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Jennifer A Davidson,1 Amitava Banerjee,2 Helen Strongman,1 Emily Herrett,1 Liam Smeeth,1 Judith Breuer,3 Charlotte Warren-Gash1 1Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK; 2Institute of Health Informatics, University College London, London, UK; 3Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UKCorrespondence: Charlotte Warren-Gash, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK, Tel +44 20 7927 2796, Email charlotte.warren-gash1@lshtm.ac.ukPurpose: To assess the risk of incident cardiovascular outcomes after COVID-19 by level of cardiovascular risk in waves one and two of the pandemic in England in 2020.Patients and methods: We conducted a self-controlled case-series study among adults aged 40– 84 years with no pre-existing cardiovascular disease using linked data from the Clinical Practice Research Datalink. We generated season-adjusted incidence ratios (IRs) for first acute cardiovascular event after SARS-CoV-2 infection compared with baseline time before and > 91 days after infection. We used composite and individual acute cardiovascular event outcomes including myocardial infarction, major ventricular arrhythmia, left ventricular heart failure, and ischemic stroke. We stratified by cardiovascular risk, using diagnosed hypertension and QRISK3 predicted risk, and by wave one and two of the pandemic.Results: We included 1762 individuals, 76.6% had a QRISK3 score ≥ 10% and 59.4% had hypertension. The risk of any cardiovascular event was elevated in the 1– 7 days after infection (IR 7.14 [95% CI 6.06– 8.41]) and, while the effect size tapered, the risk remained for 15– 28 days after infection (1.74 [1.33– 2.26]). Risks were similar for individual event type, differing by level of cardiovascular risk, and in wave one and two of the pandemic. &#x2003Conclusion: SARS-CoV-2 infection is associated with early elevations in the risk of first acute cardiovascular event, across cardiovascular risk levels and in both wave one and two of the pandemic. Prevention of COVID-19 is important to avert cardiovascular complications.Graphical Abstract: Keywords: acute coronary syndrome, COVID-19, electronic health records, epidemiology, heart failure

Jennifer Davidson,1 Amitava Banerjee,2 Rutendo Muzambi,1 Liam Smeeth,1 Charlotte Warren-Gash1 1Faculty of Epidemiology & Population Health, London School of Hygiene and Tropical Medicine, London, UK; 2Institute of Health Informatics, University College London, London, UKCorrespondence: Jennifer Davidson Email Jennifer.Davidson@lshtm.ac.ukBackground: Electronic health records are widely used in cardiovascular disease research. We appraised the validity of stroke, acute coronary syndrome and heart failure diagnoses in studies conducted using European electronic health records.Methods: Using a prespecified strategy, we systematically searched seven databases from dates of inception to April 2019. Two reviewers independently completed study selection, followed by partial parallel data extraction and risk of bias assessment. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value estimates were narratively synthesized and heterogeneity between sensitivity and PPV estimates were assessed using I2.Results: We identified 81 studies, of which 20 validated heart failure diagnoses, 31 validated acute coronary syndrome diagnoses with 29 specifically recording estimates for myocardial infarction, and 41 validated stroke diagnoses. Few studies reported specificity or negative predictive value estimates. Sensitivity was ≤ 66% in all but one heart failure study, ≥ 80% for 91% of myocardial infarction studies, and ≥ 70% for 73% of stroke studies. PPV was ≥ 80% in 74% of heart failure, 88% of myocardial infarction, and 70% of stroke studies. PPV by stroke subtype was variable, at ≥ 80% for 80% of ischaemic stroke but only 44% of haemorrhagic stroke. There was considerable heterogeneity (I2 > 75%) between sensitivity and PPV estimates for all diagnoses.Conclusion: Overall, European electronic health record stroke, acute coronary syndrome and heart failure diagnoses are accurate for use in research, although validity estimates for heart failure and individual stroke subtypes were lower. Where possible, researchers should validate data before use or carefully interpret the results of previous validation studies for their own study purposes.Keywords: validation, myocardial infarction, heart failure, stroke; routinely collected health data

Caroline E Morton,1,2 Harriet J Forbes,1 Neil Pearce,3 Liam Smeeth,1 Charlotte Warren-Gash1 1Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK; 2EBM DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, UK; 3Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UKCorrespondence: Caroline E Morton MortonEBM DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UKTel +44 1865 289300Email caroline.morton@phc.ox.ac.ukPurpose: To investigate the association between common infections and post-stroke dementia in a UK population-based cohort.Materials and Methods: A total of 60,392 stroke survivors (51.2% male, median age 74.3 years, IQR 63.9– 82.4 years) were identified using primary care records from the Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) with no history of dementia. Primary exposure was any GP-recorded infection (lower respiratory tract infection (LRTI), urinary tract infection (UTI) requiring antibiotics, skin and soft tissue infection requiring antibiotics) occurring after stroke. The primary outcome was incident all-cause dementia recorded in primary care records. In sensitivity analyses, we restricted to individuals with linked hospital records and expanded definitions to include ICD-10 coded hospital admissions. We used multivariable Cox regression to investigate the association between common infections and dementia occurring from 3 months to 5 years after stroke.Results: Of 60,392 stroke survivors, 20,969 (34.7%) experienced at least one infection and overall 4512 (7.5%) developed dementia during follow-up. Early dementia (3 months to 1-year post-stroke) risk was increased in those with at least one GP-recorded infection (HR 1.44, 95% CI 1.21– 1.71), with stronger associations when hospitalised infections were included (HR 1.84, 95% CI 1.58– 2.14). Late dementia (1– 5 years) was only associated with hospitalised, but not with GP-recorded, infections.Conclusion: There was evidence of an association between common infections and post-stroke dementia, strongest in the 3– 12 months following stroke. Better understanding of this relationship could help inform knowledge of pathways to dementia post-stroke and targeting of preventive interventions.Keywords: post-stroke dementia, infections, cohort study, electronic health records

Background: Previous studies identifying associations between influenza and acute cardiac events may have been confounded by climatic factors. Differing seasonal patterns of influenza activity in Hong Kong and England and Wales provide a natural experiment to examine associations with myocardial infarction (MI) independent of cold weather effects.Methods: Weekly clinical and laboratory influenza surveillance data, environmental temperature and humidity data, and counts of MI-associated hospitalizations and deaths were obtained for England and Wales and for Hong Kong for the period 1998-2008. We used Poisson regression models that included environmental and seasonal variables to investigate the relationship between influenza and MI.Results: There were ≥1.2 million MI-associated hospitalizations and 410,204 MI-associated deaths in England and Wales, with a marked peak in the winter season. In Hong Kong, the incidence of MI, on the basis of 65,108 hospitalizations and 18,780 deaths, had a large winter and smaller summer peak, mirroring patterns of influenza activity. There was strong evidence for a link between influenza and MI both in England and Wales, where 3.1%-3.4% of MI-associated deaths (P < .001) and 0.7%-1.2% of MI-associated hospitalizations (P < .001) were attributable to influenza, and in Hong Kong, where the corresponding figures were 3.9%-5.6% (P = .018) and 3.0%-3.3% (P = .002).Conclusions: Influenza was associated with an increase in MI-associated deaths and hospitalizations in 2 contrasting settings. [ABSTRACT FROM AUTHOR]

The article focuses on intimate partner violence's (IPV) screening in a London, England, HIV clinic and characteristics of those screening positive. Topics discussed include demographics of 348 screened patients, high lifetime risk for IPV and warrant in HIV patients and finding evidence of differences when comparing men who screened positive for IPV according to risk group.

Objectives: Direct oral anticoagulants (DOACs) are commonly co-prescribed with digoxin, but whether there is a drug interaction between them is unclear. We aimed to investigate potential drug interactions between DOACs and digoxin., Study Design and Setting: We identified DOAC users during January 1, 2011-December 31, 2019 using data from Clinical Practice Research Datalink Aurum in cohort design with propensity score to compare the hazards of effectiveness cardiovascular and mortality outcomes and safety bleeding outcomes, respectively, in DOAC + digoxin users versus DOAC + beta-blocker users. A case-crossover design was conducted to compare odds of exposure to different drug initiation patterns in hazard period versus referent period., Results: Of 397,459 DOAC users, we identified 25,251 co-prescribed digoxin and 109,779 co-prescribed beta-blockers in cohort study. A lower proportion of DOAC + digoxin users were men (46%) in contrast with that of DOAC + beta-blocker users (53%). Mean age of DOAC + digoxin users (77.1 years) were higher than DOAC + beta-blocker users (74.5 years). No increased risk of pharmacologically predictable DOAC safety outcomes or specific effectiveness outcomes was seen with DOAC + digoxin. A higher risk of all-cause mortality (hazard ratio: 1.35; 99% confidence interval [CI]: 1.14-1.61) was observed with DOAC + digoxin versus DOAC + beta-blockers. In the case-crossover study, a 24% higher odds of all-cause mortality was seen with initiating digoxin while taking DOAC (odds ratio: 1.24; 99% CI: 1.06-1.45); and a 63% higher odds was also seen with initiating DOAC while taking digoxin (odds ratio: 1.63; 99% CI: 1.41-1.88)., Conclusion: We found no increased risk of bleeding when DOACs are used with digoxin, suggesting combined use does not lead to drug-drug interaction. Future work is recommended to investigate the underlying mechanism of association with all-cause mortality., Plain Language Summary: This study aimed to examine potential drug interactions between direct oral anticoagulants (DOACs) (a drug class to prevent blood clots) and digoxin (treatment of abnormal heart rhythms). We compared a range of clinical outcomes in people prescribed DOAC and digoxin with people prescribed DOAC and beta-blockers (a treatment alternative to digoxin). We also used a new study design (case-crossover design) to compare the risk of clinical outcomes between different periods within a person as a validation. In both study designs, we found no increased risk of bleeding when DOACs are used with digoxin, suggesting combined use does not lead to drug-drug interaction. However, we found an increased risk of all-cause death associated with digoxin in DOAC users which requires further investigation., Competing Interests: Declaration of competing interest I. J. D. has received research grants from GlaxoSmithKline (GSK) and AstraZeneca and holds shares in GSK. C. W. G. participated in a Data Safety Monitoring Board for an investigator-led trial of the effect of influenza vaccination after heart attack on future cardiovascular prognosis (NCT02831608) from January 2019 to April 2020. A. Y. S. W. received honoraria from the 6th Annual Meeting of the Society for Clinical Epidemiology in Tokyo and 28th Annual Meeting of the Japanese Society for Pharmacoepidemiology in Kyoto in November 2023, outside the submitted work. All other co-authors declare no conflict of interest., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Evidence for an association between psoriasis and dementia is limited and conflicting. We aimed to investigate the association using large and representative population-based data and describe risk by dementia subtype and over time., Methods: We compared dementia risk between people with and without psoriasis using an age-, sex- and primary care practice-matched cohort of adults aged ≥40 years from the Clinical Practice Research Datalink Aurum in England (1997-2021) linked to hospital admissions data, analysed with stratified Cox regression., Results: Among 360,014 individuals with psoriasis and 1,799,617 without, psoriasis was associated with a small increased risk of all-cause dementia (adjusted hazard ratio [aHR] 1.06, 95% CI 1.04-1.08; absolute rate difference 24 per 100,000 person-years). Strength of association increased with time since psoriasis diagnosis (e.g. aHR 0.99, 0.96-1.03 within 0 to 5 years; 1.20, 1.05-1.37 within 20 to 25 years). The association was stronger for vascular dementia (aHR 1.10, 1.06-1.14) than Alzheimer's dementia (aHR 1.03, 1.00-1.06). Hazard ratios were larger for severe psoriasis (all-cause aHR 1.32, 1.25-1.39; vascular aHR 1.58, 1.44-1.74; Alzheimer's aHR 1.11, 1.02-1.21)., Interpretation: Long-term risk of all-cause dementia and vascular dementia, but not Alzheimer's dementia, was slightly higher in people with psoriasis, but absolute risk differences were small. Risks were more substantially raised with time since psoriasis diagnosis and in severe psoriasis compared to mild to moderate psoriasis, suggesting a potential dose-response relationship., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Although drug interactions between clarithromycin/erythromycin/fluconazole and direct oral anticoagulants (DOACs) are mechanistically plausible, it is uncertain whether they are clinically relevant., Objective: This study aims to investigate the association among coprescribed DOACs and antimicrobials and bleeding, cardiovascular disease and mortality., Methods: We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011 to March 29, 2021. We used a cohort design to estimate hazard ratios (HRs) for bleeding outcomes (intracranial bleeding, gastrointestinal bleeding, other bleeding), comparing DOACs + clarithromycin/erythromycin/fluconazole users with DOACs users not receiving these antimicrobials. Cardiovascular outcomes were ischaemic stroke, myocardial infarction, venous thromboembolism, cardiovascular mortality, and all-cause mortality. A 6-parameter case-crossover design comparing odds of exposure with different drug initiation patterns for all outcomes in hazard window vs referent window within an individual was also conducted., Results: Of 483,815 DOAC users, we identified 21,701 coprescribed clarithromycin, 4532 coprescribed erythromycin, and 4840 coprescribed fluconazole. We observed an increased risk of gastrointestinal bleeding over 7 days following coprescription of DOAC + erythromycin vs DOAC alone (HR 3.66; 99% confidence interval [CI] 1.27-10.51), with wide CIs in case-crossover analysis. No evidence of increased risk of bleeding outcomes was seen for DOAC + clarithromycin/fluconazole in cohort and case-crossover analyses. For cardiovascular outcomes, compared with DOAC alone, an increased risk of cardiovascular mortality with DOAC + clarithromycin (HR 3.36; 99% CI 1.73-6.52) and increased risk of all-cause mortality with DOAC + clarithromycin/erythromycin/fluconazole were observed in cohort analysis. However, similar risks were found when initiating erythromycin/fluconazole with and without DOACs., Conclusion: We found no strong evidence of increased risks of bleeding and cardiovascular outcomes in DOACs + clarithromycin/fluconazole/erythromycin users except a possible short-term increased risk of gastrointestinal bleeding in DOACs + erythromycin users., Competing Interests: Disclosures Dr Douglas has received research grants from GSK and AstraZeneca and holds shares in GSK. Dr Wong has received honoraria from the 6th Annual Meeting of the Society for Clinical Epidemiology in Tokyo and 28th Annual Meeting of the Japanese Society for Pharmacoepidemiology in Kyoto in November 2023, outside the submitted work. The other authors have no conflicts of interest to disclose., (Copyright © 2025 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Maternal mental illness (MMI) affects almost a quarter of mothers and may impact a child's development and physical health. It remains unclear whether MMI is associated with altered utilization of vaccination services. Understanding this association could help to identify families in need of additional support., Methods: Using primary care data from England, we conducted a historical cohort study of 397,519 children born in England between 2006 and 2014 with linked maternal records. Associations between different types of MMI (common mental disorders, severe mental illness and alcohol and substance use disorder) with childhood immunisation were explored using logistic regression for differences in coverage and accelerated failure time models for differences in timeliness before the child's fifth birthday., Results: While there were no differences in vaccination coverage at the age of one, children of mothers with common mental disorders had lower odds of being vaccinated at the ages of two (OR 0.95, 95 %CI: 0.93-0.98) and five (OR 0.86, 95 % CI 0.84-0.89) in comparison to children of mothers with no record of MMI. Vaccination coverage was even lower for children of mothers with comorbid substance disorder and common mental disorder (OR 0.70, 95 % CI: 0.62-0.78 at the age of five). There were no significant differences in timeliness of vaccine receipt by MMI., Conclusions: Inequalities in vaccination coverage associated with MMI grow with increasing age of the child. Extending support services for women with MMI beyond the child's first year of life could offer potential to improve vaccination uptake and reduce childhood infections., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clinicians and people with narcolepsy report varied access to higher-cost narcolepsy treatments in England associated with variations in national and local commissioning. There are no publicly available data quantifying use of these drugs to support policy decisions. We therefore aimed to describe national, regional and local prescribing trends for higher-cost narcolepsy drugs using new national databases. We used the English prescribing dataset and secondary care medicines data to quantify volumes of high-cost narcolepsy drugs issued between 01 January 2019 and 31 December 2022. Volumes were converted to World Health Organisation defined daily doses, to estimate the monthly number of defined daily doses of sodium oxybate, pitolisant and solriamfetol issued by each integrated care board and region. We compared national, integrated care board, and regional level issuance of each drug over time. Analysis of almost 6000 primary care prescriptions and 2000 cumulative months of secondary care pharmacy stock data, issued across 41/42 integrated care boards in England, revealed a 49.1% increase in issuance of high-cost narcolepsy drugs between 2019 and 2022. In 2022, sodium oxybate accounted for 52.66% of issuance, pitolisant 43.09% and solriamfetol 4.25%, with 22.31% of defined daily doses issued in primary care. Three integrated care boards (NHS Southeast London, NHS Cumbria and North-East, NHS Cheshire and Merseyside) predominate, issuing 56.33% of all defined daily doses. Variations between integrated care boards and regions differ substantially by drug and route of issuance. Our findings describe substantial variation in the use of specialist narcolepsy drugs in England, and highlight the untapped potential of using large, public domain datasets to publicly review higher-cost drug prescribing., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: Direct oral anticoagulants (DOACs) are commonly co-prescribed with amiodarone/diltiazem/verapamil, but whether there is a drug interaction between these drugs is unclear., Objective: The purpose of this study was to investigate the risk of clinical outcomes associated with concomitant use of DOACs and amiodarone/diltiazem/verapamil., Methods: We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011, to December 31, 2019. We used a cohort design to estimate hazard ratios for ischemic stroke, myocardial infarction, venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, other bleeding, cardiovascular mortality, and all-cause mortality, comparing DOACs + amiodarone/diltiazem/verapamil users and DOACs + beta-blocker users. A case-crossover design comparing odds of exposure to different drug initiation patterns for all outcomes in hazard window vs referent window within an individual also was conducted., Results: Of 397,459 DOAC users, we included 9075 co-prescribed amiodarone, 9612 co-prescribed diltiazem, and 2907 co-prescribed verapamil. There was no difference in risk of any outcomes between DOACs + amiodarone/diltiazem/verapamil users vs DOACs + beta-blocker users in the cohort design. However, in the case-crossover design, we observed an odds ratio (OR) of 2.09 (99% confidence interval [CI] 1.37-3.18) for all-cause mortality associated with initiation of a DOAC while taking amiodarone, which was greater than that observed for DOAC monotherapy (OR 1.30; 99% CI 1.25-1.35). Similar findings were observed for cardiovascular mortality and all-cause mortality respectively with diltiazem., Conclusion: Our study showed no evidence of higher bleeding or cardiovascular risk associated with co-prescribed DOACs and amiodarone, diltiazem, or verapamil. Elevated risks of cardiovascular and all-cause mortality were only observed during DOAC initiation when diltiazem/amiodarone were being taken., Competing Interests: Disclosures Dr Douglas has received research grants GlaxoSmithKline (GSK) and AstraZeneca; and holds shares in GSK. Dr Warren-Gash participated in a Data Safety Monitoring Board for an investigator-led trial of the effect of influenza vaccination after heart attack on future cardiovascular prognosis (NCT02831608) from January 2019 to April 2020. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants (DOACs) are commonly co-prescribed with statins. Although biologically plausible, whether there is a drug interaction between DOACs and atorvastatin/simvastatin is unclear., Aim: To investigate the association between co-prescribed DOACs and atorvastatin/simvastatin and bleeding, cardiovascular disease and mortality., Design and Setting: Clinical Practice Research Datalink Aurum(1/1/2011-31/12/2019)., Method: We used a cohort design to estimate hazard ratios for clinically relevant pharmacological interaction safety outcomes (intracranial bleeding, gastrointestinal bleeding, other bleeding) comparing DOACs+atorvastatin/simvastatin with DOACs+other statins (fluvastatin, pravastatin and rosuvastatin which are not anticipated to interact with DOACs). Effectiveness outcomes (ischaemic stroke, myocardial infarction, venous thromboembolism, cardiovascular mortality, and all-cause mortality) were also included. A case-crossover design comparing odds of exposure to different drug initiation patterns in hazard window versus referent window within an individual was also conducted., Results: Of 397,459 DOAC users, we selected 70,318 people co-prescribed atorvastatin, and 38,724 co-prescribed simvastatin. The cohort analysis showed no difference in risk of all outcomes comparing DOACs+atorvastatin/simvastatin versus DOACs+other statins. In case-crossover analysis, ORs for other bleeding (OR:4.04; 99%CI:3.07-5.31) amongst those initiating DOACs while taking atorvastatin, and the ORs for gastrointestinal bleeding (OR:5.16; 99%CI:3.66-7.28) and other bleeding (OR:5.12; 99%CI:3.61-7.26) amongst those initiating DOACs while taking simvastatin were greater than those initiating DOAC monotherapy. Similar patterns were also observed for cardiovascular mortality and all-cause mortality., Conclusion: This study shows no evidence of interaction between DOACs and atorvastatin/simvastatin. However, people starting a DOAC whilst taking atorvastatin/simvastatin, were at high risk of bleeding and mortality, likely due to temporal clinical vulnerability., (Copyright © 2024, The Authors.)

Infections, particularly those involving the respiratory tract, are associated with an increased incidence of cardiovascular events, both de novo and as exacerbations of pre-existing cardiovascular diseases. Influenza vaccination has consistently been shown to reduce the incidence of cardiovascular events. Nonetheless, vaccination rates among adults remain suboptimal, both in the general population and among high-risk individuals. Multiple barriers hinder achieving adequate vaccination rates, with physicians' beliefs and attitudes towards these interventions being crucial. The FLUence project was developed within the framework of the World Heart Federation's Emerging Leaders program, to address this issue. This project has two phases: a global quantitative survey to assess the perceptions, opinions, and attitudes and challenges of physicians worldwide regarding the safety and efficacy of the influenza vaccination use, and a qualitative survey to further investigate the barriers and facilitators of recommending and using this vaccination. The quantitative survey was created and disseminated in five languages (English, Spanish, French, Italian, and Portuguese) to physicians of all specialties who care for adults, with a particular focus on patients with cardiovascular disease. The survey included eight domains with a total of 36 questions with closed options; a Likert scale with five possible answers was used to gauge participants' opinions. To gain deeper insights into the complexities behind the low vaccination rates in adults, the second part of the project comprises a qualitative survey, conducted in the two lower-middle- and upper-middle-income countries: India and Argentina, respectively. These countries were selected because patients with cardiovascular diseases have access to free influenza vaccination in Argentina, whereas patients must pay for the vaccine out of pocket in India. Thus, the FLUence study will provide valuable information to better understand the perceptions and barriers to improving influenza vaccination rates from the perspective of physicians. It is imperative to actively engage all healthcare providers to improve influenza vaccination rates., Competing Interests: SGZ has conducted academic activities with Bayer, Sanofi Pasteur, Seqirus, and GlaxoSmith Kline; no external financial support has been related to this project. The other authors have nothing to declare., (Copyright: © 2024 The Author(s).)

Objectives: To examine the impact of the COVID-19 pandemic on deprivation-related inequalities in hospitalisations for cardiovascular disease (CVD) conditions in Denmark and England between March 2018 and December 2021., Design: Time-series studies in England and Denmark., Setting: With the approval of National Health Service England, we used English primary care electronic health records, linked to secondary care and death registry data through the OpenSAFELY platform and nationwide Danish health registry data., Participants: We included adults aged 18 and over without missing age, sex or deprivation information. On 1 March 2020, 16 234 700 people in England and 4 491 336 people in Denmark met the inclusion criteria., Primary Outcome Measures: Hospital admissions with the primary reason for myocardial infarction (MI), ischaemic or haemorrhagic stroke, heart failure and venous thromboembolism (VTE)., Results: We saw deprivation gradients in monthly CVD hospitalisations in both countries, with differences more pronounced in Denmark. Based on pre-pandemic trends, in England, there were an estimated 2608 fewer admissions than expected for heart failure in the most deprived quintile during the pandemic compared with an estimated 979 fewer admissions in the least deprived quintile. For all other outcomes, there was little variation by deprivation quintile. In Denmark, there were an estimated 1013 fewer admissions than expected over the pandemic for MI in the most deprived quintile compared with 619 in the least deprived quintile. Similar trends were seen for stroke and VTE, though absolute numbers were smaller. Heart failure admissions were similar to pre-pandemic levels with little variation by deprivation quintile., Conclusions: Overall, we did not find that the pandemic substantially worsened pre-existing deprivation-related differences in CVD hospitalisations, though there were exceptions in both countries., Competing Interests: Competing interests: REC has personal shares in AstraZeneca (AZ) unrelated to this work. BM is also employed by National Health Service ( NHS) England (all declarations are openly available at: https://www.whopaysthisdoctor.org/doctor/491/active ). JH has grant funding from UKRI and the Wellcome Trust, has a patent with Juli Health unrelated to this work and has received consultancy fees from Juli Health and the Wellcome Trust unrelated to this work. RM is supported by Barts Charity (MGU0504), receives salary contributions from Genes & Health and has received consultancy fees from Amgen. JKQ has grants from MRC, HDR UK, GlaxoSmithKline (GSK), BI, Asthma + Lung UK and AZ and has received fees from GSK, Evidera, AZ and Insmed. SL was co-founder and co-chair of the RECORD steering committee and has a leadership role at Health Data Research UK. KM has received consultancy fees from Amgen. LAT has grant funding from MRC, the Wellcome Trust, has consulted for Bayer and is on the MHRA expert advisory group (Women’s health) and is a member of four non-industry funded trial advisory committees (unpaid). AYSW is funded by British Heart Foundation (FS/19/19/34175) and AIR@InnoHK administered by Innovation and Technology Commission. AM has received consultancy fees from induction health and is a member of RCGP health informatics group and the NHS Digital GP data Professional Advisory Group. Department of Clinical Epidemiology, Aarhus University, receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies have any relation to the present study. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD)., Methods: Using national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions., Results: Hospitalization and mortality were 15.3% and 2.0% among 17,373,850 individuals with COVID-19 (LC rate 1.3%), and 16.8% and 1.4% among 301,115 with LC. Adjusted risk of mortality and hospitalization were reduced with COVID-19 vaccination ≥ 2 doses(COVID-19:HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalization (COVID-19:0.86 and 1.01, and LC:0.72 and 1.05). Mortality and hospitalization were reduced by CVD prevention in those with CVD, e.g., anticoagulants- COVID:19:0.69 and 0.92; LC:0.59 and 0.88; lipid lowering- COVID-19:0.69 and 0.86; LC:0.68 and 0.90. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively., Interpretation: Prior CVD and high CV risk are associated with increased hospitalization and mortality in COVID-19 and LC. Targeted COVID-19 vaccination and CVD prevention are priority interventions., Funding: NIHR. HDR UK., Competing Interests: Declarations of competing interest KK is chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and is a member of SAGE. KK (Chair) and AB are members of the LC Research Group that reports to the Chief Medical Officer for England. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Routinely collected electronic health records (EHR) offer a valuable opportunity to carry out research on immunization uptake, effectiveness, and safety, using large and representative samples of the population. In contrast to other drugs, vaccines do not require electronic prescription in many settings, which may lead to ambiguous coding of vaccination status and timing., Methodology: We propose a comprehensive algorithm to identifying childhood immunizations in routinely collected EHR. In order to deal with ambiguous coding, over-recording, and backdating in EHR, we suggest an approach combining a wide range of medical codes in combination to identify vaccination events and using appropriate wash-out periods and quality checks. We illustrate this approach on a cohort of children born between 2006 and 2014 followed up to the age of five in the Clinical Practice Research Datalink (CPRD) Aurum, a UK primary care dataset of EHR, and validate the results against national estimates of vaccine coverage by NHS Digital and Public Health England., Results: Our algorithm reproduced estimates of vaccination coverage, which are comparable to official national estimates and allows to approximate the age at vaccination. Electronic prescription data only do not cover vaccination events sufficiently., Conclusion: Our new proposed method could be used to provide a more accurate estimation of vaccination coverage and timing of vaccination for researchers and policymakers using EHR. As with all observational research using real-world data, it is important that researchers understand the context of the used dataset used and the clinical practice of recording., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: The role of children and staff in SARS-CoV-2 transmission outside and within households is still not fully understood when large numbers are in regular, frequent contact in schools., Methods: We used the self-controlled case-series method during the alpha- and delta-dominant periods to explore the incidence of infection in periods around a household member infection, relative to periods without household infection, in a cohort of primary and secondary English schoolchildren and staff from November 2020 to July 2021., Results: We found the relative incidence of infection in students and staff was highest in the 1-7 days following household infection, remaining high up to 14 days after, with risk also elevated in the 6--12 days before household infection. Younger students had a higher relative incidence following household infection, suggesting household transmission may play a more prominent role compared with older students. The relative incidence was also higher among students in the alpha variant dominant period., Conclusions: This analysis suggests SARS-CoV2 infection in children, young people and staff at English schools were more likely to be associated with within-household transmission than from outside the household, but that a small increased risk of seeding from outside is observed., (© The Author(s) 2024; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: The symptom profiles of acute SARS-CoV-2 infection and long-COVID in children and young people (CYP), risk factors, and associated healthcare needs, are poorly defined. The Schools Infection Survey 1 (SIS-1) was a nationwide study of SARS-CoV-2 infection in primary and secondary schools in England during the 2020/21 school year. The Covid-19 Mapping and Mitigation in Schools (CoMMinS) study was conducted in schools in the Bristol area over a similar period. Both studies conducted testing to identify current and previous SARS-CoV-2 infection, and recorded symptoms and school attendance. These research data have been linked to routine electronic health record (EHR) data., Aims: To better understand the short- and long-term consequences of SARS-CoV-2 infection, and their risk factors, in CYP., Methods: Retrospective cohort and nested case-control analyses will be conducted for SIS-1 and CoMMinS data linked to EHR data for the association between (1) acute symptomatic SARS-CoV-2 infection and risk factors; (2) SARS-CoV-2 infection and long-term effects on health: (a) persistent symptoms; (b) any new diagnosis; (c) a new prescription in primary care; (d) health service attendance; (e) a high rate of school absence., Results: Our study will improve understanding of long-COVID in CYP by characterising the trajectory of long-COVID in CYP in terms of things like symptoms and diagnoses of conditions. The research will inform which groups of CYP are more likely to get acute- and long-term outcomes of SARS-CoV-2 infection, and patterns of related healthcare-seeking behaviour, relevant for healthcare service planning. Digested information will be produced for affected families, doctors, schools, and the public, as appropriate., Conclusion: Linked SIS-1 and CoMMinS data represent a unique and rich resource for understanding the impact of SARS-CoV-2 infection on children's health, benefiting from enhanced SARS-CoV-2 testing and ability to assess a wide range of outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Looker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Telomeres are a measure of cellular ageing with potential links to diseases such as cardiovascular diseases and cancer. Studies have shown that some infections may be associated with telomere shortening, but whether an association exists across all types and severities of infections and in which populations is unclear. Therefore we aim to collate available evidence to enable comparison and to inform future research in this field., Methods and Analysis: We will search for studies involving telomere length and infection in various databases including MEDLINE (Ovid interface), EMBASE (Ovid interface), Web of Science, Scopus, Global Health and the Cochrane Library. For grey literature, the British Library of electronic theses databases (ETHOS) will be explored. We will not limit by study type, geographical location, infection type or method of outcome measurement. Two researchers will independently carry out study selection, data extraction and risk of bias assessment using the ROB2 and ROBINS-E tools. The overall quality of the studies will be determined using the Grading of Recommendations Assessment, Development and Evaluation criteria. We will also evaluate study heterogeneity with respect to study design, exposure and outcome measurement and if there is sufficient homogeneity, a meta-analysis will be conducted. Otherwise, we will provide a narrative synthesis with results grouped by exposure category and study design., Ethics and Dissemination: The present study does not require ethical approval. Results will be disseminated via publishing in a peer-reviewed journal and conference presentations., Prospero Registration Number: CRD42023444854., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: We aimed to investigate associations between common infections and neuroimaging markers of dementia risk (brain volume, hippocampal volume, white matter lesions) across three population-based studies., Methods: We tested associations between serology measures (pathogen serostatus, cumulative burden, continuous antibody responses) and outcomes using linear regression, including adjustments for total intracranial volume and scanner/clinic information (basic model), age, sex, ethnicity, education, socioeconomic position, alcohol, body mass index, and smoking (fully adjusted model). Interactions between serology measures and apolipoprotein E (APOE) genotype were tested. Findings were meta-analyzed across cohorts (N main  = 2632; N APOE-interaction  = 1810)., Results: Seropositivity to John Cunningham virus associated with smaller brain volumes in basic models (β = -3.89 mL [-5.81, -1.97], P adjusted  < 0.05); these were largely attenuated in fully adjusted models (β = -1.59 mL [-3.55, 0.36], P = 0.11). No other relationships were robust to multiple testing corrections and sensitivity analyses, but several suggestive associations were observed., Discussion: We did not find clear evidence for relationships between common infections and markers of dementia risk. Some suggestive findings warrant testing for replication., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: For signal detection studies investigating either drug safety or method evaluation, the choice of drug-outcome pairs needs to be tailored to the planned study design and vice versa. While this is well understood in hypothesis-testing epidemiology, it should be as important in signal detection, but this has not widely been considered. There is a need for a taxonomy framework to provide guidance and a systematic reproducible approach to the selection of appropriate drugs and outcomes for signal detection studies either investigating drug safety or assessing method performance using real-world data., Objective: The aim was to design a general framework for the selection of appropriate drugs and outcomes for signal detection studies given a study design of interest. As a motivating example, we illustrate how the framework is applied to build a reference set for a study aiming to assess the performance of the self-controlled case series with active comparators., Methods: We reviewed criteria presented in two published studies which aimed to provide practical advice for choosing the appropriate signal evaluation methodology, and assessed their relevance for signal detection. Further characteristics specific to signal detection were added. The final framework is based on: the application of study design requirements, the database(s) of interest, and the clinical importance of the drug(s) and outcome(s) under consideration. This structure was applied by selecting drug-outcome pairs as a reference set (i.e. list of drug-outcome pairs classified as positive or negative controls) for which the method is expected to work well for a signal detection study aiming to assess the performance of self-controlled case series. Eight criteria were used, related to the application of self-controlled case series assumptions, choice of active comparators, coverage in the database of interest and clinical importance of the outcomes., Results: After application of the framework, two classes of antibiotics (seven drugs) were selected for the study, and 28 outcomes from all organ classes were chosen from the drug labels, out of the 273 investigated. In total, this corresponds to 104 positive controls (drug-outcome pairs) and 58 negative controls., Conclusions: We proposed and applied a framework for the selection of drugs and outcomes for both drug safety signal detection and method assessment used in signal detection to optimise their performance given a study design. This framework will eliminate part of the bias relating to drugs and outcomes not being suited to the method or database. The main difficulty lies in the choice of the criteria and their application to ensure systematic selection, especially as some information remains unknown in signal detection, and clinical judgement was needed on occasions. The same framework could be adapted for other methods., (© 2023. The Author(s).)

Background: Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear., Objective: The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs., Methods: We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes., Results: Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years (interquartile range [IQR 61.4-75.7]); 94% male; median follow-up 4.2 years [IQR 1.9-6.6]), HZ was not associated with an increased risk of incident PD overall (adjusted HR 0.95, 95% CI 0.90-1.01) or in any sensitivity analyses., Conclusion: We found no evidence that HZ was associated with increased risk of incident PD in this cohort. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Introduction: 4.2 million individuals in the UK have type 2 diabetes, a known risk factor for dementia and mild cognitive impairment (MCI). Diabetes treatment may modify this association, but existing evidence is conflicting. We therefore aimed to assess the association between metformin therapy and risk of incident all-cause dementia or MCI compared with other oral glucose-lowering therapies (GLTs)., Research Design and Methods: We conducted an observational cohort study using the Clinical Practice Research Datalink among UK adults diagnosed with diabetes at ≥40 years between 1990 and 2019. We used an active comparator new user design to compare risks of dementia and MCI among individuals initially prescribed metformin versus an alternative oral GLT using Cox proportional hazards regression controlling for sociodemographic, lifestyle and clinical confounders. We assessed for interaction by age and sex. Sensitivity analyses included an as-treated analysis to mitigate potential exposure misclassification., Results: We included 211 396 individuals (median age 63 years; 42.8% female), of whom 179 333 (84.8%) initiated on metformin therapy. Over median follow-up of 5.4 years, metformin use was associated with a lower risk of dementia (adjusted HR (aHR) 0.86 (95% CI 0.79 to 0.94)) and MCI (aHR 0.92 (95% CI 0.86 to 0.99)). Metformin users aged under 80 years had a lower dementia risk (aHR 0.77 (95% CI 0.68 to 0.85)), which was not observed for those aged ≥80 years (aHR 0.95 (95% CI 0.87 to 1.05)). There was no interaction with sex. The as-treated analysis showed a reduced effect size compared with the main analysis (aHR 0.90 (95% CI 0.83 to 0.98))., Conclusions: Metformin use was associated with lower risks of incident dementia and MCI compared with alternative GLT among UK adults with diabetes. While our findings are consistent with a neuroprotective effect of metformin against dementia, further research is needed to reduce risks of confounding by indication and assess causality., Competing Interests: Competing interests: NC receives funds from AstraZeneca to serve on data safety and monitoring committees for clinical trials. R. Mathur is part of the Genes & Health Program, which is part-funded (including salary contributions) by a Life Sciences Consortium comprising AstraZeneca, Bristol-Myers Squibb Company, GlaxoSmithKline Research and Development Limited, Maze Therapeutics, Merck Sharp & Dohme, Novo Nordisk, Pfizer, and Takeda Development Center Americas. All other authors report no conflicts., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Vaccine surveillance for children in England focuses on coverage at ages 1, 2, and 5 years. Previous studies exploring vaccine timeliness have used different arbitrary categories to define whether vaccines were received 'late' or 'on time'. This paper aims to provide more detailed and holistic information on timing and patterns of vaccine uptake across the childhood immunisation schedule in England., Methods: We included all children born in England between 2006 and 2014 and registered in the Clinical Practice Research Datalink (CPRD) Aurum, a primary care electronic health record. We described vaccine uptake for representative antigens (pertussis, pneumococcus, measles) by age in days and stratified by ethnicity, region and birth cohort. Alluvial diagrams were used to illustrate common journeys through the vaccination schedule, and we applied survival analysis using accelerated failure time models (AFT) to predict age of vaccine receipt based on timing of previous doses., Results: 573,015 children were followed up until their fifth birthday, when they had 90.16 % coverage for two doses of measles, mumps, rubella (MMR) vaccine and 88.78% coverage for four doses of diphtheria, tetanus, pertussis (DTP) vaccine. Overall, the later the age at which a vaccine was due, the more delay in vaccination. Children of Black Ethnicity or from London showed deviating uptake patterns. If a child received their third DTP dose more than a year later than recommended, they would receive the next dose 2.7 times later than a child who was vaccinated on time. A smaller delay was found for children who did not receive first MMR dose on time., Discussion: We showed that the risk of vaccination delay increased with the age of the child and significant delay of previous doses. Primary care data can help to promptly identify children at higher risk of delayed vaccination., Competing Interests: Declaration of Competing Interest 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., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: 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., Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 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 March 23, 2020., Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults 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 the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences., Interpretation: Our study suggests that 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., Funding: LSHTM COVID-19 Response Grant (DONAT15912)., Competing Interests: SVK was co-chair of the Scottish Government's Expert Reference Group on Ethnicity and COVID-19 and a member of the Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity. RM and RME were members of the SAGE subgroup on ethnicity. REC has personal shares in AstraZeneca (AZ) unrelated to this work. BMK is also employed by NHS England (all declarations are openly available at: https://www.whopaysthisdoctor.org/doctor/491/active). JFH has grant funding from UKRI and the Wellcome Trust, has a patent with Juli Health unrelated to this work and has received consultancy fees from Juli Health and the Wellcome Trust unrelated to this work. RM is supported by Barts Charity (MGU0504), receives salary contributions from Genes & Health and has received consultancy fees from AMGEN. JKQ has grants from MRC, HDR UK, GlaxoSmithKline (GSK), BI, asthma + lung UK, and AZ and has received fees from GSK, Evidera, AZ and Insmed. SL was co-founder and co-chair of the RECORD steering committee and has a leadership role at Health Data Research UK. KM has received consultancy fees from AMGEN. LT has grant funding from MRC, the Wellcome Trust and is funded by an NIHR Research Professorship (NIHR302405), has consulted for Bayer and is on the MHRA expert advisory group (Women's health) and a member of 4 non-industry funded trial advisory committees (unpaid). All other authors declare no competing interests. AM has received consultancy fees from induction health and is a member of RCGP health informatics group and the NHS Digital GP data Professional Advisory Group., (© 2023 The Authors.)

Background: The excess risk of cardiovascular disease associated with a wide array of infectious diseases is unknown. We quantified the short- and long-term risk of major cardiovascular events in people with severe infection and estimated the population-attributable fraction., Methods: We analyzed data from 331 683 UK Biobank participants without cardiovascular disease at baseline (2006-2010) and replicated our main findings in an independent population from 3 prospective cohort studies comprising 271 329 community-dwelling participants from Finland (baseline 1986-2005). Cardiovascular risk factors were measured at baseline. We diagnosed infectious diseases (the exposure) and incident major cardiovascular events after infections, defined as myocardial infarction, cardiac death, or fatal or nonfatal stroke (the outcome) from linkage of participants to hospital and death registers. We computed adjusted hazard ratios (HRs) and 95% CIs for infectious diseases as short- and long-term risk factors for incident major cardiovascular events. We also calculated population-attributable fractions for long-term risk., Results: In the UK Biobank (mean follow-up, 11.6 years), 54 434 participants were hospitalized for an infection, and 11 649 had an incident major cardiovascular event at follow-up. Relative to participants with no record of infectious disease, those who were hospitalized experienced increased risk of major cardiovascular events, largely irrespective of the type of infection. This association was strongest during the first month after infection (HR, 7.87 [95% CI, 6.36-9.73]), but remained elevated during the entire follow-up (HR, 1.47 [95% CI, 1.40-1.54]). The findings were similar in the replication cohort (HR, 7.64 [95% CI, 5.82-10.03] during the first month; HR, 1.41 [95% CI, 1.34-1.48] during mean follow-up of 19.2 years). After controlling for traditional cardiovascular risk factors, the population-attributable fraction for severe infections and major cardiovascular events was 4.4% in the UK Biobank and 6.1% in the replication cohort., Conclusions: Infections severe enough to require hospital treatment were associated with increased risks for major cardiovascular disease events immediately after hospitalization. A small excess risk was also observed in the long-term, but residual confounding cannot be excluded., Competing Interests: Disclosures Dr Sipilä reports grant support during the conduct of the study from NordForsk (75021), Academy of Finland (311492 and 329202), Helsinki Institute of Life Science, Emil Aaltonen Foundation, and Finnish Medical Foundation. Dr Lindbohm reports grant support during the conduct of the study from the Academy of Finland (339568) and Päivikki and Sakari Sohlberg Foundation. Dr Batty reports grant support from the UK Medical Research Council (MR/P023444/1) and US National Institute on Aging (1R56AG052519-01 and 1R01AG052519-01A1). Dr Vahtera reports grant support from the Academy of Finland (321409 and 329240) and NordForsk (75021). Dr Nyberg reports grant support from NordForsk (75021). Dr Warren-Gash reports support from Wellcome Fellowship (201440/Z/16/Z). Dr Kivimäki reports grant support during the conduct of the study from NordForsk (75021), UK Medical Research Council (MRC S011676/1 and R024227/1), US National Institute on Aging (R01AG056477), Academy of Finland (329202 and 350426), Finnish Foundation for Cardiovascular Research (a86898), Finnish Work Environment Fund (190424), and Wellcome Trust (221854/Z/20/Z). The other authors report no conflicts.

Background: Both post-COVID-19 condition (long COVID) and the presence of persisting symptoms that do not meet formal definitions of post-COVID-19-condition may adversely affect quality of life and function. However, their prevalence among children and young people in England is unclear., Methods: We used data from repeated surveys in a large cohort of English schoolchildren from the COVID-19 Schools Infection Survey (SIS) for the school year 2021/22 to describe the weighted prevalence of post-COVID-19-condition and compare persisting symptoms between individuals with a positive SARS-CoV-2 test and those with neither a positive test history nor suspected infection., Results: Among 7797 children from 173 schools, 1.8% of primary school pupils (aged 4 to 11 years), 4.5% of secondary school pupils in years 7-11 (aged 11 to 16 years) and 6.9% of those in years 12-13 (aged 16 to 18 years) met a definition of post-COVID-19 condition in March 2022. Specific persisting symptoms such as anxiety or difficulty concentrating were frequently reported regardless of prior infection status and increased with age: 48.0% of primary school pupils, 52.9% of secondary school pupils in years 7-11 and 79.5% in years 12-13 reporting at least one symptom lasting more than 12 weeks. Persisting loss of smell and taste, cardiovascular and some systemic symptoms were more frequently reported by those with a previous positive test., Conclusions: We showed that ongoing symptoms were frequently reported by English schoolchildren regardless of SARS-CoV-2 test results and some specific symptoms such as loss of smell and taste were more prevalent in those with a positive test history. Our study emphasises the wide-ranging impacts of the COVID-19 pandemic on the health and wellbeing of children and young people., (© 2023. The Author(s).)

Background: While cardiovascular disease (CVD) is a risk factor for severe COVID-19, the association between predicted cardiovascular risk and severe COVID-19 among people without diagnosed CVD is unclear., Methods: We carried out historical, population-based cohort studies among adults aged 40-84 years in England using linked data from the Clinical Practice Research Datalink. Individuals were categorized into: existing CVD, raised cardiovascular risk (defined using QRISK3 score ≥10%) and low risk (QRISK3 score <10%) at 12/03/2020. We described incidence and severe outcomes of COVID-19 (deaths, intensive care unit [ICU] admissions, hospitalisations, major adverse cardiovascular events [MACE]) for each group. Among those with a COVID-19 record to 31/12/2020, we re-classified cardiovascular risk at infection and assessed the risk of severe outcomes using multivariable Cox regression with complete case analysis. We repeated analyses using hypertension to define raised cardiovascular risk., Findings: Among 6,059,055 individuals, 741,913 (12.2%) had established CVD, 1,929,627 (31.8%) had a QRISK3 score ≥10% and 3,387,515 (55.9%) had a QRISK3 score <10%. Marked gradients were seen in the incidence of all severe COVID-19 outcomes by cardiovascular risk profile. Among those with COVID-19 (N = 146,760), there was a strong association between raised QRISK3 score and death: adjusted hazard ratio [aHR] 8.77 (7.62-10.10), N = 97,725, which remained present, though attenuated in age-stratified results. Risks of other outcomes were also higher among those with raised QRISK3 score: aHR 3.66 (3.18-4.21) for ICU admissions, 3.38 (3.22-3.56) for hospitalisations, 5.43 (4.44-6.64) for MACE. When raised cardiovascular risk was redefined by hypertension status, only the association with MACE remained: aHR 1.49 (1.20-1.85), N = 57,264., Interpretation: Individuals without pre-existing CVD but with raised cardiovascular risk (by QRISK3 score) were more likely to experience severe COVID-19 outcomes and should be prioritised for prevention and treatment. Addressing cardiovascular risk factors could improve COVID-19 outcomes., Funding: BMA Foundation for Medical Research/Rosetrees Trust, Wellcome, BHF., Competing Interests: CWG reports participation in the data safety and monitoring board for the IAMI trial of influenza vaccine for cardiovascular disease (NCT02831608) ending April 2020. JB reports consulting fees from ARCbio, HVivo and GSK and participation in a data safety and monitoring board for the COM Cov trial, Oxford, now ended. AB reports grants from NIHR, AstraZeneca and the British Medical Association and leadership roles as Vice-President, Digital, Marketing, Communications for the British Cardiovascular Society and Senior Advisor to the Emerging Leaders Programme of the World Heart Federation. All other authors report no conflicts., (© 2023 The Authors.)

Objectives: Investigate risk factors for SARS-CoV-2 infections in school students and staff., Methods: In the 2020/2021 school year, we administered polymerase chain reaction, antibody tests, and questionnaires to a sample of primary and secondary school students and staff, with data linkage to COVID-19 surveillance. We fitted logistic regression models to identify the factors associated with infection., Results: We included 6799 students and 5090 staff in the autumn and 11,952 students and 4569 staff in the spring/summer terms. Infections in students in autumn 2020 were related to the percentage of students eligible for free school meals. We found no statistical association between infection risk in primary and secondary schools and reported contact patterns between students and staff in either period in our study. Using public transports was associated with increased risk in autumn in students (adjusted odds ratio = 1.72; 95% confidence interval 1.31-2.25) and staff. One or more infections in the same household during either period was the strongest risk factor for infection in students and more so among staff., Conclusion: Deprivation, community, and household factors were more strongly associated with infection than contacts patterns at school; this suggests that the additional school-based mitigation measures in England in 2020/2021 likely helped reduce transmission risk in schools., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Previous studies show a reduced incidence of first myocardial infarction and stroke 1-3 months after influenza vaccination, but it is unclear how underlying cardiovascular risk impacts the association., Methods and Results: The study used linked Clinical Practice Research Datalink, Hospital Episode Statistics Admitted Patient Care and Office for National Statistics mortality data from England between 1 September 2008 and 31 August 2019. From the data, individuals aged 40-84 years with a first acute cardiovascular event and influenza vaccination occurring within 12 months of each September were selected. Using a self-controlled case series analysis, season-adjusted cardiovascular risk stratified incidence ratios (IRs) for cardiovascular events after vaccination compared with baseline time before and >120 days after vaccination were generated. 193 900 individuals with a first acute cardiovascular event and influenza vaccine were included. 105 539 had hypertension and 172 050 had a QRISK2 score ≥10%. In main analysis, acute cardiovascular event risk was reduced in the 15-28 days after vaccination [IR 0.72 (95% CI 0.70-0.74)] and, while the effect size tapered, remained reduced to 91-120 days after vaccination [0.83 (0.81-0.88)]. Reduced cardiovascular events were seen after vaccination among individuals of all age groups and with raised and low cardiovascular risk., Conclusions: Influenza vaccine may offer cardiovascular benefit among individuals at varying cardiovascular risk. Further studies are needed to characterize the populations who could derive the most cardiovascular benefits from vaccination., Competing Interests: Conflict of interest: A.B. has received grants from Astra Zeneca, UK Research and Innovation (UKRI), British Medical Association and the NIHR. C.W.-G. has received speaker fees from Sanofi Pasteur and participated in a Data Safety Monitoring Board for an investigator-led trial of the effect of influenza vaccination after heart attack on future cardiovascular prognosis (NCT02831608) from January 2019 to April 2020. H.I.M is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation was an invited expert to the Commission on Human Medicines (CHM) COVID-19 Vaccine Safety Surveillance Methodologies Expert Working Group. I.D. has received unrestricted research grants from Glaxo Smith Kline. C.L. has received lecturer fees from Astra Zeneca and participated in a Data Safety Monitoring Board for the Université de Clermont-Ferrand (NCT03892148). J.A.D is funded by the British Heart Foundation through the grant received by C.W.-G. E.H. is funded by a NIHR postdoctoral fellowship. All other authors declare no competing interests., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Viral respiratory infections (VRIs) are common and are occupational risks for healthcare personnel (HCP). VRIs can also be acquired at home and other settings among HCPs. We sought to determine if preschool-aged household contacts are a risk factor for VRIs among HCPs working in outpatient settings., Methods: We conducted a secondary analysis of data from a cluster randomized trial at 7 medical centers in the United States over 4 influenza seasons from 2011-2012 to 2014-2015. Adult HCPs who routinely came within 6 feet of patients with respiratory infections were included. Participants were tested for respiratory viruses whenever symptomatic and at 2 random times each season when asymptomatic. The exposure of interest was the number of household contacts 0-5 years old (preschool-aged) at the beginning of each HCP-season. The primary outcome was the rate of polymerase chain reaction-detected VRIs, regardless of symptoms. The VRI incidence rate ratio (IRR) was calculated using a mixed-effects Poisson regression model that accounted for clustering at the clinic level., Results: Among the 4476 HCP-seasons, most HCPs were female (85.4%) and between 30 and 49 years of age (54.6%). The overall VRI rate was 2.04 per 100 person-weeks. In the adjusted analysis, HCPs having 1 (IRR, 1.22 [95% confidence interval {CI}, 1.05-1.43]) and ≥2 (IRR, 1.35 [95% CI, 1.09-1.67]) preschool-aged household contacts had higher VRI rates than those with zero preschool-aged household contacts., Conclusions: Preschool-aged household contacts are a risk factor for developing VRIs among HCPs working in outpatient settings., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Vaccination is an essential public health intervention to reduce morbidity and mortality from infectious diseases. Despite being at higher at risk of infectious diseases, health inequalities towards vaccine uptake in people with mental health issues have not been systematically appraised., Methods: We searched 7 databases from 1994 to 26/03/2021. We included all studies with a relative measure of effect comparing a group with a mental health issue to a control group. All studies covering any mental health issue were eligible with no constraints to study population, vaccine type or region, provided in a high-income country for comparability of health care systems. The study outcomes were synthesised by study population, mental health issue and type of vaccine., Results: From 4,069 titles, 23 eligible studies from 12 different countries were identified, focusing on adults (n = 13) or children (n = 4) with mental health issues, siblings of children with mental health issues (n = 2), and mothers with mental health issue and vaccine uptake in their children (n = 6). Most studies focused on depression (n = 12), autism, anxiety, or alcoholism (n = 4 respectively). Many studies were at high risk of selection bias., Discussion: Mental health issues were associated with considerably lower vaccine uptake in some contexts such as substance use disorder, but findings were heterogeneous overall and by age, mental health issue or types of vaccine. Only individuals with mental health issues and physical comorbidities had consistently higher uptake in comparison to other adults. Mental health should be considered as a health inequality for vaccine uptake but more context specific research is needed focusing more on specific mental health issues and subgroups of the population to understand who misses vaccination and why., (© 2023. The Author(s).)