org/10.1016/j.molmet.2020.01.009",
@@ -7666,6 +7649,23 @@
     "laySummary": "How the body breaks down fat is poorly understood, and, if this mechanism does not happen effiently in the body it can lead to metabolic diseases including obesity and type 2 diabetes. The goal of this study was to identify the genetic regulators of how the body break down fat and explain their molecular mechanisms.",
     "urls": "doi:https://doi.org/10.1016/j.molmet.2020.01.009; doi:https://doi.org/10.1016/j.molmet.2020.01.009; html:https://europepmc.org/articles/PMC7021539; pdf:https://europepmc.org/articles/PMC7021539?pdf=render"
   },
+  {
+    "id": "37663407",
+    "doi": "https://doi.org/10.1093/jamiaopen/ooad072",
+    "title": "Identifying factors associated with user retention and outcomes of a digital intervention for substance use disorder: a retrospective analysis of real-world data.",
+    "authorString": "G\u00fcnther F, Wong D, Elison-Davies S, Yau C.",
+    "authorAffiliations": "",
+    "journalTitle": "JAMIA open",
+    "pubYear": "2023",
+    "date": "2023-09-02",
+    "isOpenAccess": "Y",
+    "keywords": "Substance Use Disorder; Secondary Use; Digital Health Intervention; Real-World Data Exploration; Real-World Uptake",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>Successful delivery of digital health interventions is affected by multiple real-world factors. These factors may be identified in routinely collected, ecologically valid data from these interventions. We propose ideas for exploring these data, focusing on interventions targeting complex, comorbid conditions.<h4>Materials and methods</h4>This study retrospectively explores pre-post data collected between 2016 and 2019 from users of digital cognitive behavioral therapy (CBT)-containing psychoeducation and practical exercises-for substance use disorder (SUD) at UK addiction services. To identify factors associated with heterogenous user responses to the technology, we employed multivariable and multivariate regressions and random forest models of user-reported questionnaire data.<h4>Results</h4>The dataset contained information from 14\u200a078 individuals of which 12\u200a529 reported complete data at baseline and 2925 did so again after engagement with the CBT. Ninety-three percent screened positive for dependence on 1 of 43 substances at baseline, and 73% screened positive for anxiety or depression. Despite pre-post improvements independent of user sociodemographics, women reported more frequent and persistent symptoms of SUD, anxiety, and depression. Retention-minimum 2 use events recorded-was associated more with deployment environment than user characteristics. Prediction accuracy of post-engagement outcomes was acceptable (Area Under Curve [AUC]: 0.74-0.79), depending non-trivially on user characteristics.<h4>Discussion</h4>Traditionally, performance of digital health interventions is determined in controlled trials. Our analysis showcases multivariate models with which real-world data from these interventions can be explored and sources of user heterogeneity in retention and symptom reduction uncovered.<h4>Conclusion</h4>Real-world data from digital health interventions contain information on natural user-technology interactions which could enrich results from controlled trials.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1093/jamiaopen/ooad072; html:https://europepmc.org/articles/PMC10474970; pdf:https://europepmc.org/articles/PMC10474970?pdf=render"
+  },
   {
     "id": "33182605",
     "doi": "https://doi.org/10.3390/genes11111326",
@@ -7751,23 +7751,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; html:https://europepmc.org/articles/PMC7843148"
   },
-  {
-    "id": "PMC9644860",
-    "doi": "https://doi.org/",
-    "title": "Maternal mental health and children\u2019s development: a bi-directional relationship?",
-    "authorString": "Lowthian E, Bedston S, Akbari A, Katz A, Huxley K, Johnson R, Kristensen S, Owen R, Taylor C, Griffiths L.",
-    "authorAffiliations": "",
-    "journalTitle": "International journal of population data science",
-    "pubYear": null,
-    "date": "2022-11-21",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9644860; pdf:https://europepmc.org/articles/PMC9644860?pdf=render"
-  },
   {
     "id": "33939953",
     "doi": "https://doi.org/10.1016/s0140-6736(21)00634-6",
@@ -7785,6 +7768,23 @@
     "laySummary": "",
     "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659476/13/PIIS0140673621006346.pdf; doi:https://doi.org/10.1016/S0140-6736(21)00634-6; html:https://europepmc.org/articles/PMC8087292; pdf:https://europepmc.org/articles/PMC8087292?pdf=render"
   },
+  {
+    "id": "PMC9644860",
+    "doi": "https://doi.org/",
+    "title": "Maternal mental health and children\u2019s development: a bi-directional relationship?",
+    "authorString": "Lowthian E, Bedston S, Akbari A, Katz A, Huxley K, Johnson R, Kristensen S, Owen R, Taylor C, Griffiths L.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of population data science",
+    "pubYear": null,
+    "date": "2022-11-21",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9644860; pdf:https://europepmc.org/articles/PMC9644860?pdf=render"
+  },
   {
     "id": "33644411",
     "doi": "https://doi.org/10.23889/ijpds.v5i1.1346",
@@ -7887,23 +7887,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1093/jamia/ocad212"
   },
-  {
-    "id": "37868035",
-    "doi": "https://doi.org/10.1016/j.xgen.2023.100385",
-    "title": "Gene expression and RNA splicing explain large proportions of the heritability for complex traits in cattle.",
-    "authorString": "Xiang R, Fang L, Liu S, Macleod IM, Liu Z, Breen EJ, Gao Y, Liu GE, Tenesa A, CattleGTEx Consortium, Mason BA, Chamberlain AJ, Wray NR, Goddard ME.",
-    "authorAffiliations": "",
-    "journalTitle": "Cell genomics",
-    "pubYear": "2023",
-    "date": "2023-08-23",
-    "isOpenAccess": "Y",
-    "keywords": "RNA splicing; Heritability; Gene Expression; Complex Traits; Eqtl; Sqtl; Bayesr; Bayesrc",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Many quantitative trait loci (QTLs) are in non-coding regions. Therefore, QTLs are assumed to affect gene regulation. Gene expression and RNA splicing are primary steps of transcription, so DNA variants changing gene expression (eVariants) or RNA splicing (sVariants) are expected to significantly affect phenotypes. We quantify the contribution of eVariants and sVariants detected from 16 tissues (n\u00a0= 4,725) to 37 traits of \u223c120,000 cattle (average magnitude of genetic correlation between traits\u00a0= 0.13). Analyzed in Bayesian mixture models, averaged across 37 traits, <i>cis</i> and <i>trans</i> eVariants and sVariants detected from 16 tissues jointly explain 69.2% (SE\u00a0= 0.5%) of heritability, 44% more than expected from the same number of random variants. This 69.2% includes an average of 24% from <i>trans</i> e-/sVariants (14% more than expected). Averaged across 56 lipidomic traits, multi-tissue <i>cis</i> and <i>trans</i> e-/sVariants also explain 71.5% (SE\u00a0= 0.3%) of heritability, demonstrating the essential role of proximal and distal regulatory variants in shaping mammalian phenotypes.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.xgen.2023.100385; html:https://europepmc.org/articles/PMC10589627; pdf:https://europepmc.org/articles/PMC10589627?pdf=render"
-  },
   {
     "id": "32463370",
     "doi": "https://doi.org/10.2196/16452",
@@ -7921,6 +7904,23 @@
     "laySummary": "",
     "urls": "pdf:https://medinform.jmir.org/2020/5/e16452/PDF; doi:https://doi.org/10.2196/16452; html:https://europepmc.org/articles/PMC7290450"
   },
+  {
+    "id": "37868035",
+    "doi": "https://doi.org/10.1016/j.xgen.2023.100385",
+    "title": "Gene expression and RNA splicing explain large proportions of the heritability for complex traits in cattle.",
+    "authorString": "Xiang R, Fang L, Liu S, Macleod IM, Liu Z, Breen EJ, Gao Y, Liu GE, Tenesa A, CattleGTEx Consortium, Mason BA, Chamberlain AJ, Wray NR, Goddard ME.",
+    "authorAffiliations": "",
+    "journalTitle": "Cell genomics",
+    "pubYear": "2023",
+    "date": "2023-08-23",
+    "isOpenAccess": "Y",
+    "keywords": "RNA splicing; Heritability; Gene Expression; Complex Traits; Eqtl; Sqtl; Bayesr; Bayesrc",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Many quantitative trait loci (QTLs) are in non-coding regions. Therefore, QTLs are assumed to affect gene regulation. Gene expression and RNA splicing are primary steps of transcription, so DNA variants changing gene expression (eVariants) or RNA splicing (sVariants) are expected to significantly affect phenotypes. We quantify the contribution of eVariants and sVariants detected from 16 tissues (n\u00a0= 4,725) to 37 traits of \u223c120,000 cattle (average magnitude of genetic correlation between traits\u00a0= 0.13). Analyzed in Bayesian mixture models, averaged across 37 traits, <i>cis</i> and <i>trans</i> eVariants and sVariants detected from 16 tissues jointly explain 69.2% (SE\u00a0= 0.5%) of heritability, 44% more than expected from the same number of random variants. This 69.2% includes an average of 24% from <i>trans</i> e-/sVariants (14% more than expected). Averaged across 56 lipidomic traits, multi-tissue <i>cis</i> and <i>trans</i> e-/sVariants also explain 71.5% (SE\u00a0= 0.3%) of heritability, demonstrating the essential role of proximal and distal regulatory variants in shaping mammalian phenotypes.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.xgen.2023.100385; html:https://europepmc.org/articles/PMC10589627; pdf:https://europepmc.org/articles/PMC10589627?pdf=render"
+  },
   {
     "id": "35749561",
     "doi": "https://doi.org/10.1371/journal.pcbi.1010234",
@@ -8006,23 +8006,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/jamia/article-pdf/30/1/103/47829607/ocac203.pdf; doi:https://doi.org/10.1093/jamia/ocac203; html:https://europepmc.org/articles/PMC9619789; pdf:https://europepmc.org/articles/PMC9619789?pdf=render"
   },
-  {
-    "id": "35868811",
-    "doi": "https://doi.org/10.1016/s2589-7500(22)00122-4",
-    "title": "Data provenance and integrity of health-care systems data for clinical trials.",
-    "authorString": "Murray ML, Love SB, Carpenter JR, Hartley S, Landray MJ, Mafham M, Parmar MKB, Pinches H, Sydes MR, Healthcare Systems Data for Clinical Trials Collaborative Group.",
-    "authorAffiliations": "",
-    "journalTitle": "The Lancet. Digital health",
-    "pubYear": "2022",
-    "date": "2022-08-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "pdf:http://www.thelancet.com/article/S2589750022001224/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00122-4; html:https://europepmc.org/articles/PMC9296098; pdf:https://europepmc.org/articles/PMC9296098?pdf=render"
-  },
   {
     "id": "31591592",
     "doi": "https://doi.org/10.1038/s41591-019-0597-x",
@@ -8041,21 +8024,21 @@
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076561; doi:https://doi.org/10.1038/s41591-019-0597-x; html:https://europepmc.org/articles/PMC7076561; pdf:https://europepmc.org/articles/PMC7076561?pdf=render; doi:https://doi.org/10.1038/s41591-019-0597-x"
   },
   {
-    "id": "36384890",
-    "doi": "https://doi.org/10.1136/bmj-2022-071932",
-    "title": "Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform.",
-    "authorString": "Zheng B, Green ACA, Tazare J, Curtis HJ, Fisher L, Nab L, Schultze A, Mahalingasivam V, Parker EPK, Hulme WJ, Bacon SCJ, DeVito NJ, Bates C, Evans D, Inglesby P, Drysdale H, Davy S, Cockburn J, Morton CE, Hickman G, Ward T, Smith RM, Parry J, Hester F, Harper S, Mehrkar A, Eggo RM, Walker AJ, Evans SJW, Douglas IJ, MacKenna B, Goldacre B, Tomlinson LA.",
+    "id": "35868811",
+    "doi": "https://doi.org/10.1016/s2589-7500(22)00122-4",
+    "title": "Data provenance and integrity of health-care systems data for clinical trials.",
+    "authorString": "Murray ML, Love SB, Carpenter JR, Hartley S, Landray MJ, Mafham M, Parmar MKB, Pinches H, Sydes MR, Healthcare Systems Data for Clinical Trials Collaborative Group.",
     "authorAffiliations": "",
-    "journalTitle": "BMJ (Clinical research ed.)",
+    "journalTitle": "The Lancet. Digital health",
     "pubYear": "2022",
-    "date": "2022-11-16",
+    "date": "2022-08-01",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19.<h4>Design</h4>Observational cohort study with the OpenSAFELY platform.<h4>Setting</h4>With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings.<h4>Participants</h4>Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.<h4>Interventions</h4>Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units.<h4>Main outcome measures</h4>Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment.<h4>Results</h4>Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England.<h4>Conclusions</h4>In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.",
+    "abstract": "",
     "laySummary": "",
-    "urls": "pdf:https://www.bmj.com/content/bmj/379/bmj-2022-071932.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071932; html:https://europepmc.org/articles/PMC9667468"
+    "urls": "pdf:http://www.thelancet.com/article/S2589750022001224/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00122-4; html:https://europepmc.org/articles/PMC9296098; pdf:https://europepmc.org/articles/PMC9296098?pdf=render"
   },
   {
     "id": "31462651",
@@ -8074,6 +8057,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-019-48927-2.pdf; doi:https://doi.org/10.1038/s41598-019-48927-2; html:https://europepmc.org/articles/PMC6713749; pdf:https://europepmc.org/articles/PMC6713749?pdf=render"
   },
+  {
+    "id": "36384890",
+    "doi": "https://doi.org/10.1136/bmj-2022-071932",
+    "title": "Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform.",
+    "authorString": "Zheng B, Green ACA, Tazare J, Curtis HJ, Fisher L, Nab L, Schultze A, Mahalingasivam V, Parker EPK, Hulme WJ, Bacon SCJ, DeVito NJ, Bates C, Evans D, Inglesby P, Drysdale H, Davy S, Cockburn J, Morton CE, Hickman G, Ward T, Smith RM, Parry J, Hester F, Harper S, Mehrkar A, Eggo RM, Walker AJ, Evans SJW, Douglas IJ, MacKenna B, Goldacre B, Tomlinson LA.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ (Clinical research ed.)",
+    "pubYear": "2022",
+    "date": "2022-11-16",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19.<h4>Design</h4>Observational cohort study with the OpenSAFELY platform.<h4>Setting</h4>With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings.<h4>Participants</h4>Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.<h4>Interventions</h4>Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units.<h4>Main outcome measures</h4>Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment.<h4>Results</h4>Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England.<h4>Conclusions</h4>In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.",
+    "laySummary": "",
+    "urls": "pdf:https://www.bmj.com/content/bmj/379/bmj-2022-071932.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071932; html:https://europepmc.org/articles/PMC9667468"
+  },
   {
     "id": "36472984",
     "doi": "https://doi.org/10.1371/journal.pmed.1004124",
@@ -8261,23 +8261,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/eurheartj/article-pdf/43/2/127/42182731/ehab581.pdf; doi:https://doi.org/10.1093/eurheartj/ehab581; html:https://europepmc.org/articles/PMC8757580; pdf:https://europepmc.org/articles/PMC8757580?pdf=render"
   },
-  {
-    "id": "37550086",
-    "doi": "https://doi.org/10.1136/bmjment-2023-300762",
-    "title": "Associations between air pollution and mental health service use in dementia: a retrospective cohort study.",
-    "authorString": "Ronaldson A, Stewart R, Mueller C, Das-Munshi J, Newbury JB, Mudway IS, Broadbent M, Fisher HL, Beevers S, Dajnak D, Hotopf M, Hatch SL, Bakolis I.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ mental health",
-    "pubYear": "2023",
-    "date": "2023-07-01",
-    "isOpenAccess": "Y",
-    "keywords": "Psychiatry; Adult Psychiatry; Delirium & Cognitive Disorders",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Little is known about the role of air pollution in how people with dementia use mental health services.<h4>Objective</h4>We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia.<h4>Methods</h4>In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO<sub>2</sub>) and particulate matter (PM<sub>2.5</sub> and PM<sub>10</sub>) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models.<h4>Findings</h4>In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO<sub>2</sub>: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11\u2009to 1.45, p<0.001). Dose-response patterns between PM<sub>2.5</sub> and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO<sub>2</sub> levels were linked with poor functional status, but not cognitive function.<h4>Conclusions</h4>Residential air pollution exposure is associated with increased CMHT usage among people with dementia.<h4>Clinical implications</h4>Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?pdf=render"
-  },
   {
     "id": "34164795",
     "doi": "https://doi.org/10.1007/s40801-021-00256-5",
@@ -8295,6 +8278,23 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s40801-021-00256-5.pdf; doi:https://doi.org/10.1007/s40801-021-00256-5; html:https://europepmc.org/articles/PMC8605959; pdf:https://europepmc.org/articles/PMC8605959?pdf=render"
   },
+  {
+    "id": "37550086",
+    "doi": "https://doi.org/10.1136/bmjment-2023-300762",
+    "title": "Associations between air pollution and mental health service use in dementia: a retrospective cohort study.",
+    "authorString": "Ronaldson A, Stewart R, Mueller C, Das-Munshi J, Newbury JB, Mudway IS, Broadbent M, Fisher HL, Beevers S, Dajnak D, Hotopf M, Hatch SL, Bakolis I.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ mental health",
+    "pubYear": "2023",
+    "date": "2023-07-01",
+    "isOpenAccess": "Y",
+    "keywords": "Psychiatry; Adult Psychiatry; Delirium & Cognitive Disorders",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Little is known about the role of air pollution in how people with dementia use mental health services.<h4>Objective</h4>We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia.<h4>Methods</h4>In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO<sub>2</sub>) and particulate matter (PM<sub>2.5</sub> and PM<sub>10</sub>) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models.<h4>Findings</h4>In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO<sub>2</sub>: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11\u2009to 1.45, p<0.001). Dose-response patterns between PM<sub>2.5</sub> and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO<sub>2</sub> levels were linked with poor functional status, but not cognitive function.<h4>Conclusions</h4>Residential air pollution exposure is associated with increased CMHT usage among people with dementia.<h4>Clinical implications</h4>Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?pdf=render"
+  },
   {
     "id": "36949447",
     "doi": "https://doi.org/10.1186/s12889-023-15345-z",
@@ -8499,23 +8499,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/1422-0067/22/11/5763/pdf?version=1622194941; doi:https://doi.org/10.3390/ijms22115763; html:https://europepmc.org/articles/PMC8198673; pdf:https://europepmc.org/articles/PMC8198673?pdf=render"
   },
-  {
-    "id": "37678576",
-    "doi": "https://doi.org/10.1016/j.jaci.2023.08.025",
-    "title": "E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.",
-    "authorString": "Jasper AE, Faniyi AA, Davis LC, Grudzinska FS, Halston R, Hazeldine J, Parekh D, Sapey E, Thickett DR, Scott A.",
-    "authorAffiliations": "",
-    "journalTitle": "The Journal of allergy and clinical immunology",
-    "pubYear": "2023",
-    "date": "2023-09-05",
-    "isOpenAccess": "N",
-    "keywords": "Neutrophils; Phagocytosis; Oxidative burst; Nicotine; Netosis; E-cigarettes",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.<h4>Objective</h4>We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.<h4>Methods</h4>Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed.<h4>Results</h4>Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls.<h4>Conclusions</h4>The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jaci.2023.08.025"
-  },
   {
     "id": "35954935",
     "doi": "https://doi.org/10.3390/ijerph19159578",
@@ -8533,6 +8516,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/1660-4601/19/15/9578/pdf?version=1659598966; doi:https://doi.org/10.3390/ijerph19159578; html:https://europepmc.org/articles/PMC9368485; pdf:https://europepmc.org/articles/PMC9368485?pdf=render"
   },
+  {
+    "id": "37678576",
+    "doi": "https://doi.org/10.1016/j.jaci.2023.08.025",
+    "title": "E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.",
+    "authorString": "Jasper AE, Faniyi AA, Davis LC, Grudzinska FS, Halston R, Hazeldine J, Parekh D, Sapey E, Thickett DR, Scott A.",
+    "authorAffiliations": "",
+    "journalTitle": "The Journal of allergy and clinical immunology",
+    "pubYear": "2023",
+    "date": "2023-09-05",
+    "isOpenAccess": "N",
+    "keywords": "Neutrophils; Phagocytosis; Oxidative burst; Nicotine; Netosis; E-cigarettes",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.<h4>Objective</h4>We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.<h4>Methods</h4>Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed.<h4>Results</h4>Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls.<h4>Conclusions</h4>The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jaci.2023.08.025"
+  },
   {
     "id": "35962974",
     "doi": "https://doi.org/10.1093/ije/dyac158",
@@ -8924,23 +8924,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.026432; doi:https://doi.org/10.1161/JAHA.122.026432; html:https://europepmc.org/articles/PMC9673731; pdf:https://europepmc.org/articles/PMC9673731?pdf=render"
   },
-  {
-    "id": "37080566",
-    "doi": "https://doi.org/10.1183/13993003.01720-2022",
-    "title": "Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.",
-    "authorString": "Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Mois\u00e9s J, Pech\u00e9 R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.",
-    "authorAffiliations": "",
-    "journalTitle": "The European respiratory journal",
-    "pubYear": "2023",
-    "date": "2023-05-18",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.<h4>Methods</h4>The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.<h4>Results</h4>In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.<h4>Conclusion</h4>A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.",
-    "laySummary": "",
-    "urls": "pdf:https://erj.ersjournals.com/content/erj/early/2023/03/15/13993003.01720-2022.full.pdf; doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render"
-  },
   {
     "id": "33200120",
     "doi": "https://doi.org/10.1016/j.eclinm.2020.100630",
@@ -8959,38 +8942,38 @@
     "urls": "pdf:https://figshare.com/articles/journal_contribution/Ethnicity_and_clinical_outcomes_in_COVID-19_A_Systematic_Review_and_Meta-analysis/13147892/1/files/25502810.pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100630; html:https://europepmc.org/articles/PMC7658622; pdf:https://europepmc.org/articles/PMC7658622?pdf=render"
   },
   {
-    "id": "36753492",
-    "doi": "https://doi.org/10.1371/journal.pone.0281466",
-    "title": "Combinations of medicines in patients with polypharmacy aged 65-100 in primary care: Large variability in risks of adverse drug related and emergency hospital admissions.",
-    "authorString": "Fahmi A, Wong D, Walker L, Buchan I, Pirmohamed M, Sharma A, Cant H, Ashcroft DM, van Staa TP.",
+    "id": "37080566",
+    "doi": "https://doi.org/10.1183/13993003.01720-2022",
+    "title": "Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.",
+    "authorString": "Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Mois\u00e9s J, Pech\u00e9 R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.",
     "authorAffiliations": "",
-    "journalTitle": "PloS one",
+    "journalTitle": "The European respiratory journal",
     "pubYear": "2023",
-    "date": "2023-02-08",
+    "date": "2023-05-18",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.<h4>Methods</h4>We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.<h4>Results</h4>In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.<h4>Conclusions</h4>Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.",
+    "abstract": "<h4>Background</h4>Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.<h4>Methods</h4>The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.<h4>Results</h4>In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.<h4>Conclusion</h4>A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.",
     "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0281466&type=printable; doi:https://doi.org/10.1371/journal.pone.0281466; html:https://europepmc.org/articles/PMC9907844; pdf:https://europepmc.org/articles/PMC9907844?pdf=render"
+    "urls": "pdf:https://erj.ersjournals.com/content/erj/early/2023/03/15/13993003.01720-2022.full.pdf; doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render"
   },
   {
-    "id": "PMC9645061",
-    "doi": "https://doi.org/",
-    "title": "Using population-scale medication data to evaluate the impact of the COVID-19 pandemic on the usage of analgesics by cancer patients.",
-    "authorString": "Han J, Akbari A, Torabi F, Griffiths R, Lyons J, Rolles M, Arnold C, Huws D, Lawler M, Lyons R.",
+    "id": "36753492",
+    "doi": "https://doi.org/10.1371/journal.pone.0281466",
+    "title": "Combinations of medicines in patients with polypharmacy aged 65-100 in primary care: Large variability in risks of adverse drug related and emergency hospital admissions.",
+    "authorString": "Fahmi A, Wong D, Walker L, Buchan I, Pirmohamed M, Sharma A, Cant H, Ashcroft DM, van Staa TP.",
     "authorAffiliations": "",
-    "journalTitle": "International journal of population data science",
-    "pubYear": null,
-    "date": "2022-11-25",
+    "journalTitle": "PloS one",
+    "pubYear": "2023",
+    "date": "2023-02-08",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "",
+    "abstract": "<h4>Background</h4>Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.<h4>Methods</h4>We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.<h4>Results</h4>In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.<h4>Conclusions</h4>Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.",
     "laySummary": "",
-    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9645061; pdf:https://europepmc.org/articles/PMC9645061?pdf=render"
+    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0281466&type=printable; doi:https://doi.org/10.1371/journal.pone.0281466; html:https://europepmc.org/articles/PMC9907844; pdf:https://europepmc.org/articles/PMC9907844?pdf=render"
   },
   {
     "id": "33185672",
@@ -9009,6 +8992,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/jamia/article-pdf/28/4/791/41182395/ocaa295.pdf; doi:https://doi.org/10.1093/jamia/ocaa295; html:https://europepmc.org/articles/PMC7717299; pdf:https://europepmc.org/articles/PMC7717299?pdf=render"
   },
+  {
+    "id": "PMC9645061",
+    "doi": "https://doi.org/",
+    "title": "Using population-scale medication data to evaluate the impact of the COVID-19 pandemic on the usage of analgesics by cancer patients.",
+    "authorString": "Han J, Akbari A, Torabi F, Griffiths R, Lyons J, Rolles M, Arnold C, Huws D, Lawler M, Lyons R.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of population data science",
+    "pubYear": null,
+    "date": "2022-11-25",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9645061; pdf:https://europepmc.org/articles/PMC9645061?pdf=render"
+  },
   {
     "id": "33152012",
     "doi": "https://doi.org/10.1371/journal.pone.0241800",
@@ -9196,23 +9196,6 @@
     "laySummary": "",
     "urls": "pdf:https://heart.bmj.com/content/heartjnl/early/2022/11/15/heartjnl-2022-321733.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321733; html:https://europepmc.org/articles/PMC10086465; pdf:https://europepmc.org/articles/PMC10086465?pdf=render"
   },
-  {
-    "id": "37781298",
-    "doi": "https://doi.org/10.3389/fcvm.2023.1141026",
-    "title": "Radiomics analysis enhances the diagnostic performance of CMR stress perfusion: a proof-of-concept study using the Dan-NICAD dataset.",
-    "authorString": "Raisi-Estabragh Z, Martin-Isla C, Nissen L, Szabo L, Campello VM, Escalera S, Winther S, B\u00f8ttcher M, Lekadir K, Petersen SE.",
-    "authorAffiliations": "",
-    "journalTitle": "Frontiers in cardiovascular medicine",
-    "pubYear": "2023",
-    "date": "2023-09-15",
-    "isOpenAccess": "Y",
-    "keywords": "Machine Learning (Ml); Radiomics; Cmr (Cardiovascular Magnetic Resonance); Stress Perfusion Cardiac Mri; Dan-nicad",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>To assess the feasibility of extracting radiomics signal intensity based features from the myocardium using cardiovascular magnetic resonance (CMR) imaging stress perfusion sequences. Furthermore, to compare the diagnostic performance of radiomics models against standard-of-care qualitative visual assessment of stress perfusion images, with the ground truth stenosis label being defined by invasive Fractional Flow Reserve (FFR) and quantitative coronary angiography.<h4>Methods</h4>We used the Dan-NICAD 1 dataset, a multi-centre study with coronary computed tomography angiography, 1,5\u2005T CMR stress perfusion, and invasive FFR available for a subset of 148 patients with suspected coronary artery disease. Image segmentation was performed by two independent readers. We used the Pyradiomics platform to extract radiomics first-order (<i>n</i>\u2009=\u200914) and texture (<i>n</i>\u2009=\u200975) features from the LV myocardium (basal, mid, apical) in rest and stress perfusion images.<h4>Results</h4>Overall, 92 patients (mean age 62 years, 56 men) were included in the study, 39 with positive FFR. We double-cross validated the model and, in each inner fold, we trained and validated a per territory model. The conventional analysis results reported sensitivity of 41% and specificity of 84%. Our final radiomics model demonstrated an improvement on these results with an average sensitivity of 53% and specificity of 86%.<h4>Conclusion</h4>In this proof-of-concept study from the Dan-NICAD dataset, we demonstrate the feasibility of radiomics analysis applied to CMR perfusion images with a suggestion of superior diagnostic performance of radiomics models over conventional visual analysis of perfusion images in picking up perfusion defects defined by invasive coronary angiography.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.3389/fcvm.2023.1141026; html:https://europepmc.org/articles/PMC10541220; pdf:https://europepmc.org/articles/PMC10541220?pdf=render"
-  },
   {
     "id": "33371011",
     "doi": "https://doi.org/10.1136/bmjresp-2020-000770",
@@ -9247,6 +9230,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render"
   },
+  {
+    "id": "37781298",
+    "doi": "https://doi.org/10.3389/fcvm.2023.1141026",
+    "title": "Radiomics analysis enhances the diagnostic performance of CMR stress perfusion: a proof-of-concept study using the Dan-NICAD dataset.",
+    "authorString": "Raisi-Estabragh Z, Martin-Isla C, Nissen L, Szabo L, Campello VM, Escalera S, Winther S, B\u00f8ttcher M, Lekadir K, Petersen SE.",
+    "authorAffiliations": "",
+    "journalTitle": "Frontiers in cardiovascular medicine",
+    "pubYear": "2023",
+    "date": "2023-09-15",
+    "isOpenAccess": "Y",
+    "keywords": "Machine Learning (Ml); Radiomics; Cmr (Cardiovascular Magnetic Resonance); Stress Perfusion Cardiac Mri; Dan-nicad",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>To assess the feasibility of extracting radiomics signal intensity based features from the myocardium using cardiovascular magnetic resonance (CMR) imaging stress perfusion sequences. Furthermore, to compare the diagnostic performance of radiomics models against standard-of-care qualitative visual assessment of stress perfusion images, with the ground truth stenosis label being defined by invasive Fractional Flow Reserve (FFR) and quantitative coronary angiography.<h4>Methods</h4>We used the Dan-NICAD 1 dataset, a multi-centre study with coronary computed tomography angiography, 1,5\u2005T CMR stress perfusion, and invasive FFR available for a subset of 148 patients with suspected coronary artery disease. Image segmentation was performed by two independent readers. We used the Pyradiomics platform to extract radiomics first-order (<i>n</i>\u2009=\u200914) and texture (<i>n</i>\u2009=\u200975) features from the LV myocardium (basal, mid, apical) in rest and stress perfusion images.<h4>Results</h4>Overall, 92 patients (mean age 62 years, 56 men) were included in the study, 39 with positive FFR. We double-cross validated the model and, in each inner fold, we trained and validated a per territory model. The conventional analysis results reported sensitivity of 41% and specificity of 84%. Our final radiomics model demonstrated an improvement on these results with an average sensitivity of 53% and specificity of 86%.<h4>Conclusion</h4>In this proof-of-concept study from the Dan-NICAD dataset, we demonstrate the feasibility of radiomics analysis applied to CMR perfusion images with a suggestion of superior diagnostic performance of radiomics models over conventional visual analysis of perfusion images in picking up perfusion defects defined by invasive coronary angiography.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.3389/fcvm.2023.1141026; html:https://europepmc.org/articles/PMC10541220; pdf:https://europepmc.org/articles/PMC10541220?pdf=render"
+  },
   {
     "id": "33632765",
     "doi": "https://doi.org/10.1136/thoraxjnl-2020-215986",
@@ -9434,23 +9434,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.3389/fendo.2023.1266557; html:https://europepmc.org/articles/PMC10516571; pdf:https://europepmc.org/articles/PMC10516571?pdf=render"
   },
-  {
-    "id": "36921925",
-    "doi": "https://doi.org/10.1136/bmj-2022-072808",
-    "title": "Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.",
-    "authorString": "Hulme WJ, Horne EMF, Parker EPK, Keogh RH, Williamson EJ, Walker V, Palmer TM, Curtis HJ, Walker AJ, Andrews CD, Mehrkar A, Morley J, MacKenna B, Bacon SCJ, Goldacre B, Hern\u00e1n MA, Sterne JAC.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ (Clinical research ed.)",
-    "pubYear": "2023",
-    "date": "2023-03-15",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England.<h4>Design</h4>Matched cohort study, emulating a comparative effectiveness trial.<h4>Setting</h4>Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant.<h4>Participants</h4>3\u2009237\u2009918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1.<h4>Intervention</h4>Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose.<h4>Main outcome measures</h4>Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose.<h4>Results</h4>1\u2009618\u2009959 people were matched in each vaccine group, contributing a total 64\u2009546\u2009391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras.<h4>Conclusions</h4>This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance.",
-    "laySummary": "",
-    "urls": "pdf:https://www.bmj.com/content/bmj/380/bmj-2022-072808.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072808; html:https://europepmc.org/articles/PMC10014664; pdf:https://europepmc.org/articles/PMC10014664?pdf=render"
-  },
   {
     "id": "35497059",
     "doi": "https://doi.org/10.1016/j.eclinm.2022.101392",
@@ -9468,6 +9451,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2589537022001225/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101392; html:https://europepmc.org/articles/PMC9046106; pdf:https://europepmc.org/articles/PMC9046106?pdf=render"
   },
+  {
+    "id": "36921925",
+    "doi": "https://doi.org/10.1136/bmj-2022-072808",
+    "title": "Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.",
+    "authorString": "Hulme WJ, Horne EMF, Parker EPK, Keogh RH, Williamson EJ, Walker V, Palmer TM, Curtis HJ, Walker AJ, Andrews CD, Mehrkar A, Morley J, MacKenna B, Bacon SCJ, Goldacre B, Hern\u00e1n MA, Sterne JAC.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ (Clinical research ed.)",
+    "pubYear": "2023",
+    "date": "2023-03-15",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England.<h4>Design</h4>Matched cohort study, emulating a comparative effectiveness trial.<h4>Setting</h4>Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant.<h4>Participants</h4>3\u2009237\u2009918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1.<h4>Intervention</h4>Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose.<h4>Main outcome measures</h4>Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose.<h4>Results</h4>1\u2009618\u2009959 people were matched in each vaccine group, contributing a total 64\u2009546\u2009391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras.<h4>Conclusions</h4>This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance.",
+    "laySummary": "",
+    "urls": "pdf:https://www.bmj.com/content/bmj/380/bmj-2022-072808.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072808; html:https://europepmc.org/articles/PMC10014664; pdf:https://europepmc.org/articles/PMC10014664?pdf=render"
+  },
   {
     "id": "36541282",
     "doi": "https://doi.org/10.14814/phy2.15546",
@@ -9774,23 +9774,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2589537021001681/pdf; doi:https://doi.org/10.1016/j.eclinm.2021.100888; html:https://europepmc.org/articles/PMC8257989; pdf:https://europepmc.org/articles/PMC8257989?pdf=render"
   },
-  {
-    "id": "37543047",
-    "doi": "https://doi.org/10.1016/s2666-7568(23)00105-8",
-    "title": "Antipsychotic drug prescribing and mortality in people with dementia before and during the COVID-19 pandemic: a retrospective cohort study in Wales, UK.",
-    "authorString": "Schnier C, McCarthy A, Morales DR, Akbari A, Sofat R, Dale C, Takhar R, Mamas MA, Khunti K, Zaccardi F, Sudlow CL, Wilkinson T, CVD-COVID-UK/COVID-IMPACT Consortium.",
-    "authorAffiliations": "",
-    "journalTitle": "The lancet. Healthy longevity",
-    "pubYear": "2023",
-    "date": "2023-08-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Concerns have been raised that antipsychotic drug prescribing, which has been associated with increased mortality in people with dementia, might have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of SARS-CoV-2. We used multisource, routinely collected health-care data from Wales, UK to investigate prescribing and mortality variations in people with dementia before and during the COVID-19 pandemic.<h4>Methods</h4>In this retrospective cohort study, we used individual-level, anonymised, population-scale linked health data to identify adults aged 60 years and older with a diagnosis of dementia in Wales, UK. We used the CVD-COVID-UK initiative to access Welsh routinely collected electronic health record data from the Secure Anonymised Information Linkage (SAIL) Databank. Patients who were alive and registered with a SAIL general practice on Jan 1, 2016, and who received a dementia diagnosis before the age of 60 years and before or during the study period were included. We explored antipsychotic drug prescribing rate changes over 67 months, between Jan 1, 2016, and Aug 1, 2021, overall and stratified by age and dementia subtype. We used time-series analyses to examine all-cause and myocardial infarction and stroke mortality over the study period and identified the leading causes of death in people with dementia between Jan 1, 2020, and Aug 1, 2021.<h4>Findings</h4>Of 3\u2008106\u2008690 participants in SAIL between Jan 1, 2016 and Aug 1, 2021, 57\u2008396 people (35\u2008148 [61\u00b72%] women and 22\u2008248 [38\u00b78%] men) met inclusion criteria for this study and contributed 101\u2008428 person-years of follow-up. Of the 57\u2008396 people with dementia, 11\u2008929 (20\u00b78%) were prescribed an antipsychotic drug at any point during follow-up. Accounting for seasonality, antipsychotic drug prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 prescriptions per 10\u2008000 person-months in March, 2019, to 1305 per 10\u2008000 person-months in September, 2020. All-cause mortality and stroke mortality increased throughout 2020, while myocardial infarction mortality declined. From Jan 1, 2020, to Aug 1, 2021, 1286 (17\u00b71%) of 7508 participants who died had COVID-19 recorded as the underlying cause of death.<h4>Interpretation</h4>During the COVID-19 pandemic, antipsychotic drug prescribing in people with dementia in the UK increased slightly; however, it is unlikely that this was solely related to the pandemic and this increase was unlikely to be a major factor in the substantial increase in mortality during 2020. The long-term increase in antipsychotic drug prescribing in younger people and in those with Alzheimer's disease warrants further investigation using resources with access to more granular clinical data. Although deprescribing antipsychotic medications remains an essential aspect of dementia care, the results of this study suggest that changes in prescribing and deprescribing practices as a result of the COVID-19 pandemic are not required.<h4>Funding</h4>British Heart Foundation (via the British Heart Foundation Data Science Centre led by Health Data Research UK), and the Scottish Neurological Research Fund.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/S2666-7568(23)00105-8"
-  },
   {
     "id": "33952557",
     "doi": "https://doi.org/10.1136/bmjopen-2021-049964",
@@ -9808,6 +9791,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049964.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049964; html:https://europepmc.org/articles/PMC8103393; pdf:https://europepmc.org/articles/PMC8103393?pdf=render"
   },
+  {
+    "id": "37543047",
+    "doi": "https://doi.org/10.1016/s2666-7568(23)00105-8",
+    "title": "Antipsychotic drug prescribing and mortality in people with dementia before and during the COVID-19 pandemic: a retrospective cohort study in Wales, UK.",
+    "authorString": "Schnier C, McCarthy A, Morales DR, Akbari A, Sofat R, Dale C, Takhar R, Mamas MA, Khunti K, Zaccardi F, Sudlow CL, Wilkinson T, CVD-COVID-UK/COVID-IMPACT Consortium.",
+    "authorAffiliations": "",
+    "journalTitle": "The lancet. Healthy longevity",
+    "pubYear": "2023",
+    "date": "2023-08-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Concerns have been raised that antipsychotic drug prescribing, which has been associated with increased mortality in people with dementia, might have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of SARS-CoV-2. We used multisource, routinely collected health-care data from Wales, UK to investigate prescribing and mortality variations in people with dementia before and during the COVID-19 pandemic.<h4>Methods</h4>In this retrospective cohort study, we used individual-level, anonymised, population-scale linked health data to identify adults aged 60 years and older with a diagnosis of dementia in Wales, UK. We used the CVD-COVID-UK initiative to access Welsh routinely collected electronic health record data from the Secure Anonymised Information Linkage (SAIL) Databank. Patients who were alive and registered with a SAIL general practice on Jan 1, 2016, and who received a dementia diagnosis before the age of 60 years and before or during the study period were included. We explored antipsychotic drug prescribing rate changes over 67 months, between Jan 1, 2016, and Aug 1, 2021, overall and stratified by age and dementia subtype. We used time-series analyses to examine all-cause and myocardial infarction and stroke mortality over the study period and identified the leading causes of death in people with dementia between Jan 1, 2020, and Aug 1, 2021.<h4>Findings</h4>Of 3\u2008106\u2008690 participants in SAIL between Jan 1, 2016 and Aug 1, 2021, 57\u2008396 people (35\u2008148 [61\u00b72%] women and 22\u2008248 [38\u00b78%] men) met inclusion criteria for this study and contributed 101\u2008428 person-years of follow-up. Of the 57\u2008396 people with dementia, 11\u2008929 (20\u00b78%) were prescribed an antipsychotic drug at any point during follow-up. Accounting for seasonality, antipsychotic drug prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 prescriptions per 10\u2008000 person-months in March, 2019, to 1305 per 10\u2008000 person-months in September, 2020. All-cause mortality and stroke mortality increased throughout 2020, while myocardial infarction mortality declined. From Jan 1, 2020, to Aug 1, 2021, 1286 (17\u00b71%) of 7508 participants who died had COVID-19 recorded as the underlying cause of death.<h4>Interpretation</h4>During the COVID-19 pandemic, antipsychotic drug prescribing in people with dementia in the UK increased slightly; however, it is unlikely that this was solely related to the pandemic and this increase was unlikely to be a major factor in the substantial increase in mortality during 2020. The long-term increase in antipsychotic drug prescribing in younger people and in those with Alzheimer's disease warrants further investigation using resources with access to more granular clinical data. Although deprescribing antipsychotic medications remains an essential aspect of dementia care, the results of this study suggest that changes in prescribing and deprescribing practices as a result of the COVID-19 pandemic are not required.<h4>Funding</h4>British Heart Foundation (via the British Heart Foundation Data Science Centre led by Health Data Research UK), and the Scottish Neurological Research Fund.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/S2666-7568(23)00105-8"
+  },
   {
     "id": "34141852",
     "doi": "https://doi.org/10.1016/j.ssmph.2021.100828",
@@ -10046,23 +10046,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1111/dom.15102"
   },
-  {
-    "id": "36658423",
-    "doi": "https://doi.org/10.1038/s41591-022-02158-7",
-    "title": "The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.",
-    "authorString": "Dale CE, Takhar R, Carragher R, Katsoulis M, Torabi F, Duffield S, Kent S, Mueller T, Kurdi A, Le Anh TN, McTaggart S, Abbasizanjani H, Hollings S, Scourfield A, Lyons RA, Griffiths R, Lyons J, Davies G, Harris D, Handy A, Mizani MA, Tomlinson C, Thygesen JH, Ashworth M, Denaxas S, Banerjee A, Sterne JAC, Brown P, Bullard I, Priedon R, Mamas MA, Slee A, Lorgelly P, Pirmohamed M, Khunti K, Morris AD, Sudlow C, Akbari A, Bennie M, Sattar N, Sofat R, CVD-COVID-UK Consortium.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature medicine",
-    "pubYear": "2023",
-    "date": "2023-01-19",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41591-022-02158-7.pdf; doi:https://doi.org/10.1038/s41591-022-02158-7"
-  },
   {
     "id": "34007896",
     "doi": "https://doi.org/10.23889/ijpds.v6i1.1387",
@@ -10080,6 +10063,23 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1387/3155; doi:https://doi.org/10.23889/ijpds.v6i1.1387; html:https://europepmc.org/articles/PMC8103995; pdf:https://europepmc.org/articles/PMC8103995?pdf=render"
   },
+  {
+    "id": "36658423",
+    "doi": "https://doi.org/10.1038/s41591-022-02158-7",
+    "title": "The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.",
+    "authorString": "Dale CE, Takhar R, Carragher R, Katsoulis M, Torabi F, Duffield S, Kent S, Mueller T, Kurdi A, Le Anh TN, McTaggart S, Abbasizanjani H, Hollings S, Scourfield A, Lyons RA, Griffiths R, Lyons J, Davies G, Harris D, Handy A, Mizani MA, Tomlinson C, Thygesen JH, Ashworth M, Denaxas S, Banerjee A, Sterne JAC, Brown P, Bullard I, Priedon R, Mamas MA, Slee A, Lorgelly P, Pirmohamed M, Khunti K, Morris AD, Sudlow C, Akbari A, Bennie M, Sattar N, Sofat R, CVD-COVID-UK Consortium.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature medicine",
+    "pubYear": "2023",
+    "date": "2023-01-19",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41591-022-02158-7.pdf; doi:https://doi.org/10.1038/s41591-022-02158-7"
+  },
   {
     "id": "35485805",
     "doi": "https://doi.org/10.1017/s003329172200109x",
@@ -10335,23 +10335,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1177/18333583221135710"
   },
-  {
-    "id": "36794597",
-    "doi": "https://doi.org/10.1111/trf.17277",
-    "title": "Impact of a post-donation hemoglobin testing strategy on efficiency and safety of whole blood donation in England: A modeling study.",
-    "authorString": "Kim LG, Bolton T, Sweeting MJ, Bell S, Fahle S, McMahon A, Walker M, Ferguson E, Miflin G, Roberts DJ, Di Angelantonio E, Wood AM.",
-    "authorAffiliations": "",
-    "journalTitle": "Transfusion",
-    "pubYear": "2023",
-    "date": "2023-02-16",
-    "isOpenAccess": "N",
-    "keywords": "Blood Donation; Simulation Modeling; Low Hemoglobin Deferral; Post-donation Testing",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Deferrals due to low hemoglobin are time-consuming and costly for blood donors and donation services. Furthermore, accepting donations from those with low hemoglobin could represent a significant safety issue. One approach to reduce them is to use hemoglobin concentration alongside donor characteristics to inform personalized inter-donation intervals.<h4>Study design and methods</h4>We used data from 17,308 donors to inform a discrete event simulation model comparing personalized inter-donation intervals using \"post-donation\" testing (i.e., estimating current hemoglobin from that measured by a hematology analyzer at last donation) versus the current approach in England (i.e., pre-donation testing with fixed intervals of 12-weeks for men and 16-weeks for women). We reported the impact on total donations, low hemoglobin deferrals, inappropriate bleeds, and blood service costs. Personalized inter-donation intervals were defined using mixed-effects modeling to estimate hemoglobin trajectories and probability of crossing hemoglobin donation thresholds.<h4>Results</h4>The model had generally good internal validation, with predicted events similar to those observed. Over 1\u2009year, a personalized strategy requiring \u226590% probability of being over the hemoglobin threshold, minimized adverse events (low hemoglobin deferrals and inappropriate bleeds) in both sexes and costs in women. Donations per adverse event improved from 3.4 (95% uncertainty interval 2.8, 3.7) under the current strategy to 14.8 (11.6, 19.2) in women, and from 7.1 (6.1, 8.5) to 26.9 (20.8, 42.6) in men. In comparison, a strategy incorporating early returns for those with high certainty of being over the threshold maximized total donations in both men and women, but was less favorable in terms of adverse events, with 8.4 donations per adverse event in women (7.0, 10,1) and 14.8 (12.1, 21.0) in men.<h4>Discussion</h4>Personalized inter-donation intervals using post-donation testing combined with modeling of hemoglobin trajectories can help reduce deferrals, inappropriate bleeds, and costs.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/trf.17277; doi:https://doi.org/10.1111/trf.17277"
-  },
   {
     "id": "32424068",
     "doi": "https://doi.org/10.1101/gr.250704.119",
@@ -10386,6 +10369,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/mbe/article-pdf/38/3/1122/36533820/msaa279.pdf; doi:https://doi.org/10.1093/molbev/msaa279; html:https://europepmc.org/articles/PMC7947781; pdf:https://europepmc.org/articles/PMC7947781?pdf=render"
   },
+  {
+    "id": "36794597",
+    "doi": "https://doi.org/10.1111/trf.17277",
+    "title": "Impact of a post-donation hemoglobin testing strategy on efficiency and safety of whole blood donation in England: A modeling study.",
+    "authorString": "Kim LG, Bolton T, Sweeting MJ, Bell S, Fahle S, McMahon A, Walker M, Ferguson E, Miflin G, Roberts DJ, Di Angelantonio E, Wood AM.",
+    "authorAffiliations": "",
+    "journalTitle": "Transfusion",
+    "pubYear": "2023",
+    "date": "2023-02-16",
+    "isOpenAccess": "N",
+    "keywords": "Blood Donation; Simulation Modeling; Low Hemoglobin Deferral; Post-donation Testing",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Deferrals due to low hemoglobin are time-consuming and costly for blood donors and donation services. Furthermore, accepting donations from those with low hemoglobin could represent a significant safety issue. One approach to reduce them is to use hemoglobin concentration alongside donor characteristics to inform personalized inter-donation intervals.<h4>Study design and methods</h4>We used data from 17,308 donors to inform a discrete event simulation model comparing personalized inter-donation intervals using \"post-donation\" testing (i.e., estimating current hemoglobin from that measured by a hematology analyzer at last donation) versus the current approach in England (i.e., pre-donation testing with fixed intervals of 12-weeks for men and 16-weeks for women). We reported the impact on total donations, low hemoglobin deferrals, inappropriate bleeds, and blood service costs. Personalized inter-donation intervals were defined using mixed-effects modeling to estimate hemoglobin trajectories and probability of crossing hemoglobin donation thresholds.<h4>Results</h4>The model had generally good internal validation, with predicted events similar to those observed. Over 1\u2009year, a personalized strategy requiring \u226590% probability of being over the hemoglobin threshold, minimized adverse events (low hemoglobin deferrals and inappropriate bleeds) in both sexes and costs in women. Donations per adverse event improved from 3.4 (95% uncertainty interval 2.8, 3.7) under the current strategy to 14.8 (11.6, 19.2) in women, and from 7.1 (6.1, 8.5) to 26.9 (20.8, 42.6) in men. In comparison, a strategy incorporating early returns for those with high certainty of being over the threshold maximized total donations in both men and women, but was less favorable in terms of adverse events, with 8.4 donations per adverse event in women (7.0, 10,1) and 14.8 (12.1, 21.0) in men.<h4>Discussion</h4>Personalized inter-donation intervals using post-donation testing combined with modeling of hemoglobin trajectories can help reduce deferrals, inappropriate bleeds, and costs.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/trf.17277; doi:https://doi.org/10.1111/trf.17277"
+  },
   {
     "id": "37468148",
     "doi": "https://doi.org/10.1136/bmj-2023-075133",
@@ -10471,23 +10471,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-022-03005-w; doi:https://doi.org/10.1186/s12872-022-03005-w; html:https://europepmc.org/articles/PMC9791783; pdf:https://europepmc.org/articles/PMC9791783?pdf=render"
   },
-  {
-    "id": "36447757",
-    "doi": "https://doi.org/10.1136/gpsych-2022-100819",
-    "title": "Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area.",
-    "authorString": "Chen J, Perera G, Shetty H, Broadbent M, Xu Y, Stewart R.",
-    "authorAffiliations": "",
-    "journalTitle": "General psychiatry",
-    "pubYear": "2022",
-    "date": "2022-11-04",
-    "isOpenAccess": "Y",
-    "keywords": "Schizophrenia; Life style; Mental Health Services",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>People with schizophrenia have a high premature mortality risk. Obesity is a key potential underlying risk factor that is relatively unevaluated to date.<h4>Aims</h4>In this study, we investigated the associations of routinely recorded body size with all-cause mortality and deaths from common causes in a large cohort of people with schizophrenia spectrum disorders.<h4>Methods</h4>We assembled a retrospective observational cohort using data from a large mental health service in South London. We followed all patients over the age of 18 years with a clinical diagnosis of schizophrenia spectrum disorders from the date of their first recorded body mass index (BMI) between 1 January 2007 and 31 March 2018.<h4>Results</h4>Of 11\u2009900 patients with a BMI recording, 1566 died. The Cox proportional hazards regression models, after adjusting for sociodemographic, socioeconomic variables and comorbidities, indicated that all-cause mortality was only associated with underweight status compared with healthy weight status (hazard ratio (HR): 1.33, 95%\u2009confidence interval (CI): 1.01 to 1.76). Obesity (HR: 1.24, 95% CI: 1.01 to 1.52) and morbid obesity (HR: 1.54, 95% CI: 1.03 to 2.42) were associated with all-cause mortality in the 18-45 years age range, and obesity was associated with lower risk (HR: 0.66, 95% CI: 0.50 to 0.87) in those aged 65+ years. Cancer mortality was raised in underweight individuals (HR: 1.93, 95% CI: 1.03 to 4.10) and respiratory disease mortality raised in those with morbid obesity (HR: 2.17, 95% CI: 1.02 to 5.22).<h4>Conclusions</h4>Overall, being underweight was associated with higher mortality in this disorder group; however, this was potentially accounted for by frailty in older age groups, and obesity was a risk factor for premature mortality in younger ages. The impact of obesity on life expectancy for people with schizophrenia spectrum disorders is clear from our findings. A deeper biological understanding of the relationship between these diseases and schizophrenia will help improve clinical practice.",
-    "laySummary": "",
-    "urls": "pdf:https://gpsych.bmj.com/content/gpsych/35/5/e100819.full.pdf; doi:https://doi.org/10.1136/gpsych-2022-100819; html:https://europepmc.org/articles/PMC9639123; pdf:https://europepmc.org/articles/PMC9639123?pdf=render"
-  },
   {
     "id": "33587202",
     "doi": "https://doi.org/10.1007/s10654-021-00722-y",
@@ -10505,6 +10488,23 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00722-y.pdf; doi:https://doi.org/10.1007/s10654-021-00722-y; html:https://europepmc.org/articles/PMC7882869; pdf:https://europepmc.org/articles/PMC7882869?pdf=render"
   },
+  {
+    "id": "36447757",
+    "doi": "https://doi.org/10.1136/gpsych-2022-100819",
+    "title": "Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area.",
+    "authorString": "Chen J, Perera G, Shetty H, Broadbent M, Xu Y, Stewart R.",
+    "authorAffiliations": "",
+    "journalTitle": "General psychiatry",
+    "pubYear": "2022",
+    "date": "2022-11-04",
+    "isOpenAccess": "Y",
+    "keywords": "Schizophrenia; Life style; Mental Health Services",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>People with schizophrenia have a high premature mortality risk. Obesity is a key potential underlying risk factor that is relatively unevaluated to date.<h4>Aims</h4>In this study, we investigated the associations of routinely recorded body size with all-cause mortality and deaths from common causes in a large cohort of people with schizophrenia spectrum disorders.<h4>Methods</h4>We assembled a retrospective observational cohort using data from a large mental health service in South London. We followed all patients over the age of 18 years with a clinical diagnosis of schizophrenia spectrum disorders from the date of their first recorded body mass index (BMI) between 1 January 2007 and 31 March 2018.<h4>Results</h4>Of 11\u2009900 patients with a BMI recording, 1566 died. The Cox proportional hazards regression models, after adjusting for sociodemographic, socioeconomic variables and comorbidities, indicated that all-cause mortality was only associated with underweight status compared with healthy weight status (hazard ratio (HR): 1.33, 95%\u2009confidence interval (CI): 1.01 to 1.76). Obesity (HR: 1.24, 95% CI: 1.01 to 1.52) and morbid obesity (HR: 1.54, 95% CI: 1.03 to 2.42) were associated with all-cause mortality in the 18-45 years age range, and obesity was associated with lower risk (HR: 0.66, 95% CI: 0.50 to 0.87) in those aged 65+ years. Cancer mortality was raised in underweight individuals (HR: 1.93, 95% CI: 1.03 to 4.10) and respiratory disease mortality raised in those with morbid obesity (HR: 2.17, 95% CI: 1.02 to 5.22).<h4>Conclusions</h4>Overall, being underweight was associated with higher mortality in this disorder group; however, this was potentially accounted for by frailty in older age groups, and obesity was a risk factor for premature mortality in younger ages. The impact of obesity on life expectancy for people with schizophrenia spectrum disorders is clear from our findings. A deeper biological understanding of the relationship between these diseases and schizophrenia will help improve clinical practice.",
+    "laySummary": "",
+    "urls": "pdf:https://gpsych.bmj.com/content/gpsych/35/5/e100819.full.pdf; doi:https://doi.org/10.1136/gpsych-2022-100819; html:https://europepmc.org/articles/PMC9639123; pdf:https://europepmc.org/articles/PMC9639123?pdf=render"
+  },
   {
     "id": "37526977",
     "doi": "https://doi.org/10.5830/cvja-2023-037",
@@ -10556,23 +10556,6 @@
     "laySummary": "",
     "urls": "pdf:https://heart.bmj.com/content/heartjnl/109/2/119.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321492; html:https://europepmc.org/articles/PMC9811071; pdf:https://europepmc.org/articles/PMC9811071?pdf=render"
   },
-  {
-    "id": "37907891",
-    "doi": "https://doi.org/10.1186/s12888-023-05217-6",
-    "title": "Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.",
-    "authorString": "Bala JJ, Bala JD, Pell JP, Fleming M.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC psychiatry",
-    "pubYear": "2023",
-    "date": "2023-10-31",
-    "isOpenAccess": "Y",
-    "keywords": "attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.<h4>Methods</h4>Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.<h4>Results</h4>Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.<h4>Conclusions</h4>In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render"
-  },
   {
     "id": "33635829",
     "doi": "https://doi.org/10.1530/eje-20-1163",
@@ -10590,6 +10573,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ejendo/article-pdf/184/5/637/45221794/eje-20-1163.pdf; doi:https://doi.org/10.1530/EJE-20-1163; html:https://europepmc.org/articles/PMC8052516; pdf:https://europepmc.org/articles/PMC8052516?pdf=render"
   },
+  {
+    "id": "37907891",
+    "doi": "https://doi.org/10.1186/s12888-023-05217-6",
+    "title": "Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.",
+    "authorString": "Bala JJ, Bala JD, Pell JP, Fleming M.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC psychiatry",
+    "pubYear": "2023",
+    "date": "2023-10-31",
+    "isOpenAccess": "Y",
+    "keywords": "attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.<h4>Methods</h4>Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.<h4>Results</h4>Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.<h4>Conclusions</h4>In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render"
+  },
   {
     "id": "35105585",
     "doi": "https://doi.org/10.1136/bmjopen-2021-054376",
@@ -10709,23 +10709,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1136/bmjmed-2023-000554; html:https://europepmc.org/articles/PMC10582890; pdf:https://europepmc.org/articles/PMC10582890?pdf=render"
   },
-  {
-    "id": "35580876",
-    "doi": "https://doi.org/10.1136/bmj-2021-069704",
-    "title": "Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records.",
-    "authorString": "\u0160umilo D, Nirantharakumar K, Willis BH, Rudge GM, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Harris IM, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ (Clinical research ed.)",
-    "pubYear": "2022",
-    "date": "2022-05-17",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping.<h4>Design</h4>Observational controlled interrupted time series study.<h4>Setting</h4>UK primary and secondary care.<h4>Participants</h4>515\u2009945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7\u2009147\u2009884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3\u2009945\u2009351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping.<h4>Intervention</h4>Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure.<h4>Main outcome measures</h4>The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally.<h4>Results</h4>Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years.<h4>Conclusions</h4>This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.",
-    "laySummary": "",
-    "urls": "pdf:https://www.bmj.com/content/bmj/377/bmj-2021-069704.full.pdf; doi:https://doi.org/10.1136/bmj-2021-069704; html:https://europepmc.org/articles/PMC9112858"
-  },
   {
     "id": "35216844",
     "doi": "https://doi.org/10.1016/j.vaccine.2022.02.056",
@@ -10743,6 +10726,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.vaccine.2022.02.056; doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863"
   },
+  {
+    "id": "35580876",
+    "doi": "https://doi.org/10.1136/bmj-2021-069704",
+    "title": "Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records.",
+    "authorString": "\u0160umilo D, Nirantharakumar K, Willis BH, Rudge GM, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Harris IM, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ (Clinical research ed.)",
+    "pubYear": "2022",
+    "date": "2022-05-17",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping.<h4>Design</h4>Observational controlled interrupted time series study.<h4>Setting</h4>UK primary and secondary care.<h4>Participants</h4>515\u2009945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7\u2009147\u2009884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3\u2009945\u2009351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping.<h4>Intervention</h4>Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure.<h4>Main outcome measures</h4>The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally.<h4>Results</h4>Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years.<h4>Conclusions</h4>This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.",
+    "laySummary": "",
+    "urls": "pdf:https://www.bmj.com/content/bmj/377/bmj-2021-069704.full.pdf; doi:https://doi.org/10.1136/bmj-2021-069704; html:https://europepmc.org/articles/PMC9112858"
+  },
   {
     "id": "35079022",
     "doi": "https://doi.org/10.1038/s41467-022-28157-3",
@@ -10811,23 +10811,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2666756822000721/pdf; doi:https://doi.org/10.1016/S2666-7568(22)00072-1; html:https://europepmc.org/articles/PMC9068584"
   },
-  {
-    "id": "36879385",
-    "doi": "https://doi.org/10.1097/ta.0000000000003950",
-    "title": "Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma.",
-    "authorString": "Gabbe BJ, Reeder S, Ekegren CL, Mather A, Kimmel L, Cameron PA, Higgins AM.",
-    "authorAffiliations": "",
-    "journalTitle": "The journal of trauma and acute care surgery",
-    "pubYear": "2023",
-    "date": "2023-03-07",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.<h4>Methods</h4>The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.<h4>Results</h4>Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5-17) at baseline, 10 (5-19) in the new ward phase, and 17 (9-23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.<h4>Conclusion</h4>The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.<h4>Level of evidence</h4>Economic and Value-based Evaluations; Level III.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1097/TA.0000000000003950"
-  },
   {
     "id": "33203640",
     "doi": "https://doi.org/10.1136/bmjopen-2020-043828",
@@ -10845,6 +10828,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e043828.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043828; html:https://europepmc.org/articles/PMC7674020; pdf:https://europepmc.org/articles/PMC7674020?pdf=render"
   },
+  {
+    "id": "36879385",
+    "doi": "https://doi.org/10.1097/ta.0000000000003950",
+    "title": "Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma.",
+    "authorString": "Gabbe BJ, Reeder S, Ekegren CL, Mather A, Kimmel L, Cameron PA, Higgins AM.",
+    "authorAffiliations": "",
+    "journalTitle": "The journal of trauma and acute care surgery",
+    "pubYear": "2023",
+    "date": "2023-03-07",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.<h4>Methods</h4>The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.<h4>Results</h4>Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5-17) at baseline, 10 (5-19) in the new ward phase, and 17 (9-23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.<h4>Conclusion</h4>The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.<h4>Level of evidence</h4>Economic and Value-based Evaluations; Level III.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1097/TA.0000000000003950"
+  },
   {
     "id": "36150783",
     "doi": "https://doi.org/10.1016/s2589-7500(22)00147-9",
@@ -10913,23 +10913,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-02045-x; doi:https://doi.org/10.1186/s12916-021-02045-x; html:https://europepmc.org/articles/PMC8344166; pdf:https://europepmc.org/articles/PMC8344166?pdf=render"
   },
-  {
-    "id": "32516805",
-    "doi": "https://doi.org/10.1093/eurheartj/ehaa375",
-    "title": "Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction.",
-    "authorString": "Hung J, Roos A, Kadesj\u00f6 E, McAllister DA, Kimenai DM, Shah ASV, Anand A, Strachan FE, Fox KAA, Mills NL, Chapman AR, Holzmann MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal",
-    "pubYear": "2021",
-    "date": "2021-07-01",
-    "isOpenAccess": "Y",
-    "keywords": "Troponin; Grace; Type 2 Myocardial Infarction; High-sensitivity; Universal Definition; Type 1 Myocardial Infarction",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain.<h4>Methods and results</h4>In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n\u2009=\u200948\u00a0282) and a tertiary care hospital in Sweden (n\u2009=\u200922\u00a0589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong's test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82-0.85] and 0.85 (95% CI 0.81-0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70-0.77) and 0.73 (95% CI 0.66-0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts (P\u2009<\u20090.001 and P\u2009=\u20090.008, respectively).<h4>Conclusion</h4>The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction.<h4>Trial registration</h4>ClinicalTrials.gov number, NCT01852123.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1093/eurheartj/ehaa375; doi:https://doi.org/10.1093/eurheartj/ehaa375; html:https://europepmc.org/articles/PMC8266602; pdf:https://europepmc.org/articles/PMC8266602?pdf=render"
-  },
   {
     "id": "32620158",
     "doi": "https://doi.org/10.1186/s12915-020-00792-6",
@@ -10947,6 +10930,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcbiol.biomedcentral.com/counter/pdf/10.1186/s12915-020-00792-6; doi:https://doi.org/10.1186/s12915-020-00792-6; html:https://europepmc.org/articles/PMC7334855; pdf:https://europepmc.org/articles/PMC7334855?pdf=render"
   },
+  {
+    "id": "32516805",
+    "doi": "https://doi.org/10.1093/eurheartj/ehaa375",
+    "title": "Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction.",
+    "authorString": "Hung J, Roos A, Kadesj\u00f6 E, McAllister DA, Kimenai DM, Shah ASV, Anand A, Strachan FE, Fox KAA, Mills NL, Chapman AR, Holzmann MJ.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal",
+    "pubYear": "2021",
+    "date": "2021-07-01",
+    "isOpenAccess": "Y",
+    "keywords": "Troponin; Grace; Type 2 Myocardial Infarction; High-sensitivity; Universal Definition; Type 1 Myocardial Infarction",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain.<h4>Methods and results</h4>In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n\u2009=\u200948\u00a0282) and a tertiary care hospital in Sweden (n\u2009=\u200922\u00a0589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong's test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82-0.85] and 0.85 (95% CI 0.81-0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70-0.77) and 0.73 (95% CI 0.66-0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts (P\u2009<\u20090.001 and P\u2009=\u20090.008, respectively).<h4>Conclusion</h4>The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction.<h4>Trial registration</h4>ClinicalTrials.gov number, NCT01852123.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1093/eurheartj/ehaa375; doi:https://doi.org/10.1093/eurheartj/ehaa375; html:https://europepmc.org/articles/PMC8266602; pdf:https://europepmc.org/articles/PMC8266602?pdf=render"
+  },
   {
     "id": "36102151",
     "doi": "https://doi.org/10.1210/clinem/dgac527",
@@ -11032,23 +11032,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41597-019-0337-6.pdf; doi:https://doi.org/10.1038/s41597-019-0337-6; html:https://europepmc.org/articles/PMC6923383; pdf:https://europepmc.org/articles/PMC6923383?pdf=render"
   },
-  {
-    "id": "36806317",
-    "doi": "https://doi.org/10.1038/s41746-023-00749-3",
-    "title": "Long-term participant retention and engagement patterns in an app and wearable-based multinational remote digital depression study.",
-    "authorString": "Zhang Y, Pratap A, Folarin AA, Sun S, Cummins N, Matcham F, Vairavan S, Dineley J, Ranjan Y, Rashid Z, Conde P, Stewart C, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Rambla CH, Simblett S, Nica R, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Annas P, Narayan VA, Hotopf M, Dobson RJB, RADAR-CNS consortium.",
-    "authorAffiliations": "",
-    "journalTitle": "NPJ digital medicine",
-    "pubYear": "2023",
-    "date": "2023-02-17",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants' study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8\u2009h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants' age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41746-023-00749-3.pdf; doi:https://doi.org/10.1038/s41746-023-00749-3; html:https://europepmc.org/articles/PMC9938183; pdf:https://europepmc.org/articles/PMC9938183?pdf=render"
-  },
   {
     "id": "32206896",
     "doi": "https://doi.org/10.1007/s00394-020-02220-5",
@@ -11066,6 +11049,23 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02220-5.pdf; doi:https://doi.org/10.1007/s00394-020-02220-5; html:https://europepmc.org/articles/PMC7867553; pdf:https://europepmc.org/articles/PMC7867553?pdf=render"
   },
+  {
+    "id": "36806317",
+    "doi": "https://doi.org/10.1038/s41746-023-00749-3",
+    "title": "Long-term participant retention and engagement patterns in an app and wearable-based multinational remote digital depression study.",
+    "authorString": "Zhang Y, Pratap A, Folarin AA, Sun S, Cummins N, Matcham F, Vairavan S, Dineley J, Ranjan Y, Rashid Z, Conde P, Stewart C, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Rambla CH, Simblett S, Nica R, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Annas P, Narayan VA, Hotopf M, Dobson RJB, RADAR-CNS consortium.",
+    "authorAffiliations": "",
+    "journalTitle": "NPJ digital medicine",
+    "pubYear": "2023",
+    "date": "2023-02-17",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants' study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8\u2009h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants' age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41746-023-00749-3.pdf; doi:https://doi.org/10.1038/s41746-023-00749-3; html:https://europepmc.org/articles/PMC9938183; pdf:https://europepmc.org/articles/PMC9938183?pdf=render"
+  },
   {
     "id": "37777816",
     "doi": "https://doi.org/10.1186/s13643-023-02337-8",
@@ -11100,23 +11100,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.3389/fdgth.2023.1184919; html:https://europepmc.org/articles/PMC10569314; pdf:https://europepmc.org/articles/PMC10569314?pdf=render"
   },
-  {
-    "id": "37635632",
-    "doi": "https://doi.org/10.1111/aor.14628",
-    "title": "Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support.",
-    "authorString": "Numan L, W\u00f6sten M, Moazeni M, Aarts E, Van der Kaaij NP, Fresiello L, Asselbergs FW, Van Laake LW.",
-    "authorAffiliations": "",
-    "journalTitle": "Artificial organs",
-    "pubYear": "2023",
-    "date": "2023-08-28",
-    "isOpenAccess": "N",
-    "keywords": "Circadian rhythm; Mechanical Circulatory Support; Left Ventricular Assist Device; Lvad Parameters",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR).<h4>Methods</h4>18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2\u2009weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation.<h4>Results</h4>A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p\u2009<\u20090.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p\u2009<\u20090.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p\u2009=\u20090.19).<h4>Conclusions</h4>A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14628; doi:https://doi.org/10.1111/aor.14628"
-  },
   {
     "id": "33446033",
     "doi": "https://doi.org/10.1177/1460458220977579",
@@ -11151,6 +11134,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s42003-020-01613-w.pdf; doi:https://doi.org/10.1038/s42003-020-01613-w; html:https://europepmc.org/articles/PMC7815736; pdf:https://europepmc.org/articles/PMC7815736?pdf=render"
   },
+  {
+    "id": "37635632",
+    "doi": "https://doi.org/10.1111/aor.14628",
+    "title": "Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support.",
+    "authorString": "Numan L, W\u00f6sten M, Moazeni M, Aarts E, Van der Kaaij NP, Fresiello L, Asselbergs FW, Van Laake LW.",
+    "authorAffiliations": "",
+    "journalTitle": "Artificial organs",
+    "pubYear": "2023",
+    "date": "2023-08-28",
+    "isOpenAccess": "N",
+    "keywords": "Circadian rhythm; Mechanical Circulatory Support; Left Ventricular Assist Device; Lvad Parameters",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR).<h4>Methods</h4>18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2\u2009weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation.<h4>Results</h4>A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p\u2009<\u20090.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p\u2009<\u20090.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p\u2009=\u20090.19).<h4>Conclusions</h4>A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14628; doi:https://doi.org/10.1111/aor.14628"
+  },
   {
     "id": "37105743",
     "doi": "https://doi.org/10.3399/bjgp.2022.0353",
@@ -11287,23 +11287,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/head.14465; doi:https://doi.org/10.1111/head.14465"
   },
-  {
-    "id": "36112916",
-    "doi": "https://doi.org/10.1177/09622802211055853",
-    "title": "Inferring risks of coronavirus transmission from community household data.",
-    "authorString": "House T, Riley H, Pellis L, Pouwels KB, Bacon S, Eidukas A, Jahanshahi K, Eggo RM, Sarah Walker A.",
-    "authorAffiliations": "",
-    "journalTitle": "Statistical methods in medical research",
-    "pubYear": "2022",
-    "date": "2022-09-01",
-    "isOpenAccess": "Y",
-    "keywords": "Infection; Model; epidemic; risk factors; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics COVID-19 Infection Survey data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) susceptible-Infectious transmission probabilities of within-household transmission in the 15-35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range of 25-300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1177/09622802211055853; doi:https://doi.org/10.1177/09622802211055853; html:https://europepmc.org/articles/PMC9465559; pdf:https://europepmc.org/articles/PMC9465559?pdf=render"
-  },
   {
     "id": "35290719",
     "doi": "https://doi.org/10.1002/alz.12635",
@@ -11321,6 +11304,23 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10145566/1/ChungIncidence%2C%20morbidity%2C%20mortality%20and%20disparities%20in%20dementia_AOP.pdf; doi:https://doi.org/10.1002/alz.12635; html:https://europepmc.org/articles/PMC10078672; pdf:https://europepmc.org/articles/PMC10078672?pdf=render"
   },
+  {
+    "id": "36112916",
+    "doi": "https://doi.org/10.1177/09622802211055853",
+    "title": "Inferring risks of coronavirus transmission from community household data.",
+    "authorString": "House T, Riley H, Pellis L, Pouwels KB, Bacon S, Eidukas A, Jahanshahi K, Eggo RM, Sarah Walker A.",
+    "authorAffiliations": "",
+    "journalTitle": "Statistical methods in medical research",
+    "pubYear": "2022",
+    "date": "2022-09-01",
+    "isOpenAccess": "Y",
+    "keywords": "Infection; Model; epidemic; risk factors; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics COVID-19 Infection Survey data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) susceptible-Infectious transmission probabilities of within-household transmission in the 15-35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range of 25-300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1177/09622802211055853; doi:https://doi.org/10.1177/09622802211055853; html:https://europepmc.org/articles/PMC9465559; pdf:https://europepmc.org/articles/PMC9465559?pdf=render"
+  },
   {
     "id": "37294923",
     "doi": "https://doi.org/10.1093/eurjpc/zwad192",
@@ -11627,6 +11627,23 @@
     "laySummary": "",
     "urls": "pdf:https://boneandjoint.org.uk/article/10.1302/2633-1462.312.BJO-2022-0130.R1/pdf; doi:https://doi.org/10.1302/2633-1462.312.BJO-2022-0130.R1; html:https://europepmc.org/articles/PMC9783273; pdf:https://europepmc.org/articles/PMC9783273?pdf=render"
   },
+  {
+    "id": "30727941",
+    "doi": "https://doi.org/10.1186/s12859-019-2633-8",
+    "title": "DeepPVP: phenotype-based prioritization of causative variants using deep learning.",
+    "authorString": "Boudellioua I, Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC bioinformatics",
+    "pubYear": "2019",
+    "date": "2019-02-06",
+    "isOpenAccess": "Y",
+    "keywords": "Phenotype; Ontology; Machine Learning; Variant Prioritization",
+    "nationalPriorities": "Applied Analytics",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Prioritization of variants in personal genomic data is a major challenge. Recently, computational methods that rely on comparing phenotype similarity have shown to be useful to identify causative variants. In these methods, pathogenicity prediction is combined with a semantic similarity measure to prioritize not only variants that are likely to be dysfunctional but those that are likely involved in the pathogenesis of a patient's phenotype.<h4>Results</h4>We have developed DeepPVP, a variant prioritization method that combined automated inference with deep neural networks to identify the likely causative variants in whole exome or whole genome sequence data. We demonstrate that DeepPVP performs significantly better than existing methods, including phenotype-based methods that use similar features. DeepPVP is freely available at https://github.com/bio-ontology-research-group/phenomenet-vp .<h4>Conclusions</h4>DeepPVP further improves on existing variant prioritization methods both in terms of speed as well as accuracy.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-019-2633-8; doi:https://doi.org/10.1186/s12859-019-2633-8; html:https://europepmc.org/articles/PMC6364462; pdf:https://europepmc.org/articles/PMC6364462?pdf=render"
+  },
   {
     "id": "34784292",
     "doi": "https://doi.org/10.2196/32587",
@@ -11661,23 +11678,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render"
   },
-  {
-    "id": "30727941",
-    "doi": "https://doi.org/10.1186/s12859-019-2633-8",
-    "title": "DeepPVP: phenotype-based prioritization of causative variants using deep learning.",
-    "authorString": "Boudellioua I, Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC bioinformatics",
-    "pubYear": "2019",
-    "date": "2019-02-06",
-    "isOpenAccess": "Y",
-    "keywords": "Phenotype; Ontology; Machine Learning; Variant Prioritization",
-    "nationalPriorities": "Applied Analytics",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Prioritization of variants in personal genomic data is a major challenge. Recently, computational methods that rely on comparing phenotype similarity have shown to be useful to identify causative variants. In these methods, pathogenicity prediction is combined with a semantic similarity measure to prioritize not only variants that are likely to be dysfunctional but those that are likely involved in the pathogenesis of a patient's phenotype.<h4>Results</h4>We have developed DeepPVP, a variant prioritization method that combined automated inference with deep neural networks to identify the likely causative variants in whole exome or whole genome sequence data. We demonstrate that DeepPVP performs significantly better than existing methods, including phenotype-based methods that use similar features. DeepPVP is freely available at https://github.com/bio-ontology-research-group/phenomenet-vp .<h4>Conclusions</h4>DeepPVP further improves on existing variant prioritization methods both in terms of speed as well as accuracy.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-019-2633-8; doi:https://doi.org/10.1186/s12859-019-2633-8; html:https://europepmc.org/articles/PMC6364462; pdf:https://europepmc.org/articles/PMC6364462?pdf=render"
-  },
   {
     "id": "36763324",
     "doi": "https://doi.org/10.1007/s12687-023-00635-1",
@@ -11763,23 +11763,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047242; doi:https://doi.org/10.1093/infdis/jiac146; html:https://europepmc.org/articles/PMC9047242; pdf:https://europepmc.org/articles/PMC9047242?pdf=render"
   },
-  {
-    "id": "37828025",
-    "doi": "https://doi.org/10.1038/s41467-023-41876-5",
-    "title": "ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon.",
-    "authorString": "Hartmann S, Yasmeen S, Jacobs BM, Denaxas S, Pirmohamed M, Gamazon ER, Caulfield MJ, Genes & Health Research Team, Hemingway H, Pietzner M, Langenberg C.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2023",
-    "date": "2023-10-12",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p\u2009<\u20095\u2009\u00d7\u200910<sup>-8</sup>). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p\u2009<\u20099.6\u2009\u00d7\u200910<sup>-27</sup>) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p\u2009<\u20094.8\u2009\u00d7\u200910<sup>-13</sup>) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (r<sub>G</sub>\u2009=\u2009-0.21; p-value\u2009=\u20092.3\u2009\u00d7\u200910<sup>-3</sup>), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of \u03b1<sub>2A</sub>-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-023-41876-5.pdf; doi:https://doi.org/10.1038/s41467-023-41876-5; html:https://europepmc.org/articles/PMC10570309; pdf:https://europepmc.org/articles/PMC10570309?pdf=render"
-  },
   {
     "id": "36881701",
     "doi": "https://doi.org/10.1097/jtn.0000000000000708",
@@ -11797,6 +11780,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1097/JTN.0000000000000708"
   },
+  {
+    "id": "37828025",
+    "doi": "https://doi.org/10.1038/s41467-023-41876-5",
+    "title": "ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon.",
+    "authorString": "Hartmann S, Yasmeen S, Jacobs BM, Denaxas S, Pirmohamed M, Gamazon ER, Caulfield MJ, Genes & Health Research Team, Hemingway H, Pietzner M, Langenberg C.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature communications",
+    "pubYear": "2023",
+    "date": "2023-10-12",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p\u2009<\u20095\u2009\u00d7\u200910<sup>-8</sup>). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p\u2009<\u20099.6\u2009\u00d7\u200910<sup>-27</sup>) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p\u2009<\u20094.8\u2009\u00d7\u200910<sup>-13</sup>) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (r<sub>G</sub>\u2009=\u2009-0.21; p-value\u2009=\u20092.3\u2009\u00d7\u200910<sup>-3</sup>), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of \u03b1<sub>2A</sub>-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41467-023-41876-5.pdf; doi:https://doi.org/10.1038/s41467-023-41876-5; html:https://europepmc.org/articles/PMC10570309; pdf:https://europepmc.org/articles/PMC10570309?pdf=render"
+  },
   {
     "id": "36382153",
     "doi": "https://doi.org/10.5334/gh.1166",
@@ -11848,6 +11848,23 @@
     "laySummary": "",
     "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4668507/1/Hollestein_etal_2023_The-association-between-atopic-eczema.pdf; doi:https://doi.org/10.1111/jdv.18841"
   },
+  {
+    "id": "35776101",
+    "doi": "https://doi.org/10.1093/ije/dyac140",
+    "title": "Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records.",
+    "authorString": "Xu Z, Arnold M, Sun L, Stevens D, Chung R, Ip S, Barrett J, Kaptoge S, Pennells L, Di Angelantonio E, Wood AM.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of epidemiology",
+    "pubYear": "2022",
+    "date": "2022-12-01",
+    "isOpenAccess": "Y",
+    "keywords": "Variability; Cardiovascular disease; Type 2 diabetes; Risk Prediction; Repeated Measurements; Electronic Health Records",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.<h4>Methods</h4>We used electronic health records (EHRs) data from 83\u200a910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.<h4>Results</h4>The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P\u2009<\u20090.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index\u2009=\u20090.659, 95% CI: 0.654-0.663) as compared with using last observed values (C-index\u2009=\u20090.651, 95% CI: 0.646-0.656) or means (C-index\u2009=\u20090.650, 95% CI: 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase\u2009=\u20090.005, 95% CI: 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index\u2009increase =\u20090.002, 95% CI: 0.000-0.003), HbA1c (C-index increase\u2009=\u20090.002, 95% CI: 0.000-0.003) or HDL cholesterol (C-index\u2009increase=\u20090.003, 95% CI: 0.002-0.005).<h4>Conclusion</h4>Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render"
+  },
   {
     "id": "37773956",
     "doi": "https://doi.org/10.1371/journal.pone.0292240",
@@ -11882,23 +11899,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1097/JS9.0000000000000781"
   },
-  {
-    "id": "35776101",
-    "doi": "https://doi.org/10.1093/ije/dyac140",
-    "title": "Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records.",
-    "authorString": "Xu Z, Arnold M, Sun L, Stevens D, Chung R, Ip S, Barrett J, Kaptoge S, Pennells L, Di Angelantonio E, Wood AM.",
-    "authorAffiliations": "",
-    "journalTitle": "International journal of epidemiology",
-    "pubYear": "2022",
-    "date": "2022-12-01",
-    "isOpenAccess": "Y",
-    "keywords": "Variability; Cardiovascular disease; Type 2 diabetes; Risk Prediction; Repeated Measurements; Electronic Health Records",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.<h4>Methods</h4>We used electronic health records (EHRs) data from 83\u200a910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.<h4>Results</h4>The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P\u2009<\u20090.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index\u2009=\u20090.659, 95% CI: 0.654-0.663) as compared with using last observed values (C-index\u2009=\u20090.651, 95% CI: 0.646-0.656) or means (C-index\u2009=\u20090.650, 95% CI: 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase\u2009=\u20090.005, 95% CI: 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index\u2009increase =\u20090.002, 95% CI: 0.000-0.003), HbA1c (C-index increase\u2009=\u20090.002, 95% CI: 0.000-0.003) or HDL cholesterol (C-index\u2009increase=\u20090.003, 95% CI: 0.002-0.005).<h4>Conclusion</h4>Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render"
-  },
   {
     "id": "37794179",
     "doi": "https://doi.org/10.1038/s41416-023-02450-4",
@@ -12171,23 +12171,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-022-13453-w; doi:https://doi.org/10.1186/s12889-022-13453-w; html:https://europepmc.org/articles/PMC9150337; pdf:https://europepmc.org/articles/PMC9150337?pdf=render"
   },
-  {
-    "id": "37794871",
-    "doi": "https://doi.org/10.1093/ehjdh/ztad044",
-    "title": "An artificial intelligence tool for automated analysis of large-scale unstructured clinical cine cardiac magnetic resonance databases.",
-    "authorString": "Mariscal-Harana J, Asher C, Vergani V, Rizvi M, Keehn L, Kim RJ, Judd RM, Petersen SE, Razavi R, King AP, Ruijsink B, Puyol-Ant\u00f3n E.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal. Digital health",
-    "pubYear": "2023",
-    "date": "2023-07-13",
-    "isOpenAccess": "Y",
-    "keywords": "Artificial intelligence; Quality control; Cardiac function; Cardiac Segmentation; Cardiac Magnetic Resonance",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>Artificial intelligence (AI) techniques have been proposed for automating analysis of short-axis (SAX) cine cardiac magnetic resonance (CMR), but no CMR analysis tool exists to automatically analyse large (unstructured) clinical CMR datasets. We develop and validate a robust AI tool for start-to-end automatic quantification of cardiac function from SAX cine CMR in large clinical databases.<h4>Methods and results</h4>Our pipeline for processing and analysing CMR databases includes automated steps to identify the correct data, robust image pre-processing, an AI algorithm for biventricular segmentation of SAX CMR and estimation of functional biomarkers, and automated post-analysis quality control to detect and correct errors. The segmentation algorithm was trained on 2793 CMR scans from two NHS hospitals and validated on additional cases from this dataset (<i>n</i> = 414) and five external datasets (<i>n</i> = 6888), including scans of patients with a range of diseases acquired at 12 different centres using CMR scanners from all major vendors. Median absolute errors in cardiac biomarkers were within the range of inter-observer variability: <8.4 mL (left ventricle volume), <9.2 mL (right ventricle volume), <13.3 g (left ventricular mass), and <5.9% (ejection fraction) across all datasets. Stratification of cases according to phenotypes of cardiac disease and scanner vendors showed good performance across all groups.<h4>Conclusion</h4>We show that our proposed tool, which combines image pre-processing steps, a domain-generalizable AI algorithm trained on a large-scale multi-domain CMR dataset and quality control steps, allows robust analysis of (clinical or research) databases from multiple centres, vendors, and cardiac diseases. This enables translation of our tool for use in fully automated processing of large multi-centre databases.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1093/ehjdh/ztad044; html:https://europepmc.org/articles/PMC10545512; pdf:https://europepmc.org/articles/PMC10545512?pdf=render"
-  },
   {
     "id": "34514354",
     "doi": "https://doi.org/10.1093/jamiaopen/ooab001",
@@ -12205,6 +12188,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/jamiaopen/article-pdf/4/3/ooab001/40325375/ooab001.pdf; doi:https://doi.org/10.1093/jamiaopen/ooab001; html:https://europepmc.org/articles/PMC8423424; pdf:https://europepmc.org/articles/PMC8423424?pdf=render"
   },
+  {
+    "id": "37794871",
+    "doi": "https://doi.org/10.1093/ehjdh/ztad044",
+    "title": "An artificial intelligence tool for automated analysis of large-scale unstructured clinical cine cardiac magnetic resonance databases.",
+    "authorString": "Mariscal-Harana J, Asher C, Vergani V, Rizvi M, Keehn L, Kim RJ, Judd RM, Petersen SE, Razavi R, King AP, Ruijsink B, Puyol-Ant\u00f3n E.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal. Digital health",
+    "pubYear": "2023",
+    "date": "2023-07-13",
+    "isOpenAccess": "Y",
+    "keywords": "Artificial intelligence; Quality control; Cardiac function; Cardiac Segmentation; Cardiac Magnetic Resonance",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>Artificial intelligence (AI) techniques have been proposed for automating analysis of short-axis (SAX) cine cardiac magnetic resonance (CMR), but no CMR analysis tool exists to automatically analyse large (unstructured) clinical CMR datasets. We develop and validate a robust AI tool for start-to-end automatic quantification of cardiac function from SAX cine CMR in large clinical databases.<h4>Methods and results</h4>Our pipeline for processing and analysing CMR databases includes automated steps to identify the correct data, robust image pre-processing, an AI algorithm for biventricular segmentation of SAX CMR and estimation of functional biomarkers, and automated post-analysis quality control to detect and correct errors. The segmentation algorithm was trained on 2793 CMR scans from two NHS hospitals and validated on additional cases from this dataset (<i>n</i> = 414) and five external datasets (<i>n</i> = 6888), including scans of patients with a range of diseases acquired at 12 different centres using CMR scanners from all major vendors. Median absolute errors in cardiac biomarkers were within the range of inter-observer variability: <8.4 mL (left ventricle volume), <9.2 mL (right ventricle volume), <13.3 g (left ventricular mass), and <5.9% (ejection fraction) across all datasets. Stratification of cases according to phenotypes of cardiac disease and scanner vendors showed good performance across all groups.<h4>Conclusion</h4>We show that our proposed tool, which combines image pre-processing steps, a domain-generalizable AI algorithm trained on a large-scale multi-domain CMR dataset and quality control steps, allows robust analysis of (clinical or research) databases from multiple centres, vendors, and cardiac diseases. This enables translation of our tool for use in fully automated processing of large multi-centre databases.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1093/ehjdh/ztad044; html:https://europepmc.org/articles/PMC10545512; pdf:https://europepmc.org/articles/PMC10545512?pdf=render"
+  },
   {
     "id": "33521768",
     "doi": "https://doi.org/10.1016/s2666-7568(20)30011-8",
@@ -12290,23 +12290,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835047; doi:https://doi.org/10.1002/lrh2.10315; html:https://europepmc.org/articles/PMC9835047; pdf:https://europepmc.org/articles/PMC9835047?pdf=render"
   },
-  {
-    "id": "36448824",
-    "doi": "https://doi.org/10.1002/cpt.2807",
-    "title": "Clinical Relevance of Drug-Drug Interactions With Antibiotics as Listed in a National Medication Formulary: Results From Two Large Population-Based Case-Control Studies in Patients Aged 65-100\u2009Years Using Linked English Primary Care and Hospital Data.",
-    "authorString": "van Staa TP, Pirmohamed M, Sharma A, Buchan I, Ashcroft DM.",
-    "authorAffiliations": "",
-    "journalTitle": "Clinical pharmacology and therapeutics",
-    "pubYear": "2023",
-    "date": "2022-12-16",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "This study evaluated drug-drug interactions (DDIs) between antibiotic and nonantibiotic drugs listed with warnings of severe outcomes in the British National Formulary based on adverse drug reaction (ADR) detectable with routine International Classification of Diseases, Tenth Revision coding. Data sources were Clinical Practice Research Databank GOLD and Aurum anonymized electronic health records from English general practices linked to hospital admission records. In propensity-matched case-control study, outcomes were ADR or emergency admissions. Analyzed were 121,546 ADR-related admission cases matched to 638,238 controls. For most antibiotics, adjusted odds ratios (aORs) for ADR-related hospital admission were large (aOR for trimethoprim 4.13; 95% confidence interval (CI), 3.97-4.30). Of the 51 DDIs evaluated for ADR-related admissions, 38 DDIs (74.5%) had statistically increased aORs of concomitant exposure compared with nonexposure (mean aOR 3.96; range 1.59-11.42); for the 89 DDIs for emergency hospital admission, the results were 75 (84.3%) and mean aOR 2.40; range 1.43-4.17. Changing reference group to single antibiotic exposure reduced aORs for concomitant exposure by 76.5% and 83.0%, respectively. Medicines listed to cause nephrotoxicity substantially increased risks that were related to number of medicines (aOR was 2.55 (95% CI, 2.46-2.64) for current use of 1 and 10.44 (95% CI, 7.36-14.81) for 3 or more medicines). In conclusion, no evidence of substantial risk was found for multiple DDIs with antibiotics despite warnings of severe outcomes in a national formulary and flagging in electronic health record software. It is proposed that the evidence base for inclusion of DDIs in national formularies be strengthened and made publicly accessible and indiscriminate flagging, which compounds alert fatigue, be reduced.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1002/cpt.2807; doi:https://doi.org/10.1002/cpt.2807; html:https://europepmc.org/articles/PMC10107602; pdf:https://europepmc.org/articles/PMC10107602?pdf=render"
-  },
   {
     "id": "32855306",
     "doi": "https://doi.org/10.1136/gutjnl-2020-321650",
@@ -12324,6 +12307,23 @@
     "laySummary": "",
     "urls": "pdf:https://gut.bmj.com/content/gutjnl/70/6/1053.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-321650; html:https://europepmc.org/articles/PMC7447105; pdf:https://europepmc.org/articles/PMC7447105?pdf=render"
   },
+  {
+    "id": "36448824",
+    "doi": "https://doi.org/10.1002/cpt.2807",
+    "title": "Clinical Relevance of Drug-Drug Interactions With Antibiotics as Listed in a National Medication Formulary: Results From Two Large Population-Based Case-Control Studies in Patients Aged 65-100\u2009Years Using Linked English Primary Care and Hospital Data.",
+    "authorString": "van Staa TP, Pirmohamed M, Sharma A, Buchan I, Ashcroft DM.",
+    "authorAffiliations": "",
+    "journalTitle": "Clinical pharmacology and therapeutics",
+    "pubYear": "2023",
+    "date": "2022-12-16",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "This study evaluated drug-drug interactions (DDIs) between antibiotic and nonantibiotic drugs listed with warnings of severe outcomes in the British National Formulary based on adverse drug reaction (ADR) detectable with routine International Classification of Diseases, Tenth Revision coding. Data sources were Clinical Practice Research Databank GOLD and Aurum anonymized electronic health records from English general practices linked to hospital admission records. In propensity-matched case-control study, outcomes were ADR or emergency admissions. Analyzed were 121,546 ADR-related admission cases matched to 638,238 controls. For most antibiotics, adjusted odds ratios (aORs) for ADR-related hospital admission were large (aOR for trimethoprim 4.13; 95% confidence interval (CI), 3.97-4.30). Of the 51 DDIs evaluated for ADR-related admissions, 38 DDIs (74.5%) had statistically increased aORs of concomitant exposure compared with nonexposure (mean aOR 3.96; range 1.59-11.42); for the 89 DDIs for emergency hospital admission, the results were 75 (84.3%) and mean aOR 2.40; range 1.43-4.17. Changing reference group to single antibiotic exposure reduced aORs for concomitant exposure by 76.5% and 83.0%, respectively. Medicines listed to cause nephrotoxicity substantially increased risks that were related to number of medicines (aOR was 2.55 (95% CI, 2.46-2.64) for current use of 1 and 10.44 (95% CI, 7.36-14.81) for 3 or more medicines). In conclusion, no evidence of substantial risk was found for multiple DDIs with antibiotics despite warnings of severe outcomes in a national formulary and flagging in electronic health record software. It is proposed that the evidence base for inclusion of DDIs in national formularies be strengthened and made publicly accessible and indiscriminate flagging, which compounds alert fatigue, be reduced.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1002/cpt.2807; doi:https://doi.org/10.1002/cpt.2807; html:https://europepmc.org/articles/PMC10107602; pdf:https://europepmc.org/articles/PMC10107602?pdf=render"
+  },
   {
     "id": "34641870",
     "doi": "https://doi.org/10.1186/s12911-021-01638-z",
@@ -12698,23 +12698,6 @@
     "laySummary": "",
     "urls": "pdf:https://openres.ersjournals.com/content/erjor/8/4/00211-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00211-2022; html:https://europepmc.org/articles/PMC9589337; pdf:https://europepmc.org/articles/PMC9589337?pdf=render"
   },
-  {
-    "id": "35444210",
-    "doi": "https://doi.org/10.1038/s41698-022-00269-5",
-    "title": "Pan-cancer prognostic genetic mutations and clinicopathological factors associated with survival outcomes: a systematic review.",
-    "authorString": "Gammall J, Lai AG.",
-    "authorAffiliations": "",
-    "journalTitle": "NPJ precision oncology",
-    "pubYear": "2022",
-    "date": "2022-04-20",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Cancer is a leading cause of death, accounting for almost 10 million deaths annually worldwide. Personalised therapies harnessing genetic and clinical information may improve survival outcomes and reduce the side effects of treatments. The aim of this study is to appraise published evidence on clinicopathological factors and genetic mutations (single nucleotide polymorphisms [SNPs]) associated with prognosis across 11 cancer types: lung, colorectal, breast, prostate, melanoma, renal, glioma, bladder, leukaemia, endometrial, ovarian. A systematic literature search of PubMed/MEDLINE and Europe PMC was conducted from database inception to July 1, 2021. 2497 publications from PubMed/MEDLINE and 288 preprints from Europe PMC were included. Subsequent reference and citation search was conducted and a further 39 articles added. 2824 articles were reviewed by title/abstract and 247 articles were selected for systematic review. Majority of the articles were retrospective cohort studies focusing on one cancer type, 8 articles were on pan-cancer level and 6 articles were reviews. Studies analysing clinicopathological factors included 908,567 patients and identified 238 factors, including age, gender, stage, grade, size, site, subtype, invasion, lymph nodes. Genetic studies included 210,802 patients and identified 440 gene mutations associated with cancer survival, including genes TP53, BRCA1, BRCA2, BRAF, KRAS, BIRC5. We generated a comprehensive knowledge base of biomarkers that can be used to tailor treatment according to patients' unique genetic and clinical characteristics. Our pan-cancer investigation uncovers the biomarker landscape and their combined influence that may help guide health practitioners and researchers across the continuum of cancer care from drug development to long-term survivorship.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41698-022-00269-5.pdf; doi:https://doi.org/10.1038/s41698-022-00269-5; html:https://europepmc.org/articles/PMC9021198; pdf:https://europepmc.org/articles/PMC9021198?pdf=render"
-  },
   {
     "id": "32310142",
     "doi": "https://doi.org/10.2196/14306",
@@ -12732,6 +12715,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.2196/14306; doi:https://doi.org/10.2196/14306; html:https://europepmc.org/articles/PMC7199134"
   },
+  {
+    "id": "35444210",
+    "doi": "https://doi.org/10.1038/s41698-022-00269-5",
+    "title": "Pan-cancer prognostic genetic mutations and clinicopathological factors associated with survival outcomes: a systematic review.",
+    "authorString": "Gammall J, Lai AG.",
+    "authorAffiliations": "",
+    "journalTitle": "NPJ precision oncology",
+    "pubYear": "2022",
+    "date": "2022-04-20",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Cancer is a leading cause of death, accounting for almost 10 million deaths annually worldwide. Personalised therapies harnessing genetic and clinical information may improve survival outcomes and reduce the side effects of treatments. The aim of this study is to appraise published evidence on clinicopathological factors and genetic mutations (single nucleotide polymorphisms [SNPs]) associated with prognosis across 11 cancer types: lung, colorectal, breast, prostate, melanoma, renal, glioma, bladder, leukaemia, endometrial, ovarian. A systematic literature search of PubMed/MEDLINE and Europe PMC was conducted from database inception to July 1, 2021. 2497 publications from PubMed/MEDLINE and 288 preprints from Europe PMC were included. Subsequent reference and citation search was conducted and a further 39 articles added. 2824 articles were reviewed by title/abstract and 247 articles were selected for systematic review. Majority of the articles were retrospective cohort studies focusing on one cancer type, 8 articles were on pan-cancer level and 6 articles were reviews. Studies analysing clinicopathological factors included 908,567 patients and identified 238 factors, including age, gender, stage, grade, size, site, subtype, invasion, lymph nodes. Genetic studies included 210,802 patients and identified 440 gene mutations associated with cancer survival, including genes TP53, BRCA1, BRCA2, BRAF, KRAS, BIRC5. We generated a comprehensive knowledge base of biomarkers that can be used to tailor treatment according to patients' unique genetic and clinical characteristics. Our pan-cancer investigation uncovers the biomarker landscape and their combined influence that may help guide health practitioners and researchers across the continuum of cancer care from drug development to long-term survivorship.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41698-022-00269-5.pdf; doi:https://doi.org/10.1038/s41698-022-00269-5; html:https://europepmc.org/articles/PMC9021198; pdf:https://europepmc.org/articles/PMC9021198?pdf=render"
+  },
   {
     "id": "36745557",
     "doi": "https://doi.org/10.1093/bjd/ljac132",
@@ -12987,23 +12987,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000502&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000502; html:https://europepmc.org/articles/PMC10021296; pdf:https://europepmc.org/articles/PMC10021296?pdf=render"
   },
-  {
-    "id": "36617894",
-    "doi": "https://doi.org/10.1080/1354750x.2022.2162966",
-    "title": "Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.",
-    "authorString": "de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.",
-    "authorAffiliations": "",
-    "journalTitle": "Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals",
-    "pubYear": "2023",
-    "date": "2023-01-08",
-    "isOpenAccess": "N",
-    "keywords": "Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<b>Introduction</b>Patients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.<b>Methods</b>We conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.<b>Results</b>Cases and controls had a median (25<sup>th</sup>-75<sup>th</sup>percentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] <i>versus</i> 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (<i>P</i>\u2009=\u20090.339). In controls, the mean cell concentration was significantly (<i>P</i>\u2009=\u20090.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) <i>versus</i> 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).<b>Conclusion</b>Despite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1080/1354750x.2022.2162966; doi:https://doi.org/10.1080/1354750X.2022.2162966"
-  },
   {
     "id": "33112263",
     "doi": "https://doi.org/10.1530/eje-20-0296",
@@ -13021,6 +13004,23 @@
     "laySummary": "",
     "urls": "pdf:https://eje.bioscientifica.com/downloadpdf/journals/eje/184/1/EJE-20-0296.pdf; doi:https://doi.org/10.1530/EJE-20-0296; html:https://europepmc.org/articles/PMC7707806; pdf:https://europepmc.org/articles/PMC7707806?pdf=render"
   },
+  {
+    "id": "36617894",
+    "doi": "https://doi.org/10.1080/1354750x.2022.2162966",
+    "title": "Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.",
+    "authorString": "de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.",
+    "authorAffiliations": "",
+    "journalTitle": "Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals",
+    "pubYear": "2023",
+    "date": "2023-01-08",
+    "isOpenAccess": "N",
+    "keywords": "Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<b>Introduction</b>Patients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.<b>Methods</b>We conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.<b>Results</b>Cases and controls had a median (25<sup>th</sup>-75<sup>th</sup>percentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] <i>versus</i> 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (<i>P</i>\u2009=\u20090.339). In controls, the mean cell concentration was significantly (<i>P</i>\u2009=\u20090.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) <i>versus</i> 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).<b>Conclusion</b>Despite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1080/1354750x.2022.2162966; doi:https://doi.org/10.1080/1354750X.2022.2162966"
+  },
   {
     "id": "34158612",
     "doi": "https://doi.org/10.1038/s41366-021-00846-x",
@@ -13055,23 +13055,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ageing/article-pdf/50/4/1019/40971734/afab060.pdf; doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render"
   },
-  {
-    "id": "37717030",
-    "doi": "https://doi.org/10.1186/s13756-023-01280-6",
-    "title": "The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.",
-    "authorString": "Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",
-    "authorAffiliations": "",
-    "journalTitle": "Antimicrobial resistance and infection control",
-    "pubYear": "2023",
-    "date": "2023-09-16",
-    "isOpenAccess": "Y",
-    "keywords": "Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.<h4>Methods</h4>With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.<h4>Results</h4>Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.<h4>Conclusions</h4>Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render"
-  },
   {
     "id": "35964473",
     "doi": "https://doi.org/10.1016/j.socscimed.2022.115237",
@@ -13089,6 +13072,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.socscimed.2022.115237; doi:https://doi.org/10.1016/j.socscimed.2022.115237; html:https://europepmc.org/articles/PMC9357441; pdf:https://europepmc.org/articles/PMC9357441?pdf=render"
   },
+  {
+    "id": "37717030",
+    "doi": "https://doi.org/10.1186/s13756-023-01280-6",
+    "title": "The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.",
+    "authorString": "Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",
+    "authorAffiliations": "",
+    "journalTitle": "Antimicrobial resistance and infection control",
+    "pubYear": "2023",
+    "date": "2023-09-16",
+    "isOpenAccess": "Y",
+    "keywords": "Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.<h4>Methods</h4>With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.<h4>Results</h4>Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.<h4>Conclusions</h4>Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render"
+  },
   {
     "id": "37306981",
     "doi": "https://doi.org/10.1001/jamaneurol.2023.1580",
@@ -13123,23 +13123,6 @@
     "laySummary": "",
     "urls": "pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100356.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render"
   },
-  {
-    "id": "36446449",
-    "doi": "https://doi.org/10.1136/bmjopen-2022-061849",
-    "title": "Effect of lifting COVID-19 restrictions on utilisation of primary care services in Nepal: a difference-in-differences analysis.",
-    "authorString": "Kapoor NR, Aryal A, Mehata S, Dulal M, Kruk ME, Bauhoff S, Arsenault C.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-11-29",
-    "isOpenAccess": "Y",
-    "keywords": "Primary Care; Health Policy; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>An increasing number of studies have reported disruptions in health service utilisation due to the COVID-19 pandemic and its associated restrictions. However, little is known about the effect of lifting COVID-19 restrictions on health service utilisation. The objective of this study was to estimate the effect of lifting COVID-19 restrictions on primary care service utilisation in Nepal.<h4>Methods</h4>Data on utilisation of 10 primary care services were extracted from the Health Management Information System across all health facilities in Nepal. We used a difference-in-differences design and linear fixed effects regressions to estimate the effect of lifting COVID-19 restrictions. The treatment group included palikas that had lifted restrictions in place from 17 August 2020 to 16 September 2020 (Bhadra 2077) and the control group included palikas that had maintained restrictions during that period. The pre-period included the 4 months of national lockdown from 24 March 2020 to 22 July 2020 (Chaitra 2076 to Ashar 2077). Models included month and palika fixed effects and controlled for COVID-19 incidence.<h4>Results</h4>We found that lifting COVID-19 restrictions was associated with an average increase per palika of 57.5 contraceptive users (95% CI 14.6 to 100.5), 15.6 antenatal care visits (95% CI 5.3 to 25.9) and 1.6 child pneumonia visits (95% CI 0.2 to 2.9). This corresponded to a 9.4% increase in contraceptive users, 34.2% increase in antenatal care visits and 15.6% increase in child pneumonia visits. Utilisation of most other primary care services also increased after lifting restrictions, but coefficients were not statistically significant.<h4>Conclusions</h4>Despite the ongoing pandemic, lifting restrictions can lead to an increase in some primary care services. Our results point to a causal link between restrictions and health service utilisation and call for policy makers in low- and middle-income countries to carefully consider the trade-offs of strict lockdowns during future COVID-19 waves or future pandemics.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render"
-  },
   {
     "id": "33402395",
     "doi": "https://doi.org/10.1136/jech-2020-215204",
@@ -13157,6 +13140,23 @@
     "laySummary": "",
     "urls": "pdf:https://jech.bmj.com/content/jech/75/7/681.full.pdf; doi:https://doi.org/10.1136/jech-2020-215204; html:https://europepmc.org/articles/PMC8223662; pdf:https://europepmc.org/articles/PMC8223662?pdf=render"
   },
+  {
+    "id": "36446449",
+    "doi": "https://doi.org/10.1136/bmjopen-2022-061849",
+    "title": "Effect of lifting COVID-19 restrictions on utilisation of primary care services in Nepal: a difference-in-differences analysis.",
+    "authorString": "Kapoor NR, Aryal A, Mehata S, Dulal M, Kruk ME, Bauhoff S, Arsenault C.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-11-29",
+    "isOpenAccess": "Y",
+    "keywords": "Primary Care; Health Policy; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>An increasing number of studies have reported disruptions in health service utilisation due to the COVID-19 pandemic and its associated restrictions. However, little is known about the effect of lifting COVID-19 restrictions on health service utilisation. The objective of this study was to estimate the effect of lifting COVID-19 restrictions on primary care service utilisation in Nepal.<h4>Methods</h4>Data on utilisation of 10 primary care services were extracted from the Health Management Information System across all health facilities in Nepal. We used a difference-in-differences design and linear fixed effects regressions to estimate the effect of lifting COVID-19 restrictions. The treatment group included palikas that had lifted restrictions in place from 17 August 2020 to 16 September 2020 (Bhadra 2077) and the control group included palikas that had maintained restrictions during that period. The pre-period included the 4 months of national lockdown from 24 March 2020 to 22 July 2020 (Chaitra 2076 to Ashar 2077). Models included month and palika fixed effects and controlled for COVID-19 incidence.<h4>Results</h4>We found that lifting COVID-19 restrictions was associated with an average increase per palika of 57.5 contraceptive users (95% CI 14.6 to 100.5), 15.6 antenatal care visits (95% CI 5.3 to 25.9) and 1.6 child pneumonia visits (95% CI 0.2 to 2.9). This corresponded to a 9.4% increase in contraceptive users, 34.2% increase in antenatal care visits and 15.6% increase in child pneumonia visits. Utilisation of most other primary care services also increased after lifting restrictions, but coefficients were not statistically significant.<h4>Conclusions</h4>Despite the ongoing pandemic, lifting restrictions can lead to an increase in some primary care services. Our results point to a causal link between restrictions and health service utilisation and call for policy makers in low- and middle-income countries to carefully consider the trade-offs of strict lockdowns during future COVID-19 waves or future pandemics.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render"
+  },
   {
     "id": "37667866",
     "doi": "https://doi.org/10.1111/cen.14966",
@@ -13582,23 +13582,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcsm.12971; doi:https://doi.org/10.1002/jcsm.12971; html:https://europepmc.org/articles/PMC9178164; pdf:https://europepmc.org/articles/PMC9178164?pdf=render"
   },
-  {
-    "id": "36712153",
-    "doi": "https://doi.org/10.1093/ehjdh/ztac046",
-    "title": "Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomized trial.",
-    "authorString": "Wang X, Mobley AR, Tica O, Okoth K, Ghosh RE, Myles P, Williams T, Haynes S, Nirantharakumar K, Shukla D, Kotecha D, DaRe2THINK Trial Committees .",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal. Digital health",
-    "pubYear": "2022",
-    "date": "2022-09-16",
-    "isOpenAccess": "Y",
-    "keywords": "Coding; Anticoagulation; Atrial fibrillation; Randomized controlled trial; Primary Care; Secondary Care; Electronic Healthcare Record",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHRs), allow for large-scale screening and follow up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high-quality and high clinical value research.<h4>Methods and results</h4>The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymized pre screening of the primary-care EHR across England, digital enrolment, remote e-consent, and 'no-visit' follow up by linking all primary- and secondary-care health data with patient-reported outcomes. DaRe2THINK is a pragmatic, healthcare-embedded randomized trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This study outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics (mortality).<h4>Conclusion</h4>Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomized trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at risk.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ehjdh/article-pdf/3/3/426/47117043/ztac046.pdf; doi:https://doi.org/10.1093/ehjdh/ztac046; html:https://europepmc.org/articles/PMC9708037; pdf:https://europepmc.org/articles/PMC9708037?pdf=render"
-  },
   {
     "id": "34190735",
     "doi": "https://doi.org/",
@@ -13616,6 +13599,23 @@
     "laySummary": "",
     "urls": ""
   },
+  {
+    "id": "36712153",
+    "doi": "https://doi.org/10.1093/ehjdh/ztac046",
+    "title": "Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomized trial.",
+    "authorString": "Wang X, Mobley AR, Tica O, Okoth K, Ghosh RE, Myles P, Williams T, Haynes S, Nirantharakumar K, Shukla D, Kotecha D, DaRe2THINK Trial Committees .",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal. Digital health",
+    "pubYear": "2022",
+    "date": "2022-09-16",
+    "isOpenAccess": "Y",
+    "keywords": "Coding; Anticoagulation; Atrial fibrillation; Randomized controlled trial; Primary Care; Secondary Care; Electronic Healthcare Record",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHRs), allow for large-scale screening and follow up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high-quality and high clinical value research.<h4>Methods and results</h4>The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymized pre screening of the primary-care EHR across England, digital enrolment, remote e-consent, and 'no-visit' follow up by linking all primary- and secondary-care health data with patient-reported outcomes. DaRe2THINK is a pragmatic, healthcare-embedded randomized trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This study outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics (mortality).<h4>Conclusion</h4>Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomized trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at risk.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ehjdh/article-pdf/3/3/426/47117043/ztac046.pdf; doi:https://doi.org/10.1093/ehjdh/ztac046; html:https://europepmc.org/articles/PMC9708037; pdf:https://europepmc.org/articles/PMC9708037?pdf=render"
+  },
   {
     "id": "35898465",
     "doi": "https://doi.org/10.3389/fendo.2022.888924",
@@ -13633,23 +13633,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fendo.2022.888924/pdf; doi:https://doi.org/10.3389/fendo.2022.888924; html:https://europepmc.org/articles/PMC9309507; pdf:https://europepmc.org/articles/PMC9309507?pdf=render"
   },
-  {
-    "id": "37549998",
-    "doi": "https://doi.org/10.1136/bjsports-2022-106460",
-    "title": "Device-based measurement of physical activity in cardiovascular healthcare: possibilities and challenges.",
-    "authorString": "Chico TJ, Stamatakis E, Ciravegna F, Dunn J, Redwood S, Al-Lamee R, Sofat R, Gill J.",
-    "authorAffiliations": "",
-    "journalTitle": "British journal of sports medicine",
-    "pubYear": "2023",
-    "date": "2023-08-07",
-    "isOpenAccess": "N",
-    "keywords": "Cardiovascular diseases; Health; Physical Activity",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/bjsports-2022-106460"
-  },
   {
     "id": "32626822",
     "doi": "https://doi.org/10.1007/s41109-020-00273-3",
@@ -13684,6 +13667,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15151.1; html:https://europepmc.org/articles/PMC6449792; pdf:https://europepmc.org/articles/PMC6449792?pdf=render"
   },
+  {
+    "id": "37549998",
+    "doi": "https://doi.org/10.1136/bjsports-2022-106460",
+    "title": "Device-based measurement of physical activity in cardiovascular healthcare: possibilities and challenges.",
+    "authorString": "Chico TJ, Stamatakis E, Ciravegna F, Dunn J, Redwood S, Al-Lamee R, Sofat R, Gill J.",
+    "authorAffiliations": "",
+    "journalTitle": "British journal of sports medicine",
+    "pubYear": "2023",
+    "date": "2023-08-07",
+    "isOpenAccess": "N",
+    "keywords": "Cardiovascular diseases; Health; Physical Activity",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1136/bjsports-2022-106460"
+  },
   {
     "id": "35793336",
     "doi": "https://doi.org/10.1371/journal.pone.0266521",
@@ -13735,6 +13735,23 @@
     "laySummary": "",
     "urls": "pdf:https://ieeexplore.ieee.org/ielx7/6221020/9281055/09210178.pdf; doi:https://doi.org/10.1109/JBHI.2020.3027987; html:https://europepmc.org/articles/PMC8545177; pdf:https://europepmc.org/articles/PMC8545177?pdf=render"
   },
+  {
+    "id": "33280008",
+    "doi": "https://doi.org/10.1093/cercor/bhaa345",
+    "title": "Hierarchical Complexity of the Macro-Scale Neonatal Brain.",
+    "authorString": "Blesa M, Galdi P, Cox SR, Sullivan G, Stoye DQ, Lamb GJ, Quigley AJ, Thrippleton MJ, Escudero J, Bastin ME, Smith KM, Boardman JP.",
+    "authorAffiliations": "",
+    "journalTitle": "Cerebral cortex (New York, N.Y. : 1991)",
+    "pubYear": "2021",
+    "date": "2021-03-01",
+    "isOpenAccess": "Y",
+    "keywords": "Newborn; Network Analysis; Developing Brain; Dmri; Structural Connectome; Hierarchical Complexity",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period, assess correspondences with hierarchical complexity in adulthood, and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/cercor/article-pdf/31/4/2071/36458400/bhaa345.pdf; doi:https://doi.org/10.1093/cercor/bhaa345; html:https://europepmc.org/articles/PMC7945030; pdf:https://europepmc.org/articles/PMC7945030?pdf=render"
+  },
   {
     "id": "37705832",
     "doi": "https://doi.org/10.5837/bjc.2023.003",
@@ -13769,6 +13786,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.14336/ad.2022.0829; doi:https://doi.org/10.14336/AD.2022.0829; html:https://europepmc.org/articles/PMC10017143; pdf:https://europepmc.org/articles/PMC10017143?pdf=render"
   },
+  {
+    "id": "31000744",
+    "doi": "https://doi.org/10.1038/s41598-019-42036-w",
+    "title": "Measuring social, environmental and health inequalities using deep learning and street imagery.",
+    "authorString": "Suel E, Polak JW, Bennett JE, Ezzati M.",
+    "authorAffiliations": "",
+    "journalTitle": "Scientific reports",
+    "pubYear": "2019",
+    "date": "2019-04-18",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "Applied Analytics, Improving Public Health",
+    "healthCategories": "",
+    "abstract": "Cities are home to an increasing majority of the world's population. Currently, it is difficult to track social, economic, environmental and health outcomes in cities with high spatial and temporal resolution, needed to evaluate policies regarding urban inequalities. We applied a deep learning approach to street\u00a0images for measuring spatial distributions of income, education, unemployment, housing, living environment, health and crime. Our model predicts different outcomes directly from raw images without extracting intermediate user-defined features. To evaluate the performance of the approach, we first trained neural networks on a subset of images from London using ground truth data at high spatial resolution from official statistics. We then compared how trained networks separated the best-off from worst-off deciles for different outcomes in images not used in training. The best performance was achieved for quality of the living environment and mean income. Allocation was least successful for crime and self-reported health (but not objectively measured health). We also evaluated how networks trained in London predict outcomes three other major cities in the UK: Birmingham, Manchester, and Leeds. The transferability analysis showed that networks trained in London, fine-tuned with only 1% of images in other cities, achieved performances similar to ones from trained on data from target cities themselves. Our findings demonstrate that street\u00a0imagery has the potential complement traditional survey-based and administrative data sources for high-resolution urban surveillance to measure inequalities and monitor the impacts of policies that aim to address them.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41598-019-42036-w.pdf; doi:https://doi.org/10.1038/s41598-019-42036-w; html:https://europepmc.org/articles/PMC6473002; pdf:https://europepmc.org/articles/PMC6473002?pdf=render"
+  },
   {
     "id": "37140153",
     "doi": "https://doi.org/10.1093/ehjci/jead093",
@@ -13786,23 +13820,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093"
   },
-  {
-    "id": "33280008",
-    "doi": "https://doi.org/10.1093/cercor/bhaa345",
-    "title": "Hierarchical Complexity of the Macro-Scale Neonatal Brain.",
-    "authorString": "Blesa M, Galdi P, Cox SR, Sullivan G, Stoye DQ, Lamb GJ, Quigley AJ, Thrippleton MJ, Escudero J, Bastin ME, Smith KM, Boardman JP.",
-    "authorAffiliations": "",
-    "journalTitle": "Cerebral cortex (New York, N.Y. : 1991)",
-    "pubYear": "2021",
-    "date": "2021-03-01",
-    "isOpenAccess": "Y",
-    "keywords": "Newborn; Network Analysis; Developing Brain; Dmri; Structural Connectome; Hierarchical Complexity",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period, assess correspondences with hierarchical complexity in adulthood, and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/cercor/article-pdf/31/4/2071/36458400/bhaa345.pdf; doi:https://doi.org/10.1093/cercor/bhaa345; html:https://europepmc.org/articles/PMC7945030; pdf:https://europepmc.org/articles/PMC7945030?pdf=render"
-  },
   {
     "id": "35143670",
     "doi": "https://doi.org/10.1093/molbev/msac034",
@@ -13820,23 +13837,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf; doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?pdf=render"
   },
-  {
-    "id": "31000744",
-    "doi": "https://doi.org/10.1038/s41598-019-42036-w",
-    "title": "Measuring social, environmental and health inequalities using deep learning and street imagery.",
-    "authorString": "Suel E, Polak JW, Bennett JE, Ezzati M.",
-    "authorAffiliations": "",
-    "journalTitle": "Scientific reports",
-    "pubYear": "2019",
-    "date": "2019-04-18",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "Applied Analytics, Improving Public Health",
-    "healthCategories": "",
-    "abstract": "Cities are home to an increasing majority of the world's population. Currently, it is difficult to track social, economic, environmental and health outcomes in cities with high spatial and temporal resolution, needed to evaluate policies regarding urban inequalities. We applied a deep learning approach to street\u00a0images for measuring spatial distributions of income, education, unemployment, housing, living environment, health and crime. Our model predicts different outcomes directly from raw images without extracting intermediate user-defined features. To evaluate the performance of the approach, we first trained neural networks on a subset of images from London using ground truth data at high spatial resolution from official statistics. We then compared how trained networks separated the best-off from worst-off deciles for different outcomes in images not used in training. The best performance was achieved for quality of the living environment and mean income. Allocation was least successful for crime and self-reported health (but not objectively measured health). We also evaluated how networks trained in London predict outcomes three other major cities in the UK: Birmingham, Manchester, and Leeds. The transferability analysis showed that networks trained in London, fine-tuned with only 1% of images in other cities, achieved performances similar to ones from trained on data from target cities themselves. Our findings demonstrate that street\u00a0imagery has the potential complement traditional survey-based and administrative data sources for high-resolution urban surveillance to measure inequalities and monitor the impacts of policies that aim to address them.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41598-019-42036-w.pdf; doi:https://doi.org/10.1038/s41598-019-42036-w; html:https://europepmc.org/articles/PMC6473002; pdf:https://europepmc.org/articles/PMC6473002?pdf=render"
-  },
   {
     "id": "36834176",
     "doi": "https://doi.org/10.3390/ijerph20043477",
@@ -14143,23 +14143,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.3389/fcvm.2023.1148931; html:https://europepmc.org/articles/PMC10619754; pdf:https://europepmc.org/articles/PMC10619754?pdf=render"
   },
-  {
-    "id": "37736873",
-    "doi": "https://doi.org/10.1002/ehf2.14527",
-    "title": "Genetically predicted androgenic profiles and adverse cardiac markers: a sex-specific Mendelian randomization study.",
-    "authorString": "Chen JY, Ardissino M, Reddy RK, Mason AM, Raisi-Estabragh Z, Di Angelantonio E, Burgess S, Ng FS.",
-    "authorAffiliations": "",
-    "journalTitle": "ESC heart failure",
-    "pubYear": "2023",
-    "date": "2023-09-22",
-    "isOpenAccess": "N",
-    "keywords": "Sex hormones; Testosterone; Heart Failure; Cmr; Mendelian Randomization; Shbg",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>Observational evidence suggests associations between sex hormone levels and heart failure (HF). We used sex-specific genetic variants associated with androgenic sex hormone profiles to investigate the causal relevance of androgenic sex hormone profiles on cardiac structure and function and HF using Mendelian randomization (MR).<h4>Methods and results</h4>Sex-specific uncorrelated genome-wide significant (P\u00a0<\u00a05\u00a0\u00d7\u00a010<sup>-8</sup> ) variants predicting sex hormone-binding globulin (SHBG), total testosterone, and bioavailable testosterone were extracted from summary statistics of genome-wide association study (GWAS) on 425\u00a0097 participants in the UK Biobank. Sex-specific gene-outcome association estimates were computed for left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively), left ventricular stroke volume (LVSV), cardiac index, and cardiac output in 11\u00a0528 female and 14\u00a0356 male UK Biobank Imaging Study participants and for incident or prevalent HF in an external cohort of 47\u00a0309 cases and 930\u00a0014 controls. Inverse-variance weighted MR was the primary analysis method. In females, higher genetically predicted bioavailable testosterone was associated with lower LVEDV [\u03b2 per nmol/L\u00a0=\u00a0-0.11 (-0.19 to -0.03), P\u00a0=\u00a00.006], lower LVESV [\u03b2\u00a0=\u00a0-0.09 (-0.17 to -0.01), P\u00a0=\u00a00.022], lower LVSV [\u03b2\u00a0=\u00a0-0.11 (-0.18 to -0.03), P\u00a0=\u00a00.005], lower cardiac output [\u03b2\u00a0=\u00a0-0.08 (-0.16 to 0.00), P\u00a0=\u00a00.046], and lower cardiac index [\u03b2\u00a0=\u00a0-0.08 (-0.16 to -0.01), P\u00a0=\u00a00.034] and a higher risk of HF [odds ratio 1.10 (1.01-1.19), P\u00a0=\u00a00.026] on external validation analysis in larger scale, sex-adjusted GWAS data. Higher genetically predicted SHBG was associated with higher LVEDV [\u03b2 per nmol/L\u00a0=\u00a00.17 (0.08-0.25), P\u00a0=\u00a02\u00a0\u00d7\u00a010<sup>-4</sup> ], higher LVESV [\u03b2\u00a0=\u00a00.13 (0.05-0.22), P\u00a0=\u00a00.003], and higher LVSV [\u03b2\u00a0=\u00a00.18 (0.08-0.28), P\u00a0=\u00a02\u00a0\u00d7\u00a010<sup>-4</sup> ]. In males, higher genetically predicted total and bioavailable testosterone was associated with lower LVESV [\u03b2\u00a0=\u00a0-0.07 (-0.12 to -0.02), P\u00a0=\u00a00.007] and LVEF [\u03b2\u00a0=\u00a0-0.11 (-0.18 to -0.04), P\u00a0=\u00a00.003], respectively.<h4>Conclusions</h4>This study supports a causal effect of pro-androgenic sex hormone profiles in females on adverse markers of left ventricular structure and function typically associated with HF with preserved ejection fraction and with HF. There was weaker evidence of association in males.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14527; doi:https://doi.org/10.1002/ehf2.14527"
-  },
   {
     "id": "34861180",
     "doi": "https://doi.org/10.1016/s2213-2600(21)00491-4",
@@ -14177,6 +14160,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2213260021004914/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00491-4; html:https://europepmc.org/articles/PMC8631918"
   },
+  {
+    "id": "37736873",
+    "doi": "https://doi.org/10.1002/ehf2.14527",
+    "title": "Genetically predicted androgenic profiles and adverse cardiac markers: a sex-specific Mendelian randomization study.",
+    "authorString": "Chen JY, Ardissino M, Reddy RK, Mason AM, Raisi-Estabragh Z, Di Angelantonio E, Burgess S, Ng FS.",
+    "authorAffiliations": "",
+    "journalTitle": "ESC heart failure",
+    "pubYear": "2023",
+    "date": "2023-09-22",
+    "isOpenAccess": "N",
+    "keywords": "Sex hormones; Testosterone; Heart Failure; Cmr; Mendelian Randomization; Shbg",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>Observational evidence suggests associations between sex hormone levels and heart failure (HF). We used sex-specific genetic variants associated with androgenic sex hormone profiles to investigate the causal relevance of androgenic sex hormone profiles on cardiac structure and function and HF using Mendelian randomization (MR).<h4>Methods and results</h4>Sex-specific uncorrelated genome-wide significant (P\u00a0<\u00a05\u00a0\u00d7\u00a010<sup>-8</sup> ) variants predicting sex hormone-binding globulin (SHBG), total testosterone, and bioavailable testosterone were extracted from summary statistics of genome-wide association study (GWAS) on 425\u00a0097 participants in the UK Biobank. Sex-specific gene-outcome association estimates were computed for left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively), left ventricular stroke volume (LVSV), cardiac index, and cardiac output in 11\u00a0528 female and 14\u00a0356 male UK Biobank Imaging Study participants and for incident or prevalent HF in an external cohort of 47\u00a0309 cases and 930\u00a0014 controls. Inverse-variance weighted MR was the primary analysis method. In females, higher genetically predicted bioavailable testosterone was associated with lower LVEDV [\u03b2 per nmol/L\u00a0=\u00a0-0.11 (-0.19 to -0.03), P\u00a0=\u00a00.006], lower LVESV [\u03b2\u00a0=\u00a0-0.09 (-0.17 to -0.01), P\u00a0=\u00a00.022], lower LVSV [\u03b2\u00a0=\u00a0-0.11 (-0.18 to -0.03), P\u00a0=\u00a00.005], lower cardiac output [\u03b2\u00a0=\u00a0-0.08 (-0.16 to 0.00), P\u00a0=\u00a00.046], and lower cardiac index [\u03b2\u00a0=\u00a0-0.08 (-0.16 to -0.01), P\u00a0=\u00a00.034] and a higher risk of HF [odds ratio 1.10 (1.01-1.19), P\u00a0=\u00a00.026] on external validation analysis in larger scale, sex-adjusted GWAS data. Higher genetically predicted SHBG was associated with higher LVEDV [\u03b2 per nmol/L\u00a0=\u00a00.17 (0.08-0.25), P\u00a0=\u00a02\u00a0\u00d7\u00a010<sup>-4</sup> ], higher LVESV [\u03b2\u00a0=\u00a00.13 (0.05-0.22), P\u00a0=\u00a00.003], and higher LVSV [\u03b2\u00a0=\u00a00.18 (0.08-0.28), P\u00a0=\u00a02\u00a0\u00d7\u00a010<sup>-4</sup> ]. In males, higher genetically predicted total and bioavailable testosterone was associated with lower LVESV [\u03b2\u00a0=\u00a0-0.07 (-0.12 to -0.02), P\u00a0=\u00a00.007] and LVEF [\u03b2\u00a0=\u00a0-0.11 (-0.18 to -0.04), P\u00a0=\u00a00.003], respectively.<h4>Conclusions</h4>This study supports a causal effect of pro-androgenic sex hormone profiles in females on adverse markers of left ventricular structure and function typically associated with HF with preserved ejection fraction and with HF. There was weaker evidence of association in males.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14527; doi:https://doi.org/10.1002/ehf2.14527"
+  },
   {
     "id": "32657853",
     "doi": "https://doi.org/10.1097/sap.0000000000002434",
@@ -14449,23 +14449,6 @@
     "laySummary": "",
     "urls": "pdf:https://n.neurology.org/content/neurology/95/6/e697.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009924; html:https://europepmc.org/articles/PMC7455356; pdf:https://europepmc.org/articles/PMC7455356?pdf=render"
   },
-  {
-    "id": "37729117",
-    "doi": "https://doi.org/10.1371/journal.pdig.0000309",
-    "title": "Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.",
-    "authorString": "Fuller GW, Hasan M, Hodkinson P, McAlpine D, Goodacre S, Bath PA, Sbaffi L, Omer Y, Wallis L, Marincowitz C.",
-    "authorAffiliations": "",
-    "journalTitle": "PLOS digital health",
-    "pubYear": "2023",
-    "date": "2023-09-20",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000309&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000309; html:https://europepmc.org/articles/PMC10511129; pdf:https://europepmc.org/articles/PMC10511129?pdf=render"
-  },
   {
     "id": "32103533",
     "doi": "https://doi.org/10.1002/sim.8503",
@@ -14483,6 +14466,23 @@
     "laySummary": "",
     "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4656008/1/manuscript.pdf; doi:https://doi.org/10.1002/sim.8503; html:https://europepmc.org/articles/PMC7612316; pdf:https://europepmc.org/articles/PMC7612316?pdf=render; doi:https://doi.org/10.1002/sim.8503"
   },
+  {
+    "id": "37729117",
+    "doi": "https://doi.org/10.1371/journal.pdig.0000309",
+    "title": "Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.",
+    "authorString": "Fuller GW, Hasan M, Hodkinson P, McAlpine D, Goodacre S, Bath PA, Sbaffi L, Omer Y, Wallis L, Marincowitz C.",
+    "authorAffiliations": "",
+    "journalTitle": "PLOS digital health",
+    "pubYear": "2023",
+    "date": "2023-09-20",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000309&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000309; html:https://europepmc.org/articles/PMC10511129; pdf:https://europepmc.org/articles/PMC10511129?pdf=render"
+  },
   {
     "id": "37293269",
     "doi": "https://doi.org/10.1140/epjds/s13688-023-00394-6",
@@ -14500,23 +14500,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1140/epjds/s13688-023-00394-6; html:https://europepmc.org/articles/PMC10245348; pdf:https://europepmc.org/articles/PMC10245348?pdf=render"
   },
-  {
-    "id": "37563310",
-    "doi": "https://doi.org/10.1038/s41590-023-01588-w",
-    "title": "Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.",
-    "authorString": "Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman \u00c5K, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, V\u00f5sa U, Esko T, Hayward C, Johansson \u00c5, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Land\u00e9n M, Wilson JF, Siegbahn A, Wallentin L, M\u00e4larstig A, Butterworth AS, Peters JE.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature immunology",
-    "pubYear": "2023",
-    "date": "2023-08-10",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-\u03b1 in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1038/s41590-023-01588-w; html:https://europepmc.org/articles/PMC10457199; pdf:https://europepmc.org/articles/PMC10457199?pdf=render"
-  },
   {
     "id": "35308999",
     "doi": "https://doi.org/",
@@ -14534,6 +14517,23 @@
     "laySummary": "",
     "urls": "html:https://europepmc.org/articles/PMC8861682; pdf:https://europepmc.org/articles/PMC8861682?pdf=render"
   },
+  {
+    "id": "37563310",
+    "doi": "https://doi.org/10.1038/s41590-023-01588-w",
+    "title": "Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.",
+    "authorString": "Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman \u00c5K, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, V\u00f5sa U, Esko T, Hayward C, Johansson \u00c5, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Land\u00e9n M, Wilson JF, Siegbahn A, Wallentin L, M\u00e4larstig A, Butterworth AS, Peters JE.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature immunology",
+    "pubYear": "2023",
+    "date": "2023-08-10",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-\u03b1 in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1038/s41590-023-01588-w; html:https://europepmc.org/articles/PMC10457199; pdf:https://europepmc.org/articles/PMC10457199?pdf=render"
+  },
   {
     "id": "36538350",
     "doi": "https://doi.org/10.2196/41200",
@@ -14738,23 +14738,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render"
   },
-  {
-    "id": "36936265",
-    "doi": "https://doi.org/10.1136/bmjmed-2022-000276",
-    "title": "Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY.",
-    "authorString": "Green ACA, Curtis HJ, Higgins R, Nab L, Mahalingasivam V, Smith RM, Mehrkar A, Inglesby P, Drysdale H, DeVito NJ, Croker R, Rentsch CT, Bhaskaran K, Tazare J, Zheng B, Andrews CD, Bacon SCJ, Davy S, Dillingham I, Evans D, Fisher L, Hickman G, Hopcroft LEM, Hulme WJ, Massey J, MacDonald O, Morley J, Morton CE, Park RY, Walker AJ, Ward T, Wiedemann M, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Goldacre B, Tomlinson LA, MacKenna B.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ medicine",
-    "pubYear": "2023",
-    "date": "2023-01-13",
-    "isOpenAccess": "Y",
-    "keywords": "Therapeutics; Community health services; Public Health; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.<h4>Design</h4>Retrospective, descriptive cohort study, approved by NHS England.<h4>Setting</h4>Routine clinical data from 23.4\u2009million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.<h4>Participants</h4>Outpatients with covid-19 at high risk of severe outcomes.<h4>Interventions</h4>Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.<h4>Results</h4>93\u2009870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19\u2009040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95%\u2009confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from \u226580 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%).<h4>Conclusions</h4>Using the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged \u226580 years, those living in socioeconomically deprived areas, and care home residents.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render"
-  },
   {
     "id": "31104603",
     "doi": "https://doi.org/10.1098/rstb.2018.0276",
@@ -14789,6 +14772,23 @@
     "laySummary": "epidemiological study looking at the prevalence of ehlos danlos syndrome and joint hypermobility syndrome, using SAIL database for welsh population. They found a steady increase in the rates of diagnosis for these two diseases, higher odds of being on other medication, and association with other diseases categories.",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/11/e031365.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-031365; html:https://europepmc.org/articles/PMC6858200; pdf:https://europepmc.org/articles/PMC6858200?pdf=render"
   },
+  {
+    "id": "36936265",
+    "doi": "https://doi.org/10.1136/bmjmed-2022-000276",
+    "title": "Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY.",
+    "authorString": "Green ACA, Curtis HJ, Higgins R, Nab L, Mahalingasivam V, Smith RM, Mehrkar A, Inglesby P, Drysdale H, DeVito NJ, Croker R, Rentsch CT, Bhaskaran K, Tazare J, Zheng B, Andrews CD, Bacon SCJ, Davy S, Dillingham I, Evans D, Fisher L, Hickman G, Hopcroft LEM, Hulme WJ, Massey J, MacDonald O, Morley J, Morton CE, Park RY, Walker AJ, Ward T, Wiedemann M, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Goldacre B, Tomlinson LA, MacKenna B.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ medicine",
+    "pubYear": "2023",
+    "date": "2023-01-13",
+    "isOpenAccess": "Y",
+    "keywords": "Therapeutics; Community health services; Public Health; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.<h4>Design</h4>Retrospective, descriptive cohort study, approved by NHS England.<h4>Setting</h4>Routine clinical data from 23.4\u2009million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.<h4>Participants</h4>Outpatients with covid-19 at high risk of severe outcomes.<h4>Interventions</h4>Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.<h4>Results</h4>93\u2009870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19\u2009040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95%\u2009confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from \u226580 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%).<h4>Conclusions</h4>Using the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged \u226580 years, those living in socioeconomically deprived areas, and care home residents.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render"
+  },
   {
     "id": "36276403",
     "doi": "https://doi.org/10.3389/fpubh.2022.875198",
@@ -15079,21 +15079,21 @@
     "urls": "pdf:https://www.nature.com/articles/s41598-019-51562-6.pdf; doi:https://doi.org/10.1038/s41598-019-51562-6; html:https://europepmc.org/articles/PMC6802378; pdf:https://europepmc.org/articles/PMC6802378?pdf=render"
   },
   {
-    "id": "35698725",
-    "doi": "https://doi.org/10.1016/s2665-9913(22)00098-4",
-    "title": "Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.",
-    "authorString": "MacKenna B, Kennedy NA, Mehrkar A, Rowan A, Galloway J, Matthewman J, Mansfield KE, Bechman K, Yates M, Brown J, Schultze A, Norton S, Walker AJ, Morton CE, Harrison D, Bhaskaran K, Rentsch CT, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Davy S, Green A, Fisher L, Hulme W, Bates C, Curtis HJ, Tazare J, Eggo RM, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson LA, Mathur R, Wong AYS, Forbes H, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Lees CW, Evans SJW, Goldacre B, Smith CH, Langan SM.",
+    "id": "31951005",
+    "doi": "https://doi.org/10.1093/jamia/ocz211",
+    "title": "On classifying sepsis heterogeneity in the ICU: insight using machine learning.",
+    "authorString": "Ibrahim ZM, Wu H, Hamoud A, Stappen L, Dobson RJB, Agarossi A.",
     "authorAffiliations": "",
-    "journalTitle": "The Lancet. Rheumatology",
-    "pubYear": "2022",
-    "date": "2022-06-09",
+    "journalTitle": "Journal of the American Medical Informatics Association : JAMIA",
+    "pubYear": "2020",
+    "date": "2020-03-01",
     "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
+    "keywords": "Sepsis; Machine Learning; Artificial Intelligence In Medicine; Sepsis Prediction; Sepsis Subtypes",
+    "nationalPriorities": "Applied Analytics",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies.<h4>Methods</h4>We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate).<h4>Findings</h4>We identified 17\u2009672\u2009065 adults; 1\u2009163\u2009438 adults (640\u2009164 [55\u00b70%] women and 523\u2009274 [45\u00b70%] men, and 827\u2009457 [71\u00b71%] of White ethnicity) had immune-mediated inflammatory diseases, and 16\u2009508\u2009627 people (8\u2009215\u2009020 [49\u00b78%] women and 8\u2009293\u2009607 [50\u00b72%] men, and 10\u2009614\u2009096 [64\u00b73%] of White ethnicity) were included as the general population. Of 1\u2009163\u2009438 adults with immune-mediated inflammatory diseases, 19\u2009119 (1\u00b76%) received targeted immune-modifying therapy and 181\u2009694 (15\u00b76%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1\u00b723, 95% CI 1\u00b720-1\u00b727) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1\u00b715, 1\u00b711-1\u00b718). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1\u00b724, 95% CI 1\u00b721-1\u00b728; mediator-adjusted 1\u00b716, 1\u00b712-1\u00b719) and hospital admission (confounder-adjusted 1\u00b732, 1\u00b729-1\u00b735; mediator-adjusted 1\u00b720, 1\u00b717-1\u00b723). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1\u00b703, 95% CI 0\u00b780-1\u00b733), and after additionally adjusting for current glucocorticoid use (1\u00b701, 0\u00b778-1\u00b730). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL\u201123 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1\u00b768, 95% CI 1\u00b711-2\u00b756), with some attenuation after excluding people with haematological malignancies or organ transplants (1\u00b7<b>54, 0</b>\u00b7<b>95</b>-<b>2</b>\u00b7<b>49</b>).<h4>Interpretation</h4>COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy.<h4>Funding</h4>UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.",
-    "laySummary": "",
-    "urls": "pdf:http://www.thelancet.com/article/S2665991322000984/pdf; doi:https://doi.org/10.1016/S2665-9913(22)00098-4; html:https://europepmc.org/articles/PMC9179144; pdf:https://europepmc.org/articles/PMC9179144?pdf=render"
+    "abstract": "<h4>Objectives</h4>Current machine learning models aiming to predict sepsis from electronic health records (EHR) do not account 20 for the heterogeneity of the condition despite its emerging importance in prognosis and treatment. This work demonstrates the added value of stratifying the types of organ dysfunction observed in patients who develop sepsis in the intensive care unit (ICU) in improving the ability to recognize patients at risk of sepsis from their EHR data.<h4>Materials and methods</h4>Using an ICU dataset of 13 728 records, we identify clinically significant sepsis subpopulations with distinct organ dysfunction patterns. We perform classification experiments with random forest, gradient boost trees, and support vector machines, using the identified subpopulations to distinguish patients who develop sepsis in the ICU from those who do not.<h4>Results</h4>The classification results show that features selected using sepsis subpopulations as background knowledge yield a superior performance in distinguishing septic from non-septic patients regardless of the classification model used. The improved performance is especially pronounced in specificity, which is a current bottleneck in sepsis prediction machine learning models.<h4>Conclusion</h4>Our findings can steer machine learning efforts toward more personalized models for complex conditions including sepsis.",
+    "laySummary": "Ibrahim et al. categorized patients in groups based on the type of organ failure. This categorization helped machine based algorithms to correctly identify those at high risk of sepsis.",
+    "urls": "pdf:https://academic.oup.com/jamia/article-pdf/27/3/437/34153319/ocz211.pdf; doi:https://doi.org/10.1093/jamia/ocz211; html:https://europepmc.org/articles/PMC7025363; pdf:https://europepmc.org/articles/PMC7025363?pdf=render"
   },
   {
     "id": "34286192",
@@ -15113,21 +15113,21 @@
     "urls": "pdf:https://www.rcpjournals.org/content/futurehosp/8/2/e243.full.pdf; doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083"
   },
   {
-    "id": "31951005",
-    "doi": "https://doi.org/10.1093/jamia/ocz211",
-    "title": "On classifying sepsis heterogeneity in the ICU: insight using machine learning.",
-    "authorString": "Ibrahim ZM, Wu H, Hamoud A, Stappen L, Dobson RJB, Agarossi A.",
+    "id": "35698725",
+    "doi": "https://doi.org/10.1016/s2665-9913(22)00098-4",
+    "title": "Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.",
+    "authorString": "MacKenna B, Kennedy NA, Mehrkar A, Rowan A, Galloway J, Matthewman J, Mansfield KE, Bechman K, Yates M, Brown J, Schultze A, Norton S, Walker AJ, Morton CE, Harrison D, Bhaskaran K, Rentsch CT, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Davy S, Green A, Fisher L, Hulme W, Bates C, Curtis HJ, Tazare J, Eggo RM, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson LA, Mathur R, Wong AYS, Forbes H, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Lees CW, Evans SJW, Goldacre B, Smith CH, Langan SM.",
     "authorAffiliations": "",
-    "journalTitle": "Journal of the American Medical Informatics Association : JAMIA",
-    "pubYear": "2020",
-    "date": "2020-03-01",
+    "journalTitle": "The Lancet. Rheumatology",
+    "pubYear": "2022",
+    "date": "2022-06-09",
     "isOpenAccess": "Y",
-    "keywords": "Sepsis; Machine Learning; Artificial Intelligence In Medicine; Sepsis Prediction; Sepsis Subtypes",
-    "nationalPriorities": "Applied Analytics",
+    "keywords": "",
+    "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>Current machine learning models aiming to predict sepsis from electronic health records (EHR) do not account 20 for the heterogeneity of the condition despite its emerging importance in prognosis and treatment. This work demonstrates the added value of stratifying the types of organ dysfunction observed in patients who develop sepsis in the intensive care unit (ICU) in improving the ability to recognize patients at risk of sepsis from their EHR data.<h4>Materials and methods</h4>Using an ICU dataset of 13 728 records, we identify clinically significant sepsis subpopulations with distinct organ dysfunction patterns. We perform classification experiments with random forest, gradient boost trees, and support vector machines, using the identified subpopulations to distinguish patients who develop sepsis in the ICU from those who do not.<h4>Results</h4>The classification results show that features selected using sepsis subpopulations as background knowledge yield a superior performance in distinguishing septic from non-septic patients regardless of the classification model used. The improved performance is especially pronounced in specificity, which is a current bottleneck in sepsis prediction machine learning models.<h4>Conclusion</h4>Our findings can steer machine learning efforts toward more personalized models for complex conditions including sepsis.",
-    "laySummary": "Ibrahim et al. categorized patients in groups based on the type of organ failure. This categorization helped machine based algorithms to correctly identify those at high risk of sepsis.",
-    "urls": "pdf:https://academic.oup.com/jamia/article-pdf/27/3/437/34153319/ocz211.pdf; doi:https://doi.org/10.1093/jamia/ocz211; html:https://europepmc.org/articles/PMC7025363; pdf:https://europepmc.org/articles/PMC7025363?pdf=render"
+    "abstract": "<h4>Background</h4>The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies.<h4>Methods</h4>We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate).<h4>Findings</h4>We identified 17\u2009672\u2009065 adults; 1\u2009163\u2009438 adults (640\u2009164 [55\u00b70%] women and 523\u2009274 [45\u00b70%] men, and 827\u2009457 [71\u00b71%] of White ethnicity) had immune-mediated inflammatory diseases, and 16\u2009508\u2009627 people (8\u2009215\u2009020 [49\u00b78%] women and 8\u2009293\u2009607 [50\u00b72%] men, and 10\u2009614\u2009096 [64\u00b73%] of White ethnicity) were included as the general population. Of 1\u2009163\u2009438 adults with immune-mediated inflammatory diseases, 19\u2009119 (1\u00b76%) received targeted immune-modifying therapy and 181\u2009694 (15\u00b76%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1\u00b723, 95% CI 1\u00b720-1\u00b727) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1\u00b715, 1\u00b711-1\u00b718). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1\u00b724, 95% CI 1\u00b721-1\u00b728; mediator-adjusted 1\u00b716, 1\u00b712-1\u00b719) and hospital admission (confounder-adjusted 1\u00b732, 1\u00b729-1\u00b735; mediator-adjusted 1\u00b720, 1\u00b717-1\u00b723). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1\u00b703, 95% CI 0\u00b780-1\u00b733), and after additionally adjusting for current glucocorticoid use (1\u00b701, 0\u00b778-1\u00b730). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL\u201123 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1\u00b768, 95% CI 1\u00b711-2\u00b756), with some attenuation after excluding people with haematological malignancies or organ transplants (1\u00b7<b>54, 0</b>\u00b7<b>95</b>-<b>2</b>\u00b7<b>49</b>).<h4>Interpretation</h4>COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy.<h4>Funding</h4>UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.",
+    "laySummary": "",
+    "urls": "pdf:http://www.thelancet.com/article/S2665991322000984/pdf; doi:https://doi.org/10.1016/S2665-9913(22)00098-4; html:https://europepmc.org/articles/PMC9179144; pdf:https://europepmc.org/articles/PMC9179144?pdf=render"
   },
   {
     "id": "31765395",
@@ -15146,23 +15146,6 @@
     "laySummary": "Bean et al. looked at using clinical notes to calculate risk scores: CHADSVASC and HASBLED for 10,030 AF patients from 2011 to October 2017), they\u2019ve validated their natural language processing algorithm with getting clinicians to calculate the risk in conventional manner for 40 of cases, the two scores were in higher agreement for stroke risk compared to HAS-BLED They\u2019ve concluded on usefulness of NLP method in risk calculation at the large scale.",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225625&type=printable; doi:https://doi.org/10.1371/journal.pone.0225625; html:https://europepmc.org/articles/PMC6876873; pdf:https://europepmc.org/articles/PMC6876873?pdf=render"
   },
-  {
-    "id": "34399584",
-    "doi": "https://doi.org/10.1161/strokeaha.120.032619",
-    "title": "Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases.",
-    "authorString": "Abraham G, Rutten-Jacobs L, Inouye M.",
-    "authorAffiliations": "",
-    "journalTitle": "Stroke",
-    "pubYear": "2021",
-    "date": "2021-08-17",
-    "isOpenAccess": "N",
-    "keywords": "Genetics; Myocardial infarction; Cardiovascular disease; Stroke; risk assessment",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.",
-    "laySummary": "",
-    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.032619; doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619"
-  },
   {
     "id": "33890864",
     "doi": "https://doi.org/10.2196/24728",
@@ -15180,6 +15163,23 @@
     "laySummary": "",
     "urls": "pdf:https://aging.jmir.org/2021/2/e24728/PDF; doi:https://doi.org/10.2196/24728; html:https://europepmc.org/articles/PMC8105762; pdf:https://europepmc.org/articles/PMC8105762?pdf=render"
   },
+  {
+    "id": "34399584",
+    "doi": "https://doi.org/10.1161/strokeaha.120.032619",
+    "title": "Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases.",
+    "authorString": "Abraham G, Rutten-Jacobs L, Inouye M.",
+    "authorAffiliations": "",
+    "journalTitle": "Stroke",
+    "pubYear": "2021",
+    "date": "2021-08-17",
+    "isOpenAccess": "N",
+    "keywords": "Genetics; Myocardial infarction; Cardiovascular disease; Stroke; risk assessment",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.",
+    "laySummary": "",
+    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.032619; doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619"
+  },
   {
     "id": "34169636",
     "doi": "https://doi.org/10.1002/pst.2148",
@@ -15350,23 +15350,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1111/opo.12765"
   },
-  {
-    "id": "35921096",
-    "doi": "https://doi.org/10.1001/jamacardio.2022.2333",
-    "title": "Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.",
-    "authorString": "Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.",
-    "authorAffiliations": "",
-    "journalTitle": "JAMA cardiology",
-    "pubYear": "2022",
-    "date": "2022-09-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Importance</h4>Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.<h4>Objective</h4>To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.<h4>Design, setting, and participants</h4>Two-sample 2\u2009\u00d7\u20092 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.<h4>Exposures</h4>Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.<h4>Main outcomes and measures</h4>Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.<h4>Results</h4>Data for 425\u202f354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229\u202f399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P\u2009=\u2009.34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P\u2009=\u2009.83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).<h4>Conclusions and relevance</h4>Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333"
-  },
   {
     "id": "31416346",
     "doi": "https://doi.org/10.1161/circulationaha.119.041980",
@@ -15384,6 +15367,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1161/circulationaha.119.041980; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041980; html:https://europepmc.org/articles/PMC6749969; pdf:https://europepmc.org/articles/PMC6749969?pdf=render"
   },
+  {
+    "id": "35921096",
+    "doi": "https://doi.org/10.1001/jamacardio.2022.2333",
+    "title": "Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.",
+    "authorString": "Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.",
+    "authorAffiliations": "",
+    "journalTitle": "JAMA cardiology",
+    "pubYear": "2022",
+    "date": "2022-09-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Importance</h4>Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.<h4>Objective</h4>To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.<h4>Design, setting, and participants</h4>Two-sample 2\u2009\u00d7\u20092 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.<h4>Exposures</h4>Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.<h4>Main outcomes and measures</h4>Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.<h4>Results</h4>Data for 425\u202f354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229\u202f399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P\u2009=\u2009.34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P\u2009=\u2009.83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).<h4>Conclusions and relevance</h4>Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333"
+  },
   {
     "id": "33704068",
     "doi": "https://doi.org/10.7554/elife.64827",
@@ -15401,23 +15401,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.7554/elife.64827; doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?pdf=render"
   },
-  {
-    "id": "36644660",
-    "doi": "https://doi.org/10.1177/20552076221128677",
-    "title": "Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.",
-    "authorString": "Gardner C, Wake D, Brodie D, Silverstein A, Young S, Cunningham S, Sainsbury C, Ilia M, Lucas A, Willis T, Halligan J.",
-    "authorAffiliations": "",
-    "journalTitle": "Digital health",
-    "pubYear": "2023",
-    "date": "2023-01-08",
-    "isOpenAccess": "Y",
-    "keywords": "Artificial intelligence; Internet; Diabetes; Qualitative; risk factors; Machine Learning; Health Informatics; Behaviour Change; Personalised Medicine; Digital Health",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The prevalence of type 2 diabetes in North West London (NWL) is relatively high compared to other parts of the United Kingdom with outcomes suboptimal. This presents a need for more effective strategies to identify people living with type 2 diabetes who need additional support. An emerging subset of web-based interventions for diabetes self-management and population management has used artificial intelligence and machine learning models to stratify the risk of complications from diabetes and identify patients in need of immediate support. In this study, two prototype risk prediction tools on the MyWay Diabetes and MyWay Clinical platforms were evaluated with six clinicians and six people living with type 2 diabetes in NWL using the think aloud method. The results of the sessions with people living with type 2 diabetes showed that the concept of the tool was intuitive, however, more instruction on how to correctly use the risk prediction tool would be valuable. The feedback from the sessions with clinicians was that the data presented in the tool aligned with the key diabetes targets in NWL, and that this would be useful for identifying and inviting patients to the practice who are overdue for tests and at risk of complications. The findings of the evaluation have been used to support the development of the prototype risk predictions tools. This study demonstrates the value of conducting usability testing on web-based interventions designed to support the targeted management of type 2 diabetes in local communities.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1177/20552076221128677; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render"
-  },
   {
     "id": "32954362",
     "doi": "https://doi.org/10.1038/s43016-020-0093-y",
@@ -15435,6 +15418,23 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497842; doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y"
   },
+  {
+    "id": "36644660",
+    "doi": "https://doi.org/10.1177/20552076221128677",
+    "title": "Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.",
+    "authorString": "Gardner C, Wake D, Brodie D, Silverstein A, Young S, Cunningham S, Sainsbury C, Ilia M, Lucas A, Willis T, Halligan J.",
+    "authorAffiliations": "",
+    "journalTitle": "Digital health",
+    "pubYear": "2023",
+    "date": "2023-01-08",
+    "isOpenAccess": "Y",
+    "keywords": "Artificial intelligence; Internet; Diabetes; Qualitative; risk factors; Machine Learning; Health Informatics; Behaviour Change; Personalised Medicine; Digital Health",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The prevalence of type 2 diabetes in North West London (NWL) is relatively high compared to other parts of the United Kingdom with outcomes suboptimal. This presents a need for more effective strategies to identify people living with type 2 diabetes who need additional support. An emerging subset of web-based interventions for diabetes self-management and population management has used artificial intelligence and machine learning models to stratify the risk of complications from diabetes and identify patients in need of immediate support. In this study, two prototype risk prediction tools on the MyWay Diabetes and MyWay Clinical platforms were evaluated with six clinicians and six people living with type 2 diabetes in NWL using the think aloud method. The results of the sessions with people living with type 2 diabetes showed that the concept of the tool was intuitive, however, more instruction on how to correctly use the risk prediction tool would be valuable. The feedback from the sessions with clinicians was that the data presented in the tool aligned with the key diabetes targets in NWL, and that this would be useful for identifying and inviting patients to the practice who are overdue for tests and at risk of complications. The findings of the evaluation have been used to support the development of the prototype risk predictions tools. This study demonstrates the value of conducting usability testing on web-based interventions designed to support the targeted management of type 2 diabetes in local communities.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1177/20552076221128677; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render"
+  },
   {
     "id": "36013179",
     "doi": "https://doi.org/10.3390/jpm12081230",
@@ -15605,23 +15605,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1167/tvst.9.9.38; doi:https://doi.org/10.1167/tvst.9.9.38; html:https://europepmc.org/articles/PMC7453042; pdf:https://europepmc.org/articles/PMC7453042?pdf=render"
   },
-  {
-    "id": "37067859",
-    "doi": "https://doi.org/10.1136/bmjmed-2022-000245",
-    "title": "Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.",
-    "authorString": "Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ medicine",
-    "pubYear": "2023",
-    "date": "2023-02-14",
-    "isOpenAccess": "Y",
-    "keywords": "epidemiology; Heart Failure; Cardiology; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.<h4>Design</h4>Registry based observational study.<h4>Setting</h4>74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.<h4>Participants</h4>All adults (aged \u226518 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11\u2009167 patients).<h4>Main outcome measures</h4>Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with \u226520 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.<h4>Results</h4>Of 11\u2009167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).<h4>Conclusions</h4>In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render"
-  },
   {
     "id": "33692093",
     "doi": "https://doi.org/10.1136/heartjnl-2020-318557",
@@ -15639,6 +15622,23 @@
     "laySummary": "",
     "urls": "pdf:https://heart.bmj.com/content/heartjnl/107/11/902.full.pdf; doi:https://doi.org/10.1136/heartjnl-2020-318557; html:https://europepmc.org/articles/PMC8142420; pdf:https://europepmc.org/articles/PMC8142420?pdf=render"
   },
+  {
+    "id": "37067859",
+    "doi": "https://doi.org/10.1136/bmjmed-2022-000245",
+    "title": "Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.",
+    "authorString": "Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ medicine",
+    "pubYear": "2023",
+    "date": "2023-02-14",
+    "isOpenAccess": "Y",
+    "keywords": "epidemiology; Heart Failure; Cardiology; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.<h4>Design</h4>Registry based observational study.<h4>Setting</h4>74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.<h4>Participants</h4>All adults (aged \u226518 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11\u2009167 patients).<h4>Main outcome measures</h4>Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with \u226520 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.<h4>Results</h4>Of 11\u2009167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).<h4>Conclusions</h4>In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render"
+  },
   {
     "id": "35135774",
     "doi": "https://doi.org/10.1136/bmjopen-2021-055603",
@@ -15707,23 +15707,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1097/HTR.0000000000000741"
   },
-  {
-    "id": "37827807",
-    "doi": "https://doi.org/10.1136/bmjresp-2023-001806",
-    "title": "Observational cohort study protocol: neutrophil function and energetics in adults with pneumonia and sepsis - Pneumonia Metabolism in Ageing (PUMA).",
-    "authorString": "Grudzinska FS, Faniyi AA, Scott A, Sapey E, Thickett DR.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open respiratory research",
-    "pubYear": "2023",
-    "date": "2023-10-01",
-    "isOpenAccess": "Y",
-    "keywords": "Pneumonia; innate immunity; Bacterial Infection; respiratory infection; Neutrophil Biology",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>Community-acquired pneumonia has high mortality and is associated with significant healthcare costs. In older adults with community-acquired pneumonia neutrophil dysfunction has been identified and is associated with poor outcomes for patients. Immunometabolism is a rapidly developing field which links immune cell function to metabolism. This study aims to explore neutrophil metabolism in community-acquired pneumonia.<h4>Methods and analysis</h4>Pneumonia Metabolism in Ageing study is a prospective observational study recruiting older adults hospitalised with community-acquired pneumonia to examine neutrophil function and metabolic status. Controls will be older adults with no acute illness. The primary endpoint is neutrophil chemotaxis.<h4>Ethics and dissemination</h4>The study has ethical approval from the Research Ethics Committee Wales, reference 19/WA/0299. This study involves participants who may lack the capacity to consent to research involvement, in this situation, personal or professional assent will be sought. The results from this study will be submitted for publication in peer-reviewed journals and disseminated at local and international conferences.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001806.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001806; html:https://europepmc.org/articles/PMC10582892; pdf:https://europepmc.org/articles/PMC10582892?pdf=render"
-  },
   {
     "id": "34847088",
     "doi": "https://doi.org/10.1097/ede.0000000000001429",
@@ -15758,6 +15741,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fphys.2021.730736/pdf; doi:https://doi.org/10.3389/fphys.2021.730736; html:https://europepmc.org/articles/PMC8521153; pdf:https://europepmc.org/articles/PMC8521153?pdf=render"
   },
+  {
+    "id": "37827807",
+    "doi": "https://doi.org/10.1136/bmjresp-2023-001806",
+    "title": "Observational cohort study protocol: neutrophil function and energetics in adults with pneumonia and sepsis - Pneumonia Metabolism in Ageing (PUMA).",
+    "authorString": "Grudzinska FS, Faniyi AA, Scott A, Sapey E, Thickett DR.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open respiratory research",
+    "pubYear": "2023",
+    "date": "2023-10-01",
+    "isOpenAccess": "Y",
+    "keywords": "Pneumonia; innate immunity; Bacterial Infection; respiratory infection; Neutrophil Biology",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>Community-acquired pneumonia has high mortality and is associated with significant healthcare costs. In older adults with community-acquired pneumonia neutrophil dysfunction has been identified and is associated with poor outcomes for patients. Immunometabolism is a rapidly developing field which links immune cell function to metabolism. This study aims to explore neutrophil metabolism in community-acquired pneumonia.<h4>Methods and analysis</h4>Pneumonia Metabolism in Ageing study is a prospective observational study recruiting older adults hospitalised with community-acquired pneumonia to examine neutrophil function and metabolic status. Controls will be older adults with no acute illness. The primary endpoint is neutrophil chemotaxis.<h4>Ethics and dissemination</h4>The study has ethical approval from the Research Ethics Committee Wales, reference 19/WA/0299. This study involves participants who may lack the capacity to consent to research involvement, in this situation, personal or professional assent will be sought. The results from this study will be submitted for publication in peer-reviewed journals and disseminated at local and international conferences.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001806.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001806; html:https://europepmc.org/articles/PMC10582892; pdf:https://europepmc.org/articles/PMC10582892?pdf=render"
+  },
   {
     "id": "37645022",
     "doi": "https://doi.org/10.1183/20734735.0058-2023",
@@ -15860,23 +15860,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ageing/article-pdf/49/6/1056/33993322/afaa158.pdf; doi:https://doi.org/10.1093/ageing/afaa158; html:https://europepmc.org/articles/PMC7583515; pdf:https://europepmc.org/articles/PMC7583515?pdf=render"
   },
-  {
-    "id": "34516619",
-    "doi": "https://doi.org/10.1093/ehjci/jeab178",
-    "title": "Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers.",
-    "authorString": "Taha K, Verstraelen TE, de Brouwer R, de Bruin-Bon RHACM, Cramer MJ, Te Rijdt WP, Bouma BJ, de Boer RA, Doevendans PA, Asselbergs FW, Wilde AAM, van den Berg MP, Teske AJ.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal. Cardiovascular Imaging",
-    "pubYear": "2022",
-    "date": "2022-10-01",
-    "isOpenAccess": "Y",
-    "keywords": "Risk stratification; ventricular arrhythmia; Phospholamban; Mechanical Dispersion; Deformation Imaging; Genetic Cardiomyopathy",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers.<h4>Methods and results</h4>We included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the '45/45' rule: (i) normal left ventricular (LV) function, defined as preserved LVEF \u226545% with normal LVMD \u226445 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF \u226545% with abnormal LVMD &gt;45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF &lt;45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8-6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92-100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15-27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57-162.84)].<h4>Conclusion</h4>LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The '45/45' rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab178/40357499/jeab178.pdf; doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render"
-  },
   {
     "id": "32763878",
     "doi": "https://doi.org/10.2196/18690",
@@ -15894,6 +15877,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.researchprotocols.org/2020/8/e18690/PDF; doi:https://doi.org/10.2196/18690; html:https://europepmc.org/articles/PMC7442945"
   },
+  {
+    "id": "34516619",
+    "doi": "https://doi.org/10.1093/ehjci/jeab178",
+    "title": "Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers.",
+    "authorString": "Taha K, Verstraelen TE, de Brouwer R, de Bruin-Bon RHACM, Cramer MJ, Te Rijdt WP, Bouma BJ, de Boer RA, Doevendans PA, Asselbergs FW, Wilde AAM, van den Berg MP, Teske AJ.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal. Cardiovascular Imaging",
+    "pubYear": "2022",
+    "date": "2022-10-01",
+    "isOpenAccess": "Y",
+    "keywords": "Risk stratification; ventricular arrhythmia; Phospholamban; Mechanical Dispersion; Deformation Imaging; Genetic Cardiomyopathy",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers.<h4>Methods and results</h4>We included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the '45/45' rule: (i) normal left ventricular (LV) function, defined as preserved LVEF \u226545% with normal LVMD \u226445 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF \u226545% with abnormal LVMD &gt;45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF &lt;45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8-6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92-100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15-27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57-162.84)].<h4>Conclusion</h4>LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The '45/45' rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab178/40357499/jeab178.pdf; doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render"
+  },
   {
     "id": "37751239",
     "doi": "https://doi.org/10.2196/49438",
@@ -16098,23 +16098,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jcmg.2022.06.017"
   },
-  {
-    "id": "36825398",
-    "doi": "https://doi.org/10.1097/mcp.0000000000000948",
-    "title": "Effectiveness and safety of coronavirus disease 2019 vaccines.",
-    "authorString": "Shi T, Robertson C, Sheikh A.",
-    "authorAffiliations": "",
-    "journalTitle": "Current opinion in pulmonary medicine",
-    "pubYear": "2023",
-    "date": "2023-02-24",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Purpose of review</h4>To review and summarise recent evidence on the effectiveness of coronavirus disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 hospitalisation and death in adults as well as in specific population groups, namely pregnant women, and children and adolescents. We also sought to summarise evidence on vaccine safety in relation to cardiovascular and neurological complications. In order to do so, we drew primarily on evidence from two our own data platforms and supplement these with insights from related large population-based studies and systematic reviews.<h4>Recent findings</h4>All studies showed high vaccine effectiveness against confirmed SARS-CoV-2 infection and in particular against COVID-19 hospitalisation and death. However, vaccine effectiveness against symptomatic COVID-19 infection waned over time. These studies also found that booster vaccines would be needed to maintain high vaccine effectiveness against severe COVID-19 outcomes. Rare cardiovascular and neurological complications have been reported in association with COVID-19 vaccines.<h4>Summary</h4>The findings from this paper support current recommendations that vaccination remains the safest way for adults, pregnant women, children and adolescents to be protected against COVID-19. There is a need to continue to monitor the effectiveness and safety of COVID-19 vaccines as these continue to be deployed in the evolving pandemic.",
-    "laySummary": "",
-    "urls": "html:https://journals.lww.com/co-pulmonarymedicine/Fulltext/9900/Effectiveness_and_safety_of_coronavirus_disease.53.aspx; doi:https://doi.org/10.1097/MCP.0000000000000948; html:https://europepmc.org/articles/PMC10090353; pdf:https://europepmc.org/articles/PMC10090353?pdf=render"
-  },
   {
     "id": "32896935",
     "doi": "https://doi.org/10.1002/cbm.2166",
@@ -16132,6 +16115,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cbm.2166; doi:https://doi.org/10.1002/cbm.2166"
   },
+  {
+    "id": "36825398",
+    "doi": "https://doi.org/10.1097/mcp.0000000000000948",
+    "title": "Effectiveness and safety of coronavirus disease 2019 vaccines.",
+    "authorString": "Shi T, Robertson C, Sheikh A.",
+    "authorAffiliations": "",
+    "journalTitle": "Current opinion in pulmonary medicine",
+    "pubYear": "2023",
+    "date": "2023-02-24",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Purpose of review</h4>To review and summarise recent evidence on the effectiveness of coronavirus disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 hospitalisation and death in adults as well as in specific population groups, namely pregnant women, and children and adolescents. We also sought to summarise evidence on vaccine safety in relation to cardiovascular and neurological complications. In order to do so, we drew primarily on evidence from two our own data platforms and supplement these with insights from related large population-based studies and systematic reviews.<h4>Recent findings</h4>All studies showed high vaccine effectiveness against confirmed SARS-CoV-2 infection and in particular against COVID-19 hospitalisation and death. However, vaccine effectiveness against symptomatic COVID-19 infection waned over time. These studies also found that booster vaccines would be needed to maintain high vaccine effectiveness against severe COVID-19 outcomes. Rare cardiovascular and neurological complications have been reported in association with COVID-19 vaccines.<h4>Summary</h4>The findings from this paper support current recommendations that vaccination remains the safest way for adults, pregnant women, children and adolescents to be protected against COVID-19. There is a need to continue to monitor the effectiveness and safety of COVID-19 vaccines as these continue to be deployed in the evolving pandemic.",
+    "laySummary": "",
+    "urls": "html:https://journals.lww.com/co-pulmonarymedicine/Fulltext/9900/Effectiveness_and_safety_of_coronavirus_disease.53.aspx; doi:https://doi.org/10.1097/MCP.0000000000000948; html:https://europepmc.org/articles/PMC10090353; pdf:https://europepmc.org/articles/PMC10090353?pdf=render"
+  },
   {
     "id": "31711534",
     "doi": "https://doi.org/10.1186/s13326-019-0216-2",
@@ -16217,23 +16217,6 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10110375/1/Syed%20and%20Gilbert%20%282020%29.%20Are%20children%20who%20are%20home%20from%20school%20at%20an%20increased%20risk%20of%20child%20maltreatment.pdf; doi:https://doi.org/10.1093/pubmed/fdaa115"
   },
-  {
-    "id": "36942567",
-    "doi": "https://doi.org/10.1161/circep.122.011585",
-    "title": "Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.",
-    "authorString": "Dickow J, Kany S, Roth Cardoso V, Ellinor PT, Gkoutos GV, Van Houten HK, Kirchhof P, Metzner A, Noseworthy PA, Yao X, Rillig A.",
-    "authorAffiliations": "",
-    "journalTitle": "Circulation. Arrhythmia and electrophysiology",
-    "pubYear": "2023",
-    "date": "2023-03-21",
-    "isOpenAccess": "N",
-    "keywords": "Atrial fibrillation; Stroke; Catheter ablation; Heart Failure; Comorbidity",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden.<h4>Methods</h4>We identified 109\u2009739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11\u2009625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score \u22654); (2) ERC and lower comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 2-3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 0-1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC.<h4>Results</h4>In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72-0.95]; <i>P</i>=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; <i>P</i>=0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54-1.57]; <i>P</i>=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; <i>P</i>=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- <i>P</i>=0.027) but not in OptumLabs (interaction-<i>P</i>=0.720). ERC was not associated with an increased risk for the primary safety outcome.<h4>Conclusions</h4>ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score \u22654).",
-    "laySummary": "",
-    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.122.011585; doi:https://doi.org/10.1161/CIRCEP.122.011585"
-  },
   {
     "id": "31329239",
     "doi": "https://doi.org/10.1093/jamia/ocz105",
@@ -16251,6 +16234,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1093/jamia/ocz105; doi:https://doi.org/10.1093/jamia/ocz105; html:https://europepmc.org/articles/PMC6857510; pdf:https://europepmc.org/articles/PMC6857510?pdf=render"
   },
+  {
+    "id": "36942567",
+    "doi": "https://doi.org/10.1161/circep.122.011585",
+    "title": "Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.",
+    "authorString": "Dickow J, Kany S, Roth Cardoso V, Ellinor PT, Gkoutos GV, Van Houten HK, Kirchhof P, Metzner A, Noseworthy PA, Yao X, Rillig A.",
+    "authorAffiliations": "",
+    "journalTitle": "Circulation. Arrhythmia and electrophysiology",
+    "pubYear": "2023",
+    "date": "2023-03-21",
+    "isOpenAccess": "N",
+    "keywords": "Atrial fibrillation; Stroke; Catheter ablation; Heart Failure; Comorbidity",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden.<h4>Methods</h4>We identified 109\u2009739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11\u2009625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score \u22654); (2) ERC and lower comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 2-3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 0-1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC.<h4>Results</h4>In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72-0.95]; <i>P</i>=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; <i>P</i>=0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54-1.57]; <i>P</i>=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; <i>P</i>=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- <i>P</i>=0.027) but not in OptumLabs (interaction-<i>P</i>=0.720). ERC was not associated with an increased risk for the primary safety outcome.<h4>Conclusions</h4>ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score \u22654).",
+    "laySummary": "",
+    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.122.011585; doi:https://doi.org/10.1161/CIRCEP.122.011585"
+  },
   {
     "id": "34939031",
     "doi": "https://doi.org/10.1093/braincomms/fcab241",
@@ -16472,23 +16472,6 @@
     "laySummary": "",
     "urls": "pdf:https://bjgp.org/content/bjgp/early/2022/04/19/BJGP.2021.0689.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?pdf=render"
   },
-  {
-    "id": "34631820",
-    "doi": "https://doi.org/10.3389/fcvm.2021.716577",
-    "title": "New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.",
-    "authorString": "Rauseo E, Izquierdo Morcillo C, Raisi-Estabragh Z, Gkontra P, Aung N, Lekadir K, Petersen SE.",
-    "authorAffiliations": "",
-    "journalTitle": "Frontiers in cardiovascular medicine",
-    "pubYear": "2021",
-    "date": "2021-09-23",
-    "isOpenAccess": "Y",
-    "keywords": "Myocardial infarction; Stroke; Cerebrovascular disease; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Radiomics; Brain-heart Axis",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<b>Background:</b> Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions. <b>Objective:</b> To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. <b>Methods:</b> We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (<i>n</i> = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired <i>t</i>-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. <b>Results:</b> In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found. <b>Conclusions:</b> This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.",
-    "laySummary": "",
-    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.716577/pdf; doi:https://doi.org/10.3389/fcvm.2021.716577; html:https://europepmc.org/articles/PMC8494975; pdf:https://europepmc.org/articles/PMC8494975?pdf=render"
-  },
   {
     "id": "33820530",
     "doi": "https://doi.org/10.1186/s12916-021-01940-7",
@@ -16506,6 +16489,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-01940-7; doi:https://doi.org/10.1186/s12916-021-01940-7; html:https://europepmc.org/articles/PMC8022365; pdf:https://europepmc.org/articles/PMC8022365?pdf=render"
   },
+  {
+    "id": "34631820",
+    "doi": "https://doi.org/10.3389/fcvm.2021.716577",
+    "title": "New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.",
+    "authorString": "Rauseo E, Izquierdo Morcillo C, Raisi-Estabragh Z, Gkontra P, Aung N, Lekadir K, Petersen SE.",
+    "authorAffiliations": "",
+    "journalTitle": "Frontiers in cardiovascular medicine",
+    "pubYear": "2021",
+    "date": "2021-09-23",
+    "isOpenAccess": "Y",
+    "keywords": "Myocardial infarction; Stroke; Cerebrovascular disease; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Radiomics; Brain-heart Axis",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<b>Background:</b> Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions. <b>Objective:</b> To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. <b>Methods:</b> We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (<i>n</i> = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired <i>t</i>-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. <b>Results:</b> In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found. <b>Conclusions:</b> This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.",
+    "laySummary": "",
+    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.716577/pdf; doi:https://doi.org/10.3389/fcvm.2021.716577; html:https://europepmc.org/articles/PMC8494975; pdf:https://europepmc.org/articles/PMC8494975?pdf=render"
+  },
   {
     "id": "35188950",
     "doi": "https://doi.org/10.1001/jamaneurol.2021.5420",
@@ -16625,6 +16625,23 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127079; doi:https://doi.org/10.1038/s41591-021-01266-0; html:https://europepmc.org/articles/PMC8127079; pdf:https://europepmc.org/articles/PMC8127079?pdf=render; doi:https://doi.org/10.1038/s41591-021-01266-0"
   },
+  {
+    "id": "34270458",
+    "doi": "https://doi.org/10.4269/ajtmh.21-0482",
+    "title": "The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.",
+    "authorString": "Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",
+    "authorAffiliations": "",
+    "journalTitle": "The American journal of tropical medicine and hygiene",
+    "pubYear": "2021",
+    "date": "2021-07-16",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",
+    "laySummary": "",
+    "urls": "pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render"
+  },
   {
     "id": "37658971",
     "doi": "https://doi.org/10.1007/s11897-023-00626-w",
@@ -16659,23 +16676,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1038/s41591-023-02608-w"
   },
-  {
-    "id": "34270458",
-    "doi": "https://doi.org/10.4269/ajtmh.21-0482",
-    "title": "The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.",
-    "authorString": "Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",
-    "authorAffiliations": "",
-    "journalTitle": "The American journal of tropical medicine and hygiene",
-    "pubYear": "2021",
-    "date": "2021-07-16",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",
-    "laySummary": "",
-    "urls": "pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render"
-  },
   {
     "id": "37679551",
     "doi": "https://doi.org/10.1038/s41590-023-01635-6",
@@ -17033,23 +17033,6 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12471-022-01677-9.pdf; doi:https://doi.org/10.1007/s12471-022-01677-9; html:https://europepmc.org/articles/PMC8906525; pdf:https://europepmc.org/articles/PMC8906525?pdf=render"
   },
-  {
-    "id": "37798805",
-    "doi": "https://doi.org/10.1186/s13063-023-07576-7",
-    "title": "Medicines and Healthcare products Regulatory Agency's \"Consultation on proposals for legislative changes for clinical trials\": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.",
-    "authorString": "Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",
-    "authorAffiliations": "",
-    "journalTitle": "Trials",
-    "pubYear": "2023",
-    "date": "2023-10-05",
-    "isOpenAccess": "Y",
-    "keywords": "Legislation; data sharing; Consultation",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals \"to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines\". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",
-    "laySummary": "",
-    "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render"
-  },
   {
     "id": "35616501",
     "doi": "https://doi.org/10.1177/14791641221088824",
@@ -17067,6 +17050,23 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152198; doi:https://doi.org/10.1177/14791641221088824; html:https://europepmc.org/articles/PMC9152198; pdf:https://europepmc.org/articles/PMC9152198?pdf=render"
   },
+  {
+    "id": "37798805",
+    "doi": "https://doi.org/10.1186/s13063-023-07576-7",
+    "title": "Medicines and Healthcare products Regulatory Agency's \"Consultation on proposals for legislative changes for clinical trials\": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.",
+    "authorString": "Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",
+    "authorAffiliations": "",
+    "journalTitle": "Trials",
+    "pubYear": "2023",
+    "date": "2023-10-05",
+    "isOpenAccess": "Y",
+    "keywords": "Legislation; data sharing; Consultation",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals \"to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines\". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",
+    "laySummary": "",
+    "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render"
+  },
   {
     "id": "33328049",
     "doi": "https://doi.org/10.1016/s2589-7500(20)30219-3",
@@ -17203,23 +17203,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.ijmedinf.2020.104237"
   },
-  {
-    "id": "37230417",
-    "doi": "https://doi.org/10.1016/j.jtha.2023.05.012",
-    "title": "C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study.",
-    "authorString": "Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of thrombosis and haemostasis : JTH",
-    "pubYear": "2023",
-    "date": "2023-05-23",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jtha.2023.05.012"
-  },
   {
     "id": "31442537",
     "doi": "https://doi.org/10.1016/j.jaad.2019.08.039",
@@ -17254,6 +17237,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.science.org/history/7d0b03b2-b465-410e-a40d-7300157d8b54/science.abl9551.v1.pdf; doi:https://doi.org/10.1126/science.abl9551"
   },
+  {
+    "id": "37230417",
+    "doi": "https://doi.org/10.1016/j.jtha.2023.05.012",
+    "title": "C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study.",
+    "authorString": "Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of thrombosis and haemostasis : JTH",
+    "pubYear": "2023",
+    "date": "2023-05-23",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jtha.2023.05.012"
+  },
   {
     "id": "33990383",
     "doi": "https://doi.org/10.1136/gutjnl-2020-323546",
@@ -17322,23 +17322,6 @@
     "laySummary": "",
     "urls": "pdf:https://gh.bmj.com/content/bmjgh/7/3/e008099.full.pdf; doi:https://doi.org/10.1136/bmjgh-2021-008099; html:https://europepmc.org/articles/PMC8905410; pdf:https://europepmc.org/articles/PMC8905410?pdf=render"
   },
-  {
-    "id": "34873584",
-    "doi": "https://doi.org/10.1016/j.eclinm.2021.101212",
-    "title": "Disentangling post-vaccination symptoms from early COVID-19.",
-    "authorString": "Canas LS, \u00d6sterdahl MF, Deng J, Hu C, Selvachandran S, Polidori L, May A, Molteni E, Murray B, Chen L, Kerfoot E, Klaser K, Antonelli M, Hammers A, Spector T, Ourselin S, Steves C, Sudre CH, Modat M, Duncan EL.",
-    "authorAffiliations": "",
-    "journalTitle": "EClinicalMedicine",
-    "pubYear": "2021",
-    "date": "2021-12-01",
-    "isOpenAccess": "Y",
-    "keywords": "Vaccination; Side-effects; Early Detection; Mobile Technology; Self-reported Symptoms; Roc, Receiver Operating Curve; Severe Acute Respiratory Syndrome\u2010Related Coronavirus 2 (Sars-Cov-2); Bmem, Bayesian Mixed-effect Model; Css, Covid Symptoms Study; Di, Data Invalid; Kcl, King's College London; Lfat, Lateral Flow Antigen Test; Nhs Uk, National Health Service Of The United Kingdom; O-az, Oxford-astrazeneca Adenovirus-vectored Vaccine; Pb, Pfizer-bointech Mrna Vaccine; Sars-cov-2, Severe Acute Respiratory Syndrome-related Coronavirus-2; Uk, United Kingdom Of Great Britain And Nothern Ireland; Auc, Area Under The Curve; Bmi, Body Mass Index; Ci, Confidence Interval; Lr, Logistic Regression; Iqr, Inter Quartile Range; Rf, Random Forest; Covid-19, Coronavirus Disease 2019; Covid-19 Detection; Rtpcr, Reverse Transcription Polymerase Chain Reaction",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app.<h4>Methods</h4>We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects <i>per se</i> from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering UK testing criteria.<h4>Findings</h4>Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue).<h4>Interpretation</h4>Post-vaccination symptoms <i>per se</i> cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread.<h4>Funding</h4>UK Government Department of Health and Social Care,\u00a0Wellcome\u00a0Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Chronic Disease Research Foundation, Zoe\u00a0Limited.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.eclinm.2021.101212; doi:https://doi.org/10.1016/j.eclinm.2021.101212; html:https://europepmc.org/articles/PMC8635464; pdf:https://europepmc.org/articles/PMC8635464?pdf=render"
-  },
   {
     "id": "32065794",
     "doi": "https://doi.org/10.3233/jad-191163",
@@ -17356,6 +17339,23 @@
     "laySummary": "",
     "urls": "pdf:https://content.iospress.com:443/download/journal-of-alzheimers-disease/jad191163?id=journal-of-alzheimers-disease%2Fjad191163; doi:https://doi.org/10.3233/JAD-191163; html:https://europepmc.org/articles/PMC7175937; pdf:https://europepmc.org/articles/PMC7175937?pdf=render"
   },
+  {
+    "id": "34873584",
+    "doi": "https://doi.org/10.1016/j.eclinm.2021.101212",
+    "title": "Disentangling post-vaccination symptoms from early COVID-19.",
+    "authorString": "Canas LS, \u00d6sterdahl MF, Deng J, Hu C, Selvachandran S, Polidori L, May A, Molteni E, Murray B, Chen L, Kerfoot E, Klaser K, Antonelli M, Hammers A, Spector T, Ourselin S, Steves C, Sudre CH, Modat M, Duncan EL.",
+    "authorAffiliations": "",
+    "journalTitle": "EClinicalMedicine",
+    "pubYear": "2021",
+    "date": "2021-12-01",
+    "isOpenAccess": "Y",
+    "keywords": "Vaccination; Side-effects; Early Detection; Mobile Technology; Self-reported Symptoms; Roc, Receiver Operating Curve; Severe Acute Respiratory Syndrome\u2010Related Coronavirus 2 (Sars-Cov-2); Bmem, Bayesian Mixed-effect Model; Css, Covid Symptoms Study; Di, Data Invalid; Kcl, King's College London; Lfat, Lateral Flow Antigen Test; Nhs Uk, National Health Service Of The United Kingdom; O-az, Oxford-astrazeneca Adenovirus-vectored Vaccine; Pb, Pfizer-bointech Mrna Vaccine; Sars-cov-2, Severe Acute Respiratory Syndrome-related Coronavirus-2; Uk, United Kingdom Of Great Britain And Nothern Ireland; Auc, Area Under The Curve; Bmi, Body Mass Index; Ci, Confidence Interval; Lr, Logistic Regression; Iqr, Inter Quartile Range; Rf, Random Forest; Covid-19, Coronavirus Disease 2019; Covid-19 Detection; Rtpcr, Reverse Transcription Polymerase Chain Reaction",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app.<h4>Methods</h4>We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects <i>per se</i> from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering UK testing criteria.<h4>Findings</h4>Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue).<h4>Interpretation</h4>Post-vaccination symptoms <i>per se</i> cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread.<h4>Funding</h4>UK Government Department of Health and Social Care,\u00a0Wellcome\u00a0Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Chronic Disease Research Foundation, Zoe\u00a0Limited.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.eclinm.2021.101212; doi:https://doi.org/10.1016/j.eclinm.2021.101212; html:https://europepmc.org/articles/PMC8635464; pdf:https://europepmc.org/articles/PMC8635464?pdf=render"
+  },
   {
     "id": "34230034",
     "doi": "https://doi.org/10.1136/bmjresp-2021-000967",
@@ -17475,23 +17475,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render"
   },
-  {
-    "id": "37133927",
-    "doi": "https://doi.org/10.2196/45534",
-    "title": "Understanding Views Around the Creation of a Consented, Donated Databank of Clinical Free Text to Develop and Train Natural Language Processing Models for Research: Focus Group Interviews With Stakeholders.",
-    "authorString": "Fitzpatrick NK, Dobson R, Roberts A, Jones K, Shah AD, Nenadic G, Ford E.",
-    "authorAffiliations": "",
-    "journalTitle": "JMIR medical informatics",
-    "pubYear": "2023",
-    "date": "2023-05-03",
-    "isOpenAccess": "Y",
-    "keywords": "Consent; Governance; Electronic Health Records; Natural Language Processing; Free Text; Databank; Public Involvement; Unstructured Text",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Information stored within electronic health records is often recorded as unstructured text. Special computerized natural language processing (NLP) tools are needed to process this text; however, complex governance arrangements make such data in the National Health Service hard to access, and therefore, it is difficult to use for research in improving NLP methods. The creation of a donated databank of clinical free text could provide an important opportunity for researchers to develop NLP methods and tools and may circumvent delays in accessing the data needed to train the models. However, to date, there has been little or no engagement with stakeholders on the acceptability and design considerations of establishing a free-text databank for this purpose.<h4>Objective</h4>This study aimed to ascertain stakeholder views around the creation of a consented, donated databank of clinical free text to help create, train, and evaluate NLP for clinical research and to inform the potential next steps for adopting a partner-led approach to establish a national, funded databank of free text for use by the research community.<h4>Methods</h4>Web-based in-depth focus group interviews were conducted with 4 stakeholder groups (patients and members of the public, clinicians, information governance leads and research ethics members, and NLP researchers).<h4>Results</h4>All stakeholder groups were strongly in favor of the databank and saw great value in creating an environment where NLP tools can be tested and trained to improve their accuracy. Participants highlighted a range of complex issues for consideration as the databank is developed, including communicating the intended purpose, the approach to access and safeguarding the data, who should have access, and how to fund the databank. Participants recommended that a small-scale, gradual approach be adopted to start to gather donations and encouraged further engagement with stakeholders to develop a road map and set of standards for the databank.<h4>Conclusions</h4>These findings provide a clear mandate to begin developing the databank and a framework for stakeholder expectations, which we would aim to meet with the databank delivery.",
-    "laySummary": "",
-    "urls": "pdf:https://medinform.jmir.org/2023/1/e45534/PDF; doi:https://doi.org/10.2196/45534; html:https://europepmc.org/articles/PMC10193205"
-  },
   {
     "id": "35487738",
     "doi": "https://doi.org/10.1136/bmjopen-2021-057017",
@@ -17509,6 +17492,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057017.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057017; html:https://europepmc.org/articles/PMC9058768; pdf:https://europepmc.org/articles/PMC9058768?pdf=render"
   },
+  {
+    "id": "37133927",
+    "doi": "https://doi.org/10.2196/45534",
+    "title": "Understanding Views Around the Creation of a Consented, Donated Databank of Clinical Free Text to Develop and Train Natural Language Processing Models for Research: Focus Group Interviews With Stakeholders.",
+    "authorString": "Fitzpatrick NK, Dobson R, Roberts A, Jones K, Shah AD, Nenadic G, Ford E.",
+    "authorAffiliations": "",
+    "journalTitle": "JMIR medical informatics",
+    "pubYear": "2023",
+    "date": "2023-05-03",
+    "isOpenAccess": "Y",
+    "keywords": "Consent; Governance; Electronic Health Records; Natural Language Processing; Free Text; Databank; Public Involvement; Unstructured Text",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Information stored within electronic health records is often recorded as unstructured text. Special computerized natural language processing (NLP) tools are needed to process this text; however, complex governance arrangements make such data in the National Health Service hard to access, and therefore, it is difficult to use for research in improving NLP methods. The creation of a donated databank of clinical free text could provide an important opportunity for researchers to develop NLP methods and tools and may circumvent delays in accessing the data needed to train the models. However, to date, there has been little or no engagement with stakeholders on the acceptability and design considerations of establishing a free-text databank for this purpose.<h4>Objective</h4>This study aimed to ascertain stakeholder views around the creation of a consented, donated databank of clinical free text to help create, train, and evaluate NLP for clinical research and to inform the potential next steps for adopting a partner-led approach to establish a national, funded databank of free text for use by the research community.<h4>Methods</h4>Web-based in-depth focus group interviews were conducted with 4 stakeholder groups (patients and members of the public, clinicians, information governance leads and research ethics members, and NLP researchers).<h4>Results</h4>All stakeholder groups were strongly in favor of the databank and saw great value in creating an environment where NLP tools can be tested and trained to improve their accuracy. Participants highlighted a range of complex issues for consideration as the databank is developed, including communicating the intended purpose, the approach to access and safeguarding the data, who should have access, and how to fund the databank. Participants recommended that a small-scale, gradual approach be adopted to start to gather donations and encouraged further engagement with stakeholders to develop a road map and set of standards for the databank.<h4>Conclusions</h4>These findings provide a clear mandate to begin developing the databank and a framework for stakeholder expectations, which we would aim to meet with the databank delivery.",
+    "laySummary": "",
+    "urls": "pdf:https://medinform.jmir.org/2023/1/e45534/PDF; doi:https://doi.org/10.2196/45534; html:https://europepmc.org/articles/PMC10193205"
+  },
   {
     "id": "37712381",
     "doi": "https://doi.org/10.7189/jogh.13.04101",
@@ -17526,23 +17526,6 @@
     "laySummary": "",
     "urls": "pdf:https://jogh.org/wp-content/uploads/2023/09/jogh-13-04101.pdf; doi:https://doi.org/10.7189/jogh.13.04101; html:https://europepmc.org/articles/PMC10502767; pdf:https://europepmc.org/articles/PMC10502767?pdf=render"
   },
-  {
-    "id": "37706486",
-    "doi": "https://doi.org/10.1080/09638288.2023.2254235",
-    "title": "Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.",
-    "authorString": "Giummarra MJ, Reeder S, Williams S, Devlin A, Knol R, Ponsford J, Arnold CA, Konstantatos A, Gabbe BJ, Clarke H, Katz J, Mitchell F, Robinson E, Zatzick D.",
-    "authorAffiliations": "",
-    "journalTitle": "Disability and rehabilitation",
-    "pubYear": "2023",
-    "date": "2023-09-14",
-    "isOpenAccess": "N",
-    "keywords": "Trauma; Injury; Recovery; Pain; Hospitalization; Ptsd; Brief Intervention",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Purpose</h4>To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury.<h4>Materials and methods</h4>Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (<i>n</i>\u2009=\u200915) or intervention (<i>n</i>\u2009=\u200917) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability.<h4>Results</h4>Intervention participants received a median of 7\u2009h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months.<h4>Conclusions</h4>Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.",
-    "laySummary": "",
-    "urls": "pdf:https://www.tandfonline.com/doi/pdf/10.1080/09638288.2023.2254235?needAccess=true; doi:https://doi.org/10.1080/09638288.2023.2254235"
-  },
   {
     "id": "34639581",
     "doi": "https://doi.org/10.3390/ijerph181910265",
@@ -17560,6 +17543,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/1660-4601/18/19/10265/pdf?version=1633013750; doi:https://doi.org/10.3390/ijerph181910265; html:https://europepmc.org/articles/PMC8507693; pdf:https://europepmc.org/articles/PMC8507693?pdf=render"
   },
+  {
+    "id": "37706486",
+    "doi": "https://doi.org/10.1080/09638288.2023.2254235",
+    "title": "Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.",
+    "authorString": "Giummarra MJ, Reeder S, Williams S, Devlin A, Knol R, Ponsford J, Arnold CA, Konstantatos A, Gabbe BJ, Clarke H, Katz J, Mitchell F, Robinson E, Zatzick D.",
+    "authorAffiliations": "",
+    "journalTitle": "Disability and rehabilitation",
+    "pubYear": "2023",
+    "date": "2023-09-14",
+    "isOpenAccess": "N",
+    "keywords": "Trauma; Injury; Recovery; Pain; Hospitalization; Ptsd; Brief Intervention",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Purpose</h4>To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury.<h4>Materials and methods</h4>Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (<i>n</i>\u2009=\u200915) or intervention (<i>n</i>\u2009=\u200917) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability.<h4>Results</h4>Intervention participants received a median of 7\u2009h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months.<h4>Conclusions</h4>Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.",
+    "laySummary": "",
+    "urls": "pdf:https://www.tandfonline.com/doi/pdf/10.1080/09638288.2023.2254235?needAccess=true; doi:https://doi.org/10.1080/09638288.2023.2254235"
+  },
   {
     "id": "33653753",
     "doi": "https://doi.org/10.1136/bmjopen-2020-043290",
@@ -17594,23 +17594,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jcmg.2022.06.011; doi:https://doi.org/10.1016/j.jcmg.2022.06.011; html:https://europepmc.org/articles/PMC10102720; pdf:https://europepmc.org/articles/PMC10102720?pdf=render"
   },
-  {
-    "id": "36545688",
-    "doi": "https://doi.org/10.1192/bjb.2022.83",
-    "title": "EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.",
-    "authorString": "Hemmings A, Sharpe H, Allen K, Bartel H, Campbell IC, Desrivi\u00e8res S, Dobson RJB, Folarin AA, French T, Kelly J, Micali N, Raman S, Treasure J, Abbas R, Heslop B, Street T, Schmidt U.",
-    "authorAffiliations": "",
-    "journalTitle": "BJPsych bulletin",
-    "pubYear": "2022",
-    "date": "2022-12-22",
-    "isOpenAccess": "N",
-    "keywords": "Eating Disorders; Risk And Resilience; Prevention And Early Intervention; Youth Engagement; Interdisciplinary Working",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.",
-    "laySummary": "",
-    "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/C1E5FCC67F1D627908A5495EED02577B/S2056469422000833a.pdf/div-class-title-edify-eating-disorders-delineating-illness-and-recovery-trajectories-to-inform-personalised-prevention-and-early-intervention-in-young-people-project-outline-div.pdf; doi:https://doi.org/10.1192/bjb.2022.83"
-  },
   {
     "id": "34781301",
     "doi": "https://doi.org/10.1159/000520674",
@@ -17628,6 +17611,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.karger.com/Article/Pdf/520674; doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674"
   },
+  {
+    "id": "36545688",
+    "doi": "https://doi.org/10.1192/bjb.2022.83",
+    "title": "EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.",
+    "authorString": "Hemmings A, Sharpe H, Allen K, Bartel H, Campbell IC, Desrivi\u00e8res S, Dobson RJB, Folarin AA, French T, Kelly J, Micali N, Raman S, Treasure J, Abbas R, Heslop B, Street T, Schmidt U.",
+    "authorAffiliations": "",
+    "journalTitle": "BJPsych bulletin",
+    "pubYear": "2022",
+    "date": "2022-12-22",
+    "isOpenAccess": "N",
+    "keywords": "Eating Disorders; Risk And Resilience; Prevention And Early Intervention; Youth Engagement; Interdisciplinary Working",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.",
+    "laySummary": "",
+    "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/C1E5FCC67F1D627908A5495EED02577B/S2056469422000833a.pdf/div-class-title-edify-eating-disorders-delineating-illness-and-recovery-trajectories-to-inform-personalised-prevention-and-early-intervention-in-young-people-project-outline-div.pdf; doi:https://doi.org/10.1192/bjb.2022.83"
+  },
   {
     "id": "36137640",
     "doi": "https://doi.org/10.1136/bmjopen-2022-064586",
@@ -17679,23 +17679,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1111/bjd.18889; doi:https://doi.org/10.1111/bjd.18889; html:https://europepmc.org/articles/PMC7587014; pdf:https://europepmc.org/articles/PMC7587014?pdf=render"
   },
-  {
-    "id": "37284234",
-    "doi": "https://doi.org/10.1140/epjds/s13688-023-00391-9",
-    "title": "The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.",
-    "authorString": "Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",
-    "authorAffiliations": "",
-    "journalTitle": "EPJ data science",
-    "pubYear": "2023",
-    "date": "2023-06-05",
-    "isOpenAccess": "Y",
-    "keywords": "Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming \"digital residents.\" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render"
-  },
   {
     "id": "35403174",
     "doi": "https://doi.org/10.14218/jctp.2022.00003",
@@ -17713,6 +17696,23 @@
     "laySummary": "",
     "urls": "pdf:https://publinestorage.blob.core.windows.net/journals/JCTP.2022.2(1).23.00003.pdf; doi:https://doi.org/10.14218/jctp.2022.00003; html:https://europepmc.org/articles/PMC8994161; pdf:https://europepmc.org/articles/PMC8994161?pdf=render"
   },
+  {
+    "id": "37284234",
+    "doi": "https://doi.org/10.1140/epjds/s13688-023-00391-9",
+    "title": "The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.",
+    "authorString": "Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",
+    "authorAffiliations": "",
+    "journalTitle": "EPJ data science",
+    "pubYear": "2023",
+    "date": "2023-06-05",
+    "isOpenAccess": "Y",
+    "keywords": "Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming \"digital residents.\" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.<h4>Supplementary information</h4>The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render"
+  },
   {
     "id": "33168126",
     "doi": "https://doi.org/10.1192/bjo.2020.42",
@@ -17730,23 +17730,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00360A347FCC91E2E9D0B39FBDCE887/S2056472420000423a.pdf/div-class-title-impact-of-schizophrenia-genetic-liability-on-the-association-between-schizophrenia-and-physical-illness-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjo.2020.42; html:https://europepmc.org/articles/PMC7745237; pdf:https://europepmc.org/articles/PMC7745237?pdf=render"
   },
-  {
-    "id": "33475522",
-    "doi": "https://doi.org/10.2196/18229",
-    "title": "Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: Protocol for a Systematic Review.",
-    "authorString": "Fundikira LS, Chillo P, van Laake LW, Mutagaywa RK, Schmidt AF, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",
-    "authorAffiliations": "",
-    "journalTitle": "JMIR research protocols",
-    "pubYear": "2021",
-    "date": "2021-01-21",
-    "isOpenAccess": "Y",
-    "keywords": "Dilated cardiomyopathy; Sub-Saharan Africa; Cardiomyopathy; Cardiovascular risk factors; Heart Failure",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Cardiomyopathies, defined as diseases involving mainly the heart muscles, are linked to an estimated 5.9 of 100,000 deaths globally. In sub-Saharan Africa, cardiomyopathies constitute 21.4% of heart failure cases, with dilated cardiomyopathy (DCM) being the most common form. The etiology of DCM is heterogeneous and is broadly categorized as genetic or nongenetic, as well as a mixed disease in which genetics interact with intrinsic and environmental factors. Factors such as age, gender, family history, and ethnicity are nonmodifiable, whereas modifiable risk factors include poor nutrition, physical inactivity, and excessive alcohol consumption, among others. However, the relative contribution of the different risk factors to the etiology of DCM is not known in sub-Saharan Africa, and the prevalence of DCM among heart failure patients has not been systematically studied in the region.<h4>Objective</h4>The aim of this review is to synthesize available literature from sub-Saharan Africa on the prevalence of DCM among patients with heart failure, as well as the literature on factors associated with DCM. This paper outlines the protocol that will be followed to conduct the systematic review.<h4>Methods</h4>A limited search of the PubMed database will be performed to identify relevant keywords contained in the title, abstract, and subject descriptors using initial search terms \"heart failure,\" \"cardiomyopathy,\" and \"sub-Saharan Africa.\" These search terms and their synonyms will then be used in an extensive search in PubMed, and will address the first research question on prevalence. To address the second research question on risk factors, the terms \"heart failure,\" \"cardiomyopathy,\" and \"cardiovascular risk factors\" in \"Sub-Saharan Africa\" will be used, listing them one by one. Articles published from 2000 and in the English language will be included. Indexed articles in PubMed and Embase will be included, as well as the first 300 articles retrieved from a Google Scholar search. Collected data will be organized in Endnote and then uploaded to the Rayyan web app for systematic reviews. Two reviewers will independently select articles against the inclusion criteria. Discrepancies in reviewer selections will be resolved by an arbitrator. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for reporting systematic reviews will be applied. A map of sub-Saharan Africa with colors to show disease prevalence in each country will be included. For quantitative data, where possible, odds ratios (for categorical outcome data) or standardized mean differences (for continuous data) and their 95% CIs will be calculated.<h4>Results</h4>The primary outcomes will be the prevalence of DCM among patients with heart failure and cardiovascular risk factors associated with DCM in sub-Saharan Africa. The literature search will begin on January 1, 2021, and data analysis is expected to be completed by April 30, 2021.<h4>Conclusions</h4>This review will provide information on the current status of the prevalence and associated factors of DCM, and possibly identify gaps, including paucity of data or conflicting results that need to be addressed to improve our understanding of DCM in sub-Saharan Africa.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/18229.",
-    "laySummary": "",
-    "urls": "pdf:https://jmir.org/api/download?alt_name=resprot_v10i1e18229_app1.pdf&filename=7e28e6f3581cda60eb7faa74a1bb7968.pdf; doi:https://doi.org/10.2196/18229; html:https://europepmc.org/articles/PMC7862000"
-  },
   {
     "id": "30659777",
     "doi": "https://doi.org/10.1111/ijpo.12505",
@@ -17764,6 +17747,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ijpo.12505; doi:https://doi.org/10.1111/ijpo.12505; html:https://europepmc.org/articles/PMC6563186; pdf:https://europepmc.org/articles/PMC6563186?pdf=render"
   },
+  {
+    "id": "33475522",
+    "doi": "https://doi.org/10.2196/18229",
+    "title": "Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: Protocol for a Systematic Review.",
+    "authorString": "Fundikira LS, Chillo P, van Laake LW, Mutagaywa RK, Schmidt AF, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",
+    "authorAffiliations": "",
+    "journalTitle": "JMIR research protocols",
+    "pubYear": "2021",
+    "date": "2021-01-21",
+    "isOpenAccess": "Y",
+    "keywords": "Dilated cardiomyopathy; Sub-Saharan Africa; Cardiomyopathy; Cardiovascular risk factors; Heart Failure",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Cardiomyopathies, defined as diseases involving mainly the heart muscles, are linked to an estimated 5.9 of 100,000 deaths globally. In sub-Saharan Africa, cardiomyopathies constitute 21.4% of heart failure cases, with dilated cardiomyopathy (DCM) being the most common form. The etiology of DCM is heterogeneous and is broadly categorized as genetic or nongenetic, as well as a mixed disease in which genetics interact with intrinsic and environmental factors. Factors such as age, gender, family history, and ethnicity are nonmodifiable, whereas modifiable risk factors include poor nutrition, physical inactivity, and excessive alcohol consumption, among others. However, the relative contribution of the different risk factors to the etiology of DCM is not known in sub-Saharan Africa, and the prevalence of DCM among heart failure patients has not been systematically studied in the region.<h4>Objective</h4>The aim of this review is to synthesize available literature from sub-Saharan Africa on the prevalence of DCM among patients with heart failure, as well as the literature on factors associated with DCM. This paper outlines the protocol that will be followed to conduct the systematic review.<h4>Methods</h4>A limited search of the PubMed database will be performed to identify relevant keywords contained in the title, abstract, and subject descriptors using initial search terms \"heart failure,\" \"cardiomyopathy,\" and \"sub-Saharan Africa.\" These search terms and their synonyms will then be used in an extensive search in PubMed, and will address the first research question on prevalence. To address the second research question on risk factors, the terms \"heart failure,\" \"cardiomyopathy,\" and \"cardiovascular risk factors\" in \"Sub-Saharan Africa\" will be used, listing them one by one. Articles published from 2000 and in the English language will be included. Indexed articles in PubMed and Embase will be included, as well as the first 300 articles retrieved from a Google Scholar search. Collected data will be organized in Endnote and then uploaded to the Rayyan web app for systematic reviews. Two reviewers will independently select articles against the inclusion criteria. Discrepancies in reviewer selections will be resolved by an arbitrator. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for reporting systematic reviews will be applied. A map of sub-Saharan Africa with colors to show disease prevalence in each country will be included. For quantitative data, where possible, odds ratios (for categorical outcome data) or standardized mean differences (for continuous data) and their 95% CIs will be calculated.<h4>Results</h4>The primary outcomes will be the prevalence of DCM among patients with heart failure and cardiovascular risk factors associated with DCM in sub-Saharan Africa. The literature search will begin on January 1, 2021, and data analysis is expected to be completed by April 30, 2021.<h4>Conclusions</h4>This review will provide information on the current status of the prevalence and associated factors of DCM, and possibly identify gaps, including paucity of data or conflicting results that need to be addressed to improve our understanding of DCM in sub-Saharan Africa.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/18229.",
+    "laySummary": "",
+    "urls": "pdf:https://jmir.org/api/download?alt_name=resprot_v10i1e18229_app1.pdf&filename=7e28e6f3581cda60eb7faa74a1bb7968.pdf; doi:https://doi.org/10.2196/18229; html:https://europepmc.org/articles/PMC7862000"
+  },
   {
     "id": "31504435",
     "doi": "https://doi.org/10.1093/eurheartj/ehz569",
@@ -17968,23 +17968,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061843.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061843; html:https://europepmc.org/articles/PMC9639083; pdf:https://europepmc.org/articles/PMC9639083?pdf=render"
   },
-  {
-    "id": "37634573",
-    "doi": "https://doi.org/10.1016/j.cardfail.2023.08.008",
-    "title": "Does Heterogeneity Exist in Treatment Associations With Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?",
-    "authorString": "Uijl A, Koudstaal S, Stolfo D, Dahlstr\u00f6m U, Vaartjes I, Grobbee RE, Asselbergs FW, Lund LH, Savarese G.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of cardiac failure",
-    "pubYear": "2023",
-    "date": "2023-08-25",
-    "isOpenAccess": "N",
-    "keywords": "Personalized Medicine; Beta-blockers; Hfpef; Renin\u2013angiotensin System Inhibitors; Phenotype Clusters",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>We explored the association between use of renin-angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF).<h4>Methods and results</h4>We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation-hypertensive (32%), older-atrial fibrillation (24%), obese-diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin-angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P\u202f=\u202f.03) and non-CV hospitalisation (P\u202f=\u202f.001). In the young-low comorbidity burden and atrial fibrillation-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar.<h4>Conclusions</h4>In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.cardfail.2023.08.008"
-  },
   {
     "id": "36350810",
     "doi": "https://doi.org/10.1371/journal.pone.0276781",
@@ -18003,21 +17986,21 @@
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0276781&type=printable; doi:https://doi.org/10.1371/journal.pone.0276781; html:https://europepmc.org/articles/PMC9645600; pdf:https://europepmc.org/articles/PMC9645600?pdf=render"
   },
   {
-    "id": "37286615",
-    "doi": "https://doi.org/10.1038/s41598-023-36214-0",
-    "title": "Combining machine learning with Cox models to identify predictors for incident post-menopausal breast cancer in the UK Biobank.",
-    "authorString": "Liu X, Morelli D, Littlejohns TJ, Clifton DA, Clifton L.",
+    "id": "37634573",
+    "doi": "https://doi.org/10.1016/j.cardfail.2023.08.008",
+    "title": "Does Heterogeneity Exist in Treatment Associations With Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?",
+    "authorString": "Uijl A, Koudstaal S, Stolfo D, Dahlstr\u00f6m U, Vaartjes I, Grobbee RE, Asselbergs FW, Lund LH, Savarese G.",
     "authorAffiliations": "",
-    "journalTitle": "Scientific reports",
+    "journalTitle": "Journal of cardiac failure",
     "pubYear": "2023",
-    "date": "2023-06-07",
-    "isOpenAccess": "Y",
-    "keywords": "",
+    "date": "2023-08-25",
+    "isOpenAccess": "N",
+    "keywords": "Personalized Medicine; Beta-blockers; Hfpef; Renin\u2013angiotensin System Inhibitors; Phenotype Clusters",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "We aimed to identify potential novel predictors for breast cancer among post-menopausal women, with pre-specified interest in the role of polygenic risk scores (PRS) for risk prediction. We utilised an analysis pipeline where machine learning was used for feature selection, prior to risk prediction by classical statistical models. An \"extreme gradient boosting\" (XGBoost) machine with Shapley feature-importance measures were used for feature selection among [Formula: see text] 1.7\u00a0k features in 104,313 post-menopausal women from the UK Biobank. We constructed and compared the \"augmented\" Cox model (incorporating the two PRS, known and novel predictors) with a \"baseline\" Cox model (incorporating the two PRS and known predictors) for risk prediction. Both of the two PRS were significant in the augmented Cox model ([Formula: see text]). XGBoost identified 10 novel features, among which five showed significant associations with post-menopausal breast cancer: plasma urea (HR\u00a0=\u00a00.95, 95% CI 0.92-0.98, [Formula: see text]), plasma phosphate (HR\u00a0=\u00a00.68, 95% CI 0.53-0.88, [Formula: see text]), basal metabolic rate (HR\u00a0=\u00a01.17, 95% CI 1.11-1.24, [Formula: see text]), red blood cell count (HR\u00a0=\u00a01.21, 95% CI 1.08-1.35, [Formula: see text]), and creatinine in urine (HR\u00a0=\u00a01.05, 95% CI 1.01-1.09, [Formula: see text]). Risk discrimination was maintained in the augmented Cox model, yielding C-index 0.673 vs 0.667 (baseline Cox model) with the training data and 0.665 vs 0.664 with the test data. We identified blood/urine biomarkers as potential novel predictors for post-menopausal breast cancer. Our findings provide new insights to breast cancer risk. Future research should validate novel predictors, investigate using multiple PRS and more precise anthropometry measures for better breast cancer risk prediction.",
+    "abstract": "<h4>Background</h4>We explored the association between use of renin-angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF).<h4>Methods and results</h4>We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation-hypertensive (32%), older-atrial fibrillation (24%), obese-diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin-angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P\u202f=\u202f.03) and non-CV hospitalisation (P\u202f=\u202f.001). In the young-low comorbidity burden and atrial fibrillation-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar.<h4>Conclusions</h4>In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1038/s41598-023-36214-0; doi:https://doi.org/10.1038/s41598-023-36214-0; html:https://europepmc.org/articles/PMC10247810; pdf:https://europepmc.org/articles/PMC10247810?pdf=render"
+    "urls": "doi:https://doi.org/10.1016/j.cardfail.2023.08.008"
   },
   {
     "id": "36587850",
@@ -18036,6 +18019,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jaci.2022.12.810; doi:https://doi.org/10.1016/j.jaci.2022.12.810; html:https://europepmc.org/articles/PMC10109092; pdf:https://europepmc.org/articles/PMC10109092?pdf=render"
   },
+  {
+    "id": "37286615",
+    "doi": "https://doi.org/10.1038/s41598-023-36214-0",
+    "title": "Combining machine learning with Cox models to identify predictors for incident post-menopausal breast cancer in the UK Biobank.",
+    "authorString": "Liu X, Morelli D, Littlejohns TJ, Clifton DA, Clifton L.",
+    "authorAffiliations": "",
+    "journalTitle": "Scientific reports",
+    "pubYear": "2023",
+    "date": "2023-06-07",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "We aimed to identify potential novel predictors for breast cancer among post-menopausal women, with pre-specified interest in the role of polygenic risk scores (PRS) for risk prediction. We utilised an analysis pipeline where machine learning was used for feature selection, prior to risk prediction by classical statistical models. An \"extreme gradient boosting\" (XGBoost) machine with Shapley feature-importance measures were used for feature selection among [Formula: see text] 1.7\u00a0k features in 104,313 post-menopausal women from the UK Biobank. We constructed and compared the \"augmented\" Cox model (incorporating the two PRS, known and novel predictors) with a \"baseline\" Cox model (incorporating the two PRS and known predictors) for risk prediction. Both of the two PRS were significant in the augmented Cox model ([Formula: see text]). XGBoost identified 10 novel features, among which five showed significant associations with post-menopausal breast cancer: plasma urea (HR\u00a0=\u00a00.95, 95% CI 0.92-0.98, [Formula: see text]), plasma phosphate (HR\u00a0=\u00a00.68, 95% CI 0.53-0.88, [Formula: see text]), basal metabolic rate (HR\u00a0=\u00a01.17, 95% CI 1.11-1.24, [Formula: see text]), red blood cell count (HR\u00a0=\u00a01.21, 95% CI 1.08-1.35, [Formula: see text]), and creatinine in urine (HR\u00a0=\u00a01.05, 95% CI 1.01-1.09, [Formula: see text]). Risk discrimination was maintained in the augmented Cox model, yielding C-index 0.673 vs 0.667 (baseline Cox model) with the training data and 0.665 vs 0.664 with the test data. We identified blood/urine biomarkers as potential novel predictors for post-menopausal breast cancer. Our findings provide new insights to breast cancer risk. Future research should validate novel predictors, investigate using multiple PRS and more precise anthropometry measures for better breast cancer risk prediction.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1038/s41598-023-36214-0; doi:https://doi.org/10.1038/s41598-023-36214-0; html:https://europepmc.org/articles/PMC10247810; pdf:https://europepmc.org/articles/PMC10247810?pdf=render"
+  },
   {
     "id": "34459398",
     "doi": "https://doi.org/10.3233/jad-210462",
@@ -18087,23 +18087,6 @@
     "laySummary": "A phenotyping algorithm is presented to monitor bleeding in primary and hospital care. Model is well presented in the document and has potential to be scalable and applied to other conditions.",
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-019-1438-y; doi:https://doi.org/10.1186/s12916-019-1438-y; html:https://europepmc.org/articles/PMC6864929; pdf:https://europepmc.org/articles/PMC6864929?pdf=render"
   },
-  {
-    "id": "37438684",
-    "doi": "https://doi.org/10.1186/s12874-023-01935-3",
-    "title": "Estimating medication adherence from Electronic Health Records: comparing methods for mining and processing asthma treatment prescriptions.",
-    "authorString": "Tibble H, Sheikh A, Tsanas A.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medical research methodology",
-    "pubYear": "2023",
-    "date": "2023-07-12",
-    "isOpenAccess": "Y",
-    "keywords": "Adherence; Asthma; Compliance; corticosteroid; Electronic Health Records",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Medication adherence is usually defined as the extent of the agreement between the medication regimen agreed to by patients with their healthcare provider and the real-world implementation. Proactive identification of those with poor adherence may be useful to identify those with poor disease control and offers the opportunity for ameliorative action. Adherence can be estimated from Electronic Health Records (EHRs) by comparing medication dispensing records to the prescribed regimen. Several methods have been developed in the literature to infer adherence from EHRs, however there is no clear consensus on what should be considered the gold standard in each use case. Our objectives were to critically evaluate different measures of medication adherence in a large longitudinal Scottish EHR dataset. We used asthma, a chronic condition with high prevalence and high rates of non-adherence, as a case study.<h4>Methods</h4>Over 1.6 million asthma controllers were prescribed for our cohort of 91,334 individuals, between January 2009 and March 2017. Eight adherence measures were calculated, and different approaches to estimating the amount of medication supply available at any time were compared.<h4>Results</h4>Estimates from different measures of adherence varied substantially. Three of the main drivers of the differences between adherence measures were the expected duration (if taken as in accordance with the dose directions), whether there was overlapping supply between prescriptions, and whether treatment had been discontinued. However, there are also wider, study-related, factors which are crucial to consider when comparing the adherence measures.<h4>Conclusions</h4>We evaluated the limitations of various medication adherence measures, and highlight key considerations about the underlying data, condition, and population to guide researchers choose appropriate adherence measures. This guidance will enable researchers to make more informed decisions about the methodology they employ, ensuring that adherence is captured in the most meaningful way for their particular application needs.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-023-01935-3; doi:https://doi.org/10.1186/s12874-023-01935-3; html:https://europepmc.org/articles/PMC10337150; pdf:https://europepmc.org/articles/PMC10337150?pdf=render"
-  },
   {
     "id": "32518842",
     "doi": "https://doi.org/10.12688/wellcomeopenres.15786.1",
@@ -18121,6 +18104,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15786.1; doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render"
   },
+  {
+    "id": "37438684",
+    "doi": "https://doi.org/10.1186/s12874-023-01935-3",
+    "title": "Estimating medication adherence from Electronic Health Records: comparing methods for mining and processing asthma treatment prescriptions.",
+    "authorString": "Tibble H, Sheikh A, Tsanas A.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC medical research methodology",
+    "pubYear": "2023",
+    "date": "2023-07-12",
+    "isOpenAccess": "Y",
+    "keywords": "Adherence; Asthma; Compliance; corticosteroid; Electronic Health Records",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Medication adherence is usually defined as the extent of the agreement between the medication regimen agreed to by patients with their healthcare provider and the real-world implementation. Proactive identification of those with poor adherence may be useful to identify those with poor disease control and offers the opportunity for ameliorative action. Adherence can be estimated from Electronic Health Records (EHRs) by comparing medication dispensing records to the prescribed regimen. Several methods have been developed in the literature to infer adherence from EHRs, however there is no clear consensus on what should be considered the gold standard in each use case. Our objectives were to critically evaluate different measures of medication adherence in a large longitudinal Scottish EHR dataset. We used asthma, a chronic condition with high prevalence and high rates of non-adherence, as a case study.<h4>Methods</h4>Over 1.6 million asthma controllers were prescribed for our cohort of 91,334 individuals, between January 2009 and March 2017. Eight adherence measures were calculated, and different approaches to estimating the amount of medication supply available at any time were compared.<h4>Results</h4>Estimates from different measures of adherence varied substantially. Three of the main drivers of the differences between adherence measures were the expected duration (if taken as in accordance with the dose directions), whether there was overlapping supply between prescriptions, and whether treatment had been discontinued. However, there are also wider, study-related, factors which are crucial to consider when comparing the adherence measures.<h4>Conclusions</h4>We evaluated the limitations of various medication adherence measures, and highlight key considerations about the underlying data, condition, and population to guide researchers choose appropriate adherence measures. This guidance will enable researchers to make more informed decisions about the methodology they employ, ensuring that adherence is captured in the most meaningful way for their particular application needs.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-023-01935-3; doi:https://doi.org/10.1186/s12874-023-01935-3; html:https://europepmc.org/articles/PMC10337150; pdf:https://europepmc.org/articles/PMC10337150?pdf=render"
+  },
   {
     "id": "36134690",
     "doi": "https://doi.org/10.1242/dev.200654",
@@ -18291,23 +18291,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.media.2022.102678; doi:https://doi.org/10.1016/j.media.2022.102678"
   },
-  {
-    "id": "37269003",
-    "doi": "https://doi.org/10.1186/s13643-023-02261-x",
-    "title": "Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.",
-    "authorString": "Shahzad H, Mahmood S, McGee S, Hubbard J, Haque S, Paudyal V, Denniston AK, Hill LJ, Jalal Z.",
-    "authorAffiliations": "",
-    "journalTitle": "Systematic reviews",
-    "pubYear": "2023",
-    "date": "2023-06-02",
-    "isOpenAccess": "Y",
-    "keywords": "Meta-analysis; Intravitreal; Anti-vegf; Non-adherence; Macular; Non-persistence; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes.<h4>Methods</h4>Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors.<h4>Results</h4>Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4\u00a0months to 8\u00a0years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P\u2009=\u20090.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown.<h4>Discussion</h4>Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence.<h4>Systematic review registration</h4>PROSPERO CRD42020216205.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1186/s13643-023-02261-x; doi:https://doi.org/10.1186/s13643-023-02261-x; html:https://europepmc.org/articles/PMC10237080; pdf:https://europepmc.org/articles/PMC10237080?pdf=render"
-  },
   {
     "id": "32979970",
     "doi": "https://doi.org/10.1016/s0140-6736(20)31966-8",
@@ -18325,6 +18308,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S0140673620319668/pdf; doi:https://doi.org/10.1016/S0140-6736(20)31966-8; html:https://europepmc.org/articles/PMC7515579; pdf:https://europepmc.org/articles/PMC7515579?pdf=render"
   },
+  {
+    "id": "37269003",
+    "doi": "https://doi.org/10.1186/s13643-023-02261-x",
+    "title": "Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.",
+    "authorString": "Shahzad H, Mahmood S, McGee S, Hubbard J, Haque S, Paudyal V, Denniston AK, Hill LJ, Jalal Z.",
+    "authorAffiliations": "",
+    "journalTitle": "Systematic reviews",
+    "pubYear": "2023",
+    "date": "2023-06-02",
+    "isOpenAccess": "Y",
+    "keywords": "Meta-analysis; Intravitreal; Anti-vegf; Non-adherence; Macular; Non-persistence; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes.<h4>Methods</h4>Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors.<h4>Results</h4>Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4\u00a0months to 8\u00a0years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P\u2009=\u20090.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown.<h4>Discussion</h4>Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence.<h4>Systematic review registration</h4>PROSPERO CRD42020216205.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1186/s13643-023-02261-x; doi:https://doi.org/10.1186/s13643-023-02261-x; html:https://europepmc.org/articles/PMC10237080; pdf:https://europepmc.org/articles/PMC10237080?pdf=render"
+  },
   {
     "id": "30969971",
     "doi": "https://doi.org/10.1371/journal.pone.0213435",
@@ -18461,23 +18461,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render"
   },
-  {
-    "id": "36810251",
-    "doi": "https://doi.org/10.1172/jci.insight.156643",
-    "title": "Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.",
-    "authorString": "Tsakok T, Saklatvala J, Rispens T, Loeff FC, de Vries A, Allen MH, Barbosa IA, Baudry D, Dasandi T, Duckworth M, Meynell F, Russell A, Chapman A, McBride S, McKenna K, Perera G, Ramsay H, Ramesh R, Sands K, Shipman A, Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) Study Group, Burden AD, Griffiths CE, Reynolds NJ, Warren RB, Mahil S, Barker J, Dand N, Smith C, Simpson MA.",
-    "authorAffiliations": "",
-    "journalTitle": "JCI insight",
-    "pubYear": "2023",
-    "date": "2023-02-22",
-    "isOpenAccess": "Y",
-    "keywords": "Genetics; Drug therapy; Molecular genetics; Therapeutics; adaptive immunity",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.",
-    "laySummary": "",
-    "urls": "pdf:http://insight.jci.org/articles/view/156643/files/pdf; doi:https://doi.org/10.1172/jci.insight.156643; html:https://europepmc.org/articles/PMC9977494; pdf:https://europepmc.org/articles/PMC9977494?pdf=render"
-  },
   {
     "id": "30999919",
     "doi": "https://doi.org/10.1186/s12911-019-0805-0",
@@ -18495,6 +18478,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0805-0; doi:https://doi.org/10.1186/s12911-019-0805-0; html:https://europepmc.org/articles/PMC6472089; pdf:https://europepmc.org/articles/PMC6472089?pdf=render"
   },
+  {
+    "id": "36810251",
+    "doi": "https://doi.org/10.1172/jci.insight.156643",
+    "title": "Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.",
+    "authorString": "Tsakok T, Saklatvala J, Rispens T, Loeff FC, de Vries A, Allen MH, Barbosa IA, Baudry D, Dasandi T, Duckworth M, Meynell F, Russell A, Chapman A, McBride S, McKenna K, Perera G, Ramsay H, Ramesh R, Sands K, Shipman A, Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) Study Group, Burden AD, Griffiths CE, Reynolds NJ, Warren RB, Mahil S, Barker J, Dand N, Smith C, Simpson MA.",
+    "authorAffiliations": "",
+    "journalTitle": "JCI insight",
+    "pubYear": "2023",
+    "date": "2023-02-22",
+    "isOpenAccess": "Y",
+    "keywords": "Genetics; Drug therapy; Molecular genetics; Therapeutics; adaptive immunity",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.",
+    "laySummary": "",
+    "urls": "pdf:http://insight.jci.org/articles/view/156643/files/pdf; doi:https://doi.org/10.1172/jci.insight.156643; html:https://europepmc.org/articles/PMC9977494; pdf:https://europepmc.org/articles/PMC9977494?pdf=render"
+  },
   {
     "id": "33655501",
     "doi": "https://doi.org/10.1111/bjd.19885",
@@ -18512,23 +18512,6 @@
     "laySummary": "",
     "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660846/7/Mulick_etal_2021_Four-childhood-atopic-dermatitis-subtypes.pdf; doi:https://doi.org/10.1111/bjd.19885; html:https://europepmc.org/articles/PMC8410876; pdf:https://europepmc.org/articles/PMC8410876?pdf=render; doi:https://doi.org/10.1111/bjd.19885"
   },
-  {
-    "id": "37730605",
-    "doi": "https://doi.org/10.1186/s12889-023-16523-9",
-    "title": "Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.",
-    "authorString": "Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC public health",
-    "pubYear": "2023",
-    "date": "2023-09-20",
-    "isOpenAccess": "Y",
-    "keywords": "Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.<h4>Methods</h4>The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.<h4>Results</h4>Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.<h4>Conclusions</h4>The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?pdf=render"
-  },
   {
     "id": "36691123",
     "doi": "https://doi.org/10.1136/bmjopen-2022-063199",
@@ -18546,6 +18529,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e063199.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063199; html:https://europepmc.org/articles/PMC9453996; pdf:https://europepmc.org/articles/PMC9453996?pdf=render"
   },
+  {
+    "id": "37730605",
+    "doi": "https://doi.org/10.1186/s12889-023-16523-9",
+    "title": "Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.",
+    "authorString": "Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC public health",
+    "pubYear": "2023",
+    "date": "2023-09-20",
+    "isOpenAccess": "Y",
+    "keywords": "Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.<h4>Methods</h4>The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.<h4>Results</h4>Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.<h4>Conclusions</h4>The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?pdf=render"
+  },
   {
     "id": "36264615",
     "doi": "https://doi.org/10.1161/circgen.122.003704",
@@ -18597,23 +18597,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ajcn/article-pdf/112/6/1485/34844146/nqaa266.pdf; doi:https://doi.org/10.1093/ajcn/nqaa266"
   },
-  {
-    "id": "36713101",
-    "doi": "https://doi.org/10.1093/ehjdh/ztab082",
-    "title": "A data mining-based cross-industry process for predicting major bleeding in mechanical circulatory support.",
-    "authorString": "Felix SEA, Bagheri A, Ramjankhan FR, Spruit MR, Oberski D, de Jonge N, van Laake LW, Suyker WJL, Asselbergs FW.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal. Digital health",
-    "pubYear": "2021",
-    "date": "2021-10-01",
-    "isOpenAccess": "Y",
-    "keywords": "Prediction; Bleeding; data mining; Mechanical Circulatory Support; Cross-Industry Standard Process For Data Mining (Crisp-Dm)",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>Over a third of patients, treated with mechanical circulatory support (MCS) for end-stage heart failure, experience major bleeding. Currently, the prediction of a major bleeding in the near future is difficult because of many contributing factors. Predictive analytics using data mining could help calculating the risk of bleeding; however, its application is generally reserved for experienced researchers on this subject. We propose an easily applicable data mining tool to predict major bleeding in MCS patients.<h4>Methods and results</h4>All data of electronic health records of MCS patients in the University Medical Centre Utrecht were included. Based on the cross-industry standard process for data mining (CRISP-DM) methodology, an application named Auto-Crisp was developed. Auto-Crisp was used to evaluate the predictive models for a major bleeding in the next 3, 7, and 30 days after the first 30 days post-operatively following MCS implantation. The performance of the predictive models is investigated by the area under the curve (AUC) evaluation measure. In 25.6% of 273 patients, a total of 142 major bleedings occurred during a median follow-up period of 542 [interquartile range (IQR) 205-1044] days. The best predictive models assessed by Auto-Crisp had AUC values of 0.792, 0.788, and 0.776 for bleedings in the next 3, 7, and 30 days, respectively.<h4>Conclusion</h4>The Auto-Crisp-based predictive model created in this study had an acceptable performance to predict major bleeding in MCS patients in the near future. However, further validation of the application is needed to evaluate Auto-Crisp in other research projects.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ehjdh/article-pdf/2/4/635/41972750/ztab082.pdf; doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render"
-  },
   {
     "id": "29457906",
     "doi": "https://doi.org/10.1021/acs.jproteome.7b00879",
@@ -18632,21 +18615,21 @@
     "urls": "pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.7b00879; doi:https://doi.org/10.1021/acs.jproteome.7b00879; html:https://europepmc.org/articles/PMC5891819; pdf:https://europepmc.org/articles/PMC5891819?pdf=render"
   },
   {
-    "id": "36721180",
-    "doi": "https://doi.org/10.1186/s12961-022-00956-6",
-    "title": "Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.",
-    "authorString": "Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",
+    "id": "36713101",
+    "doi": "https://doi.org/10.1093/ehjdh/ztab082",
+    "title": "A data mining-based cross-industry process for predicting major bleeding in mechanical circulatory support.",
+    "authorString": "Felix SEA, Bagheri A, Ramjankhan FR, Spruit MR, Oberski D, de Jonge N, van Laake LW, Suyker WJL, Asselbergs FW.",
     "authorAffiliations": "",
-    "journalTitle": "Health research policy and systems",
-    "pubYear": "2023",
-    "date": "2023-01-31",
+    "journalTitle": "European heart journal. Digital health",
+    "pubYear": "2021",
+    "date": "2021-10-01",
     "isOpenAccess": "Y",
-    "keywords": "Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19",
+    "keywords": "Prediction; Bleeding; data mining; Mechanical Circulatory Support; Cross-Industry Standard Process For Data Mining (Crisp-Dm)",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and\u00a0employ mixed methods to better understand the underlying causes of service disruptions.",
+    "abstract": "<h4>Aims</h4>Over a third of patients, treated with mechanical circulatory support (MCS) for end-stage heart failure, experience major bleeding. Currently, the prediction of a major bleeding in the near future is difficult because of many contributing factors. Predictive analytics using data mining could help calculating the risk of bleeding; however, its application is generally reserved for experienced researchers on this subject. We propose an easily applicable data mining tool to predict major bleeding in MCS patients.<h4>Methods and results</h4>All data of electronic health records of MCS patients in the University Medical Centre Utrecht were included. Based on the cross-industry standard process for data mining (CRISP-DM) methodology, an application named Auto-Crisp was developed. Auto-Crisp was used to evaluate the predictive models for a major bleeding in the next 3, 7, and 30 days after the first 30 days post-operatively following MCS implantation. The performance of the predictive models is investigated by the area under the curve (AUC) evaluation measure. In 25.6% of 273 patients, a total of 142 major bleedings occurred during a median follow-up period of 542 [interquartile range (IQR) 205-1044] days. The best predictive models assessed by Auto-Crisp had AUC values of 0.792, 0.788, and 0.776 for bleedings in the next 3, 7, and 30 days, respectively.<h4>Conclusion</h4>The Auto-Crisp-based predictive model created in this study had an acceptable performance to predict major bleeding in MCS patients in the near future. However, further validation of the application is needed to evaluate Auto-Crisp in other research projects.",
     "laySummary": "",
-    "urls": "pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render"
+    "urls": "pdf:https://academic.oup.com/ehjdh/article-pdf/2/4/635/41972750/ztab082.pdf; doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render"
   },
   {
     "id": "32975552",
@@ -18665,6 +18648,23 @@
     "laySummary": "",
     "urls": "pdf:https://jamanetwork.com/journals/jamapediatrics/articlepdf/2771181/jamapediatrics_viner_2020_oi_200071_1611604170.25358.pdf; doi:https://doi.org/10.1001/jamapediatrics.2020.4573; html:https://europepmc.org/articles/PMC7519436; doi:https://doi.org/10.1001/jamapediatrics.2020.4573"
   },
+  {
+    "id": "36721180",
+    "doi": "https://doi.org/10.1186/s12961-022-00956-6",
+    "title": "Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.",
+    "authorString": "Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",
+    "authorAffiliations": "",
+    "journalTitle": "Health research policy and systems",
+    "pubYear": "2023",
+    "date": "2023-01-31",
+    "isOpenAccess": "Y",
+    "keywords": "Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and\u00a0employ mixed methods to better understand the underlying causes of service disruptions.",
+    "laySummary": "",
+    "urls": "pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render"
+  },
   {
     "id": "37101398",
     "doi": "https://doi.org/10.1002/ejhf.2868",
@@ -18852,23 +18852,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-022-28729-3.pdf; doi:https://doi.org/10.1038/s41467-022-28729-3; html:https://europepmc.org/articles/PMC8907312; pdf:https://europepmc.org/articles/PMC8907312?pdf=render"
   },
-  {
-    "id": "36729586",
-    "doi": "https://doi.org/10.2196/42965",
-    "title": "Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.",
-    "authorString": "Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.",
-    "authorAffiliations": "",
-    "journalTitle": "JMIR research protocols",
-    "pubYear": "2023",
-    "date": "2023-02-02",
-    "isOpenAccess": "Y",
-    "keywords": "Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.<h4>Objective</h4>The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.<h4>Methods</h4>We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.<h4>Results</h4>This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.<h4>Conclusions</h4>This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/42965.",
-    "laySummary": "",
-    "urls": "pdf:https://www.researchprotocols.org/2023/1/e42965/PDF; doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366"
-  },
   {
     "id": "PMC8855010",
     "doi": "https://doi.org/",
@@ -18887,21 +18870,21 @@
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855010/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855010/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8855010; pdf:https://europepmc.org/articles/PMC8855010?pdf=render"
   },
   {
-    "id": "37813531",
-    "doi": "https://doi.org/10.1136/bmjopen-2023-073162",
-    "title": "Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.",
-    "authorString": "Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",
+    "id": "36729586",
+    "doi": "https://doi.org/10.2196/42965",
+    "title": "Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.",
+    "authorString": "Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.",
     "authorAffiliations": "",
-    "journalTitle": "BMJ open",
+    "journalTitle": "JMIR research protocols",
     "pubYear": "2023",
-    "date": "2023-10-09",
+    "date": "2023-02-02",
     "isOpenAccess": "Y",
-    "keywords": "Obstetrics; epidemiology; Maternal Medicine",
+    "keywords": "Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.<h4>Methods and analysis</h4>Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3\u2009months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",
+    "abstract": "<h4>Background</h4>Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.<h4>Objective</h4>The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.<h4>Methods</h4>We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.<h4>Results</h4>This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.<h4>Conclusions</h4>This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.<h4>International registered report identifier (irrid)</h4>PRR1-10.2196/42965.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render"
+    "urls": "pdf:https://www.researchprotocols.org/2023/1/e42965/PDF; doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366"
   },
   {
     "id": "33766511",
@@ -18920,6 +18903,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jid.2021.02.744"
   },
+  {
+    "id": "37813531",
+    "doi": "https://doi.org/10.1136/bmjopen-2023-073162",
+    "title": "Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.",
+    "authorString": "Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-10-09",
+    "isOpenAccess": "Y",
+    "keywords": "Obstetrics; epidemiology; Maternal Medicine",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.<h4>Methods and analysis</h4>Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3\u2009months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render"
+  },
   {
     "id": "35487318",
     "doi": "https://doi.org/10.1016/j.ijcard.2022.04.067",
@@ -19124,23 +19124,6 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1371/2815; doi:https://doi.org/10.23889/ijpds.v5i3.1371; html:https://europepmc.org/articles/PMC7893854; pdf:https://europepmc.org/articles/PMC7893854?pdf=render"
   },
-  {
-    "id": "37217302",
-    "doi": "https://doi.org/10.1136/emermed-2022-212827",
-    "title": "External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.",
-    "authorString": "Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.",
-    "authorAffiliations": "",
-    "journalTitle": "Emergency medicine journal : EMJ",
-    "pubYear": "2023",
-    "date": "2023-05-22",
-    "isOpenAccess": "Y",
-    "keywords": "risk management; Triage; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.<h4>Methods</h4>An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.<h4>Results</h4>Of the 446\u2009084 patients, 15\u2009397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.<h4>Conclusion</h4>No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.",
-    "laySummary": "",
-    "urls": "pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render"
-  },
   {
     "id": "32831176",
     "doi": "https://doi.org/10.7554/elife.58699",
@@ -19158,6 +19141,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.7554/elife.58699; doi:https://doi.org/10.7554/eLife.58699; html:https://europepmc.org/articles/PMC7527238; pdf:https://europepmc.org/articles/PMC7527238?pdf=render"
   },
+  {
+    "id": "37217302",
+    "doi": "https://doi.org/10.1136/emermed-2022-212827",
+    "title": "External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.",
+    "authorString": "Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.",
+    "authorAffiliations": "",
+    "journalTitle": "Emergency medicine journal : EMJ",
+    "pubYear": "2023",
+    "date": "2023-05-22",
+    "isOpenAccess": "Y",
+    "keywords": "risk management; Triage; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.<h4>Methods</h4>An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.<h4>Results</h4>Of the 446\u2009084 patients, 15\u2009397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.<h4>Conclusion</h4>No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.",
+    "laySummary": "",
+    "urls": "pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render"
+  },
   {
     "id": "36285341",
     "doi": "https://doi.org/10.1080/17434440.2022.2132147",
@@ -19209,23 +19209,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6"
   },
-  {
-    "id": "34244270",
-    "doi": "https://doi.org/10.1136/bmjopen-2020-048008",
-    "title": "Protocol for development of a reporting guideline (TRIPOD-AI) and risk of bias tool (PROBAST-AI) for diagnostic and prognostic prediction model studies based on artificial intelligence.",
-    "authorString": "Collins GS, Dhiman P, Andaur Navarro CL, Ma J, Hooft L, Reitsma JB, Logullo P, Beam AL, Peng L, Van Calster B, van Smeden M, Riley RD, Moons KG.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2021",
-    "date": "2021-07-09",
-    "isOpenAccess": "Y",
-    "keywords": "epidemiology; Statistics & Research Methods; General Medicine (See Internal Medicine)",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) were both published to improve the reporting and critical appraisal of prediction model studies for diagnosis and prognosis. This paper describes the processes and methods that will be used to develop an extension to the TRIPOD statement (TRIPOD-artificial intelligence, AI) and the PROBAST (PROBAST-AI) tool for prediction model studies that applied machine learning techniques.<h4>Methods and analysis</h4>TRIPOD-AI and PROBAST-AI will be developed following published guidance from the EQUATOR Network, and will comprise five stages. Stage 1 will comprise two systematic reviews (across all medical fields and specifically in oncology) to examine the quality of reporting in published machine-learning-based prediction model studies. In stage 2, we will consult a diverse group of key stakeholders using a Delphi process to identify items to be considered for inclusion in TRIPOD-AI and PROBAST-AI. Stage 3 will be virtual consensus meetings to consolidate and prioritise key items to be included in TRIPOD-AI and PROBAST-AI. Stage 4 will involve developing the TRIPOD-AI checklist and the PROBAST-AI tool, and writing the accompanying explanation and elaboration papers. In the final stage, stage 5, we will disseminate TRIPOD-AI and PROBAST-AI via journals, conferences, blogs, websites (including TRIPOD, PROBAST and EQUATOR Network) and social media. TRIPOD-AI will provide researchers working on prediction model studies based on machine learning with a reporting guideline that can help them report key details that readers need to evaluate the study quality and interpret its findings, potentially reducing research waste. We anticipate PROBAST-AI will help researchers, clinicians, systematic reviewers and policymakers critically appraise the design, conduct and analysis of machine learning based prediction model studies, with a robust standardised tool for bias evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been granted by the Central University Research Ethics Committee, University of Oxford on 10-December-2020 (R73034/RE001). Findings from this study will be disseminated through peer-review publications.<h4>Prospero registration number</h4>CRD42019140361 and CRD42019161764.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e048008.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048008; html:https://europepmc.org/articles/PMC8273461; pdf:https://europepmc.org/articles/PMC8273461?pdf=render"
-  },
   {
     "id": "30181555",
     "doi": "https://doi.org/10.1038/s41398-018-0236-1",
@@ -19243,6 +19226,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41398-018-0236-1.pdf; doi:https://doi.org/10.1038/s41398-018-0236-1; html:https://europepmc.org/articles/PMC6123450; pdf:https://europepmc.org/articles/PMC6123450?pdf=render"
   },
+  {
+    "id": "34244270",
+    "doi": "https://doi.org/10.1136/bmjopen-2020-048008",
+    "title": "Protocol for development of a reporting guideline (TRIPOD-AI) and risk of bias tool (PROBAST-AI) for diagnostic and prognostic prediction model studies based on artificial intelligence.",
+    "authorString": "Collins GS, Dhiman P, Andaur Navarro CL, Ma J, Hooft L, Reitsma JB, Logullo P, Beam AL, Peng L, Van Calster B, van Smeden M, Riley RD, Moons KG.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2021",
+    "date": "2021-07-09",
+    "isOpenAccess": "Y",
+    "keywords": "epidemiology; Statistics & Research Methods; General Medicine (See Internal Medicine)",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) were both published to improve the reporting and critical appraisal of prediction model studies for diagnosis and prognosis. This paper describes the processes and methods that will be used to develop an extension to the TRIPOD statement (TRIPOD-artificial intelligence, AI) and the PROBAST (PROBAST-AI) tool for prediction model studies that applied machine learning techniques.<h4>Methods and analysis</h4>TRIPOD-AI and PROBAST-AI will be developed following published guidance from the EQUATOR Network, and will comprise five stages. Stage 1 will comprise two systematic reviews (across all medical fields and specifically in oncology) to examine the quality of reporting in published machine-learning-based prediction model studies. In stage 2, we will consult a diverse group of key stakeholders using a Delphi process to identify items to be considered for inclusion in TRIPOD-AI and PROBAST-AI. Stage 3 will be virtual consensus meetings to consolidate and prioritise key items to be included in TRIPOD-AI and PROBAST-AI. Stage 4 will involve developing the TRIPOD-AI checklist and the PROBAST-AI tool, and writing the accompanying explanation and elaboration papers. In the final stage, stage 5, we will disseminate TRIPOD-AI and PROBAST-AI via journals, conferences, blogs, websites (including TRIPOD, PROBAST and EQUATOR Network) and social media. TRIPOD-AI will provide researchers working on prediction model studies based on machine learning with a reporting guideline that can help them report key details that readers need to evaluate the study quality and interpret its findings, potentially reducing research waste. We anticipate PROBAST-AI will help researchers, clinicians, systematic reviewers and policymakers critically appraise the design, conduct and analysis of machine learning based prediction model studies, with a robust standardised tool for bias evaluation.<h4>Ethics and dissemination</h4>Ethical approval has been granted by the Central University Research Ethics Committee, University of Oxford on 10-December-2020 (R73034/RE001). Findings from this study will be disseminated through peer-review publications.<h4>Prospero registration number</h4>CRD42019140361 and CRD42019161764.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e048008.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048008; html:https://europepmc.org/articles/PMC8273461; pdf:https://europepmc.org/articles/PMC8273461?pdf=render"
+  },
   {
     "id": "32895316",
     "doi": "https://doi.org/10.1136/thoraxjnl-2020-215566",
@@ -19447,23 +19447,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1080/09638288.2021.1998671"
   },
-  {
-    "id": "37612010",
-    "doi": "https://doi.org/10.1016/j.jacc.2023.05.065",
-    "title": "Monitoring of Myocardial Involvement in\u00a0Early Arrhythmogenic Right Ventricular\u00a0Cardiomyopathy Across the\u00a0Age Spectrum.",
-    "authorString": "Kirkels FP, van Osta N, Rootwelt-Norberg C, Chivulescu M, van Loon T, Aabel EW, Castrini AI, Lie \u00d8H, Asselbergs FW, Delhaas T, Cramer MJ, Teske AJ, Haugaa KH, Lumens J.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of the American College of Cardiology",
-    "pubYear": "2023",
-    "date": "2023-08-01",
-    "isOpenAccess": "N",
-    "keywords": "Early Detection; Arvc; Family Screening; Arrhythmogenic Cardiomyopathy; Deformation Imaging; Digital Twin",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored.<h4>Objectives</h4>The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups.<h4>Methods</h4>We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age\u00a0<30 years, 30 to 50 years, and\u00a0\u226550 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework.<h4>Results</h4>We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 \u00b1 17 years, 10% probands) during 6.7 \u00b1 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95%\u00a0CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95%\u00a0CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up.<h4>Conclusions</h4>Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jacc.2023.05.065"
-  },
   {
     "id": "31353050",
     "doi": "https://doi.org/10.1016/s0140-6736(19)31359-5",
@@ -19481,6 +19464,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S0140673619313595/pdf; doi:https://doi.org/10.1016/S0140-6736(19)31359-5; html:https://europepmc.org/articles/PMC6717081"
   },
+  {
+    "id": "37612010",
+    "doi": "https://doi.org/10.1016/j.jacc.2023.05.065",
+    "title": "Monitoring of Myocardial Involvement in\u00a0Early Arrhythmogenic Right Ventricular\u00a0Cardiomyopathy Across the\u00a0Age Spectrum.",
+    "authorString": "Kirkels FP, van Osta N, Rootwelt-Norberg C, Chivulescu M, van Loon T, Aabel EW, Castrini AI, Lie \u00d8H, Asselbergs FW, Delhaas T, Cramer MJ, Teske AJ, Haugaa KH, Lumens J.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of the American College of Cardiology",
+    "pubYear": "2023",
+    "date": "2023-08-01",
+    "isOpenAccess": "N",
+    "keywords": "Early Detection; Arvc; Family Screening; Arrhythmogenic Cardiomyopathy; Deformation Imaging; Digital Twin",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored.<h4>Objectives</h4>The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups.<h4>Methods</h4>We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age\u00a0<30 years, 30 to 50 years, and\u00a0\u226550 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework.<h4>Results</h4>We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 \u00b1 17 years, 10% probands) during 6.7 \u00b1 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95%\u00a0CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95%\u00a0CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up.<h4>Conclusions</h4>Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jacc.2023.05.065"
+  },
   {
     "id": "34356044",
     "doi": "https://doi.org/10.3390/genes12071029",
@@ -19549,23 +19549,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e055219.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055219; html:https://europepmc.org/articles/PMC8488707; pdf:https://europepmc.org/articles/PMC8488707?pdf=render"
   },
-  {
-    "id": "35869974",
-    "doi": "https://doi.org/10.1093/ndt/gfac224",
-    "title": "Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.",
-    "authorString": "Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.",
-    "authorAffiliations": "",
-    "journalTitle": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",
-    "pubYear": "2023",
-    "date": "2023-05-01",
-    "isOpenAccess": "Y",
-    "keywords": "Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.<h4>Methods</h4>This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30\u00a0mL/min/1.73\u00a0m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.<h4>Results</h4>There were 41\u00a0313, 51\u00a0190, 32\u00a0171 and 17\u00a0781 new presentations of AKI and eGFR thresholds <60, <45 and <30 \u00a0mL/min/1.73\u00a0m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5\u00a0years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60\u00a0mL/min/1.73\u00a0m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30\u00a0mL/min/1.73\u00a0m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60\u00a0mL/min/1.73\u00a0m2, AKI, males and those <65\u00a0years of age.<h4>Conclusions</h4>Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render"
-  },
   {
     "id": "35452565",
     "doi": "https://doi.org/10.1002/cpz1.373",
@@ -19583,6 +19566,23 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10149151/1/Dobson_The%20COPILOT%20Raw%20Illumina%20Genotyping%20QC%20Protocol_VoR.pdf; doi:https://doi.org/10.1002/cpz1.373"
   },
+  {
+    "id": "35869974",
+    "doi": "https://doi.org/10.1093/ndt/gfac224",
+    "title": "Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.",
+    "authorString": "Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.",
+    "authorAffiliations": "",
+    "journalTitle": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",
+    "pubYear": "2023",
+    "date": "2023-05-01",
+    "isOpenAccess": "Y",
+    "keywords": "Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.<h4>Methods</h4>This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30\u00a0mL/min/1.73\u00a0m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.<h4>Results</h4>There were 41\u00a0313, 51\u00a0190, 32\u00a0171 and 17\u00a0781 new presentations of AKI and eGFR thresholds <60, <45 and <30 \u00a0mL/min/1.73\u00a0m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5\u00a0years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60\u00a0mL/min/1.73\u00a0m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30\u00a0mL/min/1.73\u00a0m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60\u00a0mL/min/1.73\u00a0m2, AKI, males and those <65\u00a0years of age.<h4>Conclusions</h4>Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render"
+  },
   {
     "id": "32717063",
     "doi": "https://doi.org/10.1093/cvr/cvaa233",
@@ -20008,23 +20008,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19122; doi:https://doi.org/10.1111/bjd.19122"
   },
-  {
-    "id": "35435219",
-    "doi": "https://doi.org/10.1093/ehjqcco/qcac016",
-    "title": "Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.",
-    "authorString": "Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal. Quality of care & clinical outcomes",
-    "pubYear": "2022",
-    "date": "2022-12-01",
-    "isOpenAccess": "Y",
-    "keywords": "Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.<h4>Methods and results</h4>We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629\u00a0308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).<h4>Conclusion</h4>We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render"
-  },
   {
     "id": "31827124",
     "doi": "https://doi.org/10.1038/s41598-019-54849-w",
@@ -20042,6 +20025,23 @@
     "laySummary": "This study investigates the unreliability of target identification leading to low development sucess rates, inefficiency and escalating costs to healthcare users. The more targeted use of genomics couldimprove improved efficency.",
     "urls": "pdf:https://www.nature.com/articles/s41598-019-54849-w.pdf; doi:https://doi.org/10.1038/s41598-019-54849-w; html:https://europepmc.org/articles/PMC6906499; pdf:https://europepmc.org/articles/PMC6906499?pdf=render"
   },
+  {
+    "id": "35435219",
+    "doi": "https://doi.org/10.1093/ehjqcco/qcac016",
+    "title": "Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.",
+    "authorString": "Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal. Quality of care & clinical outcomes",
+    "pubYear": "2022",
+    "date": "2022-12-01",
+    "isOpenAccess": "Y",
+    "keywords": "Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.<h4>Methods and results</h4>We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629\u00a0308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).<h4>Conclusion</h4>We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render"
+  },
   {
     "id": "35765237",
     "doi": "https://doi.org/10.1111/1747-0080.12746",
@@ -20076,23 +20076,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14308; doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render"
   },
-  {
-    "id": "35477524",
-    "doi": "https://doi.org/10.1136/bmj-2022-070230",
-    "title": "Development and validation of the symptom burden questionnaire for long covid (SBQ-LC): Rasch analysis.",
-    "authorString": "Hughes SE, Haroon S, Subramanian A, McMullan C, Aiyegbusi OL, Turner GM, Jackson L, Davies EH, Frost C, McNamara G, Price G, Matthews K, Camaradou J, Ormerod J, Walker A, Calvert MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ (Clinical research ed.)",
-    "pubYear": "2022",
-    "date": "2022-04-27",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To describe the development and validation of a novel patient reported outcome measure for symptom burden from long covid, the symptom burden questionnaire for long covid (SBQ-LC).<h4>Design</h4>Multiphase, prospective mixed methods study.<h4>Setting</h4>Remote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021.<h4>Participants</h4>13 adults (aged \u226518 years) with self-reported long covid and 10 clinicians evaluated content validity. 274 adults with long covid field tested the draft questionnaire.<h4>Main outcome measures</h4>Published systematic reviews informed development of SBQ-LC's conceptual framework and initial item pool. Thematic analysis of transcripts from cognitive debriefing interviews and online clinician surveys established content validity. Consensus discussions with the patient and public involvement group of the Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient reported outcomes and immunology to targeted therapies (TLC Study) confirmed face validity. Rasch analysis of field test data guided item and scale refinement and provided initial evidence of the SBQ-LC's measurement properties.<h4>Results</h4>SBQ-LC (version 1.0) is a modular instrument measuring patient reported outcomes and is composed of 17 independent scales with promising psychometric properties. Respondents rate their symptom burden during the past seven days using a dichotomous response or 4 point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that can be transformed to a linear (0-100) score. Higher scores represent higher symptom burden. After rating scale refinement and item reduction, all scales satisfied the Rasch model requirements for unidimensionality (principal component analysis of residuals: first residual contrast values <2.00 eigenvalue units) and item fit (outfit mean square values within 0.5 -1.5 logits). Rating scale categories were ordered with acceptable category fit statistics (outfit mean square values <2.0 logits). 14 item pairs had evidence of local dependency (residual correlation values >0.4). Across the 17 scales, person reliability ranged from 0.34 to 0.87, person separation ranged from 0.71 to 2.56, item separation ranged from 1.34 to 13.86, and internal consistency reliability (Cronbach's alpha) ranged from 0.56 to 0.91.<h4>Conclusions</h4>SBQ-LC (version 1.0) is a comprehensive patient reported outcome instrument developed using modern psychometric methods. It measures symptoms of long covid important to people with lived experience of the condition and may be used to evaluate the impact of interventions and inform best practice in clinical management.",
-    "laySummary": "",
-    "urls": "pdf:https://www.bmj.com/content/bmj/377/bmj-2022-070230.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070230; html:https://europepmc.org/articles/PMC9043395; pdf:https://europepmc.org/articles/PMC9043395?pdf=render"
-  },
   {
     "id": "31349307",
     "doi": "https://doi.org/10.3233/shti190058",
@@ -20110,6 +20093,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.3233/SHTI190058"
   },
+  {
+    "id": "35477524",
+    "doi": "https://doi.org/10.1136/bmj-2022-070230",
+    "title": "Development and validation of the symptom burden questionnaire for long covid (SBQ-LC): Rasch analysis.",
+    "authorString": "Hughes SE, Haroon S, Subramanian A, McMullan C, Aiyegbusi OL, Turner GM, Jackson L, Davies EH, Frost C, McNamara G, Price G, Matthews K, Camaradou J, Ormerod J, Walker A, Calvert MJ.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ (Clinical research ed.)",
+    "pubYear": "2022",
+    "date": "2022-04-27",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To describe the development and validation of a novel patient reported outcome measure for symptom burden from long covid, the symptom burden questionnaire for long covid (SBQ-LC).<h4>Design</h4>Multiphase, prospective mixed methods study.<h4>Setting</h4>Remote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021.<h4>Participants</h4>13 adults (aged \u226518 years) with self-reported long covid and 10 clinicians evaluated content validity. 274 adults with long covid field tested the draft questionnaire.<h4>Main outcome measures</h4>Published systematic reviews informed development of SBQ-LC's conceptual framework and initial item pool. Thematic analysis of transcripts from cognitive debriefing interviews and online clinician surveys established content validity. Consensus discussions with the patient and public involvement group of the Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient reported outcomes and immunology to targeted therapies (TLC Study) confirmed face validity. Rasch analysis of field test data guided item and scale refinement and provided initial evidence of the SBQ-LC's measurement properties.<h4>Results</h4>SBQ-LC (version 1.0) is a modular instrument measuring patient reported outcomes and is composed of 17 independent scales with promising psychometric properties. Respondents rate their symptom burden during the past seven days using a dichotomous response or 4 point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that can be transformed to a linear (0-100) score. Higher scores represent higher symptom burden. After rating scale refinement and item reduction, all scales satisfied the Rasch model requirements for unidimensionality (principal component analysis of residuals: first residual contrast values <2.00 eigenvalue units) and item fit (outfit mean square values within 0.5 -1.5 logits). Rating scale categories were ordered with acceptable category fit statistics (outfit mean square values <2.0 logits). 14 item pairs had evidence of local dependency (residual correlation values >0.4). Across the 17 scales, person reliability ranged from 0.34 to 0.87, person separation ranged from 0.71 to 2.56, item separation ranged from 1.34 to 13.86, and internal consistency reliability (Cronbach's alpha) ranged from 0.56 to 0.91.<h4>Conclusions</h4>SBQ-LC (version 1.0) is a comprehensive patient reported outcome instrument developed using modern psychometric methods. It measures symptoms of long covid important to people with lived experience of the condition and may be used to evaluate the impact of interventions and inform best practice in clinical management.",
+    "laySummary": "",
+    "urls": "pdf:https://www.bmj.com/content/bmj/377/bmj-2022-070230.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070230; html:https://europepmc.org/articles/PMC9043395; pdf:https://europepmc.org/articles/PMC9043395?pdf=render"
+  },
   {
     "id": "31446406",
     "doi": "https://doi.org/10.1136/bmjopen-2018-027577",
@@ -20280,23 +20280,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.17450; doi:https://doi.org/10.1111/jdv.17450; html:https://europepmc.org/articles/PMC8447018; pdf:https://europepmc.org/articles/PMC8447018?pdf=render"
   },
-  {
-    "id": "37393610",
-    "doi": "https://doi.org/10.1016/j.xpro.2023.102392",
-    "title": "Protocol for the automatic extraction of epidemiological information via a pre-trained language model.",
-    "authorString": "Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.",
-    "authorAffiliations": "",
-    "journalTitle": "STAR protocols",
-    "pubYear": "2023",
-    "date": "2023-07-01",
-    "isOpenAccess": "Y",
-    "keywords": "Health Sciences; Clinical Protocol; Computer Sciences",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.<sup>1</sup> We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et\u00a0al.<sup>2</sup>.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?pdf=render"
-  },
   {
     "id": "32991065",
     "doi": "https://doi.org/10.1111/dom.14203",
@@ -20315,21 +20298,21 @@
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dom.14203; doi:https://doi.org/10.1111/dom.14203; html:https://europepmc.org/articles/PMC7537530; pdf:https://europepmc.org/articles/PMC7537530?pdf=render"
   },
   {
-    "id": "35144240",
-    "doi": "https://doi.org/10.2196/32543",
-    "title": "Artificial Intelligence-Enabled Social Media Analysis for Pharmacovigilance of COVID-19 Vaccinations in the United Kingdom: Observational Study.",
-    "authorString": "Hussain Z, Sheikh Z, Tahir A, Dashtipour K, Gogate M, Sheikh A, Hussain A.",
+    "id": "37393610",
+    "doi": "https://doi.org/10.1016/j.xpro.2023.102392",
+    "title": "Protocol for the automatic extraction of epidemiological information via a pre-trained language model.",
+    "authorString": "Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.",
     "authorAffiliations": "",
-    "journalTitle": "JMIR public health and surveillance",
-    "pubYear": "2022",
-    "date": "2022-05-27",
+    "journalTitle": "STAR protocols",
+    "pubYear": "2023",
+    "date": "2023-07-01",
     "isOpenAccess": "Y",
-    "keywords": "Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19",
+    "keywords": "Health Sciences; Clinical Protocol; Computer Sciences",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>The rollout of vaccines for COVID-19 in the United Kingdom started in December 2020. Uptake has been high, and there has been a subsequent reduction in infections, hospitalizations, and deaths among vaccinated individuals. However, vaccine hesitancy remains a concern, in particular relating to adverse effects following immunization (AEFIs). Social media analysis has the potential to inform policy makers about AEFIs being discussed by the public as well as public attitudes toward the national immunization campaign.<h4>Objective</h4>We sought to assess the frequency and nature of AEFI-related mentions on social media in the United Kingdom and to provide insights on public sentiments toward COVID-19 vaccines.<h4>Methods</h4>We extracted and analyzed over 121,406 relevant Twitter and Facebook posts, from December 8, 2020, to April 30, 2021. These were thematically filtered using a 2-step approach, initially using COVID-19-related keywords and then using vaccine- and manufacturer-related keywords. We identified AEFI-related keywords and modeled their word frequency to monitor their trends over 2-week periods. We also adapted and utilized our recently developed hybrid ensemble model, which combines state-of-the-art lexicon rule-based and deep learning-based approaches, to analyze sentiment trends relating to the main vaccines available in the United Kingdom.<h4>Results</h4>Our COVID-19 AEFI search strategy identified 46,762 unique Facebook posts by 14,346 users and 74,644 tweets (excluding retweets) by 36,446 users over the 4-month period. We identified an increasing trend in the number of mentions for each AEFI on social media over the study period. The most frequent AEFI mentions were found to be symptoms related to appetite (n=79,132, 14%), allergy (n=53,924, 9%), injection site (n=56,152, 10%), and clots (n=43,907, 8%). We also found some rarely reported AEFIs such as Bell palsy (n=11,909, 2%) and Guillain-Barre syndrome (n=9576, 2%) being discussed as frequently as more well-known side effects like headache (n=10,641, 2%), fever (n=12,707, 2%), and diarrhea (n=16,559, 3%). Overall, we found public sentiment toward vaccines and their manufacturers to be largely positive (58%), with a near equal split between negative (22%) and neutral (19%) sentiments. The sentiment trend was relatively steady over time and had minor variations, likely based on political and regulatory announcements and debates.<h4>Conclusions</h4>The most frequently discussed COVID-19 AEFIs on social media were found to be broadly consistent with those reported in the literature and by government pharmacovigilance. We also detected potential safety signals from our analysis that have been detected elsewhere and are currently being investigated. As such, we believe our findings support the use of social media analysis to provide a complementary data source to conventional knowledge sources being used for pharmacovigilance purposes.",
+    "abstract": "The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.<sup>1</sup> We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et\u00a0al.<sup>2</sup>.",
     "laySummary": "",
-    "urls": "pdf:https://publichealth.jmir.org/2022/5/e32543/PDF; doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729"
+    "urls": "doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?pdf=render"
   },
   {
     "id": "33328048",
@@ -20349,21 +20332,21 @@
     "urls": "pdf:http://www.thelancet.com/article/S2589750020302181/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30218-1; html:https://europepmc.org/articles/PMC8183333; pdf:https://europepmc.org/articles/PMC8183333?pdf=render; doi:https://doi.org/10.1016/s2589-7500(20)30218-1"
   },
   {
-    "id": "35748342",
-    "doi": "https://doi.org/10.1093/ije/dyac130",
-    "title": "Linkage of multiple electronic health record datasets using a 'spine linkage' approach compared with all 'pairwise linkages'.",
-    "authorString": "Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K.",
+    "id": "35144240",
+    "doi": "https://doi.org/10.2196/32543",
+    "title": "Artificial Intelligence-Enabled Social Media Analysis for Pharmacovigilance of COVID-19 Vaccinations in the United Kingdom: Observational Study.",
+    "authorString": "Hussain Z, Sheikh Z, Tahir A, Dashtipour K, Gogate M, Sheikh A, Hussain A.",
     "authorAffiliations": "",
-    "journalTitle": "International journal of epidemiology",
-    "pubYear": "2023",
-    "date": "2023-02-01",
+    "journalTitle": "JMIR public health and surveillance",
+    "pubYear": "2022",
+    "date": "2022-05-27",
     "isOpenAccess": "Y",
-    "keywords": "Electronic Health Records; Record Linkage; Pairwise Linkage; Spine Linkage Approach",
+    "keywords": "Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all 'pairwise linkages'-linking each dataset to every other dataset-is the most inclusive, but resource-intensive, approach. The 'spine' approach links each dataset to a designated 'spine dataset', reducing the number of linkages, but potentially reducing linkage quality.<h4>Methods</h4>We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31\u00a0October\u00a02013 and 30\u00a0April\u00a02018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery.<h4>Results</h4>The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15\u200a826 patients, equating to 98.3% of the 16\u200a100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14\u200a509 patients (90.0% compared with pairwise linkage).<h4>Conclusion</h4>Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.",
+    "abstract": "<h4>Background</h4>The rollout of vaccines for COVID-19 in the United Kingdom started in December 2020. Uptake has been high, and there has been a subsequent reduction in infections, hospitalizations, and deaths among vaccinated individuals. However, vaccine hesitancy remains a concern, in particular relating to adverse effects following immunization (AEFIs). Social media analysis has the potential to inform policy makers about AEFIs being discussed by the public as well as public attitudes toward the national immunization campaign.<h4>Objective</h4>We sought to assess the frequency and nature of AEFI-related mentions on social media in the United Kingdom and to provide insights on public sentiments toward COVID-19 vaccines.<h4>Methods</h4>We extracted and analyzed over 121,406 relevant Twitter and Facebook posts, from December 8, 2020, to April 30, 2021. These were thematically filtered using a 2-step approach, initially using COVID-19-related keywords and then using vaccine- and manufacturer-related keywords. We identified AEFI-related keywords and modeled their word frequency to monitor their trends over 2-week periods. We also adapted and utilized our recently developed hybrid ensemble model, which combines state-of-the-art lexicon rule-based and deep learning-based approaches, to analyze sentiment trends relating to the main vaccines available in the United Kingdom.<h4>Results</h4>Our COVID-19 AEFI search strategy identified 46,762 unique Facebook posts by 14,346 users and 74,644 tweets (excluding retweets) by 36,446 users over the 4-month period. We identified an increasing trend in the number of mentions for each AEFI on social media over the study period. The most frequent AEFI mentions were found to be symptoms related to appetite (n=79,132, 14%), allergy (n=53,924, 9%), injection site (n=56,152, 10%), and clots (n=43,907, 8%). We also found some rarely reported AEFIs such as Bell palsy (n=11,909, 2%) and Guillain-Barre syndrome (n=9576, 2%) being discussed as frequently as more well-known side effects like headache (n=10,641, 2%), fever (n=12,707, 2%), and diarrhea (n=16,559, 3%). Overall, we found public sentiment toward vaccines and their manufacturers to be largely positive (58%), with a near equal split between negative (22%) and neutral (19%) sentiments. The sentiment trend was relatively steady over time and had minor variations, likely based on political and regulatory announcements and debates.<h4>Conclusions</h4>The most frequently discussed COVID-19 AEFIs on social media were found to be broadly consistent with those reported in the literature and by government pharmacovigilance. We also detected potential safety signals from our analysis that have been detected elsewhere and are currently being investigated. As such, we believe our findings support the use of social media analysis to provide a complementary data source to conventional knowledge sources being used for pharmacovigilance purposes.",
     "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac130/44245961/dyac130.pdf; doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render"
+    "urls": "pdf:https://publichealth.jmir.org/2022/5/e32543/PDF; doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729"
   },
   {
     "id": "32929109",
@@ -20382,6 +20365,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-020-72060-0.pdf; doi:https://doi.org/10.1038/s41598-020-72060-0; html:https://europepmc.org/articles/PMC7490405; pdf:https://europepmc.org/articles/PMC7490405?pdf=render"
   },
+  {
+    "id": "35748342",
+    "doi": "https://doi.org/10.1093/ije/dyac130",
+    "title": "Linkage of multiple electronic health record datasets using a 'spine linkage' approach compared with all 'pairwise linkages'.",
+    "authorString": "Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K.",
+    "authorAffiliations": "",
+    "journalTitle": "International journal of epidemiology",
+    "pubYear": "2023",
+    "date": "2023-02-01",
+    "isOpenAccess": "Y",
+    "keywords": "Electronic Health Records; Record Linkage; Pairwise Linkage; Spine Linkage Approach",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all 'pairwise linkages'-linking each dataset to every other dataset-is the most inclusive, but resource-intensive, approach. The 'spine' approach links each dataset to a designated 'spine dataset', reducing the number of linkages, but potentially reducing linkage quality.<h4>Methods</h4>We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31\u00a0October\u00a02013 and 30\u00a0April\u00a02018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery.<h4>Results</h4>The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15\u200a826 patients, equating to 98.3% of the 16\u200a100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14\u200a509 patients (90.0% compared with pairwise linkage).<h4>Conclusion</h4>Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac130/44245961/dyac130.pdf; doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render"
+  },
   {
     "id": "35028631",
     "doi": "https://doi.org/10.1016/s2666-7568(21)00281-6",
@@ -20400,38 +20400,38 @@
     "urls": "pdf:http://www.thelancet.com/article/S2666756821002816/pdf; doi:https://doi.org/10.1016/S2666-7568(21)00281-6; html:https://europepmc.org/articles/PMC8732286"
   },
   {
-    "id": "37563195",
-    "doi": "https://doi.org/10.1038/s41598-023-38880-6",
-    "title": "Locational memory of macrovessel vascular cells is transcriptionally imprinted.",
-    "authorString": "Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.",
+    "id": "36344532",
+    "doi": "https://doi.org/10.1038/s41598-022-21663-w",
+    "title": "Atrial fibrillation prediction by combining ECG markers and CMR radiomics.",
+    "authorString": "Pujadas ER, Raisi-Estabragh Z, Szabo L, Morcillo CI, Campello VM, Martin-Isla C, Vago H, Merkely B, Harvey NC, Petersen SE, Lekadir K.",
     "authorAffiliations": "",
     "journalTitle": "Scientific reports",
-    "pubYear": "2023",
-    "date": "2023-08-10",
+    "pubYear": "2022",
+    "date": "2022-11-07",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.",
+    "abstract": "Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with a higher risk of important adverse health outcomes such as stroke and death. AF is linked to distinct electro-anatomic alterations. The main tool for AF diagnosis is the Electrocardiogram (ECG). However, an ECG recorded at a single time point may not detect individuals with paroxysmal AF. In this study, we developed machine learning models for discrimination of prevalent AF using a combination of image-derived radiomics phenotypes and ECG features. Thus, we characterize the phenotypes of prevalent AF in terms of ECG and imaging alterations. Moreover, we explore sex-differential remodelling by building sex-specific models. Our integrative model including radiomics and ECG together resulted in a better performance than ECG alone, particularly in women. ECG had a lower performance in women than men (AUC: 0.77 vs 0.88, p\u2009<\u20090.05) but adding radiomics features, the accuracy of the model was able to improve significantly. The sensitivity also increased considerably in women by adding the radiomics (0.68 vs 0.79, p\u2009<\u20090.05) having a higher detection of AF events. Our findings provide novel insights into AF-related electro-anatomic remodelling and its variations by sex. The integrative radiomics-ECG model also presents a potential novel approach for earlier detection of AF.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41598-022-21663-w.pdf; doi:https://doi.org/10.1038/s41598-022-21663-w; html:https://europepmc.org/articles/PMC9640662; pdf:https://europepmc.org/articles/PMC9640662?pdf=render"
   },
   {
-    "id": "36344532",
-    "doi": "https://doi.org/10.1038/s41598-022-21663-w",
-    "title": "Atrial fibrillation prediction by combining ECG markers and CMR radiomics.",
-    "authorString": "Pujadas ER, Raisi-Estabragh Z, Szabo L, Morcillo CI, Campello VM, Martin-Isla C, Vago H, Merkely B, Harvey NC, Petersen SE, Lekadir K.",
+    "id": "37563195",
+    "doi": "https://doi.org/10.1038/s41598-023-38880-6",
+    "title": "Locational memory of macrovessel vascular cells is transcriptionally imprinted.",
+    "authorString": "Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.",
     "authorAffiliations": "",
     "journalTitle": "Scientific reports",
-    "pubYear": "2022",
-    "date": "2022-11-07",
+    "pubYear": "2023",
+    "date": "2023-08-10",
     "isOpenAccess": "Y",
     "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with a higher risk of important adverse health outcomes such as stroke and death. AF is linked to distinct electro-anatomic alterations. The main tool for AF diagnosis is the Electrocardiogram (ECG). However, an ECG recorded at a single time point may not detect individuals with paroxysmal AF. In this study, we developed machine learning models for discrimination of prevalent AF using a combination of image-derived radiomics phenotypes and ECG features. Thus, we characterize the phenotypes of prevalent AF in terms of ECG and imaging alterations. Moreover, we explore sex-differential remodelling by building sex-specific models. Our integrative model including radiomics and ECG together resulted in a better performance than ECG alone, particularly in women. ECG had a lower performance in women than men (AUC: 0.77 vs 0.88, p\u2009<\u20090.05) but adding radiomics features, the accuracy of the model was able to improve significantly. The sensitivity also increased considerably in women by adding the radiomics (0.68 vs 0.79, p\u2009<\u20090.05) having a higher detection of AF events. Our findings provide novel insights into AF-related electro-anatomic remodelling and its variations by sex. The integrative radiomics-ECG model also presents a potential novel approach for earlier detection of AF.",
+    "abstract": "Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41598-022-21663-w.pdf; doi:https://doi.org/10.1038/s41598-022-21663-w; html:https://europepmc.org/articles/PMC9640662; pdf:https://europepmc.org/articles/PMC9640662?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render"
   },
   {
     "id": "36576811",
@@ -20467,23 +20467,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/gigascience/article-pdf/10/11/giab076/41395024/giab076.pdf; doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render"
   },
-  {
-    "id": "36701266",
-    "doi": "https://doi.org/10.1371/journal.pmed.1004036",
-    "title": "Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.",
-    "authorString": "Vinther JL, Cadman T, Avraam D, Ekstr\u00f8m CT, S\u00f8rensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, I\u00f1iguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fern\u00e1ndez-Barr\u00e9s S, Turvey S, Santos S, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.",
-    "authorAffiliations": "",
-    "journalTitle": "PLoS medicine",
-    "pubYear": "2023",
-    "date": "2023-01-26",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.<h4>Methods and findings</h4>We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.<h4>Conclusions</h4>This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render"
-  },
   {
     "id": "34306597",
     "doi": "https://doi.org/10.1155/2021/6663884",
@@ -20518,6 +20501,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202359&type=printable; doi:https://doi.org/10.1371/journal.pone.0202359; html:https://europepmc.org/articles/PMC6124703; pdf:https://europepmc.org/articles/PMC6124703?pdf=render"
   },
+  {
+    "id": "36701266",
+    "doi": "https://doi.org/10.1371/journal.pmed.1004036",
+    "title": "Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.",
+    "authorString": "Vinther JL, Cadman T, Avraam D, Ekstr\u00f8m CT, S\u00f8rensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, I\u00f1iguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fern\u00e1ndez-Barr\u00e9s S, Turvey S, Santos S, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.",
+    "authorAffiliations": "",
+    "journalTitle": "PLoS medicine",
+    "pubYear": "2023",
+    "date": "2023-01-26",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.<h4>Methods and findings</h4>We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.<h4>Conclusions</h4>This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render"
+  },
   {
     "id": "35536740",
     "doi": "https://doi.org/10.1136/bmjopen-2021-052884",
@@ -20722,23 +20722,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630987/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630987/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10630987; pdf:https://europepmc.org/articles/PMC10630987?pdf=render"
   },
-  {
-    "id": "34409990",
-    "doi": "https://doi.org/10.1093/dote/doab058",
-    "title": "Demographic and lifestyle risk factors for gastroesophageal reflux disease and Barrett's esophagus in Australia. ",
-    "authorString": "Wang SE, Kendall BJ, Hodge AM, Dixon-Suen SC, Dashti SG, Makalic E, Williamson EM, Thomas RJS, Giles GG, English DR.",
-    "authorAffiliations": "",
-    "journalTitle": "Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus",
-    "pubYear": "2022",
-    "date": "2022-01-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8\u00a0years, risk of GERD symptoms was 7.5% (n\u2009=\u20091,318) for daily, 7.5% (n\u2009=\u20091,333) for 2-6\u00a0days/week, and 4.3% (n\u2009=\u2009751) for 1\u00a0day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/dote/article-pdf/35/1/doab058/42098674/doab058.pdf; doi:https://doi.org/10.1093/dote/doab058"
-  },
   {
     "id": "32352158",
     "doi": "https://doi.org/10.1002/bjs.11580",
@@ -20756,6 +20739,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/bjs/article-pdf/107/7/e220/35705126/bjs11580.pdf; doi:https://doi.org/10.1002/bjs.11580"
   },
+  {
+    "id": "34409990",
+    "doi": "https://doi.org/10.1093/dote/doab058",
+    "title": "Demographic and lifestyle risk factors for gastroesophageal reflux disease and Barrett's esophagus in Australia. ",
+    "authorString": "Wang SE, Kendall BJ, Hodge AM, Dixon-Suen SC, Dashti SG, Makalic E, Williamson EM, Thomas RJS, Giles GG, English DR.",
+    "authorAffiliations": "",
+    "journalTitle": "Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus",
+    "pubYear": "2022",
+    "date": "2022-01-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8\u00a0years, risk of GERD symptoms was 7.5% (n\u2009=\u20091,318) for daily, 7.5% (n\u2009=\u20091,333) for 2-6\u00a0days/week, and 4.3% (n\u2009=\u2009751) for 1\u00a0day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/dote/article-pdf/35/1/doab058/42098674/doab058.pdf; doi:https://doi.org/10.1093/dote/doab058"
+  },
   {
     "id": "37321240",
     "doi": "https://doi.org/10.1016/s2215-0366(23)00113-x",
@@ -20790,6 +20790,23 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420473; doi:https://doi.org/10.1111/tri.14010; html:https://europepmc.org/articles/PMC8420473; pdf:https://europepmc.org/articles/PMC8420473?pdf=render"
   },
+  {
+    "id": "31302040",
+    "doi": "https://doi.org/10.1016/j.jchf.2019.03.009",
+    "title": "Risk for Heart\u00a0Failure: The Opportunity for Prevention With the American Heart Association's Life's Simple 7.",
+    "authorString": "Uijl A, Koudstaal S, Vaartjes I, Boer JMA, Verschuren WMM, van der Schouw YT, Asselbergs FW, Hoes AW, Sluijs I.",
+    "authorAffiliations": "",
+    "journalTitle": "JACC. Heart failure",
+    "pubYear": "2019",
+    "date": "2019-07-10",
+    "isOpenAccess": "N",
+    "keywords": "Heart Failure; Cardiovascular Disease Risk Factors; Healthy Lifestyle; Life\u2019s Simple 7",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>The aim of this study is to determine whether combinations of specific Life's Simple 7 (LS7) components are associated with reduced risk for heart failure (HF).<h4>Background</h4>The American Heart Association recommends the concept of LS7: healthy behaviors that have been shown to reduce cardiovascular disease.<h4>Methods</h4>A total of 37,803 participants from the EPIC-NL (European Prospective Investigation Into Cancer and Nutrition-Netherlands) cohort were included (mean age: 49.4 \u00b1 11.9 years, 74.7% women). The LS7 score ranged from 0 to 14 and was calculated by assigning 0, 1, or 2 points for smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. An overall ideal score (11 to 14 points) was present in 23.2% of participants, an intermediate score (9 or 10 points) in 35.3%, and an inadequate score (0 to 8 points) in 41.5%.<h4>Results</h4>Over a median follow-up period of 15.2 years (interquartile range: 14.1 to 16.5 years), 690 participants (1.8%) developed HF. In Cox proportional hazards models, ideal and intermediate LS7 scores were associated with reduced risk for HF compared with the inadequate category (hazard ratio: 0.45 [95% confidence interval (CI): 0.34 to 0.60] and hazard ratio: 0.53 [95% CI: 0.44 to 0.64], respectively). Our analyses show that combinations with specific LS7 components, notably glucose, body mass index, smoking, and blood pressure, are associated with a lower incidence of HF.<h4>Conclusions</h4>A healthy lifestyle, as reflected in an ideal LS7 score, was associated with a 55% lower risk for HF compared with an inadequate LS7 score. Preventive strategies that target combinations of specific LS7 components could have a significant impact on decreasing incident HF in the population at large.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jchf.2019.03.009"
+  },
   {
     "id": "36469091",
     "doi": "https://doi.org/10.1093/ageing/afac252",
@@ -20824,23 +20841,6 @@
     "laySummary": "",
     "urls": "pdf:https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2785704/jamaophthalmology_kuan_2021_oi_210068_1639510445.31311.pdf; doi:https://doi.org/10.1001/jamaophthalmol.2021.4601; html:https://europepmc.org/articles/PMC8569599"
   },
-  {
-    "id": "31302040",
-    "doi": "https://doi.org/10.1016/j.jchf.2019.03.009",
-    "title": "Risk for Heart\u00a0Failure: The Opportunity for Prevention With the American Heart Association's Life's Simple 7.",
-    "authorString": "Uijl A, Koudstaal S, Vaartjes I, Boer JMA, Verschuren WMM, van der Schouw YT, Asselbergs FW, Hoes AW, Sluijs I.",
-    "authorAffiliations": "",
-    "journalTitle": "JACC. Heart failure",
-    "pubYear": "2019",
-    "date": "2019-07-10",
-    "isOpenAccess": "N",
-    "keywords": "Heart Failure; Cardiovascular Disease Risk Factors; Healthy Lifestyle; Life\u2019s Simple 7",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>The aim of this study is to determine whether combinations of specific Life's Simple 7 (LS7) components are associated with reduced risk for heart failure (HF).<h4>Background</h4>The American Heart Association recommends the concept of LS7: healthy behaviors that have been shown to reduce cardiovascular disease.<h4>Methods</h4>A total of 37,803 participants from the EPIC-NL (European Prospective Investigation Into Cancer and Nutrition-Netherlands) cohort were included (mean age: 49.4 \u00b1 11.9 years, 74.7% women). The LS7 score ranged from 0 to 14 and was calculated by assigning 0, 1, or 2 points for smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. An overall ideal score (11 to 14 points) was present in 23.2% of participants, an intermediate score (9 or 10 points) in 35.3%, and an inadequate score (0 to 8 points) in 41.5%.<h4>Results</h4>Over a median follow-up period of 15.2 years (interquartile range: 14.1 to 16.5 years), 690 participants (1.8%) developed HF. In Cox proportional hazards models, ideal and intermediate LS7 scores were associated with reduced risk for HF compared with the inadequate category (hazard ratio: 0.45 [95% confidence interval (CI): 0.34 to 0.60] and hazard ratio: 0.53 [95% CI: 0.44 to 0.64], respectively). Our analyses show that combinations with specific LS7 components, notably glucose, body mass index, smoking, and blood pressure, are associated with a lower incidence of HF.<h4>Conclusions</h4>A healthy lifestyle, as reflected in an ideal LS7 score, was associated with a 55% lower risk for HF compared with an inadequate LS7 score. Preventive strategies that target combinations of specific LS7 components could have a significant impact on decreasing incident HF in the population at large.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jchf.2019.03.009"
-  },
   {
     "id": "34038519",
     "doi": "https://doi.org/10.1093/ageing/afab084",
@@ -21028,23 +21028,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8563; doi:https://doi.org/10.1002/sim.8563"
   },
-  {
-    "id": "36828609",
-    "doi": "https://doi.org/10.1016/s2589-7500(22)00252-7",
-    "title": "Embedding patient-reported outcomes at the heart of artificial intelligence health-care technologies.",
-    "authorString": "Cruz Rivera S, Liu X, Hughes SE, Dunster H, Manna E, Denniston AK, Calvert MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "The Lancet. Digital health",
-    "pubYear": "2023",
-    "date": "2023-03-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Integration of patient-reported outcome measures (PROMs) in artificial intelligence (AI) studies is a critical part of the humanisation of AI for health. It allows AI technologies to incorporate patients' own views of their symptoms and predict outcomes, reflecting a more holistic picture of health and wellbeing and ultimately helping patients and clinicians to make the best health-care decisions together. By positioning patient-reported outcomes (PROs) as a model input or output we propose a framework to embed PROMs within the function and evaluation of AI health care. However, the integration of PROs in AI systems presents several challenges. These challenges include (1) fragmentation of PRO data collection; (2) validation of AI systems trained and validated against clinician performance, rather than outcome data; (3) scarcity of large-scale PRO datasets; (4) inadequate selection of PROMs for the target population and inadequate infrastructure for collecting PROs; and (5) clinicians might not recognise the value of PROs and therefore not prioritise their adoption; and (6) studies involving PRO or AI frequently present suboptimal design. Notwithstanding these challenges, we propose considerations for the inclusion of PROs in AI health-care technologies to avoid promoting survival at the expense of wellbeing.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/s2589-7500(22)00252-7; doi:https://doi.org/10.1016/S2589-7500(22)00252-7"
-  },
   {
     "id": "34095541",
     "doi": "https://doi.org/10.23889/ijpds.v4i2.1134",
@@ -21062,6 +21045,23 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1134/2643; doi:https://doi.org/10.23889/ijpds.v4i2.1134; html:https://europepmc.org/articles/PMC8142954; pdf:https://europepmc.org/articles/PMC8142954?pdf=render"
   },
+  {
+    "id": "36828609",
+    "doi": "https://doi.org/10.1016/s2589-7500(22)00252-7",
+    "title": "Embedding patient-reported outcomes at the heart of artificial intelligence health-care technologies.",
+    "authorString": "Cruz Rivera S, Liu X, Hughes SE, Dunster H, Manna E, Denniston AK, Calvert MJ.",
+    "authorAffiliations": "",
+    "journalTitle": "The Lancet. Digital health",
+    "pubYear": "2023",
+    "date": "2023-03-01",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Integration of patient-reported outcome measures (PROMs) in artificial intelligence (AI) studies is a critical part of the humanisation of AI for health. It allows AI technologies to incorporate patients' own views of their symptoms and predict outcomes, reflecting a more holistic picture of health and wellbeing and ultimately helping patients and clinicians to make the best health-care decisions together. By positioning patient-reported outcomes (PROs) as a model input or output we propose a framework to embed PROMs within the function and evaluation of AI health care. However, the integration of PROs in AI systems presents several challenges. These challenges include (1) fragmentation of PRO data collection; (2) validation of AI systems trained and validated against clinician performance, rather than outcome data; (3) scarcity of large-scale PRO datasets; (4) inadequate selection of PROMs for the target population and inadequate infrastructure for collecting PROs; and (5) clinicians might not recognise the value of PROs and therefore not prioritise their adoption; and (6) studies involving PRO or AI frequently present suboptimal design. Notwithstanding these challenges, we propose considerations for the inclusion of PROs in AI health-care technologies to avoid promoting survival at the expense of wellbeing.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/s2589-7500(22)00252-7; doi:https://doi.org/10.1016/S2589-7500(22)00252-7"
+  },
   {
     "id": "34761838",
     "doi": "https://doi.org/10.1002/biof.1801",
@@ -21249,23 +21249,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ije/article-pdf/52/1/132/49127281/dyac105.pdf; doi:https://doi.org/10.1093/ije/dyac105; html:https://europepmc.org/articles/PMC9908051; pdf:https://europepmc.org/articles/PMC9908051?pdf=render"
   },
-  {
-    "id": "37046260",
-    "doi": "https://doi.org/10.1186/s12913-023-09363-1",
-    "title": "Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.",
-    "authorString": "Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar \u00c1, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC health services research",
-    "pubYear": "2023",
-    "date": "2023-04-12",
-    "isOpenAccess": "Y",
-    "keywords": "Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear.\u00a0In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.<h4>Methods</h4>Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15\u00a0months pre-COVID (January 2019-March 2020). We used the\u00a0Oxford COVID-19 Government Response Tracker (OxCGRT) index and\u00a0multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.<h4>Findings</h4>Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.<h4>Conclusions</h4>Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.",
-    "laySummary": "",
-    "urls": "pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render"
-  },
   {
     "id": "33749694",
     "doi": "https://doi.org/",
@@ -21300,6 +21283,23 @@
     "laySummary": "",
     "urls": "pdf:https://diabetesjournals.org/diabetes/article-pdf/70/10/2313/628539/db200895.pdf; doi:https://doi.org/10.2337/db20-0895"
   },
+  {
+    "id": "37046260",
+    "doi": "https://doi.org/10.1186/s12913-023-09363-1",
+    "title": "Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.",
+    "authorString": "Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar \u00c1, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC health services research",
+    "pubYear": "2023",
+    "date": "2023-04-12",
+    "isOpenAccess": "Y",
+    "keywords": "Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear.\u00a0In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.<h4>Methods</h4>Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15\u00a0months pre-COVID (January 2019-March 2020). We used the\u00a0Oxford COVID-19 Government Response Tracker (OxCGRT) index and\u00a0multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.<h4>Findings</h4>Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.<h4>Conclusions</h4>Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.",
+    "laySummary": "",
+    "urls": "pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render"
+  },
   {
     "id": "34390586",
     "doi": "https://doi.org/10.1111/ejn.15423",
@@ -21436,23 +21436,6 @@
     "laySummary": "",
     "urls": "pdf:http://repositori.upf.edu/bitstream/10230/53310/1/Rambla_2022.pdf; doi:https://doi.org/10.1002/humu.24369; html:https://europepmc.org/articles/PMC9322265; pdf:https://europepmc.org/articles/PMC9322265?pdf=render"
   },
-  {
-    "id": "34275648",
-    "doi": "https://doi.org/10.1016/j.injury.2021.06.037",
-    "title": "Patterns and predictors of personal responsibility attributions after major trauma.",
-    "authorString": "Lau G, Gabbe BJ, Giummarra MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Injury",
-    "pubYear": "2021",
-    "date": "2021-07-06",
-    "isOpenAccess": "N",
-    "keywords": "wounds and injuries; Insurance, Accident; Violence; Guilt; Accidental Injuries; Liability, Legal",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>External responsibility attributions after injury are associated with worse recovery. However, there remains limited understanding of who accepts personal responsibilityfor their injury and whether or how responsibility attributions change over time.<h4>Methods</h4>This prospective cohort study included patients who received care from recovery co-ordinators following serious injury and admission to a major trauma centre in Victoria, Australia (n=850). Self-reported personal responsibility attributions (totally, partially, not responsible, or did not know) were collected at three timepoints (admission, discharge, and six months post-injury) and linked to demographic, injury and clinical characteristics from the Victorian State Trauma Registry.<h4>Results</h4>Mixed effects multinomial analyses revealed that female sex (adjusted relative risk ratio, aRRR=3.11-4.66) and compensable injury (aRRR=7.83-15.27) were associated with reporting lower personal responsibility relative to total responsibility. Falls and motorcyclists had decreased risk of reporting lower personal responsibility than non-drivers (motor vehicle/motorcycle passengers, cyclists and pedestrians) (aRRR=0.11-0.19). More than one-third of participants changed their personal responsibility attribution within six months post-injury. Kappa analyses revealed fair to moderate agreement between the three timepoints (kappa=0.38-0.59), and Stuart-Maxwell tests showed unidirectional bias towards reporting lower levels of personal responsibility between admission and discharge (p<0.001). No demographic, health or injury characteristics predicted a change in responsibility attributions in logistic regression analyses.<h4>Conclusions</h4>Personal responsibility attributions often change over time. Therefore, responsibility attributions should not be considered static, and attributions made at different times post-injury should not be used interchangeably in research or clinical settings. Given that external responsibility attributions are associated with worse post-injury outcomes, potential interventions to optimise recovery should be prioritised for patients who predominantly report lower levels of personal responsibility, especially women and people with compensable injuries. Meanwhile, factors associated with high levels of personal responsibility highlight opportunities to implement targeted injury prevention strategies.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.injury.2021.06.037"
-  },
   {
     "id": "32119825",
     "doi": "https://doi.org/10.1016/s2214-109x(20)30074-7",
@@ -21470,6 +21453,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2214109X20300747/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30074-7; html:https://europepmc.org/articles/PMC7097845; pdf:https://europepmc.org/articles/PMC7097845?pdf=render"
   },
+  {
+    "id": "34275648",
+    "doi": "https://doi.org/10.1016/j.injury.2021.06.037",
+    "title": "Patterns and predictors of personal responsibility attributions after major trauma.",
+    "authorString": "Lau G, Gabbe BJ, Giummarra MJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Injury",
+    "pubYear": "2021",
+    "date": "2021-07-06",
+    "isOpenAccess": "N",
+    "keywords": "wounds and injuries; Insurance, Accident; Violence; Guilt; Accidental Injuries; Liability, Legal",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>External responsibility attributions after injury are associated with worse recovery. However, there remains limited understanding of who accepts personal responsibilityfor their injury and whether or how responsibility attributions change over time.<h4>Methods</h4>This prospective cohort study included patients who received care from recovery co-ordinators following serious injury and admission to a major trauma centre in Victoria, Australia (n=850). Self-reported personal responsibility attributions (totally, partially, not responsible, or did not know) were collected at three timepoints (admission, discharge, and six months post-injury) and linked to demographic, injury and clinical characteristics from the Victorian State Trauma Registry.<h4>Results</h4>Mixed effects multinomial analyses revealed that female sex (adjusted relative risk ratio, aRRR=3.11-4.66) and compensable injury (aRRR=7.83-15.27) were associated with reporting lower personal responsibility relative to total responsibility. Falls and motorcyclists had decreased risk of reporting lower personal responsibility than non-drivers (motor vehicle/motorcycle passengers, cyclists and pedestrians) (aRRR=0.11-0.19). More than one-third of participants changed their personal responsibility attribution within six months post-injury. Kappa analyses revealed fair to moderate agreement between the three timepoints (kappa=0.38-0.59), and Stuart-Maxwell tests showed unidirectional bias towards reporting lower levels of personal responsibility between admission and discharge (p<0.001). No demographic, health or injury characteristics predicted a change in responsibility attributions in logistic regression analyses.<h4>Conclusions</h4>Personal responsibility attributions often change over time. Therefore, responsibility attributions should not be considered static, and attributions made at different times post-injury should not be used interchangeably in research or clinical settings. Given that external responsibility attributions are associated with worse post-injury outcomes, potential interventions to optimise recovery should be prioritised for patients who predominantly report lower levels of personal responsibility, especially women and people with compensable injuries. Meanwhile, factors associated with high levels of personal responsibility highlight opportunities to implement targeted injury prevention strategies.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.injury.2021.06.037"
+  },
   {
     "id": "36722341",
     "doi": "https://doi.org/10.1093/cei/uxad008",
@@ -21555,23 +21555,6 @@
     "laySummary": "",
     "urls": "pdf:https://jasn.asnjournals.org/content/jnephrol/32/1/127.full.pdf; doi:https://doi.org/10.1681/ASN.2020050679; html:https://europepmc.org/articles/PMC7894659; doi:https://doi.org/10.1681/asn.2020050679"
   },
-  {
-    "id": "37722858",
-    "doi": "https://doi.org/10.3399/bjgp.2023.0077",
-    "title": "Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.",
-    "authorString": "Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.",
-    "authorAffiliations": "",
-    "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners",
-    "pubYear": "2023",
-    "date": "2023-10-26",
-    "isOpenAccess": "Y",
-    "keywords": "Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.<h4>Aim</h4>To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.<h4>Design and setting</h4>A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.<h4>Method</h4>Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.<h4>Results</h4>In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged \u226550 years) were more likely to have controlled hypertension than younger patients.<h4>Conclusion</h4>Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render"
-  },
   {
     "id": "32571619",
     "doi": "https://doi.org/10.1016/j.schres.2020.05.007",
@@ -21589,6 +21572,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.schres.2020.05.007; doi:https://doi.org/10.1016/j.schres.2020.05.007; html:https://europepmc.org/articles/PMC7875179"
   },
+  {
+    "id": "37722858",
+    "doi": "https://doi.org/10.3399/bjgp.2023.0077",
+    "title": "Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.",
+    "authorString": "Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.",
+    "authorAffiliations": "",
+    "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners",
+    "pubYear": "2023",
+    "date": "2023-10-26",
+    "isOpenAccess": "Y",
+    "keywords": "Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.<h4>Aim</h4>To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.<h4>Design and setting</h4>A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.<h4>Method</h4>Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.<h4>Results</h4>In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged \u226550 years) were more likely to have controlled hypertension than younger patients.<h4>Conclusion</h4>Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render"
+  },
   {
     "id": "33144367",
     "doi": "https://doi.org/10.3399/bjgpopen20x101109",
@@ -21657,6 +21657,23 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10145565/1/Hignorani_Biological%20mechanisms%20of%20aging%20predict%20age-related%20disease%20co-occurrence%20in%20patients_AOP.pdf; doi:https://doi.org/10.1111/acel.13524; html:https://europepmc.org/articles/PMC9009120; pdf:https://europepmc.org/articles/PMC9009120?pdf=render"
   },
+  {
+    "id": "32838035",
+    "doi": "https://doi.org/10.1002/lrh2.10236",
+    "title": "Rapid translation of clinical guidelines into executable knowledge: A case study of COVID-19 and online demonstration.",
+    "authorString": "Fox J, Khan O, Curtis H, Wright A, Pal C, Cockburn N, Cooper J, Chandan JS, Nirantharakumar K.",
+    "authorAffiliations": "",
+    "journalTitle": "Learning health systems",
+    "pubYear": "2021",
+    "date": "2020-07-14",
+    "isOpenAccess": "Y",
+    "keywords": "Artificial intelligence; Covid\u201019; Rapid Learning Systems",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID-19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020.<h4>Methods</h4>The <i>PROforma</i> guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID-19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice.<h4>Results</h4><i>PROforma</i> and OpenClinical.net proved to be an effective combination for rapidly creating the COVID-19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746.<h4>Conclusions</h4>This is believed to be the first use of AI/knowledge engineering methods for disseminating best-practice in COVID-19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10236; doi:https://doi.org/10.1002/lrh2.10236; html:https://europepmc.org/articles/PMC7323421; pdf:https://europepmc.org/articles/PMC7323421?pdf=render"
+  },
   {
     "id": "36331190",
     "doi": "https://doi.org/10.1056/nejmoa2204233",
@@ -21691,23 +21708,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165682; doi:https://doi.org/10.1016/j.oret.2021.04.001; html:https://europepmc.org/articles/PMC9165682; pdf:https://europepmc.org/articles/PMC9165682?pdf=render; doi:https://doi.org/10.1016/j.oret.2021.04.001"
   },
-  {
-    "id": "32838035",
-    "doi": "https://doi.org/10.1002/lrh2.10236",
-    "title": "Rapid translation of clinical guidelines into executable knowledge: A case study of COVID-19 and online demonstration.",
-    "authorString": "Fox J, Khan O, Curtis H, Wright A, Pal C, Cockburn N, Cooper J, Chandan JS, Nirantharakumar K.",
-    "authorAffiliations": "",
-    "journalTitle": "Learning health systems",
-    "pubYear": "2021",
-    "date": "2020-07-14",
-    "isOpenAccess": "Y",
-    "keywords": "Artificial intelligence; Covid\u201019; Rapid Learning Systems",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID-19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020.<h4>Methods</h4>The <i>PROforma</i> guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID-19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice.<h4>Results</h4><i>PROforma</i> and OpenClinical.net proved to be an effective combination for rapidly creating the COVID-19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746.<h4>Conclusions</h4>This is believed to be the first use of AI/knowledge engineering methods for disseminating best-practice in COVID-19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10236; doi:https://doi.org/10.1002/lrh2.10236; html:https://europepmc.org/articles/PMC7323421; pdf:https://europepmc.org/articles/PMC7323421?pdf=render"
-  },
   {
     "id": "31757515",
     "doi": "https://doi.org/10.1016/j.jaci.2019.09.015",
@@ -21810,23 +21810,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?pdf=render"
   },
-  {
-    "id": "37278928",
-    "doi": "https://doi.org/10.1007/s12265-023-10398-2",
-    "title": "Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers.",
-    "authorString": "Jansen M, Schmidt AF, Jans JJM, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Lekanne Deprez RH, Wilde AAM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of cardiovascular translational research",
-    "pubYear": "2023",
-    "date": "2023-06-06",
-    "isOpenAccess": "N",
-    "keywords": "Metabolism; Biomarker; hypertrophic cardiomyopathy; Acylcarnitine; Mybpc3",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G\u2009+\u2009P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G\u2009+\u2009P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G\u2009+\u2009P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p\u2009=\u20090.005 and coefficient 0.803, p\u2009=\u20090.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p\u2009=\u20090.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.",
-    "laySummary": "",
-    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12265-023-10398-2.pdf; doi:https://doi.org/10.1007/s12265-023-10398-2"
-  },
   {
     "id": "34426417",
     "doi": "https://doi.org/10.1136/bmjhci-2021-100385",
@@ -21861,6 +21844,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jclinepi.2022.04.025"
   },
+  {
+    "id": "37278928",
+    "doi": "https://doi.org/10.1007/s12265-023-10398-2",
+    "title": "Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers.",
+    "authorString": "Jansen M, Schmidt AF, Jans JJM, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Lekanne Deprez RH, Wilde AAM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of cardiovascular translational research",
+    "pubYear": "2023",
+    "date": "2023-06-06",
+    "isOpenAccess": "N",
+    "keywords": "Metabolism; Biomarker; hypertrophic cardiomyopathy; Acylcarnitine; Mybpc3",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G\u2009+\u2009P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G\u2009+\u2009P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G\u2009+\u2009P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p\u2009=\u20090.005 and coefficient 0.803, p\u2009=\u20090.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p\u2009=\u20090.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.",
+    "laySummary": "",
+    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12265-023-10398-2.pdf; doi:https://doi.org/10.1007/s12265-023-10398-2"
+  },
   {
     "id": "36819459",
     "doi": "https://doi.org/10.1210/jendso/bvad020",
@@ -21980,23 +21980,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.injury.2022.02.027"
   },
-  {
-    "id": "35916366",
-    "doi": "https://doi.org/10.7554/elife.76272",
-    "title": "Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans.",
-    "authorString": "Lemmel\u00e4 S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T, Wollert KC, Blankenberg S, Zeller T, Peters JE, Salomaa V, Fritsch M, March R, Palotie A, Daly M, Butterworth AS, Kinnunen M, Paul DS, Matakidou A.",
-    "authorAffiliations": "",
-    "journalTitle": "eLife",
-    "pubYear": "2022",
-    "date": "2022-08-02",
-    "isOpenAccess": "Y",
-    "keywords": "Human; Genetics; Obesity; Genomics; BMI; epidemiology; Causality; Global Health; Gdf15; Mendelian Randomisation",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in <i>GDF15</i>, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW p<sub>FDR</sub> = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.7554/elife.76272; doi:https://doi.org/10.7554/eLife.76272; html:https://europepmc.org/articles/PMC9391041; pdf:https://europepmc.org/articles/PMC9391041?pdf=render"
-  },
   {
     "id": "34018481",
     "doi": "https://doi.org/10.2807/1560-7917.es.2021.26.20.2100428",
@@ -22014,6 +21997,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/20/eurosurv-26-20-1.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.20.2100428&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428; html:https://europepmc.org/articles/PMC8138959; pdf:https://europepmc.org/articles/PMC8138959?pdf=render"
   },
+  {
+    "id": "35916366",
+    "doi": "https://doi.org/10.7554/elife.76272",
+    "title": "Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans.",
+    "authorString": "Lemmel\u00e4 S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T, Wollert KC, Blankenberg S, Zeller T, Peters JE, Salomaa V, Fritsch M, March R, Palotie A, Daly M, Butterworth AS, Kinnunen M, Paul DS, Matakidou A.",
+    "authorAffiliations": "",
+    "journalTitle": "eLife",
+    "pubYear": "2022",
+    "date": "2022-08-02",
+    "isOpenAccess": "Y",
+    "keywords": "Human; Genetics; Obesity; Genomics; BMI; epidemiology; Causality; Global Health; Gdf15; Mendelian Randomisation",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in <i>GDF15</i>, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW p<sub>FDR</sub> = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.7554/elife.76272; doi:https://doi.org/10.7554/eLife.76272; html:https://europepmc.org/articles/PMC9391041; pdf:https://europepmc.org/articles/PMC9391041?pdf=render"
+  },
   {
     "id": "32524641",
     "doi": "https://doi.org/10.1002/sim.8556",
@@ -22099,23 +22099,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable; doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render"
   },
-  {
-    "id": "37814896",
-    "doi": "https://doi.org/10.1161/circgen.123.004181",
-    "title": "Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.",
-    "authorString": "Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Thomas Lumbers R, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.",
-    "authorAffiliations": "",
-    "journalTitle": "Circulation. Genomic and precision medicine",
-    "pubYear": "2023",
-    "date": "2023-10-10",
-    "isOpenAccess": "N",
-    "keywords": "Phenotype; Myocardial infarction; Biomarker; Cardiovascular disease; epigenomics",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1161/CIRCGEN.123.004181"
-  },
   {
     "id": "33719753",
     "doi": "https://doi.org/10.1080/13607863.2021.1893270",
@@ -22134,21 +22117,21 @@
     "urls": "pdf:https://www.tandfonline.com/doi/pdf/10.1080/13607863.2021.1893270?needAccess=true; doi:https://doi.org/10.1080/13607863.2021.1893270"
   },
   {
-    "id": "37270201",
-    "doi": "https://doi.org/10.1136/heartjnl-2023-322616",
-    "title": "Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data.",
-    "authorString": "Harper C, Mafham M, Herrington W, Staplin N, Stevens W, Wallendszus K, Haynes R, Landray MJ, Parish S, Bowman L, Armitage J.",
+    "id": "37814896",
+    "doi": "https://doi.org/10.1161/circgen.123.004181",
+    "title": "Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.",
+    "authorString": "Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Thomas Lumbers R, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.",
     "authorAffiliations": "",
-    "journalTitle": "Heart (British Cardiac Society)",
+    "journalTitle": "Circulation. Genomic and precision medicine",
     "pubYear": "2023",
-    "date": "2023-09-13",
-    "isOpenAccess": "Y",
-    "keywords": "Atherosclerosis; Research Design; Electronic Health Records; Outcome Assessment, Health Care",
+    "date": "2023-10-10",
+    "isOpenAccess": "N",
+    "keywords": "Phenotype; Myocardial infarction; Biomarker; Cardiovascular disease; epigenomics",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To assess how reliable UK routine data are for ascertaining major bleeding events compared with adjudicated follow-up.<h4>Methods</h4>The ASCEND (A Study of Cardiovascular Events iN Diabetes) primary prevention trial randomised 15\u2009480 UK people with diabetes to aspirin versus matching placebo. The primary safety outcome was major bleeding (including intracranial haemorrhage, sight-threatening eye bleeding, serious gastrointestinal bleeding and other major bleeding (epistaxis, haemoptysis, haematuria, vaginal and other bleeding)) ascertained by direct-participant mail-based follow-up, with >90% of outcomes undergoing adjudication. Nearly all participants were linked to routinely collected hospitalisation and death data (ie, routine data). An algorithm categorised bleeding events from routine data as major/minor. Kappa statistics were used to assess agreement between data sources, and randomised comparisons were re-run using routine data.<h4>Results</h4>When adjudicated follow-up and routine data were compared, there was agreement for 318 major bleeding events, with routine data identifying 281 additional-potential events, and not identifying 241 participant-reported events (kappa 0.53, 95% CI 0.49 to 0.57). Repeating ASCEND's randomised comparisons using routine data only found estimated relative and absolute effects of allocation to aspirin versus placebo on major bleeding similar to adjudicated follow-up (adjudicated follow-up: aspirin 314 (4.1%) vs placebo 245 (3.2%); rate ratio (RR) 1.29, 95%\u2009CI 1.09 to 1.52; absolute excess +6.3/5000 person-years (mean SE\u00b12.1); vs routine data: 327 (4.2%) vs 272 (3.5%); RR 1.21, 95%\u2009CI 1.03 to 1.41; absolute excess +5.0/5000 (\u00b12.2)).<h4>Conclusions</h4>Analyses of the ASCEND randomised trial found that major bleeding events ascertained via UK routine data sources provided relative and absolute treatment effects similar to adjudicated follow-up.<h4>Trial registration number</h4>ISRCTN60635500; NCT00135226.",
+    "abstract": "",
     "laySummary": "",
-    "urls": "pdf:https://heart.bmj.com/content/heartjnl/early/2023/06/02/heartjnl-2023-322616.full.pdf; doi:https://doi.org/10.1136/heartjnl-2023-322616; html:https://europepmc.org/articles/PMC10511984; pdf:https://europepmc.org/articles/PMC10511984?pdf=render"
+    "urls": "doi:https://doi.org/10.1161/CIRCGEN.123.004181"
   },
   {
     "id": "36752447",
@@ -22167,6 +22150,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jcmg.2022.11.012"
   },
+  {
+    "id": "37270201",
+    "doi": "https://doi.org/10.1136/heartjnl-2023-322616",
+    "title": "Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data.",
+    "authorString": "Harper C, Mafham M, Herrington W, Staplin N, Stevens W, Wallendszus K, Haynes R, Landray MJ, Parish S, Bowman L, Armitage J.",
+    "authorAffiliations": "",
+    "journalTitle": "Heart (British Cardiac Society)",
+    "pubYear": "2023",
+    "date": "2023-09-13",
+    "isOpenAccess": "Y",
+    "keywords": "Atherosclerosis; Research Design; Electronic Health Records; Outcome Assessment, Health Care",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To assess how reliable UK routine data are for ascertaining major bleeding events compared with adjudicated follow-up.<h4>Methods</h4>The ASCEND (A Study of Cardiovascular Events iN Diabetes) primary prevention trial randomised 15\u2009480 UK people with diabetes to aspirin versus matching placebo. The primary safety outcome was major bleeding (including intracranial haemorrhage, sight-threatening eye bleeding, serious gastrointestinal bleeding and other major bleeding (epistaxis, haemoptysis, haematuria, vaginal and other bleeding)) ascertained by direct-participant mail-based follow-up, with >90% of outcomes undergoing adjudication. Nearly all participants were linked to routinely collected hospitalisation and death data (ie, routine data). An algorithm categorised bleeding events from routine data as major/minor. Kappa statistics were used to assess agreement between data sources, and randomised comparisons were re-run using routine data.<h4>Results</h4>When adjudicated follow-up and routine data were compared, there was agreement for 318 major bleeding events, with routine data identifying 281 additional-potential events, and not identifying 241 participant-reported events (kappa 0.53, 95% CI 0.49 to 0.57). Repeating ASCEND's randomised comparisons using routine data only found estimated relative and absolute effects of allocation to aspirin versus placebo on major bleeding similar to adjudicated follow-up (adjudicated follow-up: aspirin 314 (4.1%) vs placebo 245 (3.2%); rate ratio (RR) 1.29, 95%\u2009CI 1.09 to 1.52; absolute excess +6.3/5000 person-years (mean SE\u00b12.1); vs routine data: 327 (4.2%) vs 272 (3.5%); RR 1.21, 95%\u2009CI 1.03 to 1.41; absolute excess +5.0/5000 (\u00b12.2)).<h4>Conclusions</h4>Analyses of the ASCEND randomised trial found that major bleeding events ascertained via UK routine data sources provided relative and absolute treatment effects similar to adjudicated follow-up.<h4>Trial registration number</h4>ISRCTN60635500; NCT00135226.",
+    "laySummary": "",
+    "urls": "pdf:https://heart.bmj.com/content/heartjnl/early/2023/06/02/heartjnl-2023-322616.full.pdf; doi:https://doi.org/10.1136/heartjnl-2023-322616; html:https://europepmc.org/articles/PMC10511984; pdf:https://europepmc.org/articles/PMC10511984?pdf=render"
+  },
   {
     "id": "34769922",
     "doi": "https://doi.org/10.3390/ijerph182111380",
@@ -22252,23 +22252,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2589750020302405/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30240-5"
   },
-  {
-    "id": "35355205",
-    "doi": "https://doi.org/10.1007/s11897-022-00544-3",
-    "title": "LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.",
-    "authorString": "Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Current heart failure reports",
-    "pubYear": "2022",
-    "date": "2022-03-30",
-    "isOpenAccess": "Y",
-    "keywords": "Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Purpose of review</h4>The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.<h4>Recent findings</h4>In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",
-    "laySummary": "",
-    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render"
-  },
   {
     "id": "33328453",
     "doi": "https://doi.org/10.1038/s41467-020-19996-z",
@@ -22286,6 +22269,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render"
   },
+  {
+    "id": "35355205",
+    "doi": "https://doi.org/10.1007/s11897-022-00544-3",
+    "title": "LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.",
+    "authorString": "Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Current heart failure reports",
+    "pubYear": "2022",
+    "date": "2022-03-30",
+    "isOpenAccess": "Y",
+    "keywords": "Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Purpose of review</h4>The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.<h4>Recent findings</h4>In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",
+    "laySummary": "",
+    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render"
+  },
   {
     "id": "35072885",
     "doi": "https://doi.org/10.1007/s10439-022-02905-4",
@@ -22354,23 +22354,6 @@
     "laySummary": "",
     "urls": "pdf:https://heart.bmj.com/content/heartjnl/108/1/37.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-319566"
   },
-  {
-    "id": "36224602",
-    "doi": "https://doi.org/10.1186/s12916-022-02544-5",
-    "title": "Early onset of immune-mediated diseases in minority ethnic groups in the UK. ",
-    "authorString": "Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medicine",
-    "pubYear": "2022",
-    "date": "2022-10-13",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis. This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB). After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size. Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?pdf=render"
-  },
   {
     "id": "30745170",
     "doi": "https://doi.org/10.1016/j.ebiom.2019.02.005",
@@ -22389,21 +22372,21 @@
     "urls": "pdf:http://www.thelancet.com/article/S2352396419300775/pdf; doi:https://doi.org/10.1016/j.ebiom.2019.02.005; html:https://europepmc.org/articles/PMC6442001; pdf:https://europepmc.org/articles/PMC6442001?pdf=render"
   },
   {
-    "id": "37206266",
-    "doi": "https://doi.org/10.1002/jha2.698",
-    "title": "Biallelic deleterious germline <i>SH2B3</i> variants cause a novel syndrome of myeloproliferation and multi-organ autoimmunity.",
-    "authorString": "Blombery P, Pazhakh V, Albuquerque AS, Maimaris J, Tu L, Briones Miranda B, Evans F, Thompson ER, Carpenter B, Proctor I, Curtin JA, Lambert J, Burns SO, Lieschke GJ.",
+    "id": "36224602",
+    "doi": "https://doi.org/10.1186/s12916-022-02544-5",
+    "title": "Early onset of immune-mediated diseases in minority ethnic groups in the UK. ",
+    "authorString": "Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM.",
     "authorAffiliations": "",
-    "journalTitle": "EJHaem",
-    "pubYear": "2023",
-    "date": "2023-04-30",
+    "journalTitle": "BMC medicine",
+    "pubYear": "2022",
+    "date": "2022-10-13",
     "isOpenAccess": "Y",
-    "keywords": "Genetics; Molecular diagnosis; Myeloid Function And Development",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<i>SH2B3</i> is a negative regulator of multiple cytokine receptor signalling pathways in haematopoietic tissue. To date, a single kindred has been described with germline biallelic loss-of-function <i>SH2B3</i> variants characterized by early onset developmental delay, hepatosplenomegaly and autoimmune thyroiditis/hepatitis. Herein, we described two further unrelated kindreds with germline biallelic loss-of-function <i>SH2B3</i> variants that show striking phenotypic similarity to each other as well as to the previous kindred of myeloproliferation and multi-organ autoimmunity. One proband also suffered severe thrombotic complications. CRISPR-Cas9 gene editing of zebrafish <i>sh2b3</i> created assorted deleterious variants in F0 crispants, which manifest significantly increased number of macrophages and thrombocytes, partially replicating the human phenotype. Treatment of the <i>sh2b3</i> crispant fish with ruxolitinib intercepted this myeloproliferative phenotype. Skin-derived fibroblasts from one patient demonstrated increased phosphorylation of JAK2 and STAT5 after stimulation with IL-3, GH, GM-CSF and EPO compared to healthy controls. In conclusion, these additional probands and functional data in combination with the previous kindred provide sufficient evidence for biallelic homozygous deleterious variants in <i>SH2B3</i> to be considered a valid gene-disease association for a clinical syndrome of bone marrow myeloproliferation and multi-organ autoimmune manifestations.",
+    "abstract": "The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis. This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB). After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size. Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1002/jha2.698; doi:https://doi.org/10.1002/jha2.698; html:https://europepmc.org/articles/PMC10188477; pdf:https://europepmc.org/articles/PMC10188477?pdf=render"
+    "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?pdf=render"
   },
   {
     "id": "36228971",
@@ -22422,6 +22405,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; html:https://europepmc.org/articles/PMC7613854; pdf:https://europepmc.org/articles/PMC7613854?pdf=render"
   },
+  {
+    "id": "37206266",
+    "doi": "https://doi.org/10.1002/jha2.698",
+    "title": "Biallelic deleterious germline <i>SH2B3</i> variants cause a novel syndrome of myeloproliferation and multi-organ autoimmunity.",
+    "authorString": "Blombery P, Pazhakh V, Albuquerque AS, Maimaris J, Tu L, Briones Miranda B, Evans F, Thompson ER, Carpenter B, Proctor I, Curtin JA, Lambert J, Burns SO, Lieschke GJ.",
+    "authorAffiliations": "",
+    "journalTitle": "EJHaem",
+    "pubYear": "2023",
+    "date": "2023-04-30",
+    "isOpenAccess": "Y",
+    "keywords": "Genetics; Molecular diagnosis; Myeloid Function And Development",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<i>SH2B3</i> is a negative regulator of multiple cytokine receptor signalling pathways in haematopoietic tissue. To date, a single kindred has been described with germline biallelic loss-of-function <i>SH2B3</i> variants characterized by early onset developmental delay, hepatosplenomegaly and autoimmune thyroiditis/hepatitis. Herein, we described two further unrelated kindreds with germline biallelic loss-of-function <i>SH2B3</i> variants that show striking phenotypic similarity to each other as well as to the previous kindred of myeloproliferation and multi-organ autoimmunity. One proband also suffered severe thrombotic complications. CRISPR-Cas9 gene editing of zebrafish <i>sh2b3</i> created assorted deleterious variants in F0 crispants, which manifest significantly increased number of macrophages and thrombocytes, partially replicating the human phenotype. Treatment of the <i>sh2b3</i> crispant fish with ruxolitinib intercepted this myeloproliferative phenotype. Skin-derived fibroblasts from one patient demonstrated increased phosphorylation of JAK2 and STAT5 after stimulation with IL-3, GH, GM-CSF and EPO compared to healthy controls. In conclusion, these additional probands and functional data in combination with the previous kindred provide sufficient evidence for biallelic homozygous deleterious variants in <i>SH2B3</i> to be considered a valid gene-disease association for a clinical syndrome of bone marrow myeloproliferation and multi-organ autoimmune manifestations.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1002/jha2.698; doi:https://doi.org/10.1002/jha2.698; html:https://europepmc.org/articles/PMC10188477; pdf:https://europepmc.org/articles/PMC10188477?pdf=render"
+  },
   {
     "id": "32579178",
     "doi": "https://doi.org/10.1001/jamadermatol.2020.1948",
@@ -22456,23 +22456,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcgeriatr.biomedcentral.com/track/pdf/10.1186/s12877-022-03077-5; doi:https://doi.org/10.1186/s12877-022-03077-5; html:https://europepmc.org/articles/PMC9043890; pdf:https://europepmc.org/articles/PMC9043890?pdf=render"
   },
-  {
-    "id": "35922433",
-    "doi": "https://doi.org/10.1038/s41467-022-32219-x",
-    "title": "Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities.",
-    "authorString": "Francis CM, Futschik ME, Huang J, Bai W, Sargurupremraj M, Teumer A, Breteler MMB, Petretto E, Ho ASR, Amouyel P, Engelter ST, B\u00fclow R, V\u00f6lker U, V\u00f6lzke H, D\u00f6rr M, Imtiaz MA, Aziz NA, Lohner V, Ware JS, Debette S, Elliott P, Dehghan A, Matthews PM.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2022",
-    "date": "2022-08-03",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-\u03b2, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-022-32219-x.pdf; doi:https://doi.org/10.1038/s41467-022-32219-x; html:https://europepmc.org/articles/PMC9349177; pdf:https://europepmc.org/articles/PMC9349177?pdf=render"
-  },
   {
     "id": "31714636",
     "doi": "https://doi.org/10.1002/ana.25642",
@@ -22490,6 +22473,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.25642; doi:https://doi.org/10.1002/ana.25642; html:https://europepmc.org/articles/PMC6944510; pdf:https://europepmc.org/articles/PMC6944510?pdf=render"
   },
+  {
+    "id": "35922433",
+    "doi": "https://doi.org/10.1038/s41467-022-32219-x",
+    "title": "Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities.",
+    "authorString": "Francis CM, Futschik ME, Huang J, Bai W, Sargurupremraj M, Teumer A, Breteler MMB, Petretto E, Ho ASR, Amouyel P, Engelter ST, B\u00fclow R, V\u00f6lker U, V\u00f6lzke H, D\u00f6rr M, Imtiaz MA, Aziz NA, Lohner V, Ware JS, Debette S, Elliott P, Dehghan A, Matthews PM.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature communications",
+    "pubYear": "2022",
+    "date": "2022-08-03",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-\u03b2, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41467-022-32219-x.pdf; doi:https://doi.org/10.1038/s41467-022-32219-x; html:https://europepmc.org/articles/PMC9349177; pdf:https://europepmc.org/articles/PMC9349177?pdf=render"
+  },
   {
     "id": "34870256",
     "doi": "https://doi.org/10.1016/j.lanepe.2021.100267",
@@ -22507,23 +22507,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.lanepe.2021.100267; doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?pdf=render"
   },
-  {
-    "id": "36828655",
-    "doi": "https://doi.org/10.1136/bmjopen-2022-068718",
-    "title": "Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.",
-    "authorString": "Lee SI, Hope H, O'Reilly D, Kent L, Santorelli G, Subramanian A, Moss N, Azcoaga-Lorenzo A, Fagbamigbe AF, Nelson-Piercy C, Yau C, McCowan C, Kennedy JI, Phillips K, Singh M, Mhereeg M, Cockburn N, Brocklehurst P, Plachcinski R, Riley RD, Thangaratinam S, Brophy S, Hemali Sudasinghe SPB, Agrawal U, Vowles Z, Abel KM, Nirantharakumar K, Black M, Eastwood KA, MuM-PreDiCT.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2023",
-    "date": "2023-02-24",
-    "isOpenAccess": "Y",
-    "keywords": "Obstetrics; epidemiology; Maternal Medicine",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).<h4>Methods and analysis</h4>Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.<h4>Ethics and dissemination</h4>Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e068718.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068718; html:https://europepmc.org/articles/PMC9972454; pdf:https://europepmc.org/articles/PMC9972454?pdf=render"
-  },
   {
     "id": "33053479",
     "doi": "https://doi.org/10.1016/j.chiabu.2020.104760",
@@ -22541,6 +22524,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.chiabu.2020.104760; doi:https://doi.org/10.1016/j.chiabu.2020.104760; html:https://europepmc.org/articles/PMC7718112"
   },
+  {
+    "id": "36828655",
+    "doi": "https://doi.org/10.1136/bmjopen-2022-068718",
+    "title": "Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.",
+    "authorString": "Lee SI, Hope H, O'Reilly D, Kent L, Santorelli G, Subramanian A, Moss N, Azcoaga-Lorenzo A, Fagbamigbe AF, Nelson-Piercy C, Yau C, McCowan C, Kennedy JI, Phillips K, Singh M, Mhereeg M, Cockburn N, Brocklehurst P, Plachcinski R, Riley RD, Thangaratinam S, Brophy S, Hemali Sudasinghe SPB, Agrawal U, Vowles Z, Abel KM, Nirantharakumar K, Black M, Eastwood KA, MuM-PreDiCT.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-02-24",
+    "isOpenAccess": "Y",
+    "keywords": "Obstetrics; epidemiology; Maternal Medicine",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).<h4>Methods and analysis</h4>Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.<h4>Ethics and dissemination</h4>Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e068718.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068718; html:https://europepmc.org/articles/PMC9972454; pdf:https://europepmc.org/articles/PMC9972454?pdf=render"
+  },
   {
     "id": "36054463",
     "doi": "https://doi.org/10.1111/ans.17985",
@@ -22694,23 +22694,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?pdf=render"
   },
-  {
-    "id": "35410933",
-    "doi": "https://doi.org/10.1136/bmjopen-2021-057885",
-    "title": "Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.",
-    "authorString": "Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-04-11",
-    "isOpenAccess": "Y",
-    "keywords": "Infectious diseases; Rehabilitation Medicine; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.<h4>Aims</h4>This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.<h4>Methods and analysis</h4>Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.<h4>Ethics and dissemination</h4>This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.<h4>Prospero registration number</h4>The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render"
-  },
   {
     "id": "30928915",
     "doi": "https://doi.org/10.1136/injuryprev-2018-043085",
@@ -22728,6 +22711,23 @@
     "laySummary": "",
     "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa50163/Download/0050163-25062019060819.pdf; doi:https://doi.org/10.1136/injuryprev-2018-043085"
   },
+  {
+    "id": "35410933",
+    "doi": "https://doi.org/10.1136/bmjopen-2021-057885",
+    "title": "Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.",
+    "authorString": "Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-04-11",
+    "isOpenAccess": "Y",
+    "keywords": "Infectious diseases; Rehabilitation Medicine; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.<h4>Aims</h4>This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.<h4>Methods and analysis</h4>Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.<h4>Ethics and dissemination</h4>This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.<h4>Prospero registration number</h4>The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render"
+  },
   {
     "id": "33939952",
     "doi": "https://doi.org/10.1016/s0140-6736(21)00949-1",
@@ -22779,23 +22779,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010093&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render"
   },
-  {
-    "id": "37407123",
-    "doi": "https://doi.org/10.1016/j.jcmg.2023.01.016",
-    "title": "Ischemic Heart Disease and Vascular\u00a0Risk\u00a0Factors Are Associated With Accelerated Brain Aging.",
-    "authorString": "Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",
-    "authorAffiliations": "",
-    "journalTitle": "JACC. Cardiovascular imaging",
-    "pubYear": "2023",
-    "date": "2023-04-12",
-    "isOpenAccess": "Y",
-    "keywords": "brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.<h4>Objectives</h4>The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.<h4>Methods</h4>Brain age was estimated in subjects with prevalent IHD (n\u00a0=\u00a01,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n\u00a0=\u00a035,237).<h4>Results</h4>Prevalent IHD was linked to significantly accelerated brain aging (P\u00a0< 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13\u00a0[95%\u00a0CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.<h4>Conclusions</h4>Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render"
-  },
   {
     "id": "35866236",
     "doi": "https://doi.org/10.7189/jogh.12.05033",
@@ -22814,21 +22797,21 @@
     "urls": "pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render"
   },
   {
-    "id": "36253349",
-    "doi": "https://doi.org/10.1038/s41467-022-33675-1",
-    "title": "Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke.",
-    "authorString": "Chen L, Peters JE, Prins B, Persyn E, Traylor M, Surendran P, Karthikeyan S, Yonova-Doing E, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Danesh J, Lewis CM, Bronson PG, Markus HS, Burgess S, Butterworth AS, Howson JMM.",
+    "id": "37407123",
+    "doi": "https://doi.org/10.1016/j.jcmg.2023.01.016",
+    "title": "Ischemic Heart Disease and Vascular\u00a0Risk\u00a0Factors Are Associated With Accelerated Brain Aging.",
+    "authorString": "Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",
     "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2022",
-    "date": "2022-10-17",
+    "journalTitle": "JACC. Cardiovascular imaging",
+    "pubYear": "2023",
+    "date": "2023-04-12",
     "isOpenAccess": "Y",
-    "keywords": "",
+    "keywords": "brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P\u2009\u2264\u20091.62 \u00d7 10<sup>-4</sup>). The genetic associations with stroke colocalize (Posterior Probability >0.7) with the genetic associations of four proteins (TFPI, TMPRSS5, CD6, CD40). Mendelian randomization supports atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes as stroke risk factors (P\u2009\u2264\u20090.0071). Body mass index, white matter hyperintensity and atrial fibrillation appear to mediate the TFPI, IL6RA, TMPRSS5 associations with stroke. Furthermore, thirty-six proteins are associated with one or more of these risk factors using Mendelian randomization. Our results highlight causal pathways and potential therapeutic targets for stroke.",
+    "abstract": "<h4>Background</h4>Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.<h4>Objectives</h4>The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.<h4>Methods</h4>Brain age was estimated in subjects with prevalent IHD (n\u00a0=\u00a01,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n\u00a0=\u00a035,237).<h4>Results</h4>Prevalent IHD was linked to significantly accelerated brain aging (P\u00a0< 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13\u00a0[95%\u00a0CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.<h4>Conclusions</h4>Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",
     "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-022-33675-1.pdf; doi:https://doi.org/10.1038/s41467-022-33675-1; html:https://europepmc.org/articles/PMC9576777; pdf:https://europepmc.org/articles/PMC9576777?pdf=render"
+    "urls": "doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render"
   },
   {
     "id": "36711167",
@@ -22847,6 +22830,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ehjdh/article-pdf/2/1/154/37807088/ztaa016.pdf; doi:https://doi.org/10.1093/ehjdh/ztaa016; html:https://europepmc.org/articles/PMC9707891; pdf:https://europepmc.org/articles/PMC9707891?pdf=render"
   },
+  {
+    "id": "36253349",
+    "doi": "https://doi.org/10.1038/s41467-022-33675-1",
+    "title": "Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke.",
+    "authorString": "Chen L, Peters JE, Prins B, Persyn E, Traylor M, Surendran P, Karthikeyan S, Yonova-Doing E, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Danesh J, Lewis CM, Bronson PG, Markus HS, Burgess S, Butterworth AS, Howson JMM.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature communications",
+    "pubYear": "2022",
+    "date": "2022-10-17",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P\u2009\u2264\u20091.62 \u00d7 10<sup>-4</sup>). The genetic associations with stroke colocalize (Posterior Probability >0.7) with the genetic associations of four proteins (TFPI, TMPRSS5, CD6, CD40). Mendelian randomization supports atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes as stroke risk factors (P\u2009\u2264\u20090.0071). Body mass index, white matter hyperintensity and atrial fibrillation appear to mediate the TFPI, IL6RA, TMPRSS5 associations with stroke. Furthermore, thirty-six proteins are associated with one or more of these risk factors using Mendelian randomization. Our results highlight causal pathways and potential therapeutic targets for stroke.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41467-022-33675-1.pdf; doi:https://doi.org/10.1038/s41467-022-33675-1; html:https://europepmc.org/articles/PMC9576777; pdf:https://europepmc.org/articles/PMC9576777?pdf=render"
+  },
   {
     "id": "32738956",
     "doi": "https://doi.org/10.1016/s0140-6736(20)31286-1",
@@ -22864,23 +22864,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/S0140-6736(20)31286-1"
   },
-  {
-    "id": "34606520",
-    "doi": "https://doi.org/10.1371/journal.pmed.1003815",
-    "title": "COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.",
-    "authorString": "Pearson CAB, Bozzani F, Procter SR, Davies NG, Huda M, Jensen HT, Keogh-Brown M, Khalid M, Sweeney S, Torres-Rueda S, CHiL COVID-19 Working Group, CMMID COVID-19 Working Group, Eggo RM, Vassall A, Jit M.",
-    "authorAffiliations": "",
-    "journalTitle": "PLoS medicine",
-    "pubYear": "2021",
-    "date": "2021-10-04",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).<h4>Methods and findings</h4>We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.<h4>Conclusions</h4>COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003815&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render"
-  },
   {
     "id": "32817390",
     "doi": "https://doi.org/10.1212/wnl.0000000000010463",
@@ -22898,6 +22881,23 @@
     "laySummary": "",
     "urls": "pdf:https://n.neurology.org/content/neurology/95/14/e1963.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000010463; html:https://europepmc.org/articles/PMC7682841; pdf:https://europepmc.org/articles/PMC7682841?pdf=render"
   },
+  {
+    "id": "34606520",
+    "doi": "https://doi.org/10.1371/journal.pmed.1003815",
+    "title": "COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.",
+    "authorString": "Pearson CAB, Bozzani F, Procter SR, Davies NG, Huda M, Jensen HT, Keogh-Brown M, Khalid M, Sweeney S, Torres-Rueda S, CHiL COVID-19 Working Group, CMMID COVID-19 Working Group, Eggo RM, Vassall A, Jit M.",
+    "authorAffiliations": "",
+    "journalTitle": "PLoS medicine",
+    "pubYear": "2021",
+    "date": "2021-10-04",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).<h4>Methods and findings</h4>We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.<h4>Conclusions</h4>COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003815&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render"
+  },
   {
     "id": "33372069",
     "doi": "https://doi.org/10.1136/bmjopen-2020-038360",
@@ -23051,23 +23051,6 @@
     "laySummary": "",
     "urls": "pdf:https://diabetesjournals.org/diabetes/article-pdf/71/2/359/640867/db210320.pdf; doi:https://doi.org/10.2337/db21-0320; html:https://europepmc.org/articles/PMC8914280; pdf:https://europepmc.org/articles/PMC8914280?pdf=render; doi:https://doi.org/10.2337/db21-0320"
   },
-  {
-    "id": "36609282",
-    "doi": "https://doi.org/10.1186/s13063-022-06967-6",
-    "title": "A comparison of covariate adjustment approaches under model misspecification in individually randomized trials.",
-    "authorString": "Tackney MS, Morris T, White I, Leyrat C, Diaz-Ordaz K, Williamson E.",
-    "authorAffiliations": "",
-    "journalTitle": "Trials",
-    "pubYear": "2023",
-    "date": "2023-01-06",
-    "isOpenAccess": "Y",
-    "keywords": "Randomized controlled trials; Iptw; G-computation; Tmle; Covariate Adjustment; Ancova; Misspecification; Aiptw",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the covariate and outcome is misspecified when taking an adjusted approach. Using a simulation study focusing on individually randomized trials with small sample sizes, we explore whether a range of adjustment methods are robust to misspecification, either in the covariate-outcome relationship or through an omitted covariate-treatment interaction. Specifically, we aim to identify potential settings where G-computation, inverse probability of treatment weighting (IPTW), augmented inverse probability of treatment weighting (AIPTW) and targeted maximum likelihood estimation (TMLE) offer improvement over the commonly used analysis of covariance (ANCOVA). Our simulations show that all adjustment methods are generally robust to model misspecification if adjusting for a few covariates, sample size is 100 or larger, and there are no covariate-treatment interactions. When there is a non-linear interaction of treatment with a skewed covariate and sample size is small, all adjustment methods can suffer from bias; however, methods that allow for interactions (such as G-computation with interaction and IPTW) show improved results compared to ANCOVA. When there are a high number of covariates to adjust for, ANCOVA retains good properties while other methods suffer from under- or over-coverage. An outstanding issue for G-computation, IPTW and AIPTW in small samples is that standard errors are underestimated; they should be used with caution without the availability of small-sample corrections, development of which is needed. These findings are relevant for covariate adjustment in interim analyses of larger trials.",
-    "laySummary": "",
-    "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06967-6; doi:https://doi.org/10.1186/s13063-022-06967-6; html:https://europepmc.org/articles/PMC9817411; pdf:https://europepmc.org/articles/PMC9817411?pdf=render"
-  },
   {
     "id": "33905476",
     "doi": "https://doi.org/10.1093/cid/ciab192",
@@ -23085,6 +23068,23 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/cid/article-pdf/72/Supplement_3/S172/38618862/ciab192.pdf; doi:https://doi.org/10.1093/cid/ciab192; html:https://europepmc.org/articles/PMC8201574; pdf:https://europepmc.org/articles/PMC8201574?pdf=render"
   },
+  {
+    "id": "36609282",
+    "doi": "https://doi.org/10.1186/s13063-022-06967-6",
+    "title": "A comparison of covariate adjustment approaches under model misspecification in individually randomized trials.",
+    "authorString": "Tackney MS, Morris T, White I, Leyrat C, Diaz-Ordaz K, Williamson E.",
+    "authorAffiliations": "",
+    "journalTitle": "Trials",
+    "pubYear": "2023",
+    "date": "2023-01-06",
+    "isOpenAccess": "Y",
+    "keywords": "Randomized controlled trials; Iptw; G-computation; Tmle; Covariate Adjustment; Ancova; Misspecification; Aiptw",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the covariate and outcome is misspecified when taking an adjusted approach. Using a simulation study focusing on individually randomized trials with small sample sizes, we explore whether a range of adjustment methods are robust to misspecification, either in the covariate-outcome relationship or through an omitted covariate-treatment interaction. Specifically, we aim to identify potential settings where G-computation, inverse probability of treatment weighting (IPTW), augmented inverse probability of treatment weighting (AIPTW) and targeted maximum likelihood estimation (TMLE) offer improvement over the commonly used analysis of covariance (ANCOVA). Our simulations show that all adjustment methods are generally robust to model misspecification if adjusting for a few covariates, sample size is 100 or larger, and there are no covariate-treatment interactions. When there is a non-linear interaction of treatment with a skewed covariate and sample size is small, all adjustment methods can suffer from bias; however, methods that allow for interactions (such as G-computation with interaction and IPTW) show improved results compared to ANCOVA. When there are a high number of covariates to adjust for, ANCOVA retains good properties while other methods suffer from under- or over-coverage. An outstanding issue for G-computation, IPTW and AIPTW in small samples is that standard errors are underestimated; they should be used with caution without the availability of small-sample corrections, development of which is needed. These findings are relevant for covariate adjustment in interim analyses of larger trials.",
+    "laySummary": "",
+    "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06967-6; doi:https://doi.org/10.1186/s13063-022-06967-6; html:https://europepmc.org/articles/PMC9817411; pdf:https://europepmc.org/articles/PMC9817411?pdf=render"
+  },
   {
     "id": "33206055",
     "doi": "https://doi.org/10.2196/19650",
@@ -23204,23 +23204,6 @@
     "laySummary": "",
     "urls": "pdf:https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-023-01184-y; doi:https://doi.org/10.1186/s13195-023-01184-y; html:https://europepmc.org/articles/PMC9945600; pdf:https://europepmc.org/articles/PMC9945600?pdf=render"
   },
-  {
-    "id": "36944376",
-    "doi": "https://doi.org/10.1098/rsob.220373",
-    "title": "The lipid linked oligosaccharide polymerase Wzy and its regulating co-polymerase, Wzz, from enterobacterial common antigen biosynthesis form a complex.",
-    "authorString": "Weckener M, Woodward LS, Clarke BR, Liu H, Ward PN, Le Bas A, Bhella D, Whitfield C, Naismith JH.",
-    "authorAffiliations": "",
-    "journalTitle": "Open biology",
-    "pubYear": "2023",
-    "date": "2023-03-22",
-    "isOpenAccess": "Y",
-    "keywords": "Oligosaccharides; Lipid; Regulating; Polymerase; Wzy",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The enterobacterial common antigen (ECA) is a carbohydrate polymer that is associated with the cell envelope in the <i>Enterobacteriaceae</i>. ECA contains a repeating trisaccharide which is polymerized by WzyE, a member of the Wzy membrane protein polymerase superfamily. WzyE activity is regulated by a membrane protein polysaccharide co-polymerase, WzzE. F\u00f6rster resonance energy transfer experiments demonstrate that WzyE and WzzE from <i>Pectobacterium atrosepticum</i> form a complex <i>in vivo</i>, and immunoblotting and cryo-electron microscopy (cryo-EM) analysis confirm a defined stoichiometry of approximately eight WzzE to one WzyE. Low-resolution cryo-EM reconstructions of the complex, aided by an antibody recognizing the C-terminus of WzyE, reveals WzyE sits in the central membrane lumen formed by the octameric arrangement of the transmembrane helices of WzzE. The pairing of Wzy and Wzz is found in polymerization systems for other bacterial polymers, including lipopolysaccharide O-antigens and capsular polysaccharides. The data provide new structural insight into a conserved mechanism for regulating polysaccharide chain length in bacteria.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1098/rsob.220373; doi:https://doi.org/10.1098/rsob.220373; html:https://europepmc.org/articles/PMC10030265; pdf:https://europepmc.org/articles/PMC10030265?pdf=render"
-  },
   {
     "id": "36029662",
     "doi": "https://doi.org/10.1016/j.bios.2022.114623",
@@ -23239,21 +23222,38 @@
     "urls": "pdf:https://research-information.bris.ac.uk/files/338519213/1_s2.0_S0956566322006637_main.pdf; doi:https://doi.org/10.1016/j.bios.2022.114623"
   },
   {
-    "id": "37817277",
-    "doi": "https://doi.org/10.1186/s13063-023-07656-8",
-    "title": "e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.",
-    "authorString": "Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",
+    "id": "36944376",
+    "doi": "https://doi.org/10.1098/rsob.220373",
+    "title": "The lipid linked oligosaccharide polymerase Wzy and its regulating co-polymerase, Wzz, from enterobacterial common antigen biosynthesis form a complex.",
+    "authorString": "Weckener M, Woodward LS, Clarke BR, Liu H, Ward PN, Le Bas A, Bhella D, Whitfield C, Naismith JH.",
     "authorAffiliations": "",
-    "journalTitle": "Trials",
+    "journalTitle": "Open biology",
     "pubYear": "2023",
-    "date": "2023-10-10",
+    "date": "2023-03-22",
     "isOpenAccess": "Y",
-    "keywords": "Consent; Clinical Trial; E-consent",
+    "keywords": "Oligosaccharides; Lipid; Regulating; Polymerase; Wzy",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.<h4>Methods</h4>A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.<h4>Results</h4>Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.<h4>Conclusion</h4>e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",
+    "abstract": "The enterobacterial common antigen (ECA) is a carbohydrate polymer that is associated with the cell envelope in the <i>Enterobacteriaceae</i>. ECA contains a repeating trisaccharide which is polymerized by WzyE, a member of the Wzy membrane protein polymerase superfamily. WzyE activity is regulated by a membrane protein polysaccharide co-polymerase, WzzE. F\u00f6rster resonance energy transfer experiments demonstrate that WzyE and WzzE from <i>Pectobacterium atrosepticum</i> form a complex <i>in vivo</i>, and immunoblotting and cryo-electron microscopy (cryo-EM) analysis confirm a defined stoichiometry of approximately eight WzzE to one WzyE. Low-resolution cryo-EM reconstructions of the complex, aided by an antibody recognizing the C-terminus of WzyE, reveals WzyE sits in the central membrane lumen formed by the octameric arrangement of the transmembrane helices of WzzE. The pairing of Wzy and Wzz is found in polymerization systems for other bacterial polymers, including lipopolysaccharide O-antigens and capsular polysaccharides. The data provide new structural insight into a conserved mechanism for regulating polysaccharide chain length in bacteria.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render"
+    "urls": "doi:https://doi.org/10.1098/rsob.220373; doi:https://doi.org/10.1098/rsob.220373; html:https://europepmc.org/articles/PMC10030265; pdf:https://europepmc.org/articles/PMC10030265?pdf=render"
+  },
+  {
+    "id": "36456017",
+    "doi": "https://doi.org/10.1136/bmjopen-2022-066288",
+    "title": "Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.",
+    "authorString": "Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-12-01",
+    "isOpenAccess": "Y",
+    "keywords": "Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.<h4>Design</h4>Longitudinal study using primary care electronic health records.<h4>Setting</h4>285 general practices in North East London.<h4>Participants</h4>Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).<h4>Main outcome measure</h4>Receipt of timely MMR vaccination between 12 and 18 months of age.<h4>Methods</h4>We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.<h4>Results</h4>Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (<i>n</i>=33\u2009226; 51.3% boys) and pandemic (<i>n</i>=32\u2009446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.<h4>Conclusions</h4>The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render"
   },
   {
     "id": "36774358",
@@ -23273,21 +23273,21 @@
     "urls": "pdf:https://www.nature.com/articles/s41467-023-36439-7.pdf; doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?pdf=render"
   },
   {
-    "id": "36456017",
-    "doi": "https://doi.org/10.1136/bmjopen-2022-066288",
-    "title": "Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.",
-    "authorString": "Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",
+    "id": "37817277",
+    "doi": "https://doi.org/10.1186/s13063-023-07656-8",
+    "title": "e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.",
+    "authorString": "Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",
     "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-12-01",
+    "journalTitle": "Trials",
+    "pubYear": "2023",
+    "date": "2023-10-10",
     "isOpenAccess": "Y",
-    "keywords": "Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19",
+    "keywords": "Consent; Clinical Trial; E-consent",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.<h4>Design</h4>Longitudinal study using primary care electronic health records.<h4>Setting</h4>285 general practices in North East London.<h4>Participants</h4>Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).<h4>Main outcome measure</h4>Receipt of timely MMR vaccination between 12 and 18 months of age.<h4>Methods</h4>We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.<h4>Results</h4>Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (<i>n</i>=33\u2009226; 51.3% boys) and pandemic (<i>n</i>=32\u2009446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.<h4>Conclusions</h4>The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",
+    "abstract": "<h4>Background</h4>During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.<h4>Methods</h4>A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.<h4>Results</h4>Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.<h4>Conclusion</h4>e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",
     "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render"
+    "urls": "doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render"
   },
   {
     "id": "32017129",
@@ -23306,23 +23306,6 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50485; doi:https://doi.org/10.5694/mja2.50485"
   },
-  {
-    "id": "36457326",
-    "doi": "https://doi.org/10.3389/fpubh.2022.1017337",
-    "title": "Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.",
-    "authorString": "Cerbino-Neto J, Peres IT, Varela MC, Brand\u00e3o LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.",
-    "authorAffiliations": "",
-    "journalTitle": "Frontiers in public health",
-    "pubYear": "2022",
-    "date": "2022-11-14",
-    "isOpenAccess": "Y",
-    "keywords": "Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.<h4>Objective</h4>We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.<h4>Methods</h4>We performed a seroepidemiologic survey in all residents of Paquet\u00e1 Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.<h4>Results</h4>We included in the study 3,016 residents of Paquet\u00e1 (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).<h4>Conclusions</h4>Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.",
-    "laySummary": "",
-    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render"
-  },
   {
     "id": "33148619",
     "doi": "https://doi.org/10.1136/bmj.m3919",
@@ -23340,6 +23323,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.bmj.com/content/bmj/371/bmj.m3919.full.pdf; doi:https://doi.org/10.1136/bmj.m3919; html:https://europepmc.org/articles/PMC7610202"
   },
+  {
+    "id": "36457326",
+    "doi": "https://doi.org/10.3389/fpubh.2022.1017337",
+    "title": "Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.",
+    "authorString": "Cerbino-Neto J, Peres IT, Varela MC, Brand\u00e3o LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.",
+    "authorAffiliations": "",
+    "journalTitle": "Frontiers in public health",
+    "pubYear": "2022",
+    "date": "2022-11-14",
+    "isOpenAccess": "Y",
+    "keywords": "Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.<h4>Objective</h4>We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.<h4>Methods</h4>We performed a seroepidemiologic survey in all residents of Paquet\u00e1 Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.<h4>Results</h4>We included in the study 3,016 residents of Paquet\u00e1 (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).<h4>Conclusions</h4>Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.",
+    "laySummary": "",
+    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render"
+  },
   {
     "id": "36060542",
     "doi": "https://doi.org/10.3389/fdgth.2022.939292",
@@ -23374,23 +23374,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/7/e036099.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-036099; html:https://europepmc.org/articles/PMC7380838; pdf:https://europepmc.org/articles/PMC7380838?pdf=render"
   },
-  {
-    "id": "32814581",
-    "doi": "https://doi.org/10.1186/s12916-020-01687-7",
-    "title": "Seasonal influenza vaccination in Kenya: an economic evaluation using dynamic transmission modelling.",
-    "authorString": "Dawa J, Emukule GO, Barasa E, Widdowson MA, Anzala O, van Leeuwen E, Baguelin M, Chaves SS, Eggo RM.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medicine",
-    "pubYear": "2020",
-    "date": "2020-08-20",
-    "isOpenAccess": "Y",
-    "keywords": "Economic evaluation; Influenza vaccine; Cost-effectiveness; Low- And Middle-income Countries; Dynamic Transmission Model; Vaccine Timing; Vaccine Target Group",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya.<h4>Methods</h4>We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23\u2009months (strategy I), 2-5\u2009years (strategy II) and 6-14\u2009years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872).<h4>Results</h4>The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23\u2009months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5\u2009years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14\u2009years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23\u2009months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit.<h4>Conclusion</h4>Vaccinating children 6-23\u2009months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01687-7; doi:https://doi.org/10.1186/s12916-020-01687-7; html:https://europepmc.org/articles/PMC7438179; pdf:https://europepmc.org/articles/PMC7438179?pdf=render"
-  },
   {
     "id": "31984563",
     "doi": "https://doi.org/10.1111/jce.14368",
@@ -23408,6 +23391,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1111/jce.14368"
   },
+  {
+    "id": "32814581",
+    "doi": "https://doi.org/10.1186/s12916-020-01687-7",
+    "title": "Seasonal influenza vaccination in Kenya: an economic evaluation using dynamic transmission modelling.",
+    "authorString": "Dawa J, Emukule GO, Barasa E, Widdowson MA, Anzala O, van Leeuwen E, Baguelin M, Chaves SS, Eggo RM.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC medicine",
+    "pubYear": "2020",
+    "date": "2020-08-20",
+    "isOpenAccess": "Y",
+    "keywords": "Economic evaluation; Influenza vaccine; Cost-effectiveness; Low- And Middle-income Countries; Dynamic Transmission Model; Vaccine Timing; Vaccine Target Group",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya.<h4>Methods</h4>We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23\u2009months (strategy I), 2-5\u2009years (strategy II) and 6-14\u2009years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872).<h4>Results</h4>The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23\u2009months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5\u2009years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14\u2009years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23\u2009months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit.<h4>Conclusion</h4>Vaccinating children 6-23\u2009months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01687-7; doi:https://doi.org/10.1186/s12916-020-01687-7; html:https://europepmc.org/articles/PMC7438179; pdf:https://europepmc.org/articles/PMC7438179?pdf=render"
+  },
   {
     "id": "33588321",
     "doi": "https://doi.org/10.1016/j.retram.2021.103276",
@@ -23561,23 +23561,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.xgen.2021.100086; doi:https://doi.org/10.1016/j.xgen.2021.100086; html:https://europepmc.org/articles/PMC8758502; pdf:https://europepmc.org/articles/PMC8758502?pdf=render"
   },
-  {
-    "id": "34348396",
-    "doi": "https://doi.org/10.1097/ede.0000000000001393",
-    "title": "Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.",
-    "authorString": "Katsoulis M, Stavola BD, Diaz-Ordaz K, Gomes M, Lai A, Lagiou P, Wannamethee G, Tsilidis K, Lumbers RT, Denaxas S, Banerjee A, Parisinos CA, Batterham R, Patel R, Langenberg C, Hemingway H.",
-    "authorAffiliations": "",
-    "journalTitle": "Epidemiology (Cambridge, Mass.)",
-    "pubYear": "2021",
-    "date": "2021-09-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.<h4>Methods</h4>We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group.<h4>Results</h4>Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance\u2009=\u20091.5% (0.3% to 3.0%)] and gain [RD\u2009=\u20091.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD\u2009=\u20090.7% (-0.2% to 1.7%)] and the weight gain group [RD\u2009=\u20090.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD\u2009=\u2009-1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals.<h4>Conclusion</h4>Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.",
-    "laySummary": "",
-    "urls": "html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx; doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render"
-  },
   {
     "id": "31109684",
     "doi": "https://doi.org/10.1016/j.injury.2019.05.004",
@@ -23595,6 +23578,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.injury.2019.05.004"
   },
+  {
+    "id": "34348396",
+    "doi": "https://doi.org/10.1097/ede.0000000000001393",
+    "title": "Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.",
+    "authorString": "Katsoulis M, Stavola BD, Diaz-Ordaz K, Gomes M, Lai A, Lagiou P, Wannamethee G, Tsilidis K, Lumbers RT, Denaxas S, Banerjee A, Parisinos CA, Batterham R, Patel R, Langenberg C, Hemingway H.",
+    "authorAffiliations": "",
+    "journalTitle": "Epidemiology (Cambridge, Mass.)",
+    "pubYear": "2021",
+    "date": "2021-09-01",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.<h4>Methods</h4>We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group.<h4>Results</h4>Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance\u2009=\u20091.5% (0.3% to 3.0%)] and gain [RD\u2009=\u20091.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD\u2009=\u20090.7% (-0.2% to 1.7%)] and the weight gain group [RD\u2009=\u20090.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD\u2009=\u2009-1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals.<h4>Conclusion</h4>Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.",
+    "laySummary": "",
+    "urls": "html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx; doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render"
+  },
   {
     "id": "32478737",
     "doi": "https://doi.org/10.3791/60794",
@@ -23697,23 +23697,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15842.3; html:https://europepmc.org/articles/PMC7338915; pdf:https://europepmc.org/articles/PMC7338915?pdf=render"
   },
-  {
-    "id": "37699620",
-    "doi": "https://doi.org/10.1136/bmjopen-2023-074626",
-    "title": "Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.",
-    "authorString": "Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne J, Sharp MK, Stuart EA, Hernan MA, Lee H, McAuley JH.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2023",
-    "date": "2023-09-12",
-    "isOpenAccess": "Y",
-    "keywords": "Retrospective studies; epidemiology; Statistics & Research Methods",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.<h4>Methods/design</h4>The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.<h4>Ethics and dissemination</h4>Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?pdf=render"
-  },
   {
     "id": "31671849",
     "doi": "https://doi.org/10.3390/ijerph16214178",
@@ -23731,6 +23714,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/1660-4601/16/21/4178/pdf?version=1573119054; doi:https://doi.org/10.3390/ijerph16214178; html:https://europepmc.org/articles/PMC6862192; pdf:https://europepmc.org/articles/PMC6862192?pdf=render"
   },
+  {
+    "id": "37699620",
+    "doi": "https://doi.org/10.1136/bmjopen-2023-074626",
+    "title": "Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.",
+    "authorString": "Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne J, Sharp MK, Stuart EA, Hernan MA, Lee H, McAuley JH.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-09-12",
+    "isOpenAccess": "Y",
+    "keywords": "Retrospective studies; epidemiology; Statistics & Research Methods",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.<h4>Methods/design</h4>The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.<h4>Ethics and dissemination</h4>Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?pdf=render"
+  },
   {
     "id": "37339333",
     "doi": "https://doi.org/10.1002/jia2.26104",
@@ -23799,23 +23799,6 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/id/eprint/10175737/1/1-s2.0-S0168827823004208-main.pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046"
   },
-  {
-    "id": "37748493",
-    "doi": "https://doi.org/10.1016/s2213-2600(23)00262-x",
-    "title": "Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.",
-    "authorString": "C-MORE/PHOSP-COVID Collaborative Group.",
-    "authorAffiliations": "",
-    "journalTitle": "The Lancet. Respiratory medicine",
-    "pubYear": "2023",
-    "date": "2023-09-22",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.<h4>Methods</h4>In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged \u226518 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.<h4>Findings</h4>Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5\u00b70 months (IQR 4\u00b72-6\u00b73) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0\u00b70001) and independently associated with COVID-19 status (odds ratio [OR] 2\u00b79 [95% CI 1\u00b75-5\u00b78]; p<sub>adjusted</sub>=0\u00b70023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0\u00b70001; parenchymal abnormalities), brain abnormalities (p<0\u00b70001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0\u00b7014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59\u00b78 years [SD 11\u00b77] with multiorgan abnormalities vs mean age of 52\u00b78 years [11\u00b79] without multiorgan abnormalities; p<0\u00b70001), more likely to have three or more comorbidities (OR 2\u00b747 [1\u00b732-4\u00b782]; p<sub>adjusted</sub>=0\u00b70059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3\u00b755 [1\u00b723-11\u00b788]; p<sub>adjusted</sub>=0\u00b7025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.<h4>Interpretation</h4>After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.<h4>Funding</h4>UK Research and Innovation and National Institute for Health Research.",
-    "laySummary": "",
-    "urls": "pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?pdf=render"
-  },
   {
     "id": "35115301",
     "doi": "https://doi.org/10.1136/bjophthalmol-2021-319641",
@@ -23833,6 +23816,23 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10143945/1/Keane_T2DM%20metformin%20and%20risk%20of%20AMD%20BJO%2020220111%20clean.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319641"
   },
+  {
+    "id": "37748493",
+    "doi": "https://doi.org/10.1016/s2213-2600(23)00262-x",
+    "title": "Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.",
+    "authorString": "C-MORE/PHOSP-COVID Collaborative Group.",
+    "authorAffiliations": "",
+    "journalTitle": "The Lancet. Respiratory medicine",
+    "pubYear": "2023",
+    "date": "2023-09-22",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.<h4>Methods</h4>In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged \u226518 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.<h4>Findings</h4>Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5\u00b70 months (IQR 4\u00b72-6\u00b73) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0\u00b70001) and independently associated with COVID-19 status (odds ratio [OR] 2\u00b79 [95% CI 1\u00b75-5\u00b78]; p<sub>adjusted</sub>=0\u00b70023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0\u00b70001; parenchymal abnormalities), brain abnormalities (p<0\u00b70001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0\u00b7014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59\u00b78 years [SD 11\u00b77] with multiorgan abnormalities vs mean age of 52\u00b78 years [11\u00b79] without multiorgan abnormalities; p<0\u00b70001), more likely to have three or more comorbidities (OR 2\u00b747 [1\u00b732-4\u00b782]; p<sub>adjusted</sub>=0\u00b70059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3\u00b755 [1\u00b723-11\u00b788]; p<sub>adjusted</sub>=0\u00b7025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.<h4>Interpretation</h4>After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.<h4>Funding</h4>UK Research and Innovation and National Institute for Health Research.",
+    "laySummary": "",
+    "urls": "pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?pdf=render"
+  },
   {
     "id": "31409800",
     "doi": "https://doi.org/10.1038/s41467-019-11451-y",
@@ -23935,23 +23935,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e026677.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-026677; html:https://europepmc.org/articles/PMC6720466; pdf:https://europepmc.org/articles/PMC6720466?pdf=render"
   },
-  {
-    "id": "33836256",
-    "doi": "https://doi.org/10.1016/j.jclinepi.2021.03.025",
-    "title": "Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.",
-    "authorString": "Takada T, Nijman S, Denaxas S, Snell KIE, Uijl A, Nguyen TL, Asselbergs FW, Debray TPA.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of clinical epidemiology",
-    "pubYear": "2021",
-    "date": "2021-04-06",
-    "isOpenAccess": "N",
-    "keywords": "Heterogeneity; Discrimination; Validation; Prediction model; calibration; Model Comparison",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.<h4>Study design and setting</h4>We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices.<h4>Results</h4>Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke.<h4>Conclusion</h4>In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.",
-    "laySummary": "",
-    "urls": "pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025"
-  },
   {
     "id": "31994239",
     "doi": "https://doi.org/10.1002/bimj.201900041",
@@ -23969,6 +23952,23 @@
     "laySummary": "",
     "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4655332/1/Estimating-treatment-effects-with-partially-observed-covariates-using-outcome-regression-with-missing-indicators.pdf; doi:https://doi.org/10.1002/bimj.201900041"
   },
+  {
+    "id": "33836256",
+    "doi": "https://doi.org/10.1016/j.jclinepi.2021.03.025",
+    "title": "Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.",
+    "authorString": "Takada T, Nijman S, Denaxas S, Snell KIE, Uijl A, Nguyen TL, Asselbergs FW, Debray TPA.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of clinical epidemiology",
+    "pubYear": "2021",
+    "date": "2021-04-06",
+    "isOpenAccess": "N",
+    "keywords": "Heterogeneity; Discrimination; Validation; Prediction model; calibration; Model Comparison",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.<h4>Study design and setting</h4>We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices.<h4>Results</h4>Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke.<h4>Conclusion</h4>In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.",
+    "laySummary": "",
+    "urls": "pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025"
+  },
   {
     "id": "34931349",
     "doi": "https://doi.org/10.1111/bcp.15191",
@@ -24037,23 +24037,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010726&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render"
   },
-  {
-    "id": "36512045",
-    "doi": "https://doi.org/10.1007/s00330-022-09323-z",
-    "title": "Prediction of incident cardiovascular events using machine learning and CMR radiomics.",
-    "authorString": "Pujadas ER, Raisi-Estabragh Z, Szabo L, McCracken C, Morcillo CI, Campello VM, Mart\u00edn-Isla C, Atehortua AM, Vago H, Merkely B, Maurovich-Horvat P, Harvey NC, Neubauer S, Petersen SE, Lekadir K.",
-    "authorAffiliations": "",
-    "journalTitle": "European radiology",
-    "pubYear": "2023",
-    "date": "2022-12-13",
-    "isOpenAccess": "Y",
-    "keywords": "Atrial fibrillation; Heart Failure; Preventive Medicine; Machine Learning; Radiomics",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction\u00a0(MI), and stroke using machine learning techniques.<h4>Methods</h4>We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.<h4>Results</h4>AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.<h4>Conclusions</h4>Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.<h4>Key points</h4>\u2022 Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. \u2022 CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. \u2022 The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.",
-    "laySummary": "",
-    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00330-022-09323-z.pdf; doi:https://doi.org/10.1007/s00330-022-09323-z; html:https://europepmc.org/articles/PMC10121487; pdf:https://europepmc.org/articles/PMC10121487?pdf=render"
-  },
   {
     "id": "33782427",
     "doi": "https://doi.org/10.1038/s41598-021-86266-3",
@@ -24071,6 +24054,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-021-86266-3.pdf; doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?pdf=render"
   },
+  {
+    "id": "36512045",
+    "doi": "https://doi.org/10.1007/s00330-022-09323-z",
+    "title": "Prediction of incident cardiovascular events using machine learning and CMR radiomics.",
+    "authorString": "Pujadas ER, Raisi-Estabragh Z, Szabo L, McCracken C, Morcillo CI, Campello VM, Mart\u00edn-Isla C, Atehortua AM, Vago H, Merkely B, Maurovich-Horvat P, Harvey NC, Neubauer S, Petersen SE, Lekadir K.",
+    "authorAffiliations": "",
+    "journalTitle": "European radiology",
+    "pubYear": "2023",
+    "date": "2022-12-13",
+    "isOpenAccess": "Y",
+    "keywords": "Atrial fibrillation; Heart Failure; Preventive Medicine; Machine Learning; Radiomics",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction\u00a0(MI), and stroke using machine learning techniques.<h4>Methods</h4>We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.<h4>Results</h4>AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.<h4>Conclusions</h4>Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.<h4>Key points</h4>\u2022 Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. \u2022 CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. \u2022 The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.",
+    "laySummary": "",
+    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00330-022-09323-z.pdf; doi:https://doi.org/10.1007/s00330-022-09323-z; html:https://europepmc.org/articles/PMC10121487; pdf:https://europepmc.org/articles/PMC10121487?pdf=render"
+  },
   {
     "id": "33692568",
     "doi": "https://doi.org/10.1038/s41588-021-00783-5",
@@ -24649,23 +24649,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/1660-4601/17/3/892/pdf?version=1580475934; doi:https://doi.org/10.3390/ijerph17030892; html:https://europepmc.org/articles/PMC7037699; pdf:https://europepmc.org/articles/PMC7037699?pdf=render"
   },
-  {
-    "id": "36688706",
-    "doi": "https://doi.org/10.1093/rheumatology/kead038",
-    "title": "Classification of patients with osteoarthritis through clusters of comorbidities using 633\u200a330 individuals from Spain.",
-    "authorString": "Pineda-Moncus\u00ed M, Dernie F, Dell'Isola A, Kamps A, Runhaar J, Swain S, Zhang W, Englund M, Pitsillidou I, Strauss VY, Robinson DE, Prieto-Alhambra D, Khalid S.",
-    "authorAffiliations": "",
-    "journalTitle": "Rheumatology (Oxford, England)",
-    "pubYear": "2023",
-    "date": "2023-11-01",
-    "isOpenAccess": "Y",
-    "keywords": "Clustering; epidemiology; Comorbidities; Oa",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster.<h4>Methods</h4>This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in \u22651% of the individuals (n\u2009=\u200935) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.<h4>Results</h4>We identified 633\u2009330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]).<h4>Conclusion</h4>Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead038/49101708/kead038.pdf; doi:https://doi.org/10.1093/rheumatology/kead038; html:https://europepmc.org/articles/PMC10629784; pdf:https://europepmc.org/articles/PMC10629784?pdf=render"
-  },
   {
     "id": "34002035",
     "doi": "https://doi.org/10.1038/s41366-021-00807-4",
@@ -24683,23 +24666,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41366-021-00807-4.pdf; doi:https://doi.org/10.1038/s41366-021-00807-4; html:https://europepmc.org/articles/PMC8236409; pdf:https://europepmc.org/articles/PMC8236409?pdf=render"
   },
-  {
-    "id": "37730620",
-    "doi": "https://doi.org/10.1186/s13643-023-02333-y",
-    "title": "What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.",
-    "authorString": "Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",
-    "authorAffiliations": "",
-    "journalTitle": "Systematic reviews",
-    "pubYear": "2023",
-    "date": "2023-09-20",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.<h4>Methods</h4>An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.<h4>Discussion</h4>The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",
-    "laySummary": "",
-    "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render"
-  },
   {
     "id": "33654696",
     "doi": "https://doi.org/10.1093/burnst/tkaa044",
@@ -24717,6 +24683,40 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkaa044/37307900/tkaa044.pdf; doi:https://doi.org/10.1093/burnst/tkaa044; html:https://europepmc.org/articles/PMC7901708; pdf:https://europepmc.org/articles/PMC7901708?pdf=render"
   },
+  {
+    "id": "36688706",
+    "doi": "https://doi.org/10.1093/rheumatology/kead038",
+    "title": "Classification of patients with osteoarthritis through clusters of comorbidities using 633\u200a330 individuals from Spain.",
+    "authorString": "Pineda-Moncus\u00ed M, Dernie F, Dell'Isola A, Kamps A, Runhaar J, Swain S, Zhang W, Englund M, Pitsillidou I, Strauss VY, Robinson DE, Prieto-Alhambra D, Khalid S.",
+    "authorAffiliations": "",
+    "journalTitle": "Rheumatology (Oxford, England)",
+    "pubYear": "2023",
+    "date": "2023-11-01",
+    "isOpenAccess": "Y",
+    "keywords": "Clustering; epidemiology; Comorbidities; Oa",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster.<h4>Methods</h4>This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in \u22651% of the individuals (n\u2009=\u200935) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.<h4>Results</h4>We identified 633\u2009330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]).<h4>Conclusion</h4>Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead038/49101708/kead038.pdf; doi:https://doi.org/10.1093/rheumatology/kead038; html:https://europepmc.org/articles/PMC10629784; pdf:https://europepmc.org/articles/PMC10629784?pdf=render"
+  },
+  {
+    "id": "37730620",
+    "doi": "https://doi.org/10.1186/s13643-023-02333-y",
+    "title": "What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.",
+    "authorString": "Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",
+    "authorAffiliations": "",
+    "journalTitle": "Systematic reviews",
+    "pubYear": "2023",
+    "date": "2023-09-20",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.<h4>Methods</h4>An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.<h4>Discussion</h4>The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",
+    "laySummary": "",
+    "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render"
+  },
   {
     "id": "34596018",
     "doi": "https://doi.org/10.2807/1560-7917.es.2021.26.39.2001440",
@@ -24904,23 +24904,6 @@
     "laySummary": "",
     "urls": "pdf:https://cardiooncologyjournal.biomedcentral.com/track/pdf/10.1186/s40959-020-00079-3; doi:https://doi.org/10.1186/s40959-020-00079-3; html:https://europepmc.org/articles/PMC7557080; pdf:https://europepmc.org/articles/PMC7557080?pdf=render"
   },
-  {
-    "id": "36343994",
-    "doi": "https://doi.org/10.1136/bmjopen-2022-063159",
-    "title": "Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.",
-    "authorString": "Cooper DJ, Lear S, Sithole N, Shaw A, Stark H, Ferris M, CITIID-NIHR BioResource COVID-19 collaboration consortium, Bradley J, Maxwell P, Goodfellow I, Weekes MP, Seaman S, Baker S.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-11-07",
-    "isOpenAccess": "Y",
-    "keywords": "Infection control; epidemiology; Public Health; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs.<h4>Design/setting/participants</h4>HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model.<h4>Results</h4>Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p&lt;0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p&lt;0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p&lt;0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038).<h4>Conclusions</h4>The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render"
-  },
   {
     "id": "37671353",
     "doi": "https://doi.org/10.23889/ijpds.v5i3.2133",
@@ -24938,6 +24921,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.23889/ijpds.v5i3.2133; html:https://europepmc.org/articles/PMC10476697; pdf:https://europepmc.org/articles/PMC10476697?pdf=render"
   },
+  {
+    "id": "36343994",
+    "doi": "https://doi.org/10.1136/bmjopen-2022-063159",
+    "title": "Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.",
+    "authorString": "Cooper DJ, Lear S, Sithole N, Shaw A, Stark H, Ferris M, CITIID-NIHR BioResource COVID-19 collaboration consortium, Bradley J, Maxwell P, Goodfellow I, Weekes MP, Seaman S, Baker S.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-11-07",
+    "isOpenAccess": "Y",
+    "keywords": "Infection control; epidemiology; Public Health; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs.<h4>Design/setting/participants</h4>HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model.<h4>Results</h4>Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p&lt;0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p&lt;0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p&lt;0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038).<h4>Conclusions</h4>The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render"
+  },
   {
     "id": "36351458",
     "doi": "https://doi.org/10.1016/s0140-6736(22)02074-8",
@@ -25006,23 +25006,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.internationaljournalofcardiology.com/article/S0167527320335579/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.08.030"
   },
-  {
-    "id": "35639667",
-    "doi": "https://doi.org/10.1093/eurheartj/ehac238",
-    "title": "Critical appraisal of artificial intelligence-based prediction models for cardiovascular disease.",
-    "authorString": "van Smeden M, Heinze G, Van Calster B, Asselbergs FW, Vardas PE, Bruining N, de Jaegere P, Moore JH, Denaxas S, Boulesteix AL, Moons KGM.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal",
-    "pubYear": "2022",
-    "date": "2022-08-01",
-    "isOpenAccess": "Y",
-    "keywords": "Prediction; Artificial intelligence; Diagnosis; Prognosis; Machine Learning; Digital Health",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The medical field has seen a rapid increase in the development of artificial intelligence (AI)-based prediction models. With the introduction of such AI-based prediction model tools and software in cardiovascular patient care, the cardiovascular researcher and healthcare professional are challenged to understand the opportunities as well as the limitations of the AI-based predictions. In this article, we present 12 critical questions for cardiovascular health professionals to ask when confronted with an AI-based prediction model. We aim to support medical professionals to distinguish the AI-based prediction models that can add value to patient care from the AI that does not.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render"
-  },
   {
     "id": "34980174",
     "doi": "https://doi.org/10.1186/s12967-021-03210-9",
@@ -25040,6 +25023,23 @@
     "laySummary": "",
     "urls": "pdf:https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-021-03210-9; doi:https://doi.org/10.1186/s12967-021-03210-9; html:https://europepmc.org/articles/PMC8722174; pdf:https://europepmc.org/articles/PMC8722174?pdf=render"
   },
+  {
+    "id": "35639667",
+    "doi": "https://doi.org/10.1093/eurheartj/ehac238",
+    "title": "Critical appraisal of artificial intelligence-based prediction models for cardiovascular disease.",
+    "authorString": "van Smeden M, Heinze G, Van Calster B, Asselbergs FW, Vardas PE, Bruining N, de Jaegere P, Moore JH, Denaxas S, Boulesteix AL, Moons KGM.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal",
+    "pubYear": "2022",
+    "date": "2022-08-01",
+    "isOpenAccess": "Y",
+    "keywords": "Prediction; Artificial intelligence; Diagnosis; Prognosis; Machine Learning; Digital Health",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The medical field has seen a rapid increase in the development of artificial intelligence (AI)-based prediction models. With the introduction of such AI-based prediction model tools and software in cardiovascular patient care, the cardiovascular researcher and healthcare professional are challenged to understand the opportunities as well as the limitations of the AI-based predictions. In this article, we present 12 critical questions for cardiovascular health professionals to ask when confronted with an AI-based prediction model. We aim to support medical professionals to distinguish the AI-based prediction models that can add value to patient care from the AI that does not.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render"
+  },
   {
     "id": "32763829",
     "doi": "https://doi.org/10.1016/j.ebiom.2020.102932",
@@ -25363,23 +25363,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41591-020-0916-2.pdf; doi:https://doi.org/10.1038/s41591-020-0916-2; html:https://europepmc.org/articles/PMC7751267; pdf:https://europepmc.org/articles/PMC7751267?pdf=render; doi:https://doi.org/10.1038/s41591-020-0916-2"
   },
-  {
-    "id": "36423925",
-    "doi": "https://doi.org/10.1136/thorax-2022-219591",
-    "title": "Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).",
-    "authorString": "Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe D, Davies G, Lyons RA, Griffiths C, Kee F, Sheikh A, Shaheen SO, Martineau AR.",
-    "authorAffiliations": "",
-    "journalTitle": "Thorax",
-    "pubYear": "2023",
-    "date": "2022-11-23",
-    "isOpenAccess": "Y",
-    "keywords": "Asthma; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.<h4>Methods</h4>We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.<h4>Results</h4>Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31).<h4>Conclusions</h4>Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.<h4>Study registration number</h4>NCT04330599.",
-    "laySummary": "",
-    "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render"
-  },
   {
     "id": "34040552",
     "doi": "https://doi.org/10.3389/fpsyt.2021.627996",
@@ -25397,6 +25380,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpsyt.2021.627996/pdf; doi:https://doi.org/10.3389/fpsyt.2021.627996; html:https://europepmc.org/articles/PMC8141616; pdf:https://europepmc.org/articles/PMC8141616?pdf=render"
   },
+  {
+    "id": "36423925",
+    "doi": "https://doi.org/10.1136/thorax-2022-219591",
+    "title": "Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).",
+    "authorString": "Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe D, Davies G, Lyons RA, Griffiths C, Kee F, Sheikh A, Shaheen SO, Martineau AR.",
+    "authorAffiliations": "",
+    "journalTitle": "Thorax",
+    "pubYear": "2023",
+    "date": "2022-11-23",
+    "isOpenAccess": "Y",
+    "keywords": "Asthma; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.<h4>Methods</h4>We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.<h4>Results</h4>Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31).<h4>Conclusions</h4>Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.<h4>Study registration number</h4>NCT04330599.",
+    "laySummary": "",
+    "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render"
+  },
   {
     "id": "33933530",
     "doi": "https://doi.org/10.1016/j.jinf.2021.04.027",
@@ -25635,23 +25635,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/1660-4601/17/19/7320/pdf?version=1602228180; doi:https://doi.org/10.3390/ijerph17197320; html:https://europepmc.org/articles/PMC7579145; pdf:https://europepmc.org/articles/PMC7579145?pdf=render"
   },
-  {
-    "id": "35513530",
-    "doi": "https://doi.org/10.1038/s41591-022-01781-8",
-    "title": "Patient reported outcome assessment must be inclusive and equitable.",
-    "authorString": "Calvert MJ, Cruz Rivera S, Retzer A, Hughes SE, Campbell L, Molony-Oates B, Aiyegbusi OL, Stover AM, Wilson R, McMullan C, Anderson NE, Turner GM, Davies EH, Verdi R, Velikova G, Kamudoni P, Muslim S, Gheorghe A, O'Connor D, Liu X, Wu AW, Denniston AK.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature medicine",
-    "pubYear": "2022",
-    "date": "2022-06-01",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41591-022-01781-8.pdf; doi:https://doi.org/10.1038/s41591-022-01781-8"
-  },
   {
     "id": "31089183",
     "doi": "https://doi.org/10.1038/s41598-019-43861-9",
@@ -25670,21 +25653,21 @@
     "urls": "pdf:https://www.nature.com/articles/s41598-019-43861-9.pdf; doi:https://doi.org/10.1038/s41598-019-43861-9; html:https://europepmc.org/articles/PMC6517397; pdf:https://europepmc.org/articles/PMC6517397?pdf=render"
   },
   {
-    "id": "35681241",
-    "doi": "https://doi.org/10.1186/s12933-022-01525-5",
-    "title": "Elevated plasma triglyceride concentration and risk of adverse clinical\u00a0outcomes in 1.5 million people: a CALIBER linked electronic health record study.",
-    "authorString": "Patel RS, Pasea L, Soran H, Downie P, Jones R, Hingorani AD, Neely D, Denaxas S, Hemingway H.",
+    "id": "35513530",
+    "doi": "https://doi.org/10.1038/s41591-022-01781-8",
+    "title": "Patient reported outcome assessment must be inclusive and equitable.",
+    "authorString": "Calvert MJ, Cruz Rivera S, Retzer A, Hughes SE, Campbell L, Molony-Oates B, Aiyegbusi OL, Stover AM, Wilson R, McMullan C, Anderson NE, Turner GM, Davies EH, Verdi R, Velikova G, Kamudoni P, Muslim S, Gheorghe A, O'Connor D, Liu X, Wu AW, Denniston AK.",
     "authorAffiliations": "",
-    "journalTitle": "Cardiovascular diabetology",
+    "journalTitle": "Nature medicine",
     "pubYear": "2022",
-    "date": "2022-06-09",
-    "isOpenAccess": "Y",
-    "keywords": "Lipids; Triglycerides; Myocardial infarction; Diabetes; Pancreatitis",
+    "date": "2022-06-01",
+    "isOpenAccess": "N",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Background</h4>Assessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes.<h4>Methods</h4>We used linked data from primary and secondary care for 15\u2009M people, to explore the association between triglyceride concentration and risk of acute pancreatitis, chronic pancreatitis,\u00a0new onset diabetes, myocardial infarction and all-cause mortality, over a median of 6-7\u2009years follow up.<h4>Results</h4>Triglyceride concentration was available for 1,530,411 individuals (mean age 56\u00b76\u2009\u00b1\u200915\u00b76\u2009years, 51\u00b74% female), with a median of 1\u00b73\u2009mmol/L (IQR: 0.9.to 1.9). Severe hypertriglyceridemia, defined as >\u200910\u2009mmol/L, was identified in 3289 (0\u00b721%) individuals including 620 with >\u200920\u2009mmol/L.\u00a0In multivariable analyses, a triglyceride concentration\u2009>\u200920\u2009mmol/L was associated with very high risk for acute pancreatitis (Hazard ratio (HR) 13\u00b755 (95% CI 9\u00b715-20\u00b706)); chronic pancreatitis (HR 25\u00b719 (14\u00b791-42\u00b755)); and high risk for diabetes (HR 5\u00b728 (4\u00b751-6\u00b718)) and all-cause mortality (HR 3\u00b762 (2\u00b782-4\u00b765)) when compared to the reference category of \u2264\u20091\u00b77\u2009mmol/L. An association with myocardial infarction, however, was only observed for more moderate hypertriglyceridaemia between 1.7 and 10\u2009mmol/L. We found a risk interaction with age, with higher risks for all outcomes including mortality among those\u2009\u2264\u200940\u2009years compared to >\u200940\u2009years.<h4>Conclusions</h4>We highlight an exponential association between severe hypertriglyceridaemia and risk of incident acute and chronic pancreatitis, new diabetes, and mortality, especially at younger ages, but not for myocardial infarction for which only moderate hypertriglyceridemia conferred risk.",
+    "abstract": "",
     "laySummary": "",
-    "urls": "pdf:https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-022-01525-5; doi:https://doi.org/10.1186/s12933-022-01525-5; html:https://europepmc.org/articles/PMC9185961; pdf:https://europepmc.org/articles/PMC9185961?pdf=render"
+    "urls": "pdf:https://www.nature.com/articles/s41591-022-01781-8.pdf; doi:https://doi.org/10.1038/s41591-022-01781-8"
   },
   {
     "id": "32079223",
@@ -25703,6 +25686,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/2077-0383/9/2/545/pdf?version=1581938622; doi:https://doi.org/10.3390/jcm9020545; html:https://europepmc.org/articles/PMC7073517; pdf:https://europepmc.org/articles/PMC7073517?pdf=render"
   },
+  {
+    "id": "35681241",
+    "doi": "https://doi.org/10.1186/s12933-022-01525-5",
+    "title": "Elevated plasma triglyceride concentration and risk of adverse clinical\u00a0outcomes in 1.5 million people: a CALIBER linked electronic health record study.",
+    "authorString": "Patel RS, Pasea L, Soran H, Downie P, Jones R, Hingorani AD, Neely D, Denaxas S, Hemingway H.",
+    "authorAffiliations": "",
+    "journalTitle": "Cardiovascular diabetology",
+    "pubYear": "2022",
+    "date": "2022-06-09",
+    "isOpenAccess": "Y",
+    "keywords": "Lipids; Triglycerides; Myocardial infarction; Diabetes; Pancreatitis",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Assessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes.<h4>Methods</h4>We used linked data from primary and secondary care for 15\u2009M people, to explore the association between triglyceride concentration and risk of acute pancreatitis, chronic pancreatitis,\u00a0new onset diabetes, myocardial infarction and all-cause mortality, over a median of 6-7\u2009years follow up.<h4>Results</h4>Triglyceride concentration was available for 1,530,411 individuals (mean age 56\u00b76\u2009\u00b1\u200915\u00b76\u2009years, 51\u00b74% female), with a median of 1\u00b73\u2009mmol/L (IQR: 0.9.to 1.9). Severe hypertriglyceridemia, defined as >\u200910\u2009mmol/L, was identified in 3289 (0\u00b721%) individuals including 620 with >\u200920\u2009mmol/L.\u00a0In multivariable analyses, a triglyceride concentration\u2009>\u200920\u2009mmol/L was associated with very high risk for acute pancreatitis (Hazard ratio (HR) 13\u00b755 (95% CI 9\u00b715-20\u00b706)); chronic pancreatitis (HR 25\u00b719 (14\u00b791-42\u00b755)); and high risk for diabetes (HR 5\u00b728 (4\u00b751-6\u00b718)) and all-cause mortality (HR 3\u00b762 (2\u00b782-4\u00b765)) when compared to the reference category of \u2264\u20091\u00b77\u2009mmol/L. An association with myocardial infarction, however, was only observed for more moderate hypertriglyceridaemia between 1.7 and 10\u2009mmol/L. We found a risk interaction with age, with higher risks for all outcomes including mortality among those\u2009\u2264\u200940\u2009years compared to >\u200940\u2009years.<h4>Conclusions</h4>We highlight an exponential association between severe hypertriglyceridaemia and risk of incident acute and chronic pancreatitis, new diabetes, and mortality, especially at younger ages, but not for myocardial infarction for which only moderate hypertriglyceridemia conferred risk.",
+    "laySummary": "",
+    "urls": "pdf:https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-022-01525-5; doi:https://doi.org/10.1186/s12933-022-01525-5; html:https://europepmc.org/articles/PMC9185961; pdf:https://europepmc.org/articles/PMC9185961?pdf=render"
+  },
   {
     "id": "36100927",
     "doi": "https://doi.org/10.28920/dhm52.3.164-174",
@@ -26026,23 +26026,6 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1383/2566; doi:https://doi.org/10.23889/ijpds.v5i2.1383; html:https://europepmc.org/articles/PMC7473253; pdf:https://europepmc.org/articles/PMC7473253?pdf=render"
   },
-  {
-    "id": "37808344",
-    "doi": "https://doi.org/10.1016/j.jacadv.2023.100573",
-    "title": "<i>CYP2C19</i> Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With\u00a0Clopidogrel.",
-    "authorString": "Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",
-    "authorAffiliations": "",
-    "journalTitle": "JACC. Advances",
-    "pubYear": "2023",
-    "date": "2023-09-01",
-    "isOpenAccess": "Y",
-    "keywords": "Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in <i>CYP2C19</i> and their relationship with clinical efficacy have not included South Asian populations.<h4>Objectives</h4>The objective of this study was to assess prevalence of common <i>CYP2C19</i> genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.<h4>Methods</h4>The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. <i>CYP2C19</i> diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.<h4>Results</h4>Genes & Health cohort participants (N\u00a0=\u00a044,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function <i>CYP2C19</i> allele. The prevalence of poor metabolizers carrying 2\u00a0<i>CYP2C19</i> loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; <i>P</i>\u00a0=\u00a00.019).<h4>Conclusions</h4>A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render"
-  },
   {
     "id": "32909959",
     "doi": "https://doi.org/10.1136/bmj.m3164",
@@ -26077,6 +26060,23 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01726-3; doi:https://doi.org/10.1186/s12916-020-01726-3; html:https://europepmc.org/articles/PMC7467845; pdf:https://europepmc.org/articles/PMC7467845?pdf=render"
   },
+  {
+    "id": "37808344",
+    "doi": "https://doi.org/10.1016/j.jacadv.2023.100573",
+    "title": "<i>CYP2C19</i> Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With\u00a0Clopidogrel.",
+    "authorString": "Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",
+    "authorAffiliations": "",
+    "journalTitle": "JACC. Advances",
+    "pubYear": "2023",
+    "date": "2023-09-01",
+    "isOpenAccess": "Y",
+    "keywords": "Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in <i>CYP2C19</i> and their relationship with clinical efficacy have not included South Asian populations.<h4>Objectives</h4>The objective of this study was to assess prevalence of common <i>CYP2C19</i> genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.<h4>Methods</h4>The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. <i>CYP2C19</i> diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.<h4>Results</h4>Genes & Health cohort participants (N\u00a0=\u00a044,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function <i>CYP2C19</i> allele. The prevalence of poor metabolizers carrying 2\u00a0<i>CYP2C19</i> loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; <i>P</i>\u00a0=\u00a00.019).<h4>Conclusions</h4>A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render"
+  },
   {
     "id": "33306713",
     "doi": "https://doi.org/10.1371/journal.pone.0243383",
@@ -26230,23 +26230,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-021-89743-x.pdf; doi:https://doi.org/10.1038/s41598-021-89743-x; html:https://europepmc.org/articles/PMC8119673; pdf:https://europepmc.org/articles/PMC8119673?pdf=render"
   },
-  {
-    "id": "36962407",
-    "doi": "https://doi.org/10.1371/journal.pgph.0000292",
-    "title": "Health worker experiences of implementing TB infection prevention and control: A qualitative evidence synthesis to inform implementation recommendations.",
-    "authorString": "van der Westhuizen HM, Dorward J, Roberts N, Greenhalgh T, Ehrlich R, Butler CC, Tonkin-Crine S.",
-    "authorAffiliations": "",
-    "journalTitle": "PLOS global public health",
-    "pubYear": "2022",
-    "date": "2022-07-07",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render"
-  },
   {
     "id": "31220083",
     "doi": "https://doi.org/10.1371/journal.pmed.1002833",
@@ -26264,6 +26247,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1371/journal.pmed.1002833; doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render"
   },
+  {
+    "id": "36962407",
+    "doi": "https://doi.org/10.1371/journal.pgph.0000292",
+    "title": "Health worker experiences of implementing TB infection prevention and control: A qualitative evidence synthesis to inform implementation recommendations.",
+    "authorString": "van der Westhuizen HM, Dorward J, Roberts N, Greenhalgh T, Ehrlich R, Butler CC, Tonkin-Crine S.",
+    "authorAffiliations": "",
+    "journalTitle": "PLOS global public health",
+    "pubYear": "2022",
+    "date": "2022-07-07",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render"
+  },
   {
     "id": "36210800",
     "doi": "https://doi.org/10.1038/s43856-022-00189-2",
@@ -26519,23 +26519,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S1470204523001560/pdf; doi:https://doi.org/10.1016/S1470-2045(23)00156-0"
   },
-  {
-    "id": "34791170",
-    "doi": "https://doi.org/10.1093/eurheartj/ehab759",
-    "title": "A sex-specific prediction model is not enough to achieve equality for women in preventative cardiovascular medicine.",
-    "authorString": "Kimenai DM, Shah ASV, Mills NL.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal",
-    "pubYear": "2022",
-    "date": "2022-01-01",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/eurheartj/article-pdf/43/3/239/42296399/ehab759.pdf; doi:https://doi.org/10.1093/eurheartj/ehab759; html:https://europepmc.org/articles/PMC8790764; pdf:https://europepmc.org/articles/PMC8790764?pdf=render"
-  },
   {
     "id": "32781946",
     "doi": "https://doi.org/10.1098/rspb.2020.1405",
@@ -26553,6 +26536,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1098/rspb.2020.1405; doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render"
   },
+  {
+    "id": "34791170",
+    "doi": "https://doi.org/10.1093/eurheartj/ehab759",
+    "title": "A sex-specific prediction model is not enough to achieve equality for women in preventative cardiovascular medicine.",
+    "authorString": "Kimenai DM, Shah ASV, Mills NL.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal",
+    "pubYear": "2022",
+    "date": "2022-01-01",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/eurheartj/article-pdf/43/3/239/42296399/ehab759.pdf; doi:https://doi.org/10.1093/eurheartj/ehab759; html:https://europepmc.org/articles/PMC8790764; pdf:https://europepmc.org/articles/PMC8790764?pdf=render"
+  },
   {
     "id": "37075078",
     "doi": "https://doi.org/10.1371/journal.pmed.1004223",
@@ -26961,23 +26961,6 @@
     "laySummary": "",
     "urls": "pdf:https://discovery.ucl.ac.uk/10096914/1/Hageman_Manuscript_MALE_20200211_clean.pdf; doi:https://doi.org/10.1136/heartjnl-2019-316088"
   },
-  {
-    "id": "37605204",
-    "doi": "https://doi.org/10.1186/s12916-023-03013-3",
-    "title": "The development of a core outcome set for studies of pregnant women with multimorbidity.",
-    "authorString": "Lee SI, Hanley S, Vowles Z, Plachcinski R, Moss N, Singh M, Gale C, Fagbamigbe AF, Azcoaga-Lorenzo A, Subramanian A, Taylor B, Nelson-Piercy C, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Dolk H, Hope H, Phillips K, Abel KM, Eastwood KA, Kent L, Locock L, Loane M, Mhereeg M, Brocklehurst P, McCann S, Brophy S, Wambua S, Hemali Sudasinghe SPB, Thangaratinam S, Nirantharakumar K, Black M, MuM-PreDiCT Group.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medicine",
-    "pubYear": "2023",
-    "date": "2023-08-21",
-    "isOpenAccess": "Y",
-    "keywords": "Pregnancy; Maternity; Outcome; Multimorbidity; Multiple Chronic Conditions; Core Outcome Set; Multiple Long-term Conditions",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity.<h4>Methods</h4>We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations.<h4>Results</h4>Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (\u226570% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was \u226580% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs.<h4>Conclusions</h4>Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1186/s12916-023-03013-3; html:https://europepmc.org/articles/PMC10441728; pdf:https://europepmc.org/articles/PMC10441728?pdf=render"
-  },
   {
     "id": "34062542",
     "doi": "https://doi.org/10.1159/000517521",
@@ -27012,6 +26995,23 @@
     "laySummary": "",
     "urls": "pdf:http://pure-oai.bham.ac.uk/ws/files/100688542/NEU20_1602R_Merged_PDF.pdf; doi:https://doi.org/10.1001/jamaneurol.2020.3502; html:https://europepmc.org/articles/PMC7536630; doi:https://doi.org/10.1001/jamaneurol.2020.3502"
   },
+  {
+    "id": "37605204",
+    "doi": "https://doi.org/10.1186/s12916-023-03013-3",
+    "title": "The development of a core outcome set for studies of pregnant women with multimorbidity.",
+    "authorString": "Lee SI, Hanley S, Vowles Z, Plachcinski R, Moss N, Singh M, Gale C, Fagbamigbe AF, Azcoaga-Lorenzo A, Subramanian A, Taylor B, Nelson-Piercy C, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Dolk H, Hope H, Phillips K, Abel KM, Eastwood KA, Kent L, Locock L, Loane M, Mhereeg M, Brocklehurst P, McCann S, Brophy S, Wambua S, Hemali Sudasinghe SPB, Thangaratinam S, Nirantharakumar K, Black M, MuM-PreDiCT Group.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC medicine",
+    "pubYear": "2023",
+    "date": "2023-08-21",
+    "isOpenAccess": "Y",
+    "keywords": "Pregnancy; Maternity; Outcome; Multimorbidity; Multiple Chronic Conditions; Core Outcome Set; Multiple Long-term Conditions",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity.<h4>Methods</h4>We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations.<h4>Results</h4>Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (\u226570% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was \u226580% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs.<h4>Conclusions</h4>Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1186/s12916-023-03013-3; html:https://europepmc.org/articles/PMC10441728; pdf:https://europepmc.org/articles/PMC10441728?pdf=render"
+  },
   {
     "id": "31363735",
     "doi": "https://doi.org/10.1093/hmg/ddz187",
@@ -27216,23 +27216,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmchealthservres.biomedcentral.com/track/pdf/10.1186/s12913-022-07607-0; doi:https://doi.org/10.1186/s12913-022-07607-0; html:https://europepmc.org/articles/PMC8859903; pdf:https://europepmc.org/articles/PMC8859903?pdf=render"
   },
-  {
-    "id": "35193920",
-    "doi": "https://doi.org/10.1136/bmjopen-2021-055773",
-    "title": "Investigating the optimal handling of uncertain pregnancy episodes in the CPRD GOLD Pregnancy Register: a methodological study using UK primary care data.",
-    "authorString": "Campbell J, Bhaskaran K, Thomas S, Williams R, McDonald HI, Minassian C.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-02-22",
-    "isOpenAccess": "Y",
-    "keywords": "epidemiology; Public Health; Maternal Medicine",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>To investigate why episodes of pregnancy identified from electronic health records may be incomplete or conflicting (overlapping), and provide guidance on how to handle them.<h4>Setting</h4>Pregnancy Register generated from the Clinical Practice Research Datalink (CPRD) GOLD UK primary care database.<h4>Participants</h4>Female patients with at least one pregnancy episode in the Register (01 January 1937-31 December 2017) which had no recorded outcome or conflicted with another episode.<h4>Design</h4>We identified multiple scenarios potentially explaining why uncertain episodes occur. Criteria were established and systematically applied to determine whether episodes had evidence of each scenario. Linked Hospital Episode Statistics were used to identify pregnancy events not captured in primary care.<h4>Results</h4>Of 5.8\u2009million pregnancy episodes in the Register, 932\u2009604 (16%) had no recorded outcome, and 478\u2009341 (8.5%) conflicted with another episode (251\u2009026 distinct conflicting pairs of episodes among 210\u2009593\u2009women). 826\u2009146 (89%) of the episodes without outcome recorded in primary care and 215\u2009577 (86%) of the conflicting pairs were consistent with one or more of our proposed scenarios. For 689\u2009737 (74%) episodes with recorded outcome missing and 215\u2009544 (86%) of the conflicting pairs (at least one episode), supportive evidence (eg, antenatal records, linked hospital records) suggested they were true and current pregnancies. Furthermore, 516\u2009818 (55 %) and 160\u2009936 (64%), respectively, were during research quality follow-up time. For a sizeable proportion of uncertain episode, there is evidence to suggest that historical outcomes being recorded by the general practitioner during an ongoing pregnancy may offer explanation (73\u2009208 (29.2%) and 349\u2009874 (37.5%)).<h4>Conclusions</h4>This work provides insight to users of the CPRD Pregnancy Register on why uncertain pregnancy episodes exist and indicates that most of these episodes are likely to be real pregnancies. Guidance is given to help researchers consider whether to include/exclude uncertain pregnancies from their studies, and how to tailor approaches to minimise underestimation and bias.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055773.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055773; html:https://europepmc.org/articles/PMC8867343; pdf:https://europepmc.org/articles/PMC8867343?pdf=render"
-  },
   {
     "id": "31443926",
     "doi": "https://doi.org/10.1016/s0140-6736(19)31674-5",
@@ -27250,6 +27233,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S0140673619316745/pdf; doi:https://doi.org/10.1016/S0140-6736(19)31674-5; html:https://europepmc.org/articles/PMC6857444; pdf:https://europepmc.org/articles/PMC6857444?pdf=render"
   },
+  {
+    "id": "35193920",
+    "doi": "https://doi.org/10.1136/bmjopen-2021-055773",
+    "title": "Investigating the optimal handling of uncertain pregnancy episodes in the CPRD GOLD Pregnancy Register: a methodological study using UK primary care data.",
+    "authorString": "Campbell J, Bhaskaran K, Thomas S, Williams R, McDonald HI, Minassian C.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-02-22",
+    "isOpenAccess": "Y",
+    "keywords": "epidemiology; Public Health; Maternal Medicine",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>To investigate why episodes of pregnancy identified from electronic health records may be incomplete or conflicting (overlapping), and provide guidance on how to handle them.<h4>Setting</h4>Pregnancy Register generated from the Clinical Practice Research Datalink (CPRD) GOLD UK primary care database.<h4>Participants</h4>Female patients with at least one pregnancy episode in the Register (01 January 1937-31 December 2017) which had no recorded outcome or conflicted with another episode.<h4>Design</h4>We identified multiple scenarios potentially explaining why uncertain episodes occur. Criteria were established and systematically applied to determine whether episodes had evidence of each scenario. Linked Hospital Episode Statistics were used to identify pregnancy events not captured in primary care.<h4>Results</h4>Of 5.8\u2009million pregnancy episodes in the Register, 932\u2009604 (16%) had no recorded outcome, and 478\u2009341 (8.5%) conflicted with another episode (251\u2009026 distinct conflicting pairs of episodes among 210\u2009593\u2009women). 826\u2009146 (89%) of the episodes without outcome recorded in primary care and 215\u2009577 (86%) of the conflicting pairs were consistent with one or more of our proposed scenarios. For 689\u2009737 (74%) episodes with recorded outcome missing and 215\u2009544 (86%) of the conflicting pairs (at least one episode), supportive evidence (eg, antenatal records, linked hospital records) suggested they were true and current pregnancies. Furthermore, 516\u2009818 (55 %) and 160\u2009936 (64%), respectively, were during research quality follow-up time. For a sizeable proportion of uncertain episode, there is evidence to suggest that historical outcomes being recorded by the general practitioner during an ongoing pregnancy may offer explanation (73\u2009208 (29.2%) and 349\u2009874 (37.5%)).<h4>Conclusions</h4>This work provides insight to users of the CPRD Pregnancy Register on why uncertain pregnancy episodes exist and indicates that most of these episodes are likely to be real pregnancies. Guidance is given to help researchers consider whether to include/exclude uncertain pregnancies from their studies, and how to tailor approaches to minimise underestimation and bias.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055773.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055773; html:https://europepmc.org/articles/PMC8867343; pdf:https://europepmc.org/articles/PMC8867343?pdf=render"
+  },
   {
     "id": "33724919",
     "doi": "https://doi.org/10.2196/26627",
@@ -27301,23 +27301,6 @@
     "laySummary": "",
     "urls": "pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render"
   },
-  {
-    "id": "37814053",
-    "doi": "https://doi.org/10.1038/s41588-023-01522-8",
-    "title": "Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.",
-    "authorString": "Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature genetics",
-    "pubYear": "2023",
-    "date": "2023-10-09",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1038/s41588-023-01522-8"
-  },
   {
     "id": "35251129",
     "doi": "https://doi.org/10.3389/fgene.2022.818574",
@@ -27335,6 +27318,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fgene.2022.818574/pdf; doi:https://doi.org/10.3389/fgene.2022.818574; html:https://europepmc.org/articles/PMC8894758; pdf:https://europepmc.org/articles/PMC8894758?pdf=render"
   },
+  {
+    "id": "37814053",
+    "doi": "https://doi.org/10.1038/s41588-023-01522-8",
+    "title": "Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.",
+    "authorString": "Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature genetics",
+    "pubYear": "2023",
+    "date": "2023-10-09",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1038/s41588-023-01522-8"
+  },
   {
     "id": "33560344",
     "doi": "https://doi.org/10.1210/clinem/dgab067",
@@ -27437,23 +27437,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/0141076820961776; doi:https://doi.org/10.1177/0141076820961776; html:https://europepmc.org/articles/PMC7809339; pdf:https://europepmc.org/articles/PMC7809339?pdf=render"
   },
-  {
-    "id": "36446465",
-    "doi": "https://doi.org/10.1136/bmjopen-2022-065142",
-    "title": "Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.",
-    "authorString": "Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-11-29",
-    "isOpenAccess": "Y",
-    "keywords": "epidemiology; Public Health; Protocols & Guidelines; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.<h4>Methods and analysis</h4>Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2\u2009years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.<h4>Ethics and dissemination</h4>Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.<h4>Trial registration number</h4>NCT05240742.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render"
-  },
   {
     "id": "32212911",
     "doi": "https://doi.org/10.1161/jaha.119.013684",
@@ -27471,6 +27454,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013684; doi:https://doi.org/10.1161/JAHA.119.013684; html:https://europepmc.org/articles/PMC7428631; pdf:https://europepmc.org/articles/PMC7428631?pdf=render"
   },
+  {
+    "id": "36446465",
+    "doi": "https://doi.org/10.1136/bmjopen-2022-065142",
+    "title": "Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.",
+    "authorString": "Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-11-29",
+    "isOpenAccess": "Y",
+    "keywords": "epidemiology; Public Health; Protocols & Guidelines; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.<h4>Methods and analysis</h4>Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2\u2009years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.<h4>Ethics and dissemination</h4>Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.<h4>Trial registration number</h4>NCT05240742.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render"
+  },
   {
     "id": "37208429",
     "doi": "https://doi.org/10.1038/s41598-023-33391-w",
@@ -27522,23 +27522,6 @@
     "laySummary": "",
     "urls": "pdf:https://ashpublications.org/bloodadvances/article-pdf/6/7/2319/1886257/advancesadv2021005453.pdf; doi:https://doi.org/10.1182/bloodadvances.2021005453; html:https://europepmc.org/articles/PMC9006276; pdf:https://europepmc.org/articles/PMC9006276?pdf=render"
   },
-  {
-    "id": "34468736",
-    "doi": "https://doi.org/10.1093/europace/euab162",
-    "title": "Comparing clinical performance of current implantable cardioverter-defibrillator implantation recommendations in arrhythmogenic right ventricular cardiomyopathy.",
-    "authorString": "Bosman LP, Bosman LP, Nielsen Gerlach CL, Cadrin-Tourigny J, Orgeron G, Tichnell C, Murray B, Bourfiss M, van der Heijden JF, Yap SC, Zeppenfeld K, van den Berg MP, Wilde AAM, Asselbergs FW, Tandri H, Calkins H, van Tintelen JP, James CA, Te Riele ASJM.",
-    "authorAffiliations": "",
-    "journalTitle": "Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",
-    "pubYear": "2022",
-    "date": "2022-02-01",
-    "isOpenAccess": "Y",
-    "keywords": "Prognosis; Risk stratification; Ventricular Arrhythmias; Implantable Cardioverter-defibrillator; Arrhythmogenic Right Ventricular Cardiomyopathy",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation algorithms are available The International Task Force Consensus ('ITFC'), an ITFC modification by Orgeron et al. ('mITFC'), the AHA/HRS/ACC guideline for VA management ('AHA'), and the HRS expert consensus statement ('HRS'). This study aims to validate and compare the performance of these algorithms in ARVC.<h4>Methods and results</h4>We classified 617 definite ARVC patients (38.5\u2009\u00b1\u200915.1\u2009years, 52.4% male, 39.2% prior sustained VA) according to four algorithms. Clinical performance was evaluated by sensitivity, specificity, ROC-analysis, and decision curve analysis for any sustained VA and for fast VA (>250 b.p.m.). During 6.4 [2.8-11.5] years follow-up, 282 (45.7%) patients experienced any sustained VA, and 63 (10.2%) fast VA. For any sustained VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (94.0-97.8% vs. 76.7-83.5%), but lower specificity (15.9-32.0% vs. 42.7%-60.1%). Similarly, for fast VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (95.2-97.1% vs. 76.7-78.4%) but lower specificity (42.7-43.1 vs. 76.7-78.4%). Decision curve analysis showed ITFC and mITFC to be superior for a 5-year sustained VA risk ICD indication threshold between 5-25% or 2-9% for fast VA.<h4>Conclusion</h4>The ITFC and mITFC provide the highest protection rates, whereas AHA and HRS decrease unnecessary ICD placements. ITFC or mITFC should be used if we consider the 5-year threshold for ICD indication to lie within 5-25% for sustained VA or 2-9% for fast VA. These data will inform decision-making for ICD placement in ARVC.",
-    "laySummary": "",
-    "urls": "pdf:https://academic.oup.com/europace/article-pdf/24/2/296/42370389/euab162.pdf; doi:https://doi.org/10.1093/europace/euab162; html:https://europepmc.org/articles/PMC8824519; pdf:https://europepmc.org/articles/PMC8824519?pdf=render"
-  },
   {
     "id": "31657946",
     "doi": "https://doi.org/10.1164/rccm.201903-0673oc",
@@ -27556,6 +27539,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1164/rccm.201903-0673OC"
   },
+  {
+    "id": "34468736",
+    "doi": "https://doi.org/10.1093/europace/euab162",
+    "title": "Comparing clinical performance of current implantable cardioverter-defibrillator implantation recommendations in arrhythmogenic right ventricular cardiomyopathy.",
+    "authorString": "Bosman LP, Bosman LP, Nielsen Gerlach CL, Cadrin-Tourigny J, Orgeron G, Tichnell C, Murray B, Bourfiss M, van der Heijden JF, Yap SC, Zeppenfeld K, van den Berg MP, Wilde AAM, Asselbergs FW, Tandri H, Calkins H, van Tintelen JP, James CA, Te Riele ASJM.",
+    "authorAffiliations": "",
+    "journalTitle": "Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",
+    "pubYear": "2022",
+    "date": "2022-02-01",
+    "isOpenAccess": "Y",
+    "keywords": "Prognosis; Risk stratification; Ventricular Arrhythmias; Implantable Cardioverter-defibrillator; Arrhythmogenic Right Ventricular Cardiomyopathy",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation algorithms are available The International Task Force Consensus ('ITFC'), an ITFC modification by Orgeron et al. ('mITFC'), the AHA/HRS/ACC guideline for VA management ('AHA'), and the HRS expert consensus statement ('HRS'). This study aims to validate and compare the performance of these algorithms in ARVC.<h4>Methods and results</h4>We classified 617 definite ARVC patients (38.5\u2009\u00b1\u200915.1\u2009years, 52.4% male, 39.2% prior sustained VA) according to four algorithms. Clinical performance was evaluated by sensitivity, specificity, ROC-analysis, and decision curve analysis for any sustained VA and for fast VA (>250 b.p.m.). During 6.4 [2.8-11.5] years follow-up, 282 (45.7%) patients experienced any sustained VA, and 63 (10.2%) fast VA. For any sustained VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (94.0-97.8% vs. 76.7-83.5%), but lower specificity (15.9-32.0% vs. 42.7%-60.1%). Similarly, for fast VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (95.2-97.1% vs. 76.7-78.4%) but lower specificity (42.7-43.1 vs. 76.7-78.4%). Decision curve analysis showed ITFC and mITFC to be superior for a 5-year sustained VA risk ICD indication threshold between 5-25% or 2-9% for fast VA.<h4>Conclusion</h4>The ITFC and mITFC provide the highest protection rates, whereas AHA and HRS decrease unnecessary ICD placements. ITFC or mITFC should be used if we consider the 5-year threshold for ICD indication to lie within 5-25% for sustained VA or 2-9% for fast VA. These data will inform decision-making for ICD placement in ARVC.",
+    "laySummary": "",
+    "urls": "pdf:https://academic.oup.com/europace/article-pdf/24/2/296/42370389/euab162.pdf; doi:https://doi.org/10.1093/europace/euab162; html:https://europepmc.org/articles/PMC8824519; pdf:https://europepmc.org/articles/PMC8824519?pdf=render"
+  },
   {
     "id": "34661196",
     "doi": "https://doi.org/10.1093/ehjopen/oeab019",
@@ -28576,23 +28576,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1177/0300060520931298; doi:https://doi.org/10.1177/0300060520931298; html:https://europepmc.org/articles/PMC7307394; pdf:https://europepmc.org/articles/PMC7307394?pdf=render"
   },
-  {
-    "id": "35834561",
-    "doi": "https://doi.org/10.1371/journal.pmed.1004039",
-    "title": "Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses.",
-    "authorString": "Topiwala A, Wang C, Ebmeier KP, Burgess S, Bell S, Levey DF, Zhou H, McCracken C, Roca-Fern\u00e1ndez A, Petersen SE, Raman B, Husain M, Gelernter J, Miller KL, Smith SM, Nichols TE.",
-    "authorAffiliations": "",
-    "journalTitle": "PLoS medicine",
-    "pubYear": "2022",
-    "date": "2022-07-14",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits.<h4>Methods and findings</h4>Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-sample mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 \u00b1 1.10 years after baseline) was used to ascertain iron content of each brain region (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Main outcomes were susceptibility (\u03c7) and T2*, measures used as indices of iron deposition. Brain regions of interest included putamen, caudate, hippocampi, thalami, and substantia nigra. Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation analysis. Cognition was assessed at the scan and in online follow-up (5.82 \u00b1 0.86 years after baseline). Executive function was assessed with the trail-making test, fluid intelligence with puzzle tasks, and reaction time by a task based on the \"Snap\" card game. Mean age was 54.8 \u00b1 7.4 years and 48.6% were female. Weekly alcohol consumption was 17.7 \u00b1 15.9 units and never drinkers comprised 2.7% of the sample. Alcohol consumption was associated with markers of higher iron (\u03c7) in putamen (\u03b2 = 0.08 standard deviation (SD) [95% confidence interval (CI) 0.06 to 0.09], p < 0.001), caudate (\u03b2 = 0.05 [0.04 to 0.07], p < 0.001), and substantia nigra (\u03b2 = 0.03 [0.02 to 0.05], p < 0.001) and lower iron in the thalami (\u03b2 = -0.06 [-0.07 to -0.04], p < 0.001). Quintile-based analyses found these associations in those consuming >7 units (56 g) alcohol weekly. MR analyses provided weak evidence these relationships are causal. Genetically predicted alcoholic drinks weekly positively associated with putamen and hippocampus susceptibility; however, these associations did not survive multiple testing corrections. Weak evidence for a causal relationship between genetically predicted alcohol use disorder and higher putamen susceptibility was observed; however, this was not robust to multiple comparisons correction. Genetically predicted alcohol use disorder was associated with serum iron and transferrin saturation. Elevated liver iron was observed at just >11 units (88 g) alcohol weekly c.f. <7 units (56 g). Systemic iron levels partially mediated associations of alcohol intake with brain iron. Markers of higher basal ganglia iron associated with slower executive function, lower fluid intelligence, and slower reaction times. The main limitations of the study include that \u03c7 and T2* can reflect changes in myelin as well as iron, alcohol use was self-reported, and MR estimates can be influenced by genetic pleiotropy.<h4>Conclusions</h4>To the best of our knowledge, this study represents the largest investigation of moderate alcohol consumption and iron homeostasis to date. Alcohol consumption above 7 units weekly associated with higher brain iron. Iron accumulation represents a potential mechanism for alcohol-related cognitive decline.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004039&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004039; html:https://europepmc.org/articles/PMC9282660; pdf:https://europepmc.org/articles/PMC9282660?pdf=render"
-  },
   {
     "id": "34645794",
     "doi": "https://doi.org/10.1038/s41467-021-25914-8",
@@ -28610,6 +28593,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-021-25914-8.pdf; doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render"
   },
+  {
+    "id": "35834561",
+    "doi": "https://doi.org/10.1371/journal.pmed.1004039",
+    "title": "Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses.",
+    "authorString": "Topiwala A, Wang C, Ebmeier KP, Burgess S, Bell S, Levey DF, Zhou H, McCracken C, Roca-Fern\u00e1ndez A, Petersen SE, Raman B, Husain M, Gelernter J, Miller KL, Smith SM, Nichols TE.",
+    "authorAffiliations": "",
+    "journalTitle": "PLoS medicine",
+    "pubYear": "2022",
+    "date": "2022-07-14",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits.<h4>Methods and findings</h4>Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-sample mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 \u00b1 1.10 years after baseline) was used to ascertain iron content of each brain region (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Main outcomes were susceptibility (\u03c7) and T2*, measures used as indices of iron deposition. Brain regions of interest included putamen, caudate, hippocampi, thalami, and substantia nigra. Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation analysis. Cognition was assessed at the scan and in online follow-up (5.82 \u00b1 0.86 years after baseline). Executive function was assessed with the trail-making test, fluid intelligence with puzzle tasks, and reaction time by a task based on the \"Snap\" card game. Mean age was 54.8 \u00b1 7.4 years and 48.6% were female. Weekly alcohol consumption was 17.7 \u00b1 15.9 units and never drinkers comprised 2.7% of the sample. Alcohol consumption was associated with markers of higher iron (\u03c7) in putamen (\u03b2 = 0.08 standard deviation (SD) [95% confidence interval (CI) 0.06 to 0.09], p < 0.001), caudate (\u03b2 = 0.05 [0.04 to 0.07], p < 0.001), and substantia nigra (\u03b2 = 0.03 [0.02 to 0.05], p < 0.001) and lower iron in the thalami (\u03b2 = -0.06 [-0.07 to -0.04], p < 0.001). Quintile-based analyses found these associations in those consuming >7 units (56 g) alcohol weekly. MR analyses provided weak evidence these relationships are causal. Genetically predicted alcoholic drinks weekly positively associated with putamen and hippocampus susceptibility; however, these associations did not survive multiple testing corrections. Weak evidence for a causal relationship between genetically predicted alcohol use disorder and higher putamen susceptibility was observed; however, this was not robust to multiple comparisons correction. Genetically predicted alcohol use disorder was associated with serum iron and transferrin saturation. Elevated liver iron was observed at just >11 units (88 g) alcohol weekly c.f. <7 units (56 g). Systemic iron levels partially mediated associations of alcohol intake with brain iron. Markers of higher basal ganglia iron associated with slower executive function, lower fluid intelligence, and slower reaction times. The main limitations of the study include that \u03c7 and T2* can reflect changes in myelin as well as iron, alcohol use was self-reported, and MR estimates can be influenced by genetic pleiotropy.<h4>Conclusions</h4>To the best of our knowledge, this study represents the largest investigation of moderate alcohol consumption and iron homeostasis to date. Alcohol consumption above 7 units weekly associated with higher brain iron. Iron accumulation represents a potential mechanism for alcohol-related cognitive decline.",
+    "laySummary": "",
+    "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004039&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004039; html:https://europepmc.org/articles/PMC9282660; pdf:https://europepmc.org/articles/PMC9282660?pdf=render"
+  },
   {
     "id": "35717168",
     "doi": "https://doi.org/10.1186/s12879-022-07490-4",
@@ -29256,6 +29256,23 @@
     "laySummary": "",
     "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/art.41593; doi:https://doi.org/10.1002/art.41593; html:https://europepmc.org/articles/PMC8252419; pdf:https://europepmc.org/articles/PMC8252419?pdf=render"
   },
+  {
+    "id": "31564467",
+    "doi": "https://doi.org/10.1016/s2215-0366(19)30369-4",
+    "title": "The burden of mental ill health associated with childhood maltreatment in the UK, using The Health Improvement Network database: a population-based retrospective cohort study.",
+    "authorString": "Chandan JS, Thomas T, Gokhale KM, Bandyopadhyay S, Taylor J, Nirantharakumar K.",
+    "authorAffiliations": "",
+    "journalTitle": "The lancet. Psychiatry",
+    "pubYear": "2019",
+    "date": "2019-09-26",
+    "isOpenAccess": "N",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health.<h4>Methods</h4>In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients.<h4>Findings</h4>The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11\u2008831\u2008850 patients were eligible to participate. Of these patients, we identified 217\u2008758 (1\u00b78%) patients with any recorded childhood maltreatment. These patients were matched to 423\u2008410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1\u00b78 years (IQR 0\u00b76-4\u00b73) versus 3\u00b72 years (1\u00b73-6\u00b71) in the unexposed group. During the study period, 11\u2008665 (5\u00b79%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16\u00b78 events per 1000 person-years versus 15\u2008301 (3\u00b77%) new recorded diagnoses at an incidence rate of 8\u00b73 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2\u00b714 (95% CI 2\u00b708-2\u00b719). 30\u2008911 (14\u00b78%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46\u00b75 events per 1000 person-years) versus 36\u2008390 (8\u00b79%) patients in the unexposed group (20\u00b75 per 1000 person-years) resulting in an adjusted IRR of 2\u00b744 (95% CI 2\u00b740-2\u00b748).<h4>Interpretation</h4>Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health.<h4>Funding</h4>None.",
+    "laySummary": "",
+    "urls": "pdf:http://pure-oai.bham.ac.uk/ws/files/77236664/Chandan_et_al_The_burden_of_mental_ill_health_associated_with_childhood_maltreatment_in_the_UK_using_The_Health_Improvement_Network_database_The_Lancet_Psychiatry_2019.pdf; doi:https://doi.org/10.1016/S2215-0366(19)30369-4"
+  },
   {
     "id": "35507331",
     "doi": "https://doi.org/10.1002/art.42154",
@@ -29290,23 +29307,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796396; doi:https://doi.org/10.1111/bjd.21677; html:https://europepmc.org/articles/PMC9796396; pdf:https://europepmc.org/articles/PMC9796396?pdf=render"
   },
-  {
-    "id": "31564467",
-    "doi": "https://doi.org/10.1016/s2215-0366(19)30369-4",
-    "title": "The burden of mental ill health associated with childhood maltreatment in the UK, using The Health Improvement Network database: a population-based retrospective cohort study.",
-    "authorString": "Chandan JS, Thomas T, Gokhale KM, Bandyopadhyay S, Taylor J, Nirantharakumar K.",
-    "authorAffiliations": "",
-    "journalTitle": "The lancet. Psychiatry",
-    "pubYear": "2019",
-    "date": "2019-09-26",
-    "isOpenAccess": "N",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health.<h4>Methods</h4>In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients.<h4>Findings</h4>The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11\u2008831\u2008850 patients were eligible to participate. Of these patients, we identified 217\u2008758 (1\u00b78%) patients with any recorded childhood maltreatment. These patients were matched to 423\u2008410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1\u00b78 years (IQR 0\u00b76-4\u00b73) versus 3\u00b72 years (1\u00b73-6\u00b71) in the unexposed group. During the study period, 11\u2008665 (5\u00b79%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16\u00b78 events per 1000 person-years versus 15\u2008301 (3\u00b77%) new recorded diagnoses at an incidence rate of 8\u00b73 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2\u00b714 (95% CI 2\u00b708-2\u00b719). 30\u2008911 (14\u00b78%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46\u00b75 events per 1000 person-years) versus 36\u2008390 (8\u00b79%) patients in the unexposed group (20\u00b75 per 1000 person-years) resulting in an adjusted IRR of 2\u00b744 (95% CI 2\u00b740-2\u00b748).<h4>Interpretation</h4>Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health.<h4>Funding</h4>None.",
-    "laySummary": "",
-    "urls": "pdf:http://pure-oai.bham.ac.uk/ws/files/77236664/Chandan_et_al_The_burden_of_mental_ill_health_associated_with_childhood_maltreatment_in_the_UK_using_The_Health_Improvement_Network_database_The_Lancet_Psychiatry_2019.pdf; doi:https://doi.org/10.1016/S2215-0366(19)30369-4"
-  },
   {
     "id": "34767555",
     "doi": "https://doi.org/10.1371/journal.pmed.1003832",
@@ -29341,23 +29341,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0255748&type=printable; doi:https://doi.org/10.1371/journal.pone.0255748; html:https://europepmc.org/articles/PMC8386866; pdf:https://europepmc.org/articles/PMC8386866?pdf=render"
   },
-  {
-    "id": "35331425",
-    "doi": "https://doi.org/10.1016/j.jacep.2021.09.001",
-    "title": "Clinical Characteristics and Follow-Up of Pediatric-Onset Arrhythmogenic Right\u00a0Ventricular Cardiomyopathy.",
-    "authorString": "Roudijk RW, Verheul L, Bosman LP, Bourfiss M, Breur JMPJ, Slieker MG, Blank AC, Dooijes D, van der Heijden JF, van den Heuvel F, Clur SA, Udink Ten Cate FEA, van den Berg MP, Wilde AAM, Asselbergs FW, Peter van Tintelen J, Te Riele ASJM.",
-    "authorAffiliations": "",
-    "journalTitle": "JACC. Clinical electrophysiology",
-    "pubYear": "2022",
-    "date": "2021-12-22",
-    "isOpenAccess": "N",
-    "keywords": "Genetics; Ventricular tachycardia; Heart Failure; Sudden Cardiac Death; Arrhythmogenic Right Ventricular Cardiomyopathy; Pediatric-onset; Cascade Screening",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>The goal of this study was to describe characteristics, cascade screening results, and predictors of adverse outcome in pediatric-onset arrhythmogenic right ventricular cardiomyopathy (ARVC).<h4>Background</h4>Although ARVC is increasingly recognized in children, pediatric ARVC cohorts remain underrepresented in the literature.<h4>Methods</h4>This study included 12 probands with pediatric-onset ARVC (aged\u00a0<18 years at diagnosis) and 68 pediatric relatives (aged\u00a0<18 years at first evaluation) referred for cascade screening. ARVC diagnosis was based on 2010 Task Force Criteria. Clinical presentation, diagnostic testing, and outcomes (sustained ventricular tachycardia [VT]; heart failure) were ascertained. Predictors of adverse outcome were determined by using univariable logistic regression.<h4>Results</h4>Pediatric-onset ARVC was diagnosed in 12 probands and 12 (18%) relatives at a median age of 16.6 years (interquartile range: 13.8-17.4 years), whereas 12 (18%) relatives reached ARVC diagnosis as adults (median age, 22.0 years; interquartile range: 20.0-26.7 years). Sudden cardiac death/arrest was the first disease manifestation in 3 (25%) probands and 3 (4%) relatives. In patients without ARVC diagnosis at presentation (n\u00a0=\u00a061), electrocardiogram and Holter monitoring abnormalities occurred before development of imaging Task Force Criteria (7.3 \u00b1 5.0 years vs 8.4 \u00b1 5.0 years). Clinical course was characterized by sustained VT (91%) and heart failure (36%) in probands, which were rare in relatives (2% and 0%, respectively). Male sex (P\u00a0< 0.01), T-wave inversion V<sub>1</sub>-V<sub>3</sub> (P\u00a0< 0.01), premature ventricular complexes/runs (P\u00a0\u2264 0.01), and decrease in biventricular ejection fraction (P\u00a0\u2264 0.01) were associated with VT occurrence.<h4>Conclusions</h4>Pediatric ARVC carries high arrhythmic risk, especially in probands. Disease progression is particularly observed on electrocardiogram or Holter monitoring. Arrhythmic events are associated with male sex, T-wave inversions, premature ventricular complexes/runs, and reduced biventricular ejection fraction.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.jacep.2021.09.001; doi:https://doi.org/10.1016/j.jacep.2021.09.001"
-  },
   {
     "id": "32951912",
     "doi": "https://doi.org/10.1016/j.jhep.2020.08.030",
@@ -29375,6 +29358,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.journal-of-hepatology.eu/article/S0168827820336035/pdf; doi:https://doi.org/10.1016/j.jhep.2020.08.030; html:https://europepmc.org/articles/PMC8055539; pdf:https://europepmc.org/articles/PMC8055539?pdf=render"
   },
+  {
+    "id": "35331425",
+    "doi": "https://doi.org/10.1016/j.jacep.2021.09.001",
+    "title": "Clinical Characteristics and Follow-Up of Pediatric-Onset Arrhythmogenic Right\u00a0Ventricular Cardiomyopathy.",
+    "authorString": "Roudijk RW, Verheul L, Bosman LP, Bourfiss M, Breur JMPJ, Slieker MG, Blank AC, Dooijes D, van der Heijden JF, van den Heuvel F, Clur SA, Udink Ten Cate FEA, van den Berg MP, Wilde AAM, Asselbergs FW, Peter van Tintelen J, Te Riele ASJM.",
+    "authorAffiliations": "",
+    "journalTitle": "JACC. Clinical electrophysiology",
+    "pubYear": "2022",
+    "date": "2021-12-22",
+    "isOpenAccess": "N",
+    "keywords": "Genetics; Ventricular tachycardia; Heart Failure; Sudden Cardiac Death; Arrhythmogenic Right Ventricular Cardiomyopathy; Pediatric-onset; Cascade Screening",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>The goal of this study was to describe characteristics, cascade screening results, and predictors of adverse outcome in pediatric-onset arrhythmogenic right ventricular cardiomyopathy (ARVC).<h4>Background</h4>Although ARVC is increasingly recognized in children, pediatric ARVC cohorts remain underrepresented in the literature.<h4>Methods</h4>This study included 12 probands with pediatric-onset ARVC (aged\u00a0<18 years at diagnosis) and 68 pediatric relatives (aged\u00a0<18 years at first evaluation) referred for cascade screening. ARVC diagnosis was based on 2010 Task Force Criteria. Clinical presentation, diagnostic testing, and outcomes (sustained ventricular tachycardia [VT]; heart failure) were ascertained. Predictors of adverse outcome were determined by using univariable logistic regression.<h4>Results</h4>Pediatric-onset ARVC was diagnosed in 12 probands and 12 (18%) relatives at a median age of 16.6 years (interquartile range: 13.8-17.4 years), whereas 12 (18%) relatives reached ARVC diagnosis as adults (median age, 22.0 years; interquartile range: 20.0-26.7 years). Sudden cardiac death/arrest was the first disease manifestation in 3 (25%) probands and 3 (4%) relatives. In patients without ARVC diagnosis at presentation (n\u00a0=\u00a061), electrocardiogram and Holter monitoring abnormalities occurred before development of imaging Task Force Criteria (7.3 \u00b1 5.0 years vs 8.4 \u00b1 5.0 years). Clinical course was characterized by sustained VT (91%) and heart failure (36%) in probands, which were rare in relatives (2% and 0%, respectively). Male sex (P\u00a0< 0.01), T-wave inversion V<sub>1</sub>-V<sub>3</sub> (P\u00a0< 0.01), premature ventricular complexes/runs (P\u00a0\u2264 0.01), and decrease in biventricular ejection fraction (P\u00a0\u2264 0.01) were associated with VT occurrence.<h4>Conclusions</h4>Pediatric ARVC carries high arrhythmic risk, especially in probands. Disease progression is particularly observed on electrocardiogram or Holter monitoring. Arrhythmic events are associated with male sex, T-wave inversions, premature ventricular complexes/runs, and reduced biventricular ejection fraction.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.jacep.2021.09.001; doi:https://doi.org/10.1016/j.jacep.2021.09.001"
+  },
   {
     "id": "37118290",
     "doi": "https://doi.org/10.1038/s43587-022-00293-x",
@@ -29494,23 +29494,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008"
   },
-  {
-    "id": "36470992",
-    "doi": "https://doi.org/10.1038/s41375-022-01773-0",
-    "title": "Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.",
-    "authorString": "Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",
-    "authorAffiliations": "",
-    "journalTitle": "Leukemia",
-    "pubYear": "2023",
-    "date": "2022-12-05",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n\u2009=\u2009107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render"
-  },
   {
     "id": "33692554",
     "doi": "https://doi.org/10.1038/s41586-021-03243-6",
@@ -29545,6 +29528,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.jaci.2020.08.026"
   },
+  {
+    "id": "36470992",
+    "doi": "https://doi.org/10.1038/s41375-022-01773-0",
+    "title": "Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.",
+    "authorString": "Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",
+    "authorAffiliations": "",
+    "journalTitle": "Leukemia",
+    "pubYear": "2023",
+    "date": "2022-12-05",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n\u2009=\u2009107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render"
+  },
   {
     "id": "33222494",
     "doi": "https://doi.org/10.1177/2048872620974605",
@@ -29562,23 +29562,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ehjacc/article-pdf/9/8/817/49790126/ehjacc0817.pdf; doi:https://doi.org/10.1177/2048872620974605; html:https://europepmc.org/articles/PMC7734244; pdf:https://europepmc.org/articles/PMC7734244?pdf=render"
   },
-  {
-    "id": "34708157",
-    "doi": "https://doi.org/10.12688/wellcomeopenres.16701.3",
-    "title": "Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.",
-    "authorString": "Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",
-    "authorAffiliations": "",
-    "journalTitle": "Wellcome open research",
-    "pubYear": "2021",
-    "date": "2021-12-21",
-    "isOpenAccess": "Y",
-    "keywords": "Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<b>Background:</b> The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. <b>Methods:</b> Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. <b>Results:</b> We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. <b>Conclusions:</b> These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render"
-  },
   {
     "id": "33437953",
     "doi": "https://doi.org/10.1016/j.eclinm.2020.100658",
@@ -29596,6 +29579,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S2589537020304028/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100658; html:https://europepmc.org/articles/PMC7788440; pdf:https://europepmc.org/articles/PMC7788440?pdf=render"
   },
+  {
+    "id": "34708157",
+    "doi": "https://doi.org/10.12688/wellcomeopenres.16701.3",
+    "title": "Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.",
+    "authorString": "Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",
+    "authorAffiliations": "",
+    "journalTitle": "Wellcome open research",
+    "pubYear": "2021",
+    "date": "2021-12-21",
+    "isOpenAccess": "Y",
+    "keywords": "Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<b>Background:</b> The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. <b>Methods:</b> Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. <b>Results:</b> We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. <b>Conclusions:</b> These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render"
+  },
   {
     "id": "34310590",
     "doi": "https://doi.org/10.1371/journal.pcbi.1009098",
@@ -29715,23 +29715,6 @@
     "laySummary": "",
     "urls": "html:https://eprints.keele.ac.uk/6650/1/Pharamcoepidemiology%20Lancet%20Psych%202019%20submitted%20version.docx; doi:https://doi.org/10.1016/S2215-0366(19)30298-6"
   },
-  {
-    "id": "37315048",
-    "doi": "https://doi.org/10.1371/journal.pone.0287091",
-    "title": "LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.",
-    "authorString": "Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",
-    "authorAffiliations": "",
-    "journalTitle": "PloS one",
-    "pubYear": "2023",
-    "date": "2023-06-14",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.<h4>Methods</h4>Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.<h4>Results</h4>We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV \u22650.99) who could be rapidly discharged using information collected at initial assessment.<h4>Conclusion</h4>The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.",
-    "laySummary": "",
-    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287091&type=printable; doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render"
-  },
   {
     "id": "33299071",
     "doi": "https://doi.org/10.1038/s41746-020-00357-5",
@@ -29750,21 +29733,38 @@
     "urls": "pdf:https://www.nature.com/articles/s41746-020-00357-5.pdf; doi:https://doi.org/10.1038/s41746-020-00357-5; html:https://europepmc.org/articles/PMC7648058; pdf:https://europepmc.org/articles/PMC7648058?pdf=render"
   },
   {
-    "id": "37918923",
-    "doi": "https://doi.org/10.1136/bmjopen-2023-072531",
-    "title": "Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.",
-    "authorString": "Zylbersztejn A, Lewis K, Nguyen V, Matthews J, Winterburn I, Karwatowska L, Barnes S, Lilliman M, Saxton J, Stone A, Boddy K, Downs J, Logan S, Rahi J, Black-Hawkins K, Dearden L, Ford T, Harron K, De Stavola B, Gilbert R.",
+    "id": "37315048",
+    "doi": "https://doi.org/10.1371/journal.pone.0287091",
+    "title": "LMIC-PRIEST: Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19 in a middle-income setting.",
+    "authorString": "Marincowitz C, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Sbaffi L, Hasan M, Omer Y, Wallis L.",
     "authorAffiliations": "",
-    "journalTitle": "BMJ open",
+    "journalTitle": "PloS one",
     "pubYear": "2023",
-    "date": "2023-11-02",
+    "date": "2023-06-14",
     "isOpenAccess": "Y",
-    "keywords": "epidemiology; Public Health; Qualitative Research; Health Informatics; Statistics & Research Methods; Health Equity",
+    "keywords": "",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "<h4>Introduction</h4>One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes.<h4>Methods</h4>The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation.<h4>Ethics and dissemination</h4>Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.",
+    "abstract": "<h4>Background</h4>Uneven vaccination and less resilient health care systems mean hospitals in LMICs are at risk of being overwhelmed during periods of increased COVID-19 infection. Risk-scores proposed for rapid triage of need for admission from the emergency department (ED) have been developed in higher-income settings during initial waves of the pandemic.<h4>Methods</h4>Routinely collected data for public hospitals in the Western Cape, South Africa from the 27th August 2020 to 11th March 2022 were used to derive a cohort of 446,084 ED patients with suspected COVID-19. The primary outcome was death or ICU admission at 30 days. The cohort was divided into derivation and Omicron variant validation sets. We developed the LMIC-PRIEST score based on the coefficients from multivariable analysis in the derivation cohort and existing triage practices. We externally validated accuracy in the Omicron period and a UK cohort.<h4>Results</h4>We analysed 305,564 derivation, 140,520 Omicron and 12,610 UK validation cases. Over 100 events per predictor parameter were modelled. Multivariable analyses identified eight predictor variables retained across models. We used these findings and clinical judgement to develop a score based on South African Triage Early Warning Scores and also included age, sex, oxygen saturation, inspired oxygen, diabetes and heart disease. The LMIC-PRIEST score achieved C-statistics: 0.82 (95% CI: 0.82 to 0.83) development cohort; 0.79 (95% CI: 0.78 to 0.80) Omicron cohort; and 0.79 (95% CI: 0.79 to 0.80) UK cohort. Differences in prevalence of outcomes led to imperfect calibration in external validation. However, use of the score at thresholds of three or less would allow identification of very low-risk patients (NPV \u22650.99) who could be rapidly discharged using information collected at initial assessment.<h4>Conclusion</h4>The LMIC-PRIEST score shows good discrimination and high sensitivity at lower thresholds and can be used to rapidly identify low-risk patients in LMIC ED settings.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-072531; html:https://europepmc.org/articles/PMC10626865; pdf:https://europepmc.org/articles/PMC10626865?pdf=render"
+    "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287091&type=printable; doi:https://doi.org/10.1371/journal.pone.0287091; html:https://europepmc.org/articles/PMC10266677; pdf:https://europepmc.org/articles/PMC10266677?pdf=render"
+  },
+  {
+    "id": "30887727",
+    "doi": "https://doi.org/10.1002/ppul.24314",
+    "title": "Physical activity among children with asthma: Cross-sectional analysis in the UK millennium cohort.",
+    "authorString": "Pike KC, Griffiths LJ, Dezateux C, Pearce A.",
+    "authorAffiliations": "",
+    "journalTitle": "Pediatric pulmonology",
+    "pubYear": "2019",
+    "date": "2019-03-18",
+    "isOpenAccess": "Y",
+    "keywords": "Children; Cohort study; epidemiology; Physical Activity; Asthma And Early Wheeze",
+    "nationalPriorities": "Improving Public Health",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Although beneficial for health and well-being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap.<h4>Methods</h4>We analyzed cross-sectional associations between physical activity and parent-reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7-year-old participants (3321, [49%] girls). Primary outcomes were daily moderate-to-vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60\u2009minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent-reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors.<h4>Results</h4>Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: -0.18 [-0.27, -0.08]; -0.14 [-0.24, -0.05]; -0.15, [-0.28, -0.02], respectively) and hospital admission with lower total activity (-48\u2009cpm [-68, -28]).<h4>Conclusion</h4>Children with asthma are as physically active as their asthma-free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ppul.24314; doi:https://doi.org/10.1002/ppul.24314; html:https://europepmc.org/articles/PMC6617805; pdf:https://europepmc.org/articles/PMC6617805?pdf=render"
   },
   {
     "id": "33782396",
@@ -29800,23 +29800,6 @@
     "laySummary": "",
     "urls": "pdf:https://jmir.org/api/download?alt_name=resprot_v10i5e29072_app1.pdf&filename=e079f888f9036dd40808005eb7b49b6f.pdf; doi:https://doi.org/10.2196/29072; html:https://europepmc.org/articles/PMC8153031"
   },
-  {
-    "id": "30887727",
-    "doi": "https://doi.org/10.1002/ppul.24314",
-    "title": "Physical activity among children with asthma: Cross-sectional analysis in the UK millennium cohort.",
-    "authorString": "Pike KC, Griffiths LJ, Dezateux C, Pearce A.",
-    "authorAffiliations": "",
-    "journalTitle": "Pediatric pulmonology",
-    "pubYear": "2019",
-    "date": "2019-03-18",
-    "isOpenAccess": "Y",
-    "keywords": "Children; Cohort study; epidemiology; Physical Activity; Asthma And Early Wheeze",
-    "nationalPriorities": "Improving Public Health",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Although beneficial for health and well-being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap.<h4>Methods</h4>We analyzed cross-sectional associations between physical activity and parent-reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7-year-old participants (3321, [49%] girls). Primary outcomes were daily moderate-to-vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60\u2009minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent-reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors.<h4>Results</h4>Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: -0.18 [-0.27, -0.08]; -0.14 [-0.24, -0.05]; -0.15, [-0.28, -0.02], respectively) and hospital admission with lower total activity (-48\u2009cpm [-68, -28]).<h4>Conclusion</h4>Children with asthma are as physically active as their asthma-free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ppul.24314; doi:https://doi.org/10.1002/ppul.24314; html:https://europepmc.org/articles/PMC6617805; pdf:https://europepmc.org/articles/PMC6617805?pdf=render"
-  },
   {
     "id": "34173574",
     "doi": "https://doi.org/10.1016/j.puhip.2020.100039",
@@ -29834,6 +29817,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?pdf=render"
   },
+  {
+    "id": "37918923",
+    "doi": "https://doi.org/10.1136/bmjopen-2023-072531",
+    "title": "Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.",
+    "authorString": "Zylbersztejn A, Lewis K, Nguyen V, Matthews J, Winterburn I, Karwatowska L, Barnes S, Lilliman M, Saxton J, Stone A, Boddy K, Downs J, Logan S, Rahi J, Black-Hawkins K, Dearden L, Ford T, Harron K, De Stavola B, Gilbert R.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2023",
+    "date": "2023-11-02",
+    "isOpenAccess": "Y",
+    "keywords": "epidemiology; Public Health; Qualitative Research; Health Informatics; Statistics & Research Methods; Health Equity",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Introduction</h4>One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes.<h4>Methods</h4>The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation.<h4>Ethics and dissemination</h4>Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1136/bmjopen-2023-072531; html:https://europepmc.org/articles/PMC10626865; pdf:https://europepmc.org/articles/PMC10626865?pdf=render"
+  },
   {
     "id": "35710247",
     "doi": "https://doi.org/10.1136/bmjopen-2021-060280",
@@ -29885,23 +29885,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/oncolo/article-pdf/26/1/e182/41923952/oncolo_26_1_n_a.pdf; doi:https://doi.org/10.1634/theoncologist.2020-0572; html:https://europepmc.org/articles/PMC7460944; pdf:https://europepmc.org/articles/PMC7460944?pdf=render"
   },
-  {
-    "id": "35288697",
-    "doi": "https://doi.org/10.1038/s41591-022-01750-1",
-    "title": "COVID-19 and resilience of healthcare systems in ten countries.",
-    "authorString": "Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar \u00c1, P\u00e9rez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Gui\u00f1ez F, Bauhoff S, Kruk ME.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature medicine",
-    "pubYear": "2022",
-    "date": "2022-03-14",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income\ufeff (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41591-022-01750-1.pdf; doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render"
-  },
   {
     "id": "30649175",
     "doi": "https://doi.org/10.1001/jamacardio.2018.4537",
@@ -29919,6 +29902,23 @@
     "laySummary": "",
     "urls": "pdf:https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=1451&context=sph_facpub; doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140"
   },
+  {
+    "id": "35288697",
+    "doi": "https://doi.org/10.1038/s41591-022-01750-1",
+    "title": "COVID-19 and resilience of healthcare systems in ten countries.",
+    "authorString": "Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar \u00c1, P\u00e9rez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Gui\u00f1ez F, Bauhoff S, Kruk ME.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature medicine",
+    "pubYear": "2022",
+    "date": "2022-03-14",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income\ufeff (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41591-022-01750-1.pdf; doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render"
+  },
   {
     "id": "35505938",
     "doi": "https://doi.org/10.1016/j.eclinm.2022.101417",
@@ -30072,23 +30072,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/ptj/article-pdf/100/2/332/32901113/pzz151.pdf; doi:https://doi.org/10.1093/ptj/pzz151"
   },
-  {
-    "id": "36539756",
-    "doi": "https://doi.org/10.1186/s12888-022-04429-6",
-    "title": "ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol.",
-    "authorString": "Denyer H, Ramos-Quiroga JA, Folarin A, Ramos C, Nemeth P, Bilbow A, Woodward E, Whitwell S, M\u00fcller-Sedgwick U, Larsson H, Dobson RJ, Kuntsi J.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC psychiatry",
-    "pubYear": "2022",
-    "date": "2022-12-20",
-    "isOpenAccess": "Y",
-    "keywords": "ADHD; Cardiovascular disease; Attention Deficit Hyperactivity Disorder; Medication Adherence; Remote Monitoring; Mhealth; Digital Phenotyping; Remote Measurement Technology",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD.<h4>Methods</h4>ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration 'TIMESPAN' (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform.<h4>Discussion</h4>The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04429-6; doi:https://doi.org/10.1186/s12888-022-04429-6; html:https://europepmc.org/articles/PMC9764531; pdf:https://europepmc.org/articles/PMC9764531?pdf=render"
-  },
   {
     "id": "32887683",
     "doi": "https://doi.org/10.1136/annrheumdis-2020-217421",
@@ -30106,6 +30089,23 @@
     "laySummary": "",
     "urls": "pdf:https://ard.bmj.com/content/annrheumdis/79/12/1572.full.pdf; doi:https://doi.org/10.1136/annrheumdis-2020-217421; html:https://europepmc.org/articles/PMC7677485; pdf:https://europepmc.org/articles/PMC7677485?pdf=render"
   },
+  {
+    "id": "36539756",
+    "doi": "https://doi.org/10.1186/s12888-022-04429-6",
+    "title": "ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol.",
+    "authorString": "Denyer H, Ramos-Quiroga JA, Folarin A, Ramos C, Nemeth P, Bilbow A, Woodward E, Whitwell S, M\u00fcller-Sedgwick U, Larsson H, Dobson RJ, Kuntsi J.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC psychiatry",
+    "pubYear": "2022",
+    "date": "2022-12-20",
+    "isOpenAccess": "Y",
+    "keywords": "ADHD; Cardiovascular disease; Attention Deficit Hyperactivity Disorder; Medication Adherence; Remote Monitoring; Mhealth; Digital Phenotyping; Remote Measurement Technology",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD.<h4>Methods</h4>ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration 'TIMESPAN' (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform.<h4>Discussion</h4>The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04429-6; doi:https://doi.org/10.1186/s12888-022-04429-6; html:https://europepmc.org/articles/PMC9764531; pdf:https://europepmc.org/articles/PMC9764531?pdf=render"
+  },
   {
     "id": "35073907",
     "doi": "https://doi.org/10.1186/s12916-021-02218-8",
@@ -30480,23 +30480,6 @@
     "laySummary": "",
     "urls": "pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04951-6; doi:https://doi.org/10.1186/s13063-020-04951-6; html:https://europepmc.org/articles/PMC7788716; pdf:https://europepmc.org/articles/PMC7788716?pdf=render"
   },
-  {
-    "id": "35477539",
-    "doi": "https://doi.org/10.1136/gutjnl-2021-326183",
-    "title": "Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer.",
-    "authorString": "Corry SM, McCorry AM, Lannagan TR, Leonard NA, Fisher NC, Byrne RM, Tsantoulis P, Cortes-Lavaud X, Amirkhah R, Redmond KL, McCooey AJ, Malla SB, Rogan E, Sakhnevych S, Gillespie MA, White M, Richman SD, Jackstadt RF, Campbell AD, Maguire S, S:CORT and ACRCelerate consortia, McDade SS, Longley DB, Loughrey MB, Coleman HG, Kerr EM, Tejpar S, Maughan T, Leedham SJ, Small DM, Ryan AE, Sansom OJ, Lawler M, Dunne PD.",
-    "authorAffiliations": "",
-    "journalTitle": "Gut",
-    "pubYear": "2022",
-    "date": "2022-04-27",
-    "isOpenAccess": "Y",
-    "keywords": "Cancer; Colorectal Cancer; Adjuvant Treatment; Colon Carcinogenesis",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy.<h4>Design</h4>To address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series of <i>in vitro</i> and stroma-rich <i>in vivo</i> models to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours.<h4>Results</h4>By performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Using <i>in silico, in vitro</i> and <i>in vivo</i> models, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype across <i>in vitro</i> and <i>in vivo</i> models. In an <i>in vivo</i> model of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002).<h4>Conclusion</h4>This study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.",
-    "laySummary": "",
-    "urls": "pdf:https://gut.bmj.com/content/gutjnl/early/2022/04/10/gutjnl-2021-326183.full.pdf; doi:https://doi.org/10.1136/gutjnl-2021-326183; html:https://europepmc.org/articles/PMC9664095; pdf:https://europepmc.org/articles/PMC9664095?pdf=render"
-  },
   {
     "id": "33742045",
     "doi": "https://doi.org/10.1038/s41598-021-85354-8",
@@ -30514,6 +30497,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-021-85354-8.pdf; doi:https://doi.org/10.1038/s41598-021-85354-8; html:https://europepmc.org/articles/PMC7979876; pdf:https://europepmc.org/articles/PMC7979876?pdf=render"
   },
+  {
+    "id": "35477539",
+    "doi": "https://doi.org/10.1136/gutjnl-2021-326183",
+    "title": "Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer.",
+    "authorString": "Corry SM, McCorry AM, Lannagan TR, Leonard NA, Fisher NC, Byrne RM, Tsantoulis P, Cortes-Lavaud X, Amirkhah R, Redmond KL, McCooey AJ, Malla SB, Rogan E, Sakhnevych S, Gillespie MA, White M, Richman SD, Jackstadt RF, Campbell AD, Maguire S, S:CORT and ACRCelerate consortia, McDade SS, Longley DB, Loughrey MB, Coleman HG, Kerr EM, Tejpar S, Maughan T, Leedham SJ, Small DM, Ryan AE, Sansom OJ, Lawler M, Dunne PD.",
+    "authorAffiliations": "",
+    "journalTitle": "Gut",
+    "pubYear": "2022",
+    "date": "2022-04-27",
+    "isOpenAccess": "Y",
+    "keywords": "Cancer; Colorectal Cancer; Adjuvant Treatment; Colon Carcinogenesis",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy.<h4>Design</h4>To address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series of <i>in vitro</i> and stroma-rich <i>in vivo</i> models to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours.<h4>Results</h4>By performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Using <i>in silico, in vitro</i> and <i>in vivo</i> models, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype across <i>in vitro</i> and <i>in vivo</i> models. In an <i>in vivo</i> model of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002).<h4>Conclusion</h4>This study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.",
+    "laySummary": "",
+    "urls": "pdf:https://gut.bmj.com/content/gutjnl/early/2022/04/10/gutjnl-2021-326183.full.pdf; doi:https://doi.org/10.1136/gutjnl-2021-326183; html:https://europepmc.org/articles/PMC9664095; pdf:https://europepmc.org/articles/PMC9664095?pdf=render"
+  },
   {
     "id": "32073627",
     "doi": "https://doi.org/10.1093/ije/dyaa002",
@@ -30701,23 +30701,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S235230261830053X/pdf; doi:https://doi.org/10.1016/S2352-3026(18)30053-X; html:https://europepmc.org/articles/PMC6438177; pdf:https://europepmc.org/articles/PMC6438177?pdf=render; doi:https://doi.org/10.1016/s2352-3026(18)30053-x"
   },
-  {
-    "id": "37418234",
-    "doi": "https://doi.org/10.1007/s12265-023-10403-8",
-    "title": "A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.",
-    "authorString": "Nagyova E, Hoorntje ET, Te Rijdt WP, Bosman LP, Syrris P, Protonotarios A, Elliott PM, Tsatsopoulou A, Mestroni L, Taylor MRG, Sinagra G, Merlo M, Wada Y, Horie M, Mogensen J, Christensen AH, Gerull B, Song L, Yao Y, Fan S, Saguner AM, Duru F, Koskenvuo JW, Cruz Marino T, Tichnell C, Judge DP, Dooijes D, Lekanne Deprez RH, Basso C, Pilichou K, Bauce B, Wilde AAM, Charron P, Fressart V, van der Heijden JF, van den Berg MP, Asselbergs FW, James CA, Jongbloed JDH, Harakalova M, van Tintelen JP.",
-    "authorAffiliations": "",
-    "journalTitle": "Journal of cardiovascular translational research",
-    "pubYear": "2023",
-    "date": "2023-07-07",
-    "isOpenAccess": "N",
-    "keywords": "Genetics; Arrhythmia; Arvc; Composite Endpoint; Multiple Variants; Desmosomal Genes",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n\u2009=\u2009331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1007/s12265-023-10403-8"
-  },
   {
     "id": "32888427",
     "doi": "https://doi.org/10.1016/j.ajhg.2020.08.009",
@@ -30735,6 +30718,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.cell.com/article/S0002929720302779/pdf; doi:https://doi.org/10.1016/j.ajhg.2020.08.009; html:https://europepmc.org/articles/PMC7536582; pdf:https://europepmc.org/articles/PMC7536582?pdf=render"
   },
+  {
+    "id": "37418234",
+    "doi": "https://doi.org/10.1007/s12265-023-10403-8",
+    "title": "A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.",
+    "authorString": "Nagyova E, Hoorntje ET, Te Rijdt WP, Bosman LP, Syrris P, Protonotarios A, Elliott PM, Tsatsopoulou A, Mestroni L, Taylor MRG, Sinagra G, Merlo M, Wada Y, Horie M, Mogensen J, Christensen AH, Gerull B, Song L, Yao Y, Fan S, Saguner AM, Duru F, Koskenvuo JW, Cruz Marino T, Tichnell C, Judge DP, Dooijes D, Lekanne Deprez RH, Basso C, Pilichou K, Bauce B, Wilde AAM, Charron P, Fressart V, van der Heijden JF, van den Berg MP, Asselbergs FW, James CA, Jongbloed JDH, Harakalova M, van Tintelen JP.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of cardiovascular translational research",
+    "pubYear": "2023",
+    "date": "2023-07-07",
+    "isOpenAccess": "N",
+    "keywords": "Genetics; Arrhythmia; Arvc; Composite Endpoint; Multiple Variants; Desmosomal Genes",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n\u2009=\u2009331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1007/s12265-023-10403-8"
+  },
   {
     "id": "32678323",
     "doi": "https://doi.org/10.1038/s41366-020-0642-3",
@@ -31007,23 +31007,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054302; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.054302; html:https://europepmc.org/articles/PMC8360674; pdf:https://europepmc.org/articles/PMC8360674?pdf=render"
   },
-  {
-    "id": "36647047",
-    "doi": "https://doi.org/10.1186/s12916-022-02722-5",
-    "title": "Polypharmacy during pregnancy and\u00a0associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.",
-    "authorString": "Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medicine",
-    "pubYear": "2023",
-    "date": "2023-01-16",
-    "isOpenAccess": "Y",
-    "keywords": "Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.<h4>Methods</h4>A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.<h4>Results</h4>During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.<h4>Conclusions</h4>The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render"
-  },
   {
     "id": "32548911",
     "doi": "https://doi.org/10.1002/ehf2.12779",
@@ -31042,21 +31025,21 @@
     "urls": "doi:https://doi.org/10.1002/ehf2.12779; doi:https://doi.org/10.1002/ehf2.12779; html:https://europepmc.org/articles/PMC7524089; pdf:https://europepmc.org/articles/PMC7524089?pdf=render"
   },
   {
-    "id": "37338017",
-    "doi": "https://doi.org/10.1111/jvh.13863",
-    "title": "Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies.",
-    "authorString": "Trickey A, Ingle SM, Boyd A, Gill MJ, Grabar S, Jarrin I, Obel N, Touloumi G, Zangerle R, Rauch A, Rentsch CT, Satre DD, Silverberg MJ, Bonnet F, Guest J, Burkholder G, Crane H, Teira R, Berenguer J, Wyen C, Abgrall S, Hessamfar M, Reiss P, d'Arminio Monforte A, McGinnis KA, Sterne JAC, Wittkop L, Antiretroviral Therapy Cohort Collaboration.",
+    "id": "36647047",
+    "doi": "https://doi.org/10.1186/s12916-022-02722-5",
+    "title": "Polypharmacy during pregnancy and\u00a0associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.",
+    "authorString": "Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",
     "authorAffiliations": "",
-    "journalTitle": "Journal of viral hepatitis",
+    "journalTitle": "BMC medicine",
     "pubYear": "2023",
-    "date": "2023-06-20",
-    "isOpenAccess": "N",
-    "keywords": "Mortality; Alcohol; Hepatitis C virus; HIV; Cohort; Cause-specific",
+    "date": "2023-01-16",
+    "isOpenAccess": "Y",
+    "keywords": "Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions",
     "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0\u2009g/day, 0.1-20.0\u2009g/day, and\u2009>\u200920.0\u2009g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0\u2009g/day and 1.84 (1.62-2.09) for >20.0\u2009g/day compared with 0.1-20.0\u2009g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0\u2009g/day and 1.64 (1.33-2.02) for >20.0\u2009g/day compared with 0.1-20.0\u2009g/day (interaction p\u2009<\u2009.001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.",
+    "abstract": "<h4>Background</h4>The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.<h4>Methods</h4>A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.<h4>Results</h4>During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.<h4>Conclusions</h4>The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.",
     "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863; doi:https://doi.org/10.1111/jvh.13863"
+    "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render"
   },
   {
     "id": "35255491",
@@ -31075,6 +31058,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41586-022-04569-5.pdf; doi:https://doi.org/10.1038/s41586-022-04569-5; html:https://europepmc.org/articles/PMC9046077; pdf:https://europepmc.org/articles/PMC9046077?pdf=render"
   },
+  {
+    "id": "37338017",
+    "doi": "https://doi.org/10.1111/jvh.13863",
+    "title": "Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies.",
+    "authorString": "Trickey A, Ingle SM, Boyd A, Gill MJ, Grabar S, Jarrin I, Obel N, Touloumi G, Zangerle R, Rauch A, Rentsch CT, Satre DD, Silverberg MJ, Bonnet F, Guest J, Burkholder G, Crane H, Teira R, Berenguer J, Wyen C, Abgrall S, Hessamfar M, Reiss P, d'Arminio Monforte A, McGinnis KA, Sterne JAC, Wittkop L, Antiretroviral Therapy Cohort Collaboration.",
+    "authorAffiliations": "",
+    "journalTitle": "Journal of viral hepatitis",
+    "pubYear": "2023",
+    "date": "2023-06-20",
+    "isOpenAccess": "N",
+    "keywords": "Mortality; Alcohol; Hepatitis C virus; HIV; Cohort; Cause-specific",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0\u2009g/day, 0.1-20.0\u2009g/day, and\u2009>\u200920.0\u2009g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0\u2009g/day and 1.84 (1.62-2.09) for >20.0\u2009g/day compared with 0.1-20.0\u2009g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0\u2009g/day and 1.64 (1.33-2.02) for >20.0\u2009g/day compared with 0.1-20.0\u2009g/day (interaction p\u2009<\u2009.001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863; doi:https://doi.org/10.1111/jvh.13863"
+  },
   {
     "id": "37128097",
     "doi": "https://doi.org/10.1038/s43016-020-0092-z",
@@ -31755,23 +31755,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41588-022-01233-6.pdf; doi:https://doi.org/10.1038/s41588-022-01233-6; html:https://europepmc.org/articles/PMC9729111; pdf:https://europepmc.org/articles/PMC9729111?pdf=render"
   },
-  {
-    "id": "37538507",
-    "doi": "https://doi.org/10.1016/j.rpth.2023.100175",
-    "title": "<i>PIK3R3</i> is a candidate regulator of platelet count in people of Bangladeshi ancestry.",
-    "authorString": "Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.",
-    "authorAffiliations": "",
-    "journalTitle": "Research and practice in thrombosis and haemostasis",
-    "pubYear": "2023",
-    "date": "2023-05-14",
-    "isOpenAccess": "Y",
-    "keywords": "Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.<h4>Objectives</h4>To reveal new regulatory genes for platelet count (PLT).<h4>Methods</h4>Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.<h4>Results</h4>Of 1588 significantly associated variants (<i>P</i>\u00a0< 5\u00a0\u00d7 10<sup>-8</sup>) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (<i>r</i><sup>2</sup> \u2265 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be <i>PIK3R3</i> encoding a regulator of phosphoinositol 3-kinase (PI3K).<h4>Conclusion</h4>Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between <i>PIK3R3</i> and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render"
-  },
   {
     "id": "32340307",
     "doi": "https://doi.org/10.3390/genes11040460",
@@ -31789,6 +31772,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/2073-4425/11/4/460/pdf?version=1587647599; doi:https://doi.org/10.3390/genes11040460; html:https://europepmc.org/articles/PMC7230372; pdf:https://europepmc.org/articles/PMC7230372?pdf=render"
   },
+  {
+    "id": "37538507",
+    "doi": "https://doi.org/10.1016/j.rpth.2023.100175",
+    "title": "<i>PIK3R3</i> is a candidate regulator of platelet count in people of Bangladeshi ancestry.",
+    "authorString": "Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.",
+    "authorAffiliations": "",
+    "journalTitle": "Research and practice in thrombosis and haemostasis",
+    "pubYear": "2023",
+    "date": "2023-05-14",
+    "isOpenAccess": "Y",
+    "keywords": "Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.<h4>Objectives</h4>To reveal new regulatory genes for platelet count (PLT).<h4>Methods</h4>Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.<h4>Results</h4>Of 1588 significantly associated variants (<i>P</i>\u00a0< 5\u00a0\u00d7 10<sup>-8</sup>) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (<i>r</i><sup>2</sup> \u2265 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be <i>PIK3R3</i> encoding a regulator of phosphoinositol 3-kinase (PI3K).<h4>Conclusion</h4>Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between <i>PIK3R3</i> and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render"
+  },
   {
     "id": "34455223",
     "doi": "https://doi.org/10.1016/j.media.2021.102213",
@@ -32010,23 +32010,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e049611.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049611; html:https://europepmc.org/articles/PMC8275361; pdf:https://europepmc.org/articles/PMC8275361?pdf=render"
   },
-  {
-    "id": "36244350",
-    "doi": "https://doi.org/10.1016/s2468-2667(22)00225-0",
-    "title": "The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.",
-    "authorString": "European Antimicrobial Resistance Collaborators.",
-    "authorAffiliations": "",
-    "journalTitle": "The Lancet. Public health",
-    "pubYear": "2022",
-    "date": "2022-10-14",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.<h4>Methods</h4>We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.<h4>Findings</h4>We estimated 541\u2008000 deaths (95% UI 370\u2008000-763\u2008000) associated with bacterial AMR and 133\u2008000 deaths (90\u2008100-188\u2008000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195\u2008000 deaths (104\u2008000-333\u2008000) associated with resistance, followed by intra-abdominal infections (127\u2008000 deaths [81\u2008900-185\u2008000]) and respiratory infections (120\u2008000 deaths [94\u2008500-154\u2008000]). Seven leading pathogens were responsible for about 457\u2008000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.<h4>Interpretation</h4>The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.<h4>Funding</h4>Bill &amp; Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.",
-    "laySummary": "",
-    "urls": "pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf; doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253"
-  },
   {
     "id": "34216337",
     "doi": "https://doi.org/10.1007/s10552-021-01466-6",
@@ -32044,6 +32027,23 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10552-021-01466-6.pdf; doi:https://doi.org/10.1007/s10552-021-01466-6; html:https://europepmc.org/articles/PMC8492588; pdf:https://europepmc.org/articles/PMC8492588?pdf=render"
   },
+  {
+    "id": "36244350",
+    "doi": "https://doi.org/10.1016/s2468-2667(22)00225-0",
+    "title": "The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.",
+    "authorString": "European Antimicrobial Resistance Collaborators.",
+    "authorAffiliations": "",
+    "journalTitle": "The Lancet. Public health",
+    "pubYear": "2022",
+    "date": "2022-10-14",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.<h4>Methods</h4>We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.<h4>Findings</h4>We estimated 541\u2008000 deaths (95% UI 370\u2008000-763\u2008000) associated with bacterial AMR and 133\u2008000 deaths (90\u2008100-188\u2008000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195\u2008000 deaths (104\u2008000-333\u2008000) associated with resistance, followed by intra-abdominal infections (127\u2008000 deaths [81\u2008900-185\u2008000]) and respiratory infections (120\u2008000 deaths [94\u2008500-154\u2008000]). Seven leading pathogens were responsible for about 457\u2008000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.<h4>Interpretation</h4>The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.<h4>Funding</h4>Bill &amp; Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.",
+    "laySummary": "",
+    "urls": "pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf; doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253"
+  },
   {
     "id": "35948708",
     "doi": "https://doi.org/10.1038/s41586-022-05023-2",
@@ -32248,23 +32248,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8C3760ED596F1ED8B80F729AC5E47B9B/S0033291722002501a.pdf/div-class-title-depression-anxiety-and-ptsd-symptoms-before-and-during-the-covid-19-pandemic-in-the-uk-div.pdf; doi:https://doi.org/10.1017/S0033291722002501; html:https://europepmc.org/articles/PMC10482709; pdf:https://europepmc.org/articles/PMC10482709?pdf=render"
   },
-  {
-    "id": "37247330",
-    "doi": "https://doi.org/10.1093/eurheartj/ehad260",
-    "title": "SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.",
-    "authorString": "SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.",
-    "authorAffiliations": "",
-    "journalTitle": "European heart journal",
-    "pubYear": "2023",
-    "date": "2023-07-01",
-    "isOpenAccess": "Y",
-    "keywords": "Cardiovascular diseases; Prediction model; Diabetes",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims</h4>To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.<h4>Methods and results</h4>SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.<h4>Conclusion</h4>SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1093/eurheartj/ehad260; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render"
-  },
   {
     "id": "32576090",
     "doi": "https://doi.org/10.1161/strokeaha.120.029042",
@@ -32299,6 +32282,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render; pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935"
   },
+  {
+    "id": "37247330",
+    "doi": "https://doi.org/10.1093/eurheartj/ehad260",
+    "title": "SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.",
+    "authorString": "SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.",
+    "authorAffiliations": "",
+    "journalTitle": "European heart journal",
+    "pubYear": "2023",
+    "date": "2023-07-01",
+    "isOpenAccess": "Y",
+    "keywords": "Cardiovascular diseases; Prediction model; Diabetes",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims</h4>To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.<h4>Methods and results</h4>SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.<h4>Conclusion</h4>SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1093/eurheartj/ehad260; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render"
+  },
   {
     "id": "35545669",
     "doi": "https://doi.org/10.1038/s41586-022-04712-2",
@@ -32741,23 +32741,6 @@
     "laySummary": "Grist et al. team trained computers to analyse brain images from children for identification of tumours. They\u2019ve shown that applying analytical methods to enable machine distinguishes between the entire brain area and the tumour area in the images more than 80% improves how machine analyses the image to identify exact tumour area. ",
     "urls": "doi:https://doi.org/10.1016/j.nicl.2020.102172; doi:https://doi.org/10.1016/j.nicl.2020.102172; html:https://europepmc.org/articles/PMC7005468; pdf:https://europepmc.org/articles/PMC7005468?pdf=render"
   },
-  {
-    "id": "35017564",
-    "doi": "https://doi.org/10.1038/s41467-021-27950-w",
-    "title": "Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies.",
-    "authorString": "Keown JR, Zhu Z, Carrique L, Fan H, Walker AP, Serna Martin I, Pardon E, Steyaert J, Fodor E, Grimes JM.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2022",
-    "date": "2022-01-11",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-021-27950-w.pdf; doi:https://doi.org/10.1038/s41467-021-27950-w; html:https://europepmc.org/articles/PMC8752864; pdf:https://europepmc.org/articles/PMC8752864?pdf=render"
-  },
   {
     "id": "32360702",
     "doi": "https://doi.org/10.1016/j.ijcard.2020.04.068",
@@ -32775,6 +32758,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.internationaljournalofcardiology.com/article/S016752732031679X/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.04.068"
   },
+  {
+    "id": "35017564",
+    "doi": "https://doi.org/10.1038/s41467-021-27950-w",
+    "title": "Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies.",
+    "authorString": "Keown JR, Zhu Z, Carrique L, Fan H, Walker AP, Serna Martin I, Pardon E, Steyaert J, Fodor E, Grimes JM.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature communications",
+    "pubYear": "2022",
+    "date": "2022-01-11",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41467-021-27950-w.pdf; doi:https://doi.org/10.1038/s41467-021-27950-w; html:https://europepmc.org/articles/PMC8752864; pdf:https://europepmc.org/articles/PMC8752864?pdf=render"
+  },
   {
     "id": "33714592",
     "doi": "https://doi.org/10.1016/j.mayocp.2021.02.007",
@@ -32911,23 +32911,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render"
   },
-  {
-    "id": "33430602",
-    "doi": "https://doi.org/10.1161/circheartfailure.120.007022",
-    "title": "Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.",
-    "authorString": "Schuldt M, Pei J, Harakalova M, Dorsch LM, Schlossarek S, Mokry M, Knol JC, Pham TV, Schelfhorst T, Piersma SR, Dos Remedios C, Dalinghaus M, Michels M, Asselbergs FW, Moutin MJ, Carrier L, Jimenez CR, van der Velden J, Kuster DWD.",
-    "authorAffiliations": "",
-    "journalTitle": "Circulation. Heart failure",
-    "pubYear": "2021",
-    "date": "2021-01-12",
-    "isOpenAccess": "Y",
-    "keywords": "Mutation; Genotype; Tubulin; Heart diseases; Proteomics; Treatment; Cardiomyopathies",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While \u224850% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCM<sub>SMP</sub>), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCM<sub>SMN</sub>). Genotype-specific differences have been reported in cardiac function. Moreover, HCM<sub>SMN</sub> patients have later disease onset and a better prognosis than HCM<sub>SMP</sub> patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group.<h4>Methods</h4>A proteomics screen was performed in cardiac tissue from 39 HCM<sub>SMP</sub> patients, 11HCM<sub>SMN</sub> patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel <i>MYBPC3</i><sub>2373insG</sub> mouse model was used to confirm functional relevance of our proteomic findings.<h4>Results</h4>In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated \u03b1-tubulin were markedly higher in HCM<sub>SMP</sub> than in HCM<sub>SMN</sub> and controls. Higher tubulin detyrosination was also found in 2 unrelated <i>MYBPC3</i> mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes.<h4>Conclusions</h4>Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCM<sub>SMP</sub>. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCM<sub>SMP</sub>, whereas a beneficial effect may be limited in patients with HCM<sub>SMN</sub>.",
-    "laySummary": "",
-    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.120.007022; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render"
-  },
   {
     "id": "30981377",
     "doi": "https://doi.org/10.1016/j.aap.2019.03.007",
@@ -32945,6 +32928,23 @@
     "laySummary": "",
     "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa50030/Download/0050030-20052019102229.pdf; doi:https://doi.org/10.1016/j.aap.2019.03.007"
   },
+  {
+    "id": "33430602",
+    "doi": "https://doi.org/10.1161/circheartfailure.120.007022",
+    "title": "Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.",
+    "authorString": "Schuldt M, Pei J, Harakalova M, Dorsch LM, Schlossarek S, Mokry M, Knol JC, Pham TV, Schelfhorst T, Piersma SR, Dos Remedios C, Dalinghaus M, Michels M, Asselbergs FW, Moutin MJ, Carrier L, Jimenez CR, van der Velden J, Kuster DWD.",
+    "authorAffiliations": "",
+    "journalTitle": "Circulation. Heart failure",
+    "pubYear": "2021",
+    "date": "2021-01-12",
+    "isOpenAccess": "Y",
+    "keywords": "Mutation; Genotype; Tubulin; Heart diseases; Proteomics; Treatment; Cardiomyopathies",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While \u224850% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCM<sub>SMP</sub>), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCM<sub>SMN</sub>). Genotype-specific differences have been reported in cardiac function. Moreover, HCM<sub>SMN</sub> patients have later disease onset and a better prognosis than HCM<sub>SMP</sub> patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group.<h4>Methods</h4>A proteomics screen was performed in cardiac tissue from 39 HCM<sub>SMP</sub> patients, 11HCM<sub>SMN</sub> patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel <i>MYBPC3</i><sub>2373insG</sub> mouse model was used to confirm functional relevance of our proteomic findings.<h4>Results</h4>In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated \u03b1-tubulin were markedly higher in HCM<sub>SMP</sub> than in HCM<sub>SMN</sub> and controls. Higher tubulin detyrosination was also found in 2 unrelated <i>MYBPC3</i> mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes.<h4>Conclusions</h4>Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCM<sub>SMP</sub>. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCM<sub>SMP</sub>, whereas a beneficial effect may be limited in patients with HCM<sub>SMN</sub>.",
+    "laySummary": "",
+    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.120.007022; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render"
+  },
   {
     "id": "31196905",
     "doi": "https://doi.org/10.1136/bmjopen-2019-028929",
@@ -33388,21 +33388,21 @@
     "urls": "pdf:https://ueaeprints.uea.ac.uk/id/eprint/76368/1/Zheng_et_al_final_manuscript.pdf; doi:https://doi.org/10.1038/s41588-020-0682-6; html:https://europepmc.org/articles/PMC7610464; pdf:https://europepmc.org/articles/PMC7610464?pdf=render"
   },
   {
-    "id": "35103486",
-    "doi": "https://doi.org/10.1128/msystems.01132-21",
-    "title": "Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.",
-    "authorString": "Shenhav L, Azad MB.",
+    "id": "31666364",
+    "doi": "https://doi.org/10.1128/jcm.00963-19",
+    "title": "Metagenomic Nanopore Sequencing of Influenza Virus Direct from Clinical Respiratory Samples.",
+    "authorString": "Lewandowski K, Xu Y, Pullan ST, Lumley SF, Foster D, Sanderson N, Vaughan A, Morgan M, Bright N, Kavanagh J, Vipond R, Carroll M, Marriott AC, Gooch KE, Andersson M, Jeffery K, Peto TEA, Crook DW, Walker AS, Matthews PC.",
     "authorAffiliations": "",
-    "journalTitle": "mSystems",
-    "pubYear": "2022",
-    "date": "2022-02-01",
+    "journalTitle": "Journal of clinical microbiology",
+    "pubYear": "2019",
+    "date": "2019-12-23",
     "isOpenAccess": "Y",
-    "keywords": "Lactation; Human Milk; Breastfeeding; Chronobiology; Computational Methods; System Biology; Human Microbiome; Community Ecology Theory",
-    "nationalPriorities": "",
+    "keywords": "DNA sequencing; Sequencing; Influenza; Diagnosis; Molecular epidemiology; epidemiology; Diagnostics; Metagenomics; Nanopore; Metagenomic",
+    "nationalPriorities": "Understanding the Causes of Disease",
     "healthCategories": "",
-    "abstract": "Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, \"our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation\" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant \"triad\" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a \"system within a system.\"",
+    "abstract": "Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential for a diagnostic test for influenza virus which also provides insights on transmission, evolution, and drug resistance and simultaneously detects other viruses. We therefore set out to apply the Oxford Nanopore Technologies sequencing method to metagenomic sequencing of respiratory samples. We generated influenza virus reads down to a limit of detection of 10<sup>2</sup> to 10<sup>3</sup> genome copies/ml in pooled samples, observing a strong relationship between the viral titer and the proportion of influenza virus reads (<i>P</i>\u2009=\u20094.7\u2009\u00d7\u200910<sup>-5</sup>). Applying our methods to clinical throat swabs, we generated influenza virus reads for 27/27 samples with mid-to-high viral titers (cycle threshold [<i>C<sub>T</sub></i> ] values, <30) and 6/13 samples with low viral titers (<i>C<sub>T</sub></i> values, 30 to 40). No false-positive reads were generated from 10 influenza virus-negative samples. Thus, Nanopore sequencing operated with 83% sensitivity (95% confidence interval [CI], 67 to 93%) and 100% specificity (95% CI, 69 to 100%) compared to the current diagnostic standard. Coverage of full-length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza virus titers, we were able to reconstruct >99% complete sequences for all eight gene segments. We also detected a human coronavirus coinfection in one clinical sample. While further optimization is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza virus and other respiratory viruses.",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1128/msystems.01132-21; doi:https://doi.org/10.1128/msystems.01132-21; html:https://europepmc.org/articles/PMC8805635; pdf:https://europepmc.org/articles/PMC8805635?pdf=render"
+    "urls": "doi:https://doi.org/10.1128/jcm.00963-19; doi:https://doi.org/10.1128/JCM.00963-19; html:https://europepmc.org/articles/PMC6935926; pdf:https://europepmc.org/articles/PMC6935926?pdf=render"
   },
   {
     "id": "32546850",
@@ -33422,21 +33422,21 @@
     "urls": "pdf:https://www.nature.com/articles/s41598-020-66737-9.pdf; doi:https://doi.org/10.1038/s41598-020-66737-9; html:https://europepmc.org/articles/PMC7297971; pdf:https://europepmc.org/articles/PMC7297971?pdf=render"
   },
   {
-    "id": "31666364",
-    "doi": "https://doi.org/10.1128/jcm.00963-19",
-    "title": "Metagenomic Nanopore Sequencing of Influenza Virus Direct from Clinical Respiratory Samples.",
-    "authorString": "Lewandowski K, Xu Y, Pullan ST, Lumley SF, Foster D, Sanderson N, Vaughan A, Morgan M, Bright N, Kavanagh J, Vipond R, Carroll M, Marriott AC, Gooch KE, Andersson M, Jeffery K, Peto TEA, Crook DW, Walker AS, Matthews PC.",
+    "id": "35103486",
+    "doi": "https://doi.org/10.1128/msystems.01132-21",
+    "title": "Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.",
+    "authorString": "Shenhav L, Azad MB.",
     "authorAffiliations": "",
-    "journalTitle": "Journal of clinical microbiology",
-    "pubYear": "2019",
-    "date": "2019-12-23",
+    "journalTitle": "mSystems",
+    "pubYear": "2022",
+    "date": "2022-02-01",
     "isOpenAccess": "Y",
-    "keywords": "DNA sequencing; Sequencing; Influenza; Diagnosis; Molecular epidemiology; epidemiology; Diagnostics; Metagenomics; Nanopore; Metagenomic",
-    "nationalPriorities": "Understanding the Causes of Disease",
+    "keywords": "Lactation; Human Milk; Breastfeeding; Chronobiology; Computational Methods; System Biology; Human Microbiome; Community Ecology Theory",
+    "nationalPriorities": "",
     "healthCategories": "",
-    "abstract": "Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential for a diagnostic test for influenza virus which also provides insights on transmission, evolution, and drug resistance and simultaneously detects other viruses. We therefore set out to apply the Oxford Nanopore Technologies sequencing method to metagenomic sequencing of respiratory samples. We generated influenza virus reads down to a limit of detection of 10<sup>2</sup> to 10<sup>3</sup> genome copies/ml in pooled samples, observing a strong relationship between the viral titer and the proportion of influenza virus reads (<i>P</i>\u2009=\u20094.7\u2009\u00d7\u200910<sup>-5</sup>). Applying our methods to clinical throat swabs, we generated influenza virus reads for 27/27 samples with mid-to-high viral titers (cycle threshold [<i>C<sub>T</sub></i> ] values, <30) and 6/13 samples with low viral titers (<i>C<sub>T</sub></i> values, 30 to 40). No false-positive reads were generated from 10 influenza virus-negative samples. Thus, Nanopore sequencing operated with 83% sensitivity (95% confidence interval [CI], 67 to 93%) and 100% specificity (95% CI, 69 to 100%) compared to the current diagnostic standard. Coverage of full-length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza virus titers, we were able to reconstruct >99% complete sequences for all eight gene segments. We also detected a human coronavirus coinfection in one clinical sample. While further optimization is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza virus and other respiratory viruses.",
+    "abstract": "Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, \"our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation\" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant \"triad\" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a \"system within a system.\"",
     "laySummary": "",
-    "urls": "doi:https://doi.org/10.1128/jcm.00963-19; doi:https://doi.org/10.1128/JCM.00963-19; html:https://europepmc.org/articles/PMC6935926; pdf:https://europepmc.org/articles/PMC6935926?pdf=render"
+    "urls": "doi:https://doi.org/10.1128/msystems.01132-21; doi:https://doi.org/10.1128/msystems.01132-21; html:https://europepmc.org/articles/PMC8805635; pdf:https://europepmc.org/articles/PMC8805635?pdf=render"
   },
   {
     "id": "30609404",
@@ -33455,23 +33455,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.cell.com/article/S0002929718304221/pdf; doi:https://doi.org/10.1016/j.ajhg.2018.11.014; html:https://europepmc.org/articles/PMC6323624; pdf:https://europepmc.org/articles/PMC6323624?pdf=render; doi:https://doi.org/10.1016/j.ajhg.2018.11.014"
   },
-  {
-    "id": "37743838",
-    "doi": "https://doi.org/10.1017/s0033291722003671",
-    "title": "The association between persistent cognitive difficulties and depression and functional outcomes in people with major depressive disorder.",
-    "authorString": "Matcham F, Simblett SK, Leightley D, Dalby M, Siddi S, Haro JM, Lamers F, Penninx BWHJ, Bruce S, Nica R, Zormpas S, Gilpin G, White KM, Oetzmann C, Annas P, Brasen JC, Narayan VA, Hotopf M, Wykes T, RADAR-CNS consortium.",
-    "authorAffiliations": "",
-    "journalTitle": "Psychological medicine",
-    "pubYear": "2023",
-    "date": "2022-12-13",
-    "isOpenAccess": "Y",
-    "keywords": "Cognitive function; epidemiology; Longitudinal; Major Depressive Disorder; Predictive; Remote Measurement",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Cognitive symptoms are common during and following episodes of depression. Little is known about the persistence of self-reported and performance-based cognition with depression and functional outcomes.<h4>Methods</h4>This is a secondary analysis of a prospective naturalistic observational clinical cohort study of individuals with recurrent major depressive disorder (MDD; <i>N</i> = 623). Participants completed app-based self-reported and performance-based cognitive function assessments alongside validated measures of depression, functional disability, and self-esteem every 3 months. Participants were followed-up for a maximum of 2-years. Multilevel hierarchically nested modelling was employed to explore between- and within-participant variation over time to identify whether persistent cognitive difficulties are related to levels of depression and functional impairment during follow-up.<h4>Results</h4>508 individuals (81.5%) provided data (mean age: 46.6, s.d.: 15.6; 76.2% female). Increasing persistence of self-reported cognitive difficulty was associated with higher levels of depression and functional impairment throughout the follow-up. In comparison to low persistence of objective cognitive difficulty (<25% of timepoints), those with high persistence (>75% of timepoints) reported significantly higher levels of depression (<i>B</i> = 5.17, s.e. = 2.21, <i>p</i> = 0.019) and functional impairment (<i>B</i> = 4.82, s.e. = 1.79, <i>p</i> = 0.002) over time. Examination of the individual cognitive modules shows that persistently impaired executive function is associated with worse functioning, and poor processing speed is particularly important for worsened depressive symptoms.<h4>Conclusions</h4>We replicated previous findings of greater persistence of cognitive difficulty with increasing severity of depression and further demonstrate that these cognitive difficulties are associated with pervasive functional disability. Difficulties with cognition may be an indicator and target for further treatment input.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1017/S0033291722003671; html:https://europepmc.org/articles/PMC10520589; pdf:https://europepmc.org/articles/PMC10520589?pdf=render"
-  },
   {
     "id": "33220850",
     "doi": "https://doi.org/10.1016/s0140-6736(20)32465-x",
@@ -33489,6 +33472,23 @@
     "laySummary": "",
     "urls": "pdf:http://www.thelancet.com/article/S014067362032465X/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32465-X; html:https://europepmc.org/articles/PMC7831890; pdf:https://europepmc.org/articles/PMC7831890?pdf=render"
   },
+  {
+    "id": "37743838",
+    "doi": "https://doi.org/10.1017/s0033291722003671",
+    "title": "The association between persistent cognitive difficulties and depression and functional outcomes in people with major depressive disorder.",
+    "authorString": "Matcham F, Simblett SK, Leightley D, Dalby M, Siddi S, Haro JM, Lamers F, Penninx BWHJ, Bruce S, Nica R, Zormpas S, Gilpin G, White KM, Oetzmann C, Annas P, Brasen JC, Narayan VA, Hotopf M, Wykes T, RADAR-CNS consortium.",
+    "authorAffiliations": "",
+    "journalTitle": "Psychological medicine",
+    "pubYear": "2023",
+    "date": "2022-12-13",
+    "isOpenAccess": "Y",
+    "keywords": "Cognitive function; epidemiology; Longitudinal; Major Depressive Disorder; Predictive; Remote Measurement",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Cognitive symptoms are common during and following episodes of depression. Little is known about the persistence of self-reported and performance-based cognition with depression and functional outcomes.<h4>Methods</h4>This is a secondary analysis of a prospective naturalistic observational clinical cohort study of individuals with recurrent major depressive disorder (MDD; <i>N</i> = 623). Participants completed app-based self-reported and performance-based cognitive function assessments alongside validated measures of depression, functional disability, and self-esteem every 3 months. Participants were followed-up for a maximum of 2-years. Multilevel hierarchically nested modelling was employed to explore between- and within-participant variation over time to identify whether persistent cognitive difficulties are related to levels of depression and functional impairment during follow-up.<h4>Results</h4>508 individuals (81.5%) provided data (mean age: 46.6, s.d.: 15.6; 76.2% female). Increasing persistence of self-reported cognitive difficulty was associated with higher levels of depression and functional impairment throughout the follow-up. In comparison to low persistence of objective cognitive difficulty (<25% of timepoints), those with high persistence (>75% of timepoints) reported significantly higher levels of depression (<i>B</i> = 5.17, s.e. = 2.21, <i>p</i> = 0.019) and functional impairment (<i>B</i> = 4.82, s.e. = 1.79, <i>p</i> = 0.002) over time. Examination of the individual cognitive modules shows that persistently impaired executive function is associated with worse functioning, and poor processing speed is particularly important for worsened depressive symptoms.<h4>Conclusions</h4>We replicated previous findings of greater persistence of cognitive difficulty with increasing severity of depression and further demonstrate that these cognitive difficulties are associated with pervasive functional disability. Difficulties with cognition may be an indicator and target for further treatment input.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1017/S0033291722003671; html:https://europepmc.org/articles/PMC10520589; pdf:https://europepmc.org/articles/PMC10520589?pdf=render"
+  },
   {
     "id": "31862893",
     "doi": "https://doi.org/10.1038/s41467-019-13848-1",
@@ -33523,23 +33523,6 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00134-023-07039-2.pdf; doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render"
   },
-  {
-    "id": "34039579",
-    "doi": "https://doi.org/10.1136/bmjopen-2021-049721",
-    "title": "Changes in daily mental health service use and mortality at the commencement and lifting of COVID-19 'lockdown' policy in 10 UK sites: a regression discontinuity in time design.",
-    "authorString": "Bakolis I, Stewart R, Baldwin D, Beenstock J, Bibby P, Broadbent M, Cardinal R, Chen S, Chinnasamy K, Cipriani A, Douglas S, Horner P, Jackson CA, John A, Joyce DW, Lee SC, Lewis J, McIntosh A, Nixon N, Osborn D, Phiri P, Rathod S, Smith T, Sokal R, Waller R, Landau S.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2021",
-    "date": "2021-05-26",
-    "isOpenAccess": "Y",
-    "keywords": "Mental health; Adult Psychiatry; Old Age Psychiatry; Organisation Of Health Services; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objectives</h4>To investigate changes in daily mental health (MH) service use and mortality in response to the introduction and the lifting of the COVID-19 'lockdown' policy in Spring 2020.<h4>Design</h4>A regression discontinuity in time (RDiT) analysis of daily service-level activity.<h4>Setting and participants</h4>Mental healthcare data were extracted from 10 UK providers.<h4>Outcome measures</h4>Daily (weekly for one site) deaths from all causes, referrals and discharges, inpatient care (admissions, discharges, caseloads) and community services (face-to-face (f2f)/non-f2f contacts, caseloads): Adult, older adult and child/adolescent mental health; early intervention in psychosis; home treatment teams and liaison/Accident and Emergency (A&E). Data were extracted from 1 Jan 2019 to 31 May 2020 for all sites, supplemented to 31 July 2020 for four sites. Changes around the commencement and lifting of COVID-19 'lockdown' policy (23 March and 10 May, respectively) were estimated using a RDiT design with a difference-in-difference approach generating incidence rate ratios (IRRs), meta-analysed across sites.<h4>Results</h4>Pooled estimates for the lockdown transition showed increased daily deaths (IRR 2.31, 95% CI 1.86 to 2.87), reduced referrals (IRR 0.62, 95% CI 0.55 to 0.70) and reduced inpatient admissions (IRR 0.75, 95% CI 0.67 to 0.83) and caseloads (IRR 0.85, 95% CI 0.79 to 0.91) compared with the pre lockdown period. All community services saw shifts from f2f to non-f2f contacts, but varied in caseload changes. Lift of lockdown was associated with reduced deaths (IRR 0.42, 95% CI 0.27 to 0.66), increased referrals (IRR 1.36, 95% CI 1.15 to 1.60) and increased inpatient admissions (IRR 1.21, 95% CI 1.04 to 1.42) and caseloads (IRR 1.06, 95% CI 1.00 to 1.12) compared with the lockdown period. Site-wide activity, inpatient care and community services did not return to pre lockdown levels after lift of lockdown, while number of deaths did. Between-site heterogeneity most often indicated variation in size rather than direction of effect.<h4>Conclusions</h4>MH service delivery underwent sizeable changes during the first national lockdown, with as-yet unknown and unevaluated consequences.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049721.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049721; html:https://europepmc.org/articles/PMC8159668; pdf:https://europepmc.org/articles/PMC8159668?pdf=render"
-  },
   {
     "id": "32724860",
     "doi": "https://doi.org/10.12688/wellcomeopenres.15651.2",
@@ -33557,6 +33540,23 @@
     "laySummary": "",
     "urls": "pdf:https://wellcomeopenresearch.org/articles/5-24/v2/pdf; doi:https://doi.org/10.12688/wellcomeopenres.15651.2; html:https://europepmc.org/articles/PMC7361507; pdf:https://europepmc.org/articles/PMC7361507?pdf=render"
   },
+  {
+    "id": "34039579",
+    "doi": "https://doi.org/10.1136/bmjopen-2021-049721",
+    "title": "Changes in daily mental health service use and mortality at the commencement and lifting of COVID-19 'lockdown' policy in 10 UK sites: a regression discontinuity in time design.",
+    "authorString": "Bakolis I, Stewart R, Baldwin D, Beenstock J, Bibby P, Broadbent M, Cardinal R, Chen S, Chinnasamy K, Cipriani A, Douglas S, Horner P, Jackson CA, John A, Joyce DW, Lee SC, Lewis J, McIntosh A, Nixon N, Osborn D, Phiri P, Rathod S, Smith T, Sokal R, Waller R, Landau S.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2021",
+    "date": "2021-05-26",
+    "isOpenAccess": "Y",
+    "keywords": "Mental health; Adult Psychiatry; Old Age Psychiatry; Organisation Of Health Services; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objectives</h4>To investigate changes in daily mental health (MH) service use and mortality in response to the introduction and the lifting of the COVID-19 'lockdown' policy in Spring 2020.<h4>Design</h4>A regression discontinuity in time (RDiT) analysis of daily service-level activity.<h4>Setting and participants</h4>Mental healthcare data were extracted from 10 UK providers.<h4>Outcome measures</h4>Daily (weekly for one site) deaths from all causes, referrals and discharges, inpatient care (admissions, discharges, caseloads) and community services (face-to-face (f2f)/non-f2f contacts, caseloads): Adult, older adult and child/adolescent mental health; early intervention in psychosis; home treatment teams and liaison/Accident and Emergency (A&E). Data were extracted from 1 Jan 2019 to 31 May 2020 for all sites, supplemented to 31 July 2020 for four sites. Changes around the commencement and lifting of COVID-19 'lockdown' policy (23 March and 10 May, respectively) were estimated using a RDiT design with a difference-in-difference approach generating incidence rate ratios (IRRs), meta-analysed across sites.<h4>Results</h4>Pooled estimates for the lockdown transition showed increased daily deaths (IRR 2.31, 95% CI 1.86 to 2.87), reduced referrals (IRR 0.62, 95% CI 0.55 to 0.70) and reduced inpatient admissions (IRR 0.75, 95% CI 0.67 to 0.83) and caseloads (IRR 0.85, 95% CI 0.79 to 0.91) compared with the pre lockdown period. All community services saw shifts from f2f to non-f2f contacts, but varied in caseload changes. Lift of lockdown was associated with reduced deaths (IRR 0.42, 95% CI 0.27 to 0.66), increased referrals (IRR 1.36, 95% CI 1.15 to 1.60) and increased inpatient admissions (IRR 1.21, 95% CI 1.04 to 1.42) and caseloads (IRR 1.06, 95% CI 1.00 to 1.12) compared with the lockdown period. Site-wide activity, inpatient care and community services did not return to pre lockdown levels after lift of lockdown, while number of deaths did. Between-site heterogeneity most often indicated variation in size rather than direction of effect.<h4>Conclusions</h4>MH service delivery underwent sizeable changes during the first national lockdown, with as-yet unknown and unevaluated consequences.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049721.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049721; html:https://europepmc.org/articles/PMC8159668; pdf:https://europepmc.org/articles/PMC8159668?pdf=render"
+  },
   {
     "id": "32505923",
     "doi": "https://doi.org/10.1016/j.ebiom.2020.102818",
@@ -33710,23 +33710,6 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1099/mgen.0.000630; doi:https://doi.org/10.1099/mgen.0.000630; html:https://europepmc.org/articles/PMC8627209; pdf:https://europepmc.org/articles/PMC8627209?pdf=render"
   },
-  {
-    "id": "36568709",
-    "doi": "https://doi.org/10.1136/bmjmed-2022-000215",
-    "title": "Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.",
-    "authorString": "Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ medicine",
-    "pubYear": "2022",
-    "date": "2022-09-28",
-    "isOpenAccess": "Y",
-    "keywords": "Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.<h4>Design</h4>Cohort study.<h4>Setting</h4>Patients registered at primary care practices in England.<h4>Participants</h4>106\u2009789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.<h4>Main outcome measures</h4>In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.<h4>Results</h4>680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.<h4>Conclusions</h4>Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render"
-  },
   {
     "id": "34321180",
     "doi": "https://doi.org/10.1016/j.aucc.2021.05.013",
@@ -33744,6 +33727,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.aucc.2021.05.013"
   },
+  {
+    "id": "36568709",
+    "doi": "https://doi.org/10.1136/bmjmed-2022-000215",
+    "title": "Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.",
+    "authorString": "Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ medicine",
+    "pubYear": "2022",
+    "date": "2022-09-28",
+    "isOpenAccess": "Y",
+    "keywords": "Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.<h4>Design</h4>Cohort study.<h4>Setting</h4>Patients registered at primary care practices in England.<h4>Participants</h4>106\u2009789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.<h4>Main outcome measures</h4>In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.<h4>Results</h4>680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.<h4>Conclusions</h4>Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render"
+  },
   {
     "id": "37173061",
     "doi": "https://doi.org/10.1016/j.ajcnut.2022.12.021",
@@ -33965,23 +33965,6 @@
     "laySummary": "",
     "urls": "pdf:https://ijpds.org/article/download/1093/1035; doi:https://doi.org/10.23889/ijpds.v4i1.1093; html:https://europepmc.org/articles/PMC7482514; pdf:https://europepmc.org/articles/PMC7482514?pdf=render"
   },
-  {
-    "id": "36527096",
-    "doi": "https://doi.org/10.1186/s12910-022-00875-9",
-    "title": "\"Data makes the story come to life:\" understanding the ethical and legal implications of Big Data research involving ethnic minority healthcare workers in the United Kingdom-a qualitative study.",
-    "authorString": "Dove ES, Reed-Berendt R, Pareek M, UK-REACH Study Collaborative Group.",
-    "authorAffiliations": "",
-    "journalTitle": "BMC medical ethics",
-    "pubYear": "2022",
-    "date": "2022-12-16",
-    "isOpenAccess": "Y",
-    "keywords": "Ethics; Public Health; United Kingdom; Healthcare Workers; Ethnic Minorities; Big Data; Covid-19",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The aim of UK-REACH (\"The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers\") is to understand if, how, and why healthcare workers (HCWs) in the United Kingdom (UK) from ethnic minority groups are at increased risk of poor outcomes from COVID-19. In this article, we present findings from the ethical and legal stream of the study, which undertook qualitative research seeking to understand and address legal, ethical, and social acceptability issues around data protection, privacy, and information governance associated with the linkage of HCWs' registration data and healthcare data. We interviewed 22 key opinion leaders in healthcare and health research from across the UK in two-to-one semi-structured interviews. Transcripts were coded using qualitative thematic analysis. Participants told us that a significant aspect of Big Data research in public health is varying drivers of mistrust-of the research itself, research staff and funders, and broader concerns of mistrust within participant communities, particularly in the context of COVID-19 and those situated in more marginalised community settings. However, despite the challenges, participants also identified ways in which legally compliant and ethically informed approaches to research can be crafted to mitigate or overcome mistrust and establish greater confidence in Big Data public health research. Overall, our research indicates that a \"Big Data Ethics by Design\" approach to research in this area can help assure (1) that meaningful community and participant engagement is taking place and that extant challenges are addressed, and (2) that any new challenges or hitherto unknown unknowns can be rapidly and properly considered to ensure potential (but material) harms are identified and minimised where necessary. Our findings indicate such an approach, in turn, will help drive better scientific breakthroughs that translate into medical innovations and effective public health interventions, which benefit the publics studied, including those who are often marginalised in research.",
-    "laySummary": "",
-    "urls": "pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?pdf=render"
-  },
   {
     "id": "34252085",
     "doi": "https://doi.org/10.1371/journal.pcbi.1009162",
@@ -33999,6 +33982,23 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009162&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009162; html:https://europepmc.org/articles/PMC8297940; pdf:https://europepmc.org/articles/PMC8297940?pdf=render"
   },
+  {
+    "id": "36527096",
+    "doi": "https://doi.org/10.1186/s12910-022-00875-9",
+    "title": "\"Data makes the story come to life:\" understanding the ethical and legal implications of Big Data research involving ethnic minority healthcare workers in the United Kingdom-a qualitative study.",
+    "authorString": "Dove ES, Reed-Berendt R, Pareek M, UK-REACH Study Collaborative Group.",
+    "authorAffiliations": "",
+    "journalTitle": "BMC medical ethics",
+    "pubYear": "2022",
+    "date": "2022-12-16",
+    "isOpenAccess": "Y",
+    "keywords": "Ethics; Public Health; United Kingdom; Healthcare Workers; Ethnic Minorities; Big Data; Covid-19",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The aim of UK-REACH (\"The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers\") is to understand if, how, and why healthcare workers (HCWs) in the United Kingdom (UK) from ethnic minority groups are at increased risk of poor outcomes from COVID-19. In this article, we present findings from the ethical and legal stream of the study, which undertook qualitative research seeking to understand and address legal, ethical, and social acceptability issues around data protection, privacy, and information governance associated with the linkage of HCWs' registration data and healthcare data. We interviewed 22 key opinion leaders in healthcare and health research from across the UK in two-to-one semi-structured interviews. Transcripts were coded using qualitative thematic analysis. Participants told us that a significant aspect of Big Data research in public health is varying drivers of mistrust-of the research itself, research staff and funders, and broader concerns of mistrust within participant communities, particularly in the context of COVID-19 and those situated in more marginalised community settings. However, despite the challenges, participants also identified ways in which legally compliant and ethically informed approaches to research can be crafted to mitigate or overcome mistrust and establish greater confidence in Big Data public health research. Overall, our research indicates that a \"Big Data Ethics by Design\" approach to research in this area can help assure (1) that meaningful community and participant engagement is taking place and that extant challenges are addressed, and (2) that any new challenges or hitherto unknown unknowns can be rapidly and properly considered to ensure potential (but material) harms are identified and minimised where necessary. Our findings indicate such an approach, in turn, will help drive better scientific breakthroughs that translate into medical innovations and effective public health interventions, which benefit the publics studied, including those who are often marginalised in research.",
+    "laySummary": "",
+    "urls": "pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?pdf=render"
+  },
   {
     "id": "35189575",
     "doi": "https://doi.org/10.1016/j.ebiom.2022.103878",
@@ -34186,23 +34186,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.jclinepi.com/article/S0895435621001384/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.04.015; html:https://europepmc.org/articles/PMC8443839"
   },
-  {
-    "id": "35296488",
-    "doi": "https://doi.org/10.1136/bmjopen-2021-058552",
-    "title": "AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353\u2009157 patients in London, UK.",
-    "authorString": "Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.",
-    "authorAffiliations": "",
-    "journalTitle": "BMJ open",
-    "pubYear": "2022",
-    "date": "2022-03-16",
-    "isOpenAccess": "Y",
-    "keywords": "Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Purpose</h4>Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.<h4>Participants</h4>Between 1 January 2008 and 1 April 2018, 353\u2009157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.<h4>Findings to date</h4>Among the 353\u2009157 individuals, 186\u2009651 had a total of 1\u2009337\u2009711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12\u2009022 patients with myocardial infarction, 11\u2009735 with all-cause stroke and 13\u2009363 with all-cause dementia. A total of 6\u2009261\u2009931 retinal images of seven different modalities and across three manufacturers were acquired from 1\u200954\u2009830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).<h4>Future plans</h4>AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.",
-    "laySummary": "",
-    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/3/e058552.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render"
-  },
   {
     "id": "34036180",
     "doi": "https://doi.org/10.23889/ijpds.v5i2.1385",
@@ -34220,6 +34203,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.23889/ijpds.v5i2.1385; html:https://europepmc.org/articles/PMC8133060; pdf:https://europepmc.org/articles/PMC8133060?pdf=render"
   },
+  {
+    "id": "35296488",
+    "doi": "https://doi.org/10.1136/bmjopen-2021-058552",
+    "title": "AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353\u2009157 patients in London, UK.",
+    "authorString": "Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.",
+    "authorAffiliations": "",
+    "journalTitle": "BMJ open",
+    "pubYear": "2022",
+    "date": "2022-03-16",
+    "isOpenAccess": "Y",
+    "keywords": "Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Purpose</h4>Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.<h4>Participants</h4>Between 1 January 2008 and 1 April 2018, 353\u2009157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.<h4>Findings to date</h4>Among the 353\u2009157 individuals, 186\u2009651 had a total of 1\u2009337\u2009711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12\u2009022 patients with myocardial infarction, 11\u2009735 with all-cause stroke and 13\u2009363 with all-cause dementia. A total of 6\u2009261\u2009931 retinal images of seven different modalities and across three manufacturers were acquired from 1\u200954\u2009830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).<h4>Future plans</h4>AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.",
+    "laySummary": "",
+    "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/3/e058552.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render"
+  },
   {
     "id": "35585198",
     "doi": "https://doi.org/10.1038/s41591-022-01772-9",
@@ -34305,23 +34305,6 @@
     "laySummary": "",
     "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003981&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003981; html:https://europepmc.org/articles/PMC9119501; pdf:https://europepmc.org/articles/PMC9119501?pdf=render"
   },
-  {
-    "id": "33972514",
-    "doi": "https://doi.org/10.1038/s41467-021-22338-2",
-    "title": "Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.",
-    "authorString": "Pazoki R, Vujkovic M, Elliott J, Evangelou E, Gill D, Ghanbari M, van der Most PJ, Pinto RC, Wielscher M, Farlik M, Zuber V, de Knegt RJ, Snieder H, Uitterlinden AG, Lifelines Cohort Study, Lynch JA, Jiang X, Said S, Kaplan DE, Lee KM, Serper M, Carr RM, Tsao PS, Atkinson SR, Dehghan A, Tzoulaki I, Ikram MA, Herzig KH, J\u00e4rvelin MR, Alizadeh BZ, O'Donnell CJ, Saleheen D, Voight BF, Chang KM, Thursz MR, Elliott P, VA Million Veteran Program.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature communications",
-    "pubYear": "2021",
-    "date": "2021-05-10",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41467-021-22338-2.pdf; doi:https://doi.org/10.1038/s41467-021-22338-2; html:https://europepmc.org/articles/PMC8110798; pdf:https://europepmc.org/articles/PMC8110798?pdf=render"
-  },
   {
     "id": "31382511",
     "doi": "https://doi.org/10.3390/toxins11080454",
@@ -34339,6 +34322,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.mdpi.com/2072-6651/11/8/454/pdf?version=1565690179; doi:https://doi.org/10.3390/toxins11080454; html:https://europepmc.org/articles/PMC6723868; pdf:https://europepmc.org/articles/PMC6723868?pdf=render"
   },
+  {
+    "id": "33972514",
+    "doi": "https://doi.org/10.1038/s41467-021-22338-2",
+    "title": "Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.",
+    "authorString": "Pazoki R, Vujkovic M, Elliott J, Evangelou E, Gill D, Ghanbari M, van der Most PJ, Pinto RC, Wielscher M, Farlik M, Zuber V, de Knegt RJ, Snieder H, Uitterlinden AG, Lifelines Cohort Study, Lynch JA, Jiang X, Said S, Kaplan DE, Lee KM, Serper M, Carr RM, Tsao PS, Atkinson SR, Dehghan A, Tzoulaki I, Ikram MA, Herzig KH, J\u00e4rvelin MR, Alizadeh BZ, O'Donnell CJ, Saleheen D, Voight BF, Chang KM, Thursz MR, Elliott P, VA Million Veteran Program.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature communications",
+    "pubYear": "2021",
+    "date": "2021-05-10",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41467-021-22338-2.pdf; doi:https://doi.org/10.1038/s41467-021-22338-2; html:https://europepmc.org/articles/PMC8110798; pdf:https://europepmc.org/articles/PMC8110798?pdf=render"
+  },
   {
     "id": "35042708",
     "doi": "https://doi.org/10.1136/bmjopen-2021-055572",
@@ -35053,23 +35053,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41598-019-44907-8.pdf; doi:https://doi.org/10.1038/s41598-019-44907-8; html:https://europepmc.org/articles/PMC6554413; pdf:https://europepmc.org/articles/PMC6554413?pdf=render"
   },
-  {
-    "id": "37414900",
-    "doi": "https://doi.org/10.1038/s41591-023-02429-x",
-    "title": "A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.",
-    "authorString": "Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, Genes & Health Research Team; the Million Veteran Program, Tsao PS, Sun YV, Cho K, Wilson PWF, Assimes TL, van Heel DA, Butterworth AS, Aragam KG, Natarajan P, Khera AV.",
-    "authorAffiliations": "",
-    "journalTitle": "Nature medicine",
-    "pubYear": "2023",
-    "date": "2023-07-06",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPS<sub>Mult</sub>, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPS<sub>Mult</sub> strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P\u2009<\u20090.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPS<sub>Mult</sub> was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P\u2009<\u20090.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPS<sub>Mult</sub> demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPS<sub>Mult</sub> for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41591-023-02429-x.pdf; doi:https://doi.org/10.1038/s41591-023-02429-x; html:https://europepmc.org/articles/PMC10353935; pdf:https://europepmc.org/articles/PMC10353935?pdf=render"
-  },
   {
     "id": "34972825",
     "doi": "https://doi.org/10.1038/s41564-021-01029-0",
@@ -35087,6 +35070,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render"
   },
+  {
+    "id": "37414900",
+    "doi": "https://doi.org/10.1038/s41591-023-02429-x",
+    "title": "A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.",
+    "authorString": "Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, Genes & Health Research Team; the Million Veteran Program, Tsao PS, Sun YV, Cho K, Wilson PWF, Assimes TL, van Heel DA, Butterworth AS, Aragam KG, Natarajan P, Khera AV.",
+    "authorAffiliations": "",
+    "journalTitle": "Nature medicine",
+    "pubYear": "2023",
+    "date": "2023-07-06",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPS<sub>Mult</sub>, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPS<sub>Mult</sub> strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P\u2009<\u20090.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPS<sub>Mult</sub> was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P\u2009<\u20090.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPS<sub>Mult</sub> demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPS<sub>Mult</sub> for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41591-023-02429-x.pdf; doi:https://doi.org/10.1038/s41591-023-02429-x; html:https://europepmc.org/articles/PMC10353935; pdf:https://europepmc.org/articles/PMC10353935?pdf=render"
+  },
   {
     "id": "32127008",
     "doi": "https://doi.org/10.1186/s13059-020-01969-6",
@@ -35342,23 +35342,6 @@
     "laySummary": "",
     "urls": "pdf:https://academic.oup.com/jcem/article-pdf/105/12/e4230/41829325/dgaa627.pdf; doi:https://doi.org/10.1210/clinem/dgaa627; html:https://europepmc.org/articles/PMC7499588; pdf:https://europepmc.org/articles/PMC7499588?pdf=render"
   },
-  {
-    "id": "37757828",
-    "doi": "https://doi.org/10.1016/j.cell.2023.08.028",
-    "title": "Influence of autozygosity on common disease risk across the phenotypic spectrum.",
-    "authorString": "Malawsky DS, van Walree E, Jacobs BM, Heng TH, Huang QQ, Sabir AH, Rahman S, Sharif SM, Khan A, Mirkov MU, 23andMe Research Team, Genes & Health Research Team, Kuwahara H, Gao X, Alkuraya FS, Posthuma D, Newman WG, Griffiths CJ, Mathur R, van Heel DA, Finer S, O'Connell J, Martin HC.",
-    "authorAffiliations": "",
-    "journalTitle": "Cell",
-    "pubYear": "2023",
-    "date": "2023-09-26",
-    "isOpenAccess": "Y",
-    "keywords": "Consanguinity; Medical genetics; Recessive; Autozygosity; Common Diseases; Diverse Cohorts",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F<sub>ROH</sub>) and common diseases in Genes\u00a0& Health (n\u00a0= 23,978 British South Asians), UK Biobank (n\u00a0= 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F<sub>ROH</sub>. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F<sub>ROH</sub> and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n\u00a0= 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.",
-    "laySummary": "",
-    "urls": "doi:https://doi.org/10.1016/j.cell.2023.08.028; html:https://europepmc.org/articles/PMC10580289; pdf:https://europepmc.org/articles/PMC10580289?pdf=render"
-  },
   {
     "id": "33174830",
     "doi": "https://doi.org/10.1099/mgen.0.000453",
@@ -35376,6 +35359,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1099/mgen.0.000453; doi:https://doi.org/10.1099/mgen.0.000453; html:https://europepmc.org/articles/PMC7725331; pdf:https://europepmc.org/articles/PMC7725331?pdf=render"
   },
+  {
+    "id": "37757828",
+    "doi": "https://doi.org/10.1016/j.cell.2023.08.028",
+    "title": "Influence of autozygosity on common disease risk across the phenotypic spectrum.",
+    "authorString": "Malawsky DS, van Walree E, Jacobs BM, Heng TH, Huang QQ, Sabir AH, Rahman S, Sharif SM, Khan A, Mirkov MU, 23andMe Research Team, Genes & Health Research Team, Kuwahara H, Gao X, Alkuraya FS, Posthuma D, Newman WG, Griffiths CJ, Mathur R, van Heel DA, Finer S, O'Connell J, Martin HC.",
+    "authorAffiliations": "",
+    "journalTitle": "Cell",
+    "pubYear": "2023",
+    "date": "2023-09-26",
+    "isOpenAccess": "Y",
+    "keywords": "Consanguinity; Medical genetics; Recessive; Autozygosity; Common Diseases; Diverse Cohorts",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F<sub>ROH</sub>) and common diseases in Genes\u00a0& Health (n\u00a0= 23,978 British South Asians), UK Biobank (n\u00a0= 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F<sub>ROH</sub>. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F<sub>ROH</sub> and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n\u00a0= 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.",
+    "laySummary": "",
+    "urls": "doi:https://doi.org/10.1016/j.cell.2023.08.028; html:https://europepmc.org/articles/PMC10580289; pdf:https://europepmc.org/articles/PMC10580289?pdf=render"
+  },
   {
     "id": "37316763",
     "doi": "https://doi.org/10.1007/s10875-023-01530-7",
@@ -35988,23 +35988,6 @@
     "laySummary": "",
     "urls": "pdf:http://www.cell.com/article/S1074761322000462/pdf; doi:https://doi.org/10.1016/j.immuni.2022.01.017; html:https://europepmc.org/articles/PMC8789571; pdf:https://europepmc.org/articles/PMC8789571?pdf=render"
   },
-  {
-    "id": "35608616",
-    "doi": "https://doi.org/10.1007/s00125-022-05714-5",
-    "title": "Risk of incident obstructive sleep apnoea in patients with type 1 diabetes: a population-based retrospective cohort study.",
-    "authorString": "Alshehri Z, Subramanian A, Adderley NJ, Gokhale KM, Karamat MA, Ray CJ, Kumar P, Nirantharakumar K, Tahrani AA.",
-    "authorAffiliations": "",
-    "journalTitle": "Diabetologia",
-    "pubYear": "2022",
-    "date": "2022-05-24",
-    "isOpenAccess": "Y",
-    "keywords": "Obesity; Depression; type 1 diabetes; Sleep Apnoea",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aims/hypothesis</h4>People with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes.<h4>Methods</h4>We used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis.<h4>Results</h4>In total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43\u00a0years ((IQR 2.19-10.11), and the mean BMI was 25.82\u00a0kg/m<sup>2</sup> (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p<0.001). Predictors of incident obstructive sleep apnoea in patients with type 1 diabetes were older age, male sex, obesity, being prescribed antihypertensive or lipid-lowering drugs, atrial fibrillation and depression.<h4>Conclusions/interpretation</h4>Individuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs.",
-    "laySummary": "",
-    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00125-022-05714-5.pdf; doi:https://doi.org/10.1007/s00125-022-05714-5; html:https://europepmc.org/articles/PMC9283161; pdf:https://europepmc.org/articles/PMC9283161?pdf=render"
-  },
   {
     "id": "32095773",
     "doi": "https://doi.org/10.1159/000503957",
@@ -36022,6 +36005,23 @@
     "laySummary": "The authors of this publication have developed a set of guidelines for planning, running and writing up research that uses mobile technologies in clinical trials. The guidelines they have put together should make it easer for patient experience to be recorded in clinical trials.",
     "urls": "pdf:https://www.karger.com/Article/Pdf/503957; doi:https://doi.org/10.1159/000503957; html:https://europepmc.org/articles/PMC7011727; pdf:https://europepmc.org/articles/PMC7011727?pdf=render; doi:https://doi.org/10.1159/000503957"
   },
+  {
+    "id": "35608616",
+    "doi": "https://doi.org/10.1007/s00125-022-05714-5",
+    "title": "Risk of incident obstructive sleep apnoea in patients with type 1 diabetes: a population-based retrospective cohort study.",
+    "authorString": "Alshehri Z, Subramanian A, Adderley NJ, Gokhale KM, Karamat MA, Ray CJ, Kumar P, Nirantharakumar K, Tahrani AA.",
+    "authorAffiliations": "",
+    "journalTitle": "Diabetologia",
+    "pubYear": "2022",
+    "date": "2022-05-24",
+    "isOpenAccess": "Y",
+    "keywords": "Obesity; Depression; type 1 diabetes; Sleep Apnoea",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aims/hypothesis</h4>People with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes.<h4>Methods</h4>We used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis.<h4>Results</h4>In total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43\u00a0years ((IQR 2.19-10.11), and the mean BMI was 25.82\u00a0kg/m<sup>2</sup> (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p<0.001). Predictors of incident obstructive sleep apnoea in patients with type 1 diabetes were older age, male sex, obesity, being prescribed antihypertensive or lipid-lowering drugs, atrial fibrillation and depression.<h4>Conclusions/interpretation</h4>Individuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs.",
+    "laySummary": "",
+    "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00125-022-05714-5.pdf; doi:https://doi.org/10.1007/s00125-022-05714-5; html:https://europepmc.org/articles/PMC9283161; pdf:https://europepmc.org/articles/PMC9283161?pdf=render"
+  },
   {
     "id": "37645200",
     "doi": "https://doi.org/10.12688/openreseurope.13860.2",
@@ -36175,23 +36175,6 @@
     "laySummary": "",
     "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12325-023-02511-3.pdf; doi:https://doi.org/10.1007/s12325-023-02511-3; html:https://europepmc.org/articles/PMC10092909; pdf:https://europepmc.org/articles/PMC10092909?pdf=render"
   },
-  {
-    "id": "37794492",
-    "doi": "https://doi.org/10.1186/s13073-023-01233-z",
-    "title": "Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.",
-    "authorString": "Neumann A, Ohlei O, K\u00fc\u00e7\u00fckali F, Bos IJ, Timsina J, Vos S, Prokopenko D, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Scheltens P, Teunissen CE, Engelborghs S, Frisoni GB, Blin O, Richardson JC, Bordet R, Lle\u00f3 A, Alcolea D, Popp J, Marsh TW, Gorijala P, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Van Broeckhoven C, Tanzi RE, Ten Kate M, Lill CM, Barkhof F, Cruchaga C, Lovestone S, Streffer J, Zetterberg H, Visser PJ, Sleegers K, Bertram L, EMIF-AD & ADNI study group.",
-    "authorAffiliations": "",
-    "journalTitle": "Genome medicine",
-    "pubYear": "2023",
-    "date": "2023-10-04",
-    "isOpenAccess": "Y",
-    "keywords": "Principal component analysis; Biomarkers; Alzheimer\u2019s disease; Dementia; Cerebrospinal fluid (CSF); multivariate analysis; Structural Equation Modeling; Mediation; Genome-wide Association Study (Gwas)",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (\u03b2-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.<h4>Methods</h4>We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n\u2009=\u2009205 controls, n\u2009=\u2009546 mild cognitive impairment, n\u2009=\u2009222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.<h4>Results</h4>Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses\u00a0of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.<h4>Conclusions</h4>These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.",
-    "laySummary": "",
-    "urls": "pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01233-z; doi:https://doi.org/10.1186/s13073-023-01233-z; html:https://europepmc.org/articles/PMC10548686; pdf:https://europepmc.org/articles/PMC10548686?pdf=render"
-  },
   {
     "id": "31408153",
     "doi": "https://doi.org/10.1093/europace/euz220",
@@ -36209,6 +36192,23 @@
     "laySummary": "This study identified EHR records of AF and vavular heard disease in over 70k UK individuals and looked for associations with stroke, systemic embolism and mortality. They used CALIBER - a data source connecting office of national statistics, CPRD and HES data from over 10 years. They reported clear methodology on how the EHR was used to classify disease, showed overall prevalence change in different AF related diseases over time, and were able to provide insights at a more granular level - for example, valvular heart disease subtypes in AF than previous studies. The full code list (EHR codes) is provided in supplement, so methods are theoretically reproducible. Immediate impact to patient is less strong and there is wasn't much emphasis on diversity and inclusion.",
     "urls": "pdf:https://academic.oup.com/europace/article-pdf/21/12/1776/31175830/euz220.pdf; doi:https://doi.org/10.1093/europace/euz220; html:https://europepmc.org/articles/PMC6888023; pdf:https://europepmc.org/articles/PMC6888023?pdf=render"
   },
+  {
+    "id": "37794492",
+    "doi": "https://doi.org/10.1186/s13073-023-01233-z",
+    "title": "Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.",
+    "authorString": "Neumann A, Ohlei O, K\u00fc\u00e7\u00fckali F, Bos IJ, Timsina J, Vos S, Prokopenko D, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Scheltens P, Teunissen CE, Engelborghs S, Frisoni GB, Blin O, Richardson JC, Bordet R, Lle\u00f3 A, Alcolea D, Popp J, Marsh TW, Gorijala P, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Van Broeckhoven C, Tanzi RE, Ten Kate M, Lill CM, Barkhof F, Cruchaga C, Lovestone S, Streffer J, Zetterberg H, Visser PJ, Sleegers K, Bertram L, EMIF-AD & ADNI study group.",
+    "authorAffiliations": "",
+    "journalTitle": "Genome medicine",
+    "pubYear": "2023",
+    "date": "2023-10-04",
+    "isOpenAccess": "Y",
+    "keywords": "Principal component analysis; Biomarkers; Alzheimer\u2019s disease; Dementia; Cerebrospinal fluid (CSF); multivariate analysis; Structural Equation Modeling; Mediation; Genome-wide Association Study (Gwas)",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (\u03b2-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.<h4>Methods</h4>We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n\u2009=\u2009205 controls, n\u2009=\u2009546 mild cognitive impairment, n\u2009=\u2009222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.<h4>Results</h4>Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses\u00a0of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.<h4>Conclusions</h4>These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.",
+    "laySummary": "",
+    "urls": "pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01233-z; doi:https://doi.org/10.1186/s13073-023-01233-z; html:https://europepmc.org/articles/PMC10548686; pdf:https://europepmc.org/articles/PMC10548686?pdf=render"
+  },
   {
     "id": "31978332",
     "doi": "https://doi.org/10.1016/j.ajhg.2020.01.003",
@@ -36311,23 +36311,6 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-019-10724-w.pdf; doi:https://doi.org/10.1038/s41467-019-10724-w; html:https://europepmc.org/articles/PMC6616926; pdf:https://europepmc.org/articles/PMC6616926?pdf=render"
   },
-  {
-    "id": "36315390",
-    "doi": "https://doi.org/10.1002/eat.23834",
-    "title": "Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.",
-    "authorString": "Davies HL, H\u00fcbel C, Herle M, Kakar S, Mundy J, Peel AJ, Ter Kuile AR, Zvrskovec J, Monssen D, Lim KX, Davies MR, Palmos AB, Lin Y, Kalsi G, Rogers HC, Bristow S, Glen K, Malouf CM, Kelly EJ, Purves KL, Young KS, Hotopf M, Armour C, McIntosh AM, Eley TC, Treasure J, Breen G.",
-    "authorAffiliations": "",
-    "journalTitle": "The International journal of eating disorders",
-    "pubYear": "2023",
-    "date": "2022-10-31",
-    "isOpenAccess": "Y",
-    "keywords": "Mental health; Psychiatric disorders; Eating Disorders; Comorbidity; Suicidal Ideation",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Objective</h4>The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic.<h4>Method</h4>Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n\u00a0=\u200936,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n\u00a0=\u200924,211), low weight (n\u00a0=\u200924,364), suicidal and/or self-harm ideation (n\u00a0=\u200918,040), and self-harm (n\u00a0=\u200929,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes.<h4>Results</h4>Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation.<h4>Discussion</h4>Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics.<h4>Public significance</h4>In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.",
-    "laySummary": "",
-    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eat.23834; doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?pdf=render"
-  },
   {
     "id": "31641117",
     "doi": "https://doi.org/10.1038/s41467-019-12682-9",
@@ -36345,6 +36328,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-019-12682-9.pdf; doi:https://doi.org/10.1038/s41467-019-12682-9; html:https://europepmc.org/articles/PMC6805929; pdf:https://europepmc.org/articles/PMC6805929?pdf=render"
   },
+  {
+    "id": "36315390",
+    "doi": "https://doi.org/10.1002/eat.23834",
+    "title": "Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.",
+    "authorString": "Davies HL, H\u00fcbel C, Herle M, Kakar S, Mundy J, Peel AJ, Ter Kuile AR, Zvrskovec J, Monssen D, Lim KX, Davies MR, Palmos AB, Lin Y, Kalsi G, Rogers HC, Bristow S, Glen K, Malouf CM, Kelly EJ, Purves KL, Young KS, Hotopf M, Armour C, McIntosh AM, Eley TC, Treasure J, Breen G.",
+    "authorAffiliations": "",
+    "journalTitle": "The International journal of eating disorders",
+    "pubYear": "2023",
+    "date": "2022-10-31",
+    "isOpenAccess": "Y",
+    "keywords": "Mental health; Psychiatric disorders; Eating Disorders; Comorbidity; Suicidal Ideation",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Objective</h4>The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic.<h4>Method</h4>Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n\u00a0=\u200936,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n\u00a0=\u200924,211), low weight (n\u00a0=\u200924,364), suicidal and/or self-harm ideation (n\u00a0=\u200918,040), and self-harm (n\u00a0=\u200929,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes.<h4>Results</h4>Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation.<h4>Discussion</h4>Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics.<h4>Public significance</h4>In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.",
+    "laySummary": "",
+    "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eat.23834; doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?pdf=render"
+  },
   {
     "id": "31822727",
     "doi": "https://doi.org/10.1038/s41598-019-55098-7",
@@ -36396,23 +36396,6 @@
     "laySummary": "",
     "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610517; doi:https://doi.org/10.1038/s41588-019-0484-x; html:https://europepmc.org/articles/PMC7610517; pdf:https://europepmc.org/articles/PMC7610517?pdf=render; doi:https://doi.org/10.1038/s41588-019-0484-x"
   },
-  {
-    "id": "36258219",
-    "doi": "https://doi.org/10.1186/s13063-022-06824-6",
-    "title": "Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.",
-    "authorString": "Sandercock PAG, Darbyshire J, DeMets D, Fowler R, Lalloo DG, Munavvar M, Staplin N, Warris A, Wittes J, Emberson JR.",
-    "authorAffiliations": "",
-    "journalTitle": "Trials",
-    "pubYear": "2022",
-    "date": "2022-10-18",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Aim</h4>To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.<h4>Methods and findings</h4>During the first 24\u00a0months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving\u2009>\u200945,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively 'competing' for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab\u2009+\u2009imdevimab, and tocilizumab.<h4>Conclusions</h4>RECOVERY's streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial's efficiency, without compromising the DMC's ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.",
-    "laySummary": "",
-    "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06824-6; doi:https://doi.org/10.1186/s13063-022-06824-6; html:https://europepmc.org/articles/PMC9579551; pdf:https://europepmc.org/articles/PMC9579551?pdf=render"
-  },
   {
     "id": "31539079",
     "doi": "https://doi.org/10.1001/jamanetworkopen.2019.11970",
@@ -36430,6 +36413,23 @@
     "laySummary": "",
     "urls": "pdf:https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2751559/seow_2019_oi_190459.pdf; doi:https://doi.org/10.1001/jamanetworkopen.2019.11970; html:https://europepmc.org/articles/PMC6755532"
   },
+  {
+    "id": "36258219",
+    "doi": "https://doi.org/10.1186/s13063-022-06824-6",
+    "title": "Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19.",
+    "authorString": "Sandercock PAG, Darbyshire J, DeMets D, Fowler R, Lalloo DG, Munavvar M, Staplin N, Warris A, Wittes J, Emberson JR.",
+    "authorAffiliations": "",
+    "journalTitle": "Trials",
+    "pubYear": "2022",
+    "date": "2022-10-18",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Aim</h4>To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.<h4>Methods and findings</h4>During the first 24\u00a0months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving\u2009>\u200945,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively 'competing' for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab\u2009+\u2009imdevimab, and tocilizumab.<h4>Conclusions</h4>RECOVERY's streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial's efficiency, without compromising the DMC's ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.",
+    "laySummary": "",
+    "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06824-6; doi:https://doi.org/10.1186/s13063-022-06824-6; html:https://europepmc.org/articles/PMC9579551; pdf:https://europepmc.org/articles/PMC9579551?pdf=render"
+  },
   {
     "id": "33770123",
     "doi": "https://doi.org/10.1371/journal.pone.0249189",
@@ -36617,23 +36617,6 @@
     "laySummary": "",
     "urls": "pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2770779/jamadermatology_benzianolsson_2020_oi_200054_1604610894.93046.pdf; doi:https://doi.org/10.1001/jamadermatol.2020.3275; html:https://europepmc.org/articles/PMC7495329"
   },
-  {
-    "id": "36589292",
-    "doi": "https://doi.org/10.3389/fncel.2022.1050596",
-    "title": "Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data.",
-    "authorString": "Al Khleifat A, Iacoangeli A, Jones AR, van Vugt JJFA, Moisse M, Shatunov A, Zwamborn RAJ, van der Spek RAA, Cooper-Knock J, Topp S, van Rheenen W, Kenna B, Van Eijk KR, Kenna K, Byrne R, L\u00f3pez V, Opie-Martin S, Vural A, Campos Y, Weber M, Smith B, Fogh I, Silani V, Morrison KE, Dobson R, van Es MA, McLaughlin RL, Vourc'h P, Chio A, Corcia P, de Carvalho M, Gotkine M, Panades MP, Mora JS, Shaw PJ, Landers JE, Glass JD, Shaw CE, Basak N, Hardiman O, Robberecht W, Van Damme P, van den Berg LH, Veldink JH, Al-Chalabi A.",
-    "authorAffiliations": "",
-    "journalTitle": "Frontiers in cellular neuroscience",
-    "pubYear": "2022",
-    "date": "2022-12-15",
-    "isOpenAccess": "Y",
-    "keywords": "Genomics; Amyotrophic Lateral Sclerosis (Als); Bigdata; Whole Genome Sequence (Wgs); Telomere\u2013Genetics; Mnd\u2013Motor Neuron Disorders",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS.<h4>Methods</h4>Samples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression.<h4>Results</h4>There were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 \u00d7 10<sup>-12</sup>), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0\u00d710<sup>-7</sup>). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded <i>C9orf72</i> repeats was shorter than in those without expanded <i>C9orf72</i> repeats (p = 5.0\u00d710<sup>-4</sup>).<h4>Discussion</h4>Although telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS.",
-    "laySummary": "",
-    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fncel.2022.1050596/pdf; doi:https://doi.org/10.3389/fncel.2022.1050596; html:https://europepmc.org/articles/PMC9799999; pdf:https://europepmc.org/articles/PMC9799999?pdf=render"
-  },
   {
     "id": "33623019",
     "doi": "https://doi.org/10.1038/s41467-021-21505-9",
@@ -36651,6 +36634,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.nature.com/articles/s41467-021-21505-9.pdf; doi:https://doi.org/10.1038/s41467-021-21505-9; html:https://europepmc.org/articles/PMC7902656; pdf:https://europepmc.org/articles/PMC7902656?pdf=render"
   },
+  {
+    "id": "36589292",
+    "doi": "https://doi.org/10.3389/fncel.2022.1050596",
+    "title": "Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data.",
+    "authorString": "Al Khleifat A, Iacoangeli A, Jones AR, van Vugt JJFA, Moisse M, Shatunov A, Zwamborn RAJ, van der Spek RAA, Cooper-Knock J, Topp S, van Rheenen W, Kenna B, Van Eijk KR, Kenna K, Byrne R, L\u00f3pez V, Opie-Martin S, Vural A, Campos Y, Weber M, Smith B, Fogh I, Silani V, Morrison KE, Dobson R, van Es MA, McLaughlin RL, Vourc'h P, Chio A, Corcia P, de Carvalho M, Gotkine M, Panades MP, Mora JS, Shaw PJ, Landers JE, Glass JD, Shaw CE, Basak N, Hardiman O, Robberecht W, Van Damme P, van den Berg LH, Veldink JH, Al-Chalabi A.",
+    "authorAffiliations": "",
+    "journalTitle": "Frontiers in cellular neuroscience",
+    "pubYear": "2022",
+    "date": "2022-12-15",
+    "isOpenAccess": "Y",
+    "keywords": "Genomics; Amyotrophic Lateral Sclerosis (Als); Bigdata; Whole Genome Sequence (Wgs); Telomere\u2013Genetics; Mnd\u2013Motor Neuron Disorders",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS.<h4>Methods</h4>Samples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression.<h4>Results</h4>There were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 \u00d7 10<sup>-12</sup>), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0\u00d710<sup>-7</sup>). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded <i>C9orf72</i> repeats was shorter than in those without expanded <i>C9orf72</i> repeats (p = 5.0\u00d710<sup>-4</sup>).<h4>Discussion</h4>Although telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS.",
+    "laySummary": "",
+    "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fncel.2022.1050596/pdf; doi:https://doi.org/10.3389/fncel.2022.1050596; html:https://europepmc.org/articles/PMC9799999; pdf:https://europepmc.org/articles/PMC9799999?pdf=render"
+  },
   {
     "id": "34767815",
     "doi": "https://doi.org/10.1016/j.jid.2021.08.446",
@@ -37501,23 +37501,6 @@
     "laySummary": "",
     "urls": "pdf:https://epjdatascience.springeropen.com/track/pdf/10.1140/epjds/s13688-020-00257-4; doi:https://doi.org/10.1140/epjds/s13688-020-00257-4; html:https://europepmc.org/articles/PMC7790778; pdf:https://europepmc.org/articles/PMC7790778?pdf=render"
   },
-  {
-    "id": "36215124",
-    "doi": "https://doi.org/10.1161/circgen.121.003598",
-    "title": "Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.",
-    "authorString": "Khera AV, Wang M, Chaffin M, Emdin CA, Samani NJ, Schunkert H, Watkins H, McPherson R, Erdmann J, Elosua R, Boerwinkle E, Ardissino D, Butterworth AS, Di Angelantonio E, Naheed A, Danesh J, Chowdhury R, Krumholz HM, Sheu WH, Rich SS, Rotter JI, Chen YI, Gabriel S, Lander ES, Saleheen D, Kathiresan S.",
-    "authorAffiliations": "",
-    "journalTitle": "Circulation. Genomic and precision medicine",
-    "pubYear": "2022",
-    "date": "2022-10-10",
-    "isOpenAccess": "N",
-    "keywords": "Atherosclerosis; coronary artery disease; Genetic Association Studies; Nitric Oxide Synthase Type Iii; Precision Medicine",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "<h4>Background</h4>A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (<i>LDLR</i>) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.<h4>Methods</h4>To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.<h4>Results</h4>Rare variants in <i>LDLR</i> were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (<i>NOS3</i>), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in <i>NOS3</i> was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; <i>P</i>=5.50\u00d710<sup>-9</sup>). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; <i>P</i>=5.00\u00d710<sup>-6</sup>) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; <i>P</i>=2.00\u00d710<sup>-4</sup>) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk.<h4>Conclusions</h4>Beyond <i>LDLR</i>, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the <i>NOS3</i> gene.",
-    "laySummary": "",
-    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.121.003598; doi:https://doi.org/10.1161/CIRCGEN.121.003598"
-  },
   {
     "id": "29743285",
     "doi": "https://doi.org/10.1136/bmj.k1717",
@@ -37535,6 +37518,23 @@
     "laySummary": "",
     "urls": "pdf:https://www.bmj.com/content/bmj/361/bmj.k1717.full.pdf; doi:https://doi.org/10.1136/bmj.k1717; html:https://europepmc.org/articles/PMC5942157"
   },
+  {
+    "id": "36215124",
+    "doi": "https://doi.org/10.1161/circgen.121.003598",
+    "title": "Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.",
+    "authorString": "Khera AV, Wang M, Chaffin M, Emdin CA, Samani NJ, Schunkert H, Watkins H, McPherson R, Erdmann J, Elosua R, Boerwinkle E, Ardissino D, Butterworth AS, Di Angelantonio E, Naheed A, Danesh J, Chowdhury R, Krumholz HM, Sheu WH, Rich SS, Rotter JI, Chen YI, Gabriel S, Lander ES, Saleheen D, Kathiresan S.",
+    "authorAffiliations": "",
+    "journalTitle": "Circulation. Genomic and precision medicine",
+    "pubYear": "2022",
+    "date": "2022-10-10",
+    "isOpenAccess": "N",
+    "keywords": "Atherosclerosis; coronary artery disease; Genetic Association Studies; Nitric Oxide Synthase Type Iii; Precision Medicine",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "<h4>Background</h4>A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (<i>LDLR</i>) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.<h4>Methods</h4>To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.<h4>Results</h4>Rare variants in <i>LDLR</i> were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (<i>NOS3</i>), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in <i>NOS3</i> was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; <i>P</i>=5.50\u00d710<sup>-9</sup>). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; <i>P</i>=5.00\u00d710<sup>-6</sup>) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; <i>P</i>=2.00\u00d710<sup>-4</sup>) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk.<h4>Conclusions</h4>Beyond <i>LDLR</i>, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the <i>NOS3</i> gene.",
+    "laySummary": "",
+    "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.121.003598; doi:https://doi.org/10.1161/CIRCGEN.121.003598"
+  },
   {
     "id": "36113526",
     "doi": "https://doi.org/10.1016/s2214-109x(22)00332-1",
@@ -38266,23 +38266,6 @@
     "laySummary": "",
     "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02588-7; doi:https://doi.org/10.1186/s12916-022-02588-7; html:https://europepmc.org/articles/PMC9548389; pdf:https://europepmc.org/articles/PMC9548389?pdf=render"
   },
-  {
-    "id": "35908040",
-    "doi": "https://doi.org/10.1038/s41597-022-01534-9",
-    "title": "ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.",
-    "authorString": "ISARIC Clinical Characterization Group, Garcia-Gallo E, Merson L, Kennon K, Kelly S, Citarella BW, Fryer DV, Shrapnel S, Lee J, Duque S, Fuentes YV, Balan V, Smith S, Wei J, Gon\u00e7alves BP, Russell CD, Sigfrid L, Dagens A, Olliaro PL, Baruch J, Kartsonaki C, Dunning J, Rojek A, Rashan A, Beane A, Murthy S, Reyes LF.",
-    "authorAffiliations": "",
-    "journalTitle": "Scientific data",
-    "pubYear": "2022",
-    "date": "2022-07-30",
-    "isOpenAccess": "Y",
-    "keywords": "",
-    "nationalPriorities": "",
-    "healthCategories": "",
-    "abstract": "The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.",
-    "laySummary": "",
-    "urls": "pdf:https://www.nature.com/articles/s41597-022-01534-9.pdf; doi:https://doi.org/10.1038/s41597-022-01534-9; html:https://europepmc.org/articles/PMC9339000; pdf:https://europepmc.org/articles/PMC9339000?pdf=render"
-  },
   {
     "id": "32062083",
     "doi": "https://doi.org/10.1016/j.neuroimage.2020.116604",
@@ -38300,6 +38283,23 @@
     "laySummary": "",
     "urls": "doi:https://doi.org/10.1016/j.neuroimage.2020.116604; doi:https://doi.org/10.1016/j.neuroimage.2020.116604; html:https://europepmc.org/articles/PMC7086233"
   },
+  {
+    "id": "35908040",
+    "doi": "https://doi.org/10.1038/s41597-022-01534-9",
+    "title": "ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.",
+    "authorString": "ISARIC Clinical Characterization Group, Garcia-Gallo E, Merson L, Kennon K, Kelly S, Citarella BW, Fryer DV, Shrapnel S, Lee J, Duque S, Fuentes YV, Balan V, Smith S, Wei J, Gon\u00e7alves BP, Russell CD, Sigfrid L, Dagens A, Olliaro PL, Baruch J, Kartsonaki C, Dunning J, Rojek A, Rashan A, Beane A, Murthy S, Reyes LF.",
+    "authorAffiliations": "",
+    "journalTitle": "Scientific data",
+    "pubYear": "2022",
+    "date": "2022-07-30",
+    "isOpenAccess": "Y",
+    "keywords": "",
+    "nationalPriorities": "",
+    "healthCategories": "",
+    "abstract": "The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.",
+    "laySummary": "",
+    "urls": "pdf:https://www.nature.com/articles/s41597-022-01534-9.pdf; doi:https://doi.org/10.1038/s41597-022-01534-9; html:https://europepmc.org/articles/PMC9339000; pdf:https://europepmc.org/articles/PMC9339000?pdf=render"
+  },
   {
     "id": "31122927",
     "doi": "https://doi.org/10.1136/bmj.l1778",