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Sara Hatam,1,* Sean Timothy Scully,2,* Sarah Cook,3,* Hywel T Evans,2,* Alastair Hume,4 Constantinos Kallis,3 Ian Farr,2 Chris Orton,2 Aziz Sheikh,1 Jennifer K Quint3 1Usher Institute, The University of Edinburgh, Edinburgh, UK; 2Population Data Science, Swansea University Medical School, Swansea, UK; 3School of Public Health, Imperial College London, London, UK; 4EPCC, The University of Edinburgh, Edinburgh, UK*These authors contributed equally to this workCorrespondence: Jennifer K Quint, Email j.quint@imperial.ac.ukBackground: Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations.Methods and Results: We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons.Conclusion: Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.Keywords: COPD, asthma, ILD, HER, harmonisation, data curation

Constantinos Kallis,1– 3 Amit Kaura,1,3 Nathan A Samuel,4 Abdulrahim Mulla,3 Ben Glampson,3 Kevin O’Gallagher,5 Jim Davies,4 Dimitri Papadimitriou,3 Kerrie J Woods,4 Anoop D Shah,6,7 Bryan Williams,6,7 Folkert W Asselbergs,6,7 Erik K Mayer,3,8 Richard W Lee,1,9 Christopher Herbert,10 Stuart W Grant,11 Nick Curzen,12 Iain B Squire,13 Thomas Johnson,14 Ajay M Shah,15 Divaka Perera,5 Rajesh K Kharbanda,4 Riyaz S Patel,6 Keith M Channon,4 Jamil Mayet,1,3 Jennifer K Quint1– 3 1National Heart and Lung Institute, Imperial College London, London, UK; 2School of Public Health, Imperial College London, London, UK; 3NIHR Imperial Biomedical Research Centre, Imperial College London and Imperial College Healthcare NHS Trust, London, UK; 4NIHR Oxford Biomedical Research Centre, University of Oxford and Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 5NIHR King’s Biomedical Research Centre, King’s College London and King’s College Hospital NHS Foundation Trust, London, UK; 6NIHR University College London Biomedical Research Centre, University College London and University College London Hospitals NHS Foundation Trust, London, UK; 7Institute of Health Informatics, University College London, London, UK; 8Imperial Clinical Analytics, Research & Evaluation (iCARE) and Department of Surgery & Cancer, Imperial College London, London, UK; 9Early Diagnosis and Detection Centre, NIHR BRC at The Royal Marsden and Institute of Cancer Research, London, UK; 10NIHR Leeds Clinical Research Facility, Leeds Teaching Hospitals Trust and University of Leeds, Leeds, UK; 11NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust and the University of Manchester, Manchester, UK; 12NIHR Southampton Clinical Research Facility and Biomedical Research Centre, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK; 13NIHR Leicester Biomedical Research Centre, Glenfield Hospital, and Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; 14NIHR Bristol Biomedical Research Centre, University of Bristol and University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 15NIHR Guys & St Thomas’ Hospital Clinical Research Facility, King’s College Hospital, and King’s College London British Heart Foundation Centre of Excellence, London, UKCorrespondence: Jennifer K Quint, School of Public Health, Imperial College London, Floor 9, Sir Michael Uren Building, 86 Wood Ln, London, W12 0BZ, United Kingdom, Email j.quint@imperial.ac.ukBackground: No single biomarker currently risk stratifies chronic obstructive pulmonary disease (COPD) patients at the time of an exacerbation, though previous studies have suggested that patients with elevated troponin at exacerbation have worse outcomes. This study evaluated the relationship between peak cardiac troponin and subsequent major adverse cardiac events (MACE) including all-cause mortality and COPD hospital readmission, among patients admitted with COPD exacerbation.Methods: Data from five cross-regional hospitals in England were analysed using the National Institute of Health Research Health Informatics Collaborative (NIHR-HIC) acute coronary syndrome database (2008– 2017). People hospitalised with a COPD exacerbation were included, and peak troponin levels were standardised relative to the 99th percentile (upper limit of normal). We used Cox Proportional Hazard models adjusting for age, sex, laboratory results and clinical risk factors, and implemented logarithmic transformation (base-10 logarithm). The primary outcome was risk of MACE within 90 days from peak troponin measurement. Secondary outcome was risk of COPD readmission within 90 days from peak troponin measurement.Results: There were 2487 patients included. Of these, 377 (15.2%) patients had a MACE event and 203 (8.2%) were readmitted within 90 days from peak troponin measurement. A total of 1107 (44.5%) patients had an elevated troponin level. Of 1107 patients with elevated troponin at exacerbation, 256 (22.8%) had a MACE event and 101 (9.0%) a COPD readmission within 90 days from peak troponin measurement. Patients with troponin above the upper limit of normal had a higher risk of MACE (adjusted HR 2.20, 95% CI 1.75– 2.77) and COPD hospital readmission (adjusted HR 1.37, 95% CI 1.02– 1.83) when compared with patients without elevated troponin.Conclusion: An elevated troponin level at the time of COPD exacerbation may be a useful tool for predicting MACE in COPD patients. The relationship between degree of troponin elevation and risk of future events is complex and requires further investigation.Keywords: COPD, CVD, exacerbation

Constantinos Kallis,1 Rafael A Calvo,2 Bjorn Schuller,3 Jennifer K Quint1 1National Heart and Lung Institute, and School of Public Health, Imperial College London, London, UK; 2Dyson School of Engineering, Faculty of Engineering, Imperial College London, London, UK; 3Department of Computing, Faculty of Engineering, Imperial College London, London, UKCorrespondence: Jennifer K Quint, National Heart and Lung Institute and School of Public Health, Floor 9, Sir Michael Uren Building, 86 Wood Ln, London, W12 0BZ, United Kingdom, Email j.quint@imperial.ac.ukBackground: Improving accurate risk assessment of asthma exacerbations, and reduction via relevant behaviour change among people with asthma could save lives and reduce health care costs. We developed a simple personalised risk prediction model for asthma exacerbations using factors collected in routine healthcare data for use in a risk modelling feature for automated conversational systems.Methods: We used pseudonymised primary care electronic healthcare records from the Clinical Practice Research Datalink (CPRD) Aurum database in England. We combined variables for prediction of asthma exacerbations using logistic regression including age, gender, ethnicity, Index of Multiple Deprivation, geographical region and clinical variables related to asthma events.Results: We included 1,203,741 patients divided into three cohorts to implement temporal validation: 898,763 (74.7%) in the training sample, 226,754 (18.8%) in the testing sample and 78,224 (6.5%) in the validation sample. The Area under the ROC curve (AUC) for the full model was 0.72 and for the restricted model was 0.71. Using a cut-off point of 0.1, approximately 27 asthma reviews by clinicians per 100 patients would be prevented compared with a strategy that all patients are regarded as high risk. Compared with patients without an exacerbation, patients who exacerbated were older, more likely to be female, prescribed more SABA and ICS in the preceding 12 months, have history of GORD, COPD, anxiety, depression, live in very deprived areas and have more severe disease.Conclusion: Using information available from routinely collected electronic healthcare record data, we developed a model that has moderate ability to separate patients who had an asthma exacerbation within 3 months from their index date from patients who did not. When comparing this model with a simplified model with variables that can easily be self-reported through a WhatsApp chatbot, we have shown that the predictive performance of the model is not substantially different.Keywords: asthma, exacerbation, risk prediction, electronic healthcare records

Constantinos Kallis,1,2,&ast; Ann Morgan,1,2,&ast; Louise Fleming,1 Jennifer K Quint1,2 1National Heart and Lung Institute, Imperial College London, London, UK; 2School of Public Health, Imperial College London, London, UK&ast;These authors contributed equally to this workCorrespondence: Jennifer K Quint, National Heart and Lung Institute and School of Public Health, Imperial College London, Sir Michael Uren Building, White City Campus, Imperial College, London, UK, Tel +44 207 594 8821, Email j.quint@imperial.ac.ukBackground: Significant morbidity and mortality are associated with poor asthma control. The aim of this study was to determine factors associated with poor control and referral to specialist secondary care services.Methods: We used primary care data from the Clinical Practice Research Datalink Aurum (CPRD) linked with Hospital Episode Statistics (HES) records from 1st January 2007 to 31st December 2019. We selected patients aged 6– 17 years old. Poor control was defined as six or more prescriptions of short-acting beta-agonist (SABA) inhalers, two or more courses of oral corticosteroids (OCS), an Asthma Control test (ACT) or childhood ACT < 20, one hospital admission for asthma, or one visit to Accident & Emergency (A&E) department for asthma-related episodes in the 12 months following asthma diagnosis. Asthma severity was defined following GINA guidelines 2021.Results: About 17.6% of children aged between 6 and 17 years with active asthma had poor control. Severe asthma, eczema, food allergies, increased BMI and living in deprived areas were identified as risk factors for poor control. Among those with poor control, referral rates to specialist care were extremely low, only 2% overall. Those with severe asthma were three-times more likely to be referred than those with mild-to-moderate asthma [HRcrude = 4.04 (95% CI, 3.35– 4.87); HRadj = 2.72 (95% CI: 2.13– 3.49)]. Other factors associated with referral were food allergy and living in a more deprived area.Conclusion: Around 1 in 6 children and adolescents with active asthma are not achieving adequate control of their symptoms. Among the subset of 6– 17-year olds with poorly controlled asthma, timely referral for specialist advice in secondary care is rare, especially in those with so-called mild asthma who nevertheless are at significant risk for poor asthma outcomes.Keywords: asthma, poor control, referral to specialist

Few studies on resilience in young children model risk appropriately and test theory-led hypotheses about its moderation. This study addressed both issues. Our hypothesis was that for preschool children's emotional/behavioral adjustment in the face of contextual risk protective factors should be located in the cognitive domain. Data were from the first two sweeps of the UK's Millennium Cohort Study. The final study sample was 4,748 three-year-old children clustered in 1,549 Lower layer Super Output Areas in nine strata. Contextual risk was measured at both area (with the Index of Multiple Deprivation) and family (with proximal and distal adverse life events experienced) level. Moderator variables were parenting, verbal and non-verbal ability, developmental milestones, and temperament. Multivariate multilevel models-that allowed for correlated residuals at both individual and area level-and univariate multilevel models estimated risk effects on specific and broad psychopathology. At baseline, proximal family risk, distal family risk and area risk were all associated with broad psychopathology, although the most parsimonious was the proximal family risk model. The area risk/broad psychopathology association remained significant even after family risk was controlled but not after family level socioeconomic disadvantage was controlled. The cumulative family risk was more parsimonious than the specific family risks model. Non-verbal ability moderated the effect of proximal family risk on conduct and emotional problems, and developmental milestones moderated the effect of proximal family risk on conduct problems. The findings highlight the importance of modeling contextual risk appropriately and of locating in the cognitive domain factors that buffer its effect on young children's adjustment. [ABSTRACT FROM AUTHOR]

Background: Whether inhaled corticosteroids (ICSs) reduce major adverse cardiovascular events (MACEs) in people with chronic obstructive pulmonary disease (COPD) is debated., Objectives: To establish, within people with COPD, (1) whether ICS reduced MACE rates (acute coronary syndrome (ACS), heart failure (HF), ischaemic strokes or cardiovascular-specific death) compared with long-acting bronchodilators; and (2) whether drug class, incident usership or patient cardiovascular history influenced the ICS-MACE relationship., Methods: We conducted a cohort study including patients with COPD in England, using Clinical Practice Research Datalink Aurum data, linked with Hospital Episode Statistics and Office of National Statistics death data, between 1 January 2010 and 31 December 2019. We implemented Cox proportional hazard regressions, adjusting for time interactions or using propensity score-adjusted models, as necessary. Our exposures included prescriptions of any ICS (vs any long-acting bronchodilators) and triple therapy (vs combination long-acting bronchodilators), determined during the year prior to follow-up. The outcomes of interest were MACE collectively and individual MACE subtypes., Measurements and Main Results: Among 113 353 people with COPD (mean age 67.9 years old, 53.3% male), ICS prescription was not associated with MACE (adjusted HR (95% CI)=0.98 (0.95, 1.02), p=0.41) but was associated with reduced HF, specifically, until year 6 of follow-up (average adjusted HR (95% CI)=0.91 (0.86, 0.96), p<0.001). HF reduction was driven by the ICS group containing mometasone furoate, beclomethasone, budesonide or ciclesonide (HR (95% CI)=0.89 (0.84, 0.94), p<0.001). Incident ICS use was associated with increased ACS (HR (95% CI)=1.27 (1.09, 1.47), p<0.001) but was not sustained beyond incident use. There was no association between triple therapy and MACE. Results did not differ by cardiovascular history., Conclusions: ICS did not reduce MACE, except HF, likely by reducing misclassified COPD exacerbations., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/. AEI and CK have no conflicting interests to declare. HW has received grants from HDR UK and Biomedical Research Centre (BRC). JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, British Lung Foundation, IQVIA, Chiesi AZ, Insmed and Asthma UK. JKQ has received personal fees for advisory board participation or speaking fees from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Bayer and Insmed. This research was supported by the NIHR Imperial BRC., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Study Objectives: Obstructive sleep apnea (OSA) can induce excessive sleepiness, causing work-related injuries and low productivity. Most individuals with OSA in the United Kingdom are undiagnosed, and thus, theoretically, workplace screening, might by identifying these individuals improve both their individual health and overall productivity. However, the prevalence of OSA in different workplaces is unclear. This study aimed to estimate the prevalence of OSA by industries and occupations in England., Methods: The Health Survey for England 2019 dataset was combined with Sleep Heart Health Study dataset. We applied multiple imputation for the combined dataset to estimate OSA in the English population aged 40-64. We estimated the pooled prevalence of OSA by both industry and occupation by separating samples by Standard Industry Classification and Standard Occupation Classification., Results: The overall OSA prevalence estimated by imputation for ages 40-64 was 17.8% (95% CI = 15.9% to 19.9%). Separating those samples into industrial/occupational groups, the estimated prevalence of OSA varied widely by industry/occupation. Descriptive analysis revealed that the estimated prevalence of OSA was relatively higher in the Accommodation and food, Public administration and defence; compulsory social security, Construction industries, and Protective service occupations, health and social care associate professionals, and skilled construction and building trades occupations., Conclusions: In England in 2019, Accommodation and food, Public administration and defence; compulsory social security, Construction industries, and Protective service occupations, health and social care associate professionals, and skilled construction and building trades occupations showed a relatively higher prevalence of OSA indicating that they may be target populations for workplace screening., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Background: Estimates for the prevalence of food allergy vary widely, with a paucity of data for adults. The aim of this analysis was to report trends in the incidence and prevalence of food allergy in England, using a national primary care dataset., Methods: We analysed data from Clinical Practice Research Datalink between 1998 and 2018, with linked data to relevant hospital encounters in England. The main outcomes were incidence and prevalence of food allergy, according to three definitions of food allergy: possible food allergy, probable food allergy, and probable food allergy with adrenaline autoinjectors prescription. We also evaluated the difference in proportion of patients prescribed adrenaline autoinjectors by English Index of Multiple Deprivation (IMD), age, and by previous food anaphylaxis, and explored differences in patient encounters (general practice vs emergency department setting)., Findings: 7 627 607 individuals in the dataset were eligible for inclusion, of whom 150 018 (median age 19 years [IQR 4-34]; 82 614 [55·1%] female and 67 404 [44·9%] male) had a possible food allergy. 121 706 met diagnostic criteria for probable food allergy, of whom 38 288 were prescribed adrenaline autoinjectors. Estimated incidence of probable food allergy doubled between 2008 and 2018, from 75·8 individuals per 100 000 person-years (95% CI 73·7-77·9) in 2008 to 159·5 (156·6-162·3) individuals per 100 000 person-years in 2018. Prevalence increased from 0·4% (23 399 of 6 432 383) to 1·1% (82 262 of 7 627 607) over the same period and was highest in children under 5 years (11 951 [4·0%] of 296 406 in 2018) with lower prevalence in school-aged children (from 11 353 [2·4%] of 473 597 in 2018 for children aged 5-9 years to 6896 [1·7%] of 404 525 for those aged 15-19 years) and adults (42 848 [0·7%] of 5 992 454 in 2018). In those with previous food anaphylaxis, only 2321 (58·3%) of 3980 (975 [64·0%] of 1524 children and young people and 1346 [54·8%] of 2456 adults) had a prescription for adrenaline autoinjector. Adrenaline autoinjectors prescription was less common in those resident in more deprived areas (according to IMD). In the analysis of health-care encounters, 488 604 (97·1%) of 503 198 visits recorded for food allergy occurred in primary care, with 115 655 (88·4%) of 130 832 patients managed exclusively in primary care., Interpretation: These estimates indicate an important and increasing burden of food allergy in England. Our findings that most patients with food allergy are managed outside the hospital system, with low rates of adrenaline autoinjector prescription in those with previous anaphylaxis, highlight a need to better support those working in primary care to ensure optimal management of patients with food allergy., Funding: UK Food Standards Agency and UK Medical Research Council., Competing Interests: Declaration of interests PJT reports grants from JM Charitable Foundation, National Institute for Health and Care Research (NIHR)–Imperial Biomedical Research Centre, and End Allergies Together, outside the submitted work; and personal fees from UK Food Standards Agency, DBV Technologies, Aimmune Therapeutics, Allergenis, and ILSI Europe outside the submitted work. AC reports personal fees from Novartis, Sanofi, Stallergenes Greer, AstraZeneca, GSK, and La Roche-Posay, outside the submitted work. JKQ reports grants from Medical Research Council, Health Data Research UK, GSK, Boehringer Ingelheim, Asthma + Lung UK, and AstraZeneca outside the submitted work; and personal fees from GSK, Evidera, AstraZeneca, and Insmed. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: In primary care, identifying pneumonia events in people with chronic obstructive pulmonary disease (COPD) may be challenging due to similarities in symptoms with COPD exacerbations and lack of diagnostic testing. This study explored the accuracy of pneumonia diagnosis coded in primary care by comparing diagnosis in primary care with diagnosis in hospital., Methods: A study population of people with COPD in England was created using the Clinical Practice Research Datalink Aurum database linked with Hospital Episode Statistics inpatient data. Pneumonia codes only, and pneumonia code with associated clinical and/or treatment codes (chest x-ray, symptoms, antibiotics, sputum and blood culture) were used to determine pneumonia events in primary care. Events that were followed by hospitalisation within 7 days were used to estimate the positive predictive value (PPV) of pneumonia coding in primary care, using primary diagnosis of pneumonia in secondary care as the gold standard. The PPV of primary care recording of hospitalised pneumonia was also calculated., Results: Two hundred seventy-four thousand one hundred fifty-six COPD patients were eligible for inclusion, of whom 7,560 had an eligible pneumonia event in primary care diagnosed between 2015-2019 which was not 'hospital-acquired' and was diagnosed and entered on the same day. Of the 2,094 events which were followed by hospitalisation within 7 days, 1,208 had a primary diagnosis of pneumonia in hospital, representing a PPV of pneumonia coding in primary care of 57.7% (95% CI 55.6%-59.8%). Another 284 (13.6%) were diagnosed as a COPD exacerbation and 114 (5.4%) were diagnosed as another respiratory disease. Use of additional pneumonia clinical and treatment codes had a modest effect on the PPV but substantially lowered the number of events. Of the 33,603 eligible pneumonia events identified in secondary care, only 11,445 were recorded in primary care within 42 days, representing a sensitivity of 34.1% (95% CI 33.6%-34.6%)., Conclusions: Use of primary care pneumonia codes and associated clinical and treatment codes to determine pneumonia is not recommended due to significant levels of misdiagnosis and many hospitalised events failing to be recorded in primary care., (© 2024. The Author(s).)

Background: An immediate, temporal risk of heart failure and arrhythmias after a Chronic Obstructive Pulmonary Disease (COPD) exacerbation has been demonstrated, particularly in the first month post-exacerbation. However, the clinical profile of patients who develop heart failure (HF) or atrial fibrillation/flutter (AF) following exacerbation is unclear. Therefore we examined factors associated with people being hospitalized for HF or AF, respectively, following a COPD exacerbation., Methods: We conducted two nested case-control studies, using primary care electronic healthcare records from the Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, Office for National Statistics for mortality, and socioeconomic data (2014-2020). Cases had hospitalization for HF or AF within 30 days of a COPD exacerbation, with controls matched by GP practice (HF 2:1;AF 3:1). We used conditional logistic regression to explore demographic and clinical factors associated with HF and AF hospitalization., Results: Odds of HF hospitalization (1,569 cases, 3,138 controls) increased with age, type II diabetes, obesity, HF and arrhythmia history, exacerbation severity (hospitalization), most cardiovascular medications, GOLD airflow obstruction, MRC dyspnea score, and chronic kidney disease. Strongest associations were for severe exacerbations (adjusted odds ratio (aOR)=6.25, 95%CI 5.10-7.66), prior HF (aOR=2.57, 95%CI 1.73-3.83), age≥80 years (aOR=2.41, 95%CI 1.88-3.09), and prior diuretics prescription (aOR=2.81, 95%CI 2.29-3.45). Odds of AF hospitalization (841 cases, 2,523 controls) increased with age, male sex, severe exacerbation, arrhythmia and pulmonary hypertension history and most cardiovascular medications. Strongest associations were for severe exacerbations (aOR=5.78, 95%CI 4.45-7.50), age≥80 years (aOR=3.15, 95%CI 2.26-4.40), arrhythmia (aOR=3.55, 95%CI 2.53-4.98), pulmonary hypertension (aOR=3.05, 95%CI 1.21-7.68), and prescription of anticoagulants (aOR=3.81, 95%CI 2.57-5.64), positive inotropes (aOR=2.29, 95%CI 1.41-3.74) and anti-arrhythmic drugs (aOR=2.14, 95%CI 1.10-4.15)., Conclusions: Cardiopulmonary factors were associated with hospitalization for HF in the 30 days following a COPD exacerbation, while only cardiovascular-related factors and exacerbation severity were associated with AF hospitalization. Understanding factors will help target people for prevention., (© 2024. The Author(s).)

Rationale: Cardiovascular events after chronic obstructive pulmonary disease (COPD) exacerbations are recognized. Studies to date have been post hoc analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally. Objectives: We explore temporal relationships between moderate and severe exacerbations and incident, nonfatal hospitalized cardiovascular events in a primary care-derived COPD cohort. Methods: We included people with COPD in England from 2014 to 2020, from the Clinical Practice Research Datalink Aurum primary care database. The index date was the date of first COPD exacerbation or, for those without exacerbations, date upon eligibility. We determined composite and individual cardiovascular events (acute coronary syndrome, arrhythmia, heart failure, ischemic stroke, and pulmonary hypertension) from linked hospital data. Adjusted Cox regression models were used to estimate average and time-stratified adjusted hazard ratios (aHRs). Measurements and Main Results: Among 213,466 patients, 146,448 (68.6%) had any exacerbation; 119,124 (55.8%) had moderate exacerbations, and 27,324 (12.8%) had severe exacerbations. A total of 40,773 cardiovascular events were recorded. There was an immediate period of cardiovascular relative rate after any exacerbation (1-14 d; aHR, 3.19 [95% confidence interval (CI), 2.71-3.76]), followed by progressively declining yet maintained effects, elevated after one year (aHR, 1.84 [95% CI, 1.78-1.91]). Hazard ratios were highest 1-14 days after severe exacerbations (aHR, 14.5 [95% CI, 12.2-17.3]) but highest 14-30 days after moderate exacerbations (aHR, 1.94 [95% CI, 1.63-2.31]). Cardiovascular outcomes with the greatest two-week effects after a severe exacerbation were arrhythmia (aHR, 12.7 [95% CI, 10.3-15.7]) and heart failure (aHR, 8.31 [95% CI, 6.79-10.2]). Conclusions: Cardiovascular events after moderate COPD exacerbations occur slightly later than after severe exacerbations; heightened relative rates remain beyond one year irrespective of severity. The period immediately after an exacerbation presents a critical opportunity for clinical intervention and treatment optimization to prevent future cardiovascular events.

Background: COVID-19 is associated with cardiovascular outcomes in the general population, but it is unknown whether people with chronic respiratory disease (CRD) have a higher risk of cardiovascular events post-COVID-19 compared with the general population and, if so, what respiratory-related factors may modify this risk in these people., Methods: Primary and secondary care data from the National Health Service England were used to define a population of adults in England with COVID-19 (index date) between 1 January 2020 and 30 November 2021. Adjusted Cox proportional hazard regression was used to quantify the association between CRD, asthma-related factors, chronic obstructive pulmonary disease (COPD)-related factors, and risk of cardiovascular events. Asthma-specific factors included baseline asthma control, exacerbations, and inhaled corticosteroid (ICS) dose. COPD-specific risk factors included baseline ICS and exacerbations. Secondary objectives quantified the impact of COVID-19 hospitalisation and vaccine dose on cardiovascular outcomes., Results: Of 3 670 455 people, those with CRD had a higher risk of cardiovascular events [adjusted hazard ratio (HRadj), 1.08; 95% confidence interval (CI) 1.06-1.11], heart failure (HRadj, 1.17; 95% CI, 1.12-1.22), angina (HRadj, 1.13; 95% CI, 1.06-1.20) and pulmonary emboli (HRadj, 1.24; 95% CI, 1.15-1.33) compared with people without CRD. In people with asthma or COPD, baseline exacerbations were associated with a higher risk of cardiovascular outcomes (HRadj, 1.36; 95% CI, 1.27-1.00 and HRadj, 1.35; 95% CI, 1.24-1.46, respectively). Regardless of CRD, the risk of cardiovascular events was lower with increasing COVID-19 vaccine dose., Conclusions: Higher risk of cardiovascular events post-COVID-19 might be explained by the underlying severity of the CRD, and COVID-19 vaccines were beneficial to both people with and those without CRD with regards to cardiovascualr events., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Asthma-related burden remains poorly characterised in children in the UK. We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds)., Methods: The Clinical Practice Research Datalink Aurum database (2008‒2018) was used to assess annual asthma incidence and prevalence in 1‒17-year-olds and preschool wheeze in 1‒5-year-olds, stratified by sex and age. During the same period, annual asthma exacerbation rates were assessed in those with either a diagnosis of preschool wheeze or asthma., Results: Annual asthma incidence rates decreased by 51% from 1403.4 (95% CI 1383.7 to 1423.2) in 2008 to 688.0 (95% CI 676.3 to 699.9) per 10 5 person-years (PYs) in 2018, with the most pronounced decrease observed in 1‒5-year olds (decreasing by 65%, from 2556.9 (95% CI 2509.8 to 2604.7) to 892.3 (95% CI 866.9 to 918.3) per 10 5 PYs). The corresponding decreases for the 6‒11- and 12‒17-year-olds were 36% (1139.9 (95% CI 1110.6 to 1169.7) to 739.9 (95% CI 720.5 to 759.8)) and 20% (572.3 (95% CI 550.4 to 594.9) to 459.5 (95% CI 442.9 to 476.4)) per 10 5 PYs, respectively. The incidence of preschool wheeze decreased over time and was slightly more pronounced in the 1‒3 year-olds than in the 4-year-olds. Prevalence of asthma and preschool wheeze also decreased over time, from 18.0% overall in 2008 to 10.2% in 2018 for asthma. Exacerbation rates increased over time from 1.33 (95% CI 1.31 to 1.35) per 10 PYs in 2008 to 1.81 (95% CI 1.78 to 1.83) per 10 PYs in 2018., Conclusion: Paediatric asthma incidence decreased in the UK since 2008, particularly in 1-5-year-olds; this was accompanied by a decline in asthma prevalence. Preschool wheeze incidence also decreased in this age group. However, exacerbation rates have been increasing., Competing Interests: Competing interests: EM is an employee of AstraZeneca and owns stock in AstraZeneca. IS received consultancy from AstraZeneca to their institutions for this work. GR received consultancy from AstraZeneca to their institutions for this work. RJPvdV is an employee of AstraZeneca and owns stock in AstraZeneca and GlaxoSmithKline. JKQ reports grants from AUK-BLF and The Health Foundation; grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Bayer; and grants from Chiesi, outside the submitted work. JKQ’s research group received funding from AstraZeneca for this work. TNT is an employee of AstraZeneca and owns stock in AstraZeneca. CK and ADM have nothing to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival., Methods: We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions. Qualitative and quantitative analysis considering steps per day and gait speed and their association with clinical outcomes in COPD patients was performed., Results: 21 studies (6076 participants) were included. Nine studies evaluated steps per day and 11 evaluated a measure reflecting gait speed in daily life. Negative associations were demonstrated between mortality risk and steps per day (per 1000 steps) (hazard ratio (HR) 0.81, 95% CI 0.75-0.88, p<0.001), gait speed (<0.80 m·s -1 ) (HR 3.55, 95% CI 1.72-7.36, p<0.001) and gait speed (per 1.0 m·s -1 ) (HR 7.55, 95% CI 1.11-51.3, p=0.04). Fewer steps per day (per 1000) and slow gait speed (<0.80 m·s -1 ) were also associated with increased healthcare utilisation (HR 0.80, 95% CI 0.72-0.88, p<0.001; OR 3.36, 95% CI 1.42-7.94, p=0.01, respectively). Available evidence was of low-moderate quality with few studies eligible for meta-analysis., Conclusion: Daily step count and gait speed are negatively associated with mortality risk and other important outcomes in people with COPD and therefore may have value as prognostic indicators in clinical trials, but the quantity and quality of evidence is limited. Larger studies with consistent methodologies are called for., Competing Interests: Conflicts of interest declaration: S.C. Buttery reports educational speaker fees for Pulmonx. J.K. Quint has received grants from the Medical Research Council, the National Institute for Health Data Science (HDR UK), GlaxoSmithKline, Bohringer Ingelheim and Taskforce via Asthma + Lung UK, and AstraZeneca; and personal fees for advisory board participation, consultancy or speaking fees from GlaxoSmithKline, Evidera, AstraZeneca and Insmed. M.I. Polkey reports consultancy for Philips Respironics. J. Garcia-Aymerich reports speaker honoraria from Chiesi and a grant from AstraZeneca paid to her institution for a COVID-19-related project and is also a paid advisory board member for AstraZeneca. A. Polhemus is a paid employee of Merck & Co, Inc. and IQVIA AG. T. Troosters reports a Mobilise-D Innotive Medicines Initiative grant. All other authors report no conflicts of interest., (Copyright ©The authors 2023.)

Background: The ever-growing size, breadth, and availability of patient data allows for a wide variety of clinical features to serve as inputs for phenotype discovery using cluster analysis. Data of mixed types in particular are not straightforward to combine into a single feature vector, and techniques used to address this can be biased towards certain data types in ways that are not immediately obvious or intended. In this context, the process of constructing clinically meaningful patient representations from complex datasets has not been systematically evaluated., Aims: Our aim was to a) outline and b) implement an analytical framework to evaluate distinct methods of constructing patient representations from routine electronic health record data for the purpose of measuring patient similarity. We applied the analysis on a patient cohort diagnosed with chronic obstructive pulmonary disease., Methods: Using data from the CALIBER data resource, we extracted clinically relevant features for a cohort of patients diagnosed with chronic obstructive pulmonary disease. We used four different data processing pipelines to construct lower dimensional patient representations from which we calculated patient similarity scores. We described the resulting representations, ranked the influence of each individual feature on patient similarity and evaluated the effect of different pipelines on clustering outcomes. Experts evaluated the resulting representations by rating the clinical relevance of similar patient suggestions with regard to a reference patient., Results: Each of the four pipelines resulted in similarity scores primarily driven by a unique set of features. It was demonstrated that data transformations according to each pipeline prior to clustering can result in a variation of clustering results of over 40%. The most appropriate pipeline was selected on the basis of feature ranking and clinical expertise. There was moderate agreement between clinicians as measured by Cohen's kappa coefficient., Conclusions: Data transformation has downstream and unforeseen consequences in cluster analysis. Rather than viewing this process as a black box, we have shown ways to quantitatively and qualitatively evaluate and select the appropriate preprocessing pipeline., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mona Bafadhel has received grants from AstraZeneca, Roche (to institution). Has received honoraria from AstraZeneca, Chiesi, Cipla, GlaxoSmithKline, Sanofi (to institution) and is Scientific advisor to AlbusHealth® and ProAxsis®. The rest of 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: © 2023 Pikoula 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.)

Background: Prescription of three or more short-acting β 2 -agonist (SABA) canisters per year in adult and adolescent asthma populations is associated with a risk of severe exacerbations; however, evidence in children aged <12 years is limited., Methods: This study analysed data on children and adolescents with asthma in three age cohorts: 1‒5 years, 6‒11 years and 12‒17 years from the Clinical Practice Research Datalink Aurum database for the period 1 January 2007 to 31 December 2019. Associations between SABA prescriptions (three or more versus fewer than three canisters per year) at baseline, defined as 6 months after an asthma diagnosis as a binary exposure variable, and the rate of future asthma exacerbations, defined as oral corticosteroid burst therapy, an emergency department visit or hospital admission, were assessed by multilevel negative binomial regression, adjusted for relevant demographic and clinical confounders., Results: Overall 48 560, 110 091 and 111 891 paediatric patients with asthma were aged 1‒5, 6‒11 and 12‒17 years, respectively. During the baseline period, 22 423 (46.2%), 42 137 (38.3%) and 40 288 (36.0%) in these three age cohorts, respectively, were prescribed three or more SABA canisters per year. Across all age ranges, the rate of future asthma exacerbations in those prescribed three or more versus fewer than three SABA canisters per year was at least two-fold higher. >30% of patients across all age cohorts were not prescribed inhaled corticosteroids (ICS), and the median proportion of days covered was only 33%, suggesting inadequate prescribing of ICS., Conclusion: In children, higher SABA prescriptions at baseline were associated with increased future exacerbation rates. These findings highlight the need for monitoring prescription of three or more SABA canisters per year to identify children with asthma at risk of exacerbations., Competing Interests: Conflict of interest: A. Morgan and C. Kallis have nothing to declare. E. Maslova, T.N. Tran and R.J.P. van der Valk are employees of AstraZeneca and hold AstraZeneca shares. R.J.P. van der Valk holds shares in GlaxoSmithKline. G. Roberts and I. Sinha received consultancy from AstraZeneca to their institutions for this work. J.K. Quint reports grants from AUK-BLF and The Health Foundation; grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Bayer; and grants from Chiesi, outside the submitted work. J.K. Quint's research group received funding from AstraZeneca for this work., (Copyright ©The authors 2023.)

Background: 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., Objective: 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., Methods: 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., Results: 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., Conclusions: 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., International Registered Report Identifier (irrid): PRR1-10.2196/42965., (©Rafael A Calvo, Dorian Peters, Laura Moradbakhti, Darren Cook, Georgios Rizos, Bjoern Schuller, Constantinos Kallis, Ernie Wong, Jennifer Quint. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 02.02.2023.)

Background: We aimed to determine whether children and adults with poorly controlled or more severe asthma have greater risk of hospitalisation and/or death from COVID-19., Methods: We used individual-level data from the Office for National Statistics Public Health Data Asset, based on the 2011 census in England, and the General Practice Extraction Service data for pandemic planning and research linked to death registration records and Hospital Episode Statistics admission data. Adults were followed from 1 January 2020 to 30 September 2021 for hospitalisation or death from COVID-19. For children, only hospitalisation was included., Results: Our cohort comprised 35 202 533 adults and 2 996 503 children aged 12-17 years. After controlling for sociodemographic factors, pre-existing health conditions and vaccine status, the risk of death involving COVID-19 for adults with asthma prescribed low dose inhaled corticosteroids (ICS) was not significantly different from those without asthma. Adults with asthma prescribed medium and high dosage ICS had an elevated risk of COVID-19 death; HRs 1.18 (95% CI 1.14 to 1.23) and 1.36 (95% CI 1.28 to 1.44), respectively. A similar pattern was observed for COVID-19 hospitalisation; fully adjusted HRs 1.53 (95% CI 1.50 to 1.56) and 1.52 (95% CI 1.46 to 1.56) for adults with asthma prescribed medium and high-dosage ICS, respectively. Risk of hospitalisation was greater for children with asthma prescribed one (2.58 (95% CI 1.82 to 3.66)) or two or more (3.80 (95% CI 2.41 to 5.95)) courses of oral corticosteroids in the year prior to the pandemic., Discussion: People with mild and/or well-controlled asthma are neither at significantly increased risk of hospitalisation with nor more likely to die from COVID-19 than adults without asthma., Competing Interests: Competing interests: JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, AUK-BLF, HDR UK, Chiesi and AZ and personal fees for advisory board participation or speaking fees from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Chiesi, Insmed and Bayer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: To evaluate the association between having concomitant chronic obstructive pulmonary disease (COPD) or asthma, and in-patient mortality and post-discharge management among patients hospitalised for acute heart failure (HF)., Setting: Data were obtained from patients enrolled in the National Heart Failure Audit., Participants: 217 329 patients hospitalised for HF in England-Wales between March 2012 and 2018., Outcomes: In-hospital mortality, referrals to cardiology follow-up and prescriptions for HF medications were compared between patients with comorbid COPD (COPD-HF) or asthma (asthma-HF) versus HF-alone using mixed-effects logistic regression., Results: Patients with COPD-HF were more likely to die during hospitalisation, and those with asthma-HF had a reduced likelihood of death, compared with patients who had HF-alone ((adjusted)OR adj , 95% CI: 1.10, 1.06 to 1.14 and OR adj , 95% CI: 0.84, 0.79 to 0.88). In patients who survived to discharge, referral to HF follow-up services differed between groups: patients with COPD-HF had reduced odds of cardiology follow-up (OR adj , 95% CI 0.79, 0.77 to 0.81), while cardiology referral odds for asthma-HF were similar to HF-alone. Overall, proportions of HF medication prescriptions at discharge were low for both COPD-HF and asthma-HF groups, particularly prescriptions for beta-blockers., Conclusions: In this nationwide analysis, we showed that COPD and asthma significantly impact the clinical course in patients hospitalised for HF. COPD is associated with higher in-patient mortality and lower cardiology referral odds, while COPD and asthma are both associated with lower use of prognostic HF therapies on discharge. These data highlight therapeutic gaps and a need for better integration of cardiopulmonary services to improve healthcare provision for patients with HF and coexisting respiratory disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiovascular disease is prevalent in idiopathic pulmonary fibrosis (IPF), yet the extent of left-sided heart failure (HF) burden, whether this has changed with time and whether HF impacts mortality risk in these patients are unknown. The aims of this study were therefore to determine the temporal trends in incidence and prevalence of left-sided HF in patients with IPF in England and compare these to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as determine the risk of all-cause and cause-specific mortality in patients with comorbid left-sided HF and IPF at population-level using electronic healthcare data., Methods: Clinical Practice Research Datalink (CPRD) Aurum primary-care data linked to mortality and secondary-care data was used to identify IPF patients in England. Left-sided HF prevalence and incidence rates were calculated for each calendar year between 2010 and 2019, stratified by age and sex. Risk of all-cause, cardiovascular and IPF-specific mortality was calculated using multivariate Cox regression., Results: From 40,577patients with an IPF code in CPRD Aurum, 25, 341 IPF patients met inclusion criteria. Left-sided HF prevalence decreased from 33.4% (95% CI 32.2-34.6) in 2010 to 20.9% (20.0-21.7) in 2019. Left-sided HF incidence rate per 100 person-years (95% CI) remained stable between 2010 and 2017 but decreased from 4.3 (3.9-4.8) in 2017 to 3.4 (3.0-3.9) in 2019. Throughout follow-up, prevalence and incidence were higher in men and with increasing age. Comorbid HF was associated with poorer survival (adjusted HR (95%CI) 1.08 (1.03-1.14) for all-cause mortality; 1.32 (1.09-1.59) for cardiovascular mortality)., Conclusion: Left-sided HF burden in IPF patients in England remains high, with incidence almost 4 times higher than in COPD, a comparable lung disease with similar cardiovascular risk factors. Comorbid left-sided HF is also a poor prognostic marker. More substantial reduction in left-sided HF prevalence than incidence suggests persistently high IPF mortality. Given rising IPF incidence in the UK, this calls for better management of comorbidities such as left-sided HF to help optimise IPF survival., (© 2022. The Author(s).)

Adult gang involvement attracts little empirical attention, so little is known about how they compare to nongang violent men in social harms beyond gang contexts. This study, based on unpublished data of 1,539 adult males, aged 19 to 34, from the Coid et al. national survey, compared gang members' (embedded in a gang; n  = 108), affiliates' (less embedded in a gang; n  = 119), and violent men's (no gang association; n  = 1,312) perpetration of social harms by assessing their violence-related dispositions and beliefs, victim types, and locations of violence. Results showed that compared with violent men, gang members and affiliates were equally more likely to: cause social harms to a wider range of victims, including family and friends; seek violence; be excited by violence; and carry weapons. Gang members and affiliates were equally more likely than violent men to be violent at home, in friends' homes, and at work; they also thought about hurting people, but felt regret for some of their violence. A decreasing gradient was identified in gang members' (highest), affiliates' (next highest) and violent men's (lowest) beliefs in violent retaliation when disrespected, the use of violence instrumentally and when angry, and worry about being violently victimized. Implications of findings are that interventions need to address anger issues across all levels of adult gang membership. Importantly, adult gang members' regrets regarding violence and anxiety about being violently victimized could be key factors that interventions could use to help them relinquish their gang involvement.

Objectives: Knowledge of the extent of variation in outcome assessment for inflammatory bowel disease (IBD) in routine practice is limited. We aimed to describe and quantify variation in outcome coverage and to explore patient, clinician and practitioner factors associated with it., Design: Prospective exploratory mixed-methods study., Setting: IBD clinics at six hospitals in North West England with differing electronic health record (EHR) systems., Methods: Mixed-methods study comprising: (a) structured observations of outcomes elicited during consultations (102 patients consulting 24 clinicians); (b) retrospective analysis of outcomes recorded in the EHR (909 consultations; 127 clinicians) and (c) semistructured interviews with the 24 observed clinicians. We determined whether specific outcome 'sets' were elicited or recorded, including: (1) a minimum set of symptom pairs ('PRO-2'); (2) symptom sets from disease activity indices and (3) a reference list of 37 symptoms, signs and impacts. Factors associated with variation were explored in univariate and multivariate binary logistic regression analyses and from clinician interviews., Results: PRO-2 coverage was not invariable (elicited during 81% of observed consultations; recorded in 56% of EHR) and infrequent for complete activity indices (all domains from Harvey-Bradshaw Index: elicited, 18%; recorded, 5%). The median number of outcomes from the reference list elicited per consultation was 12 (13-fold variation) and recorded in EHR was 7 (>20-fold variation). Symptom quantification (PRO-2) seldom adhered closely to standardised descriptors and an explicit timeframe was defined rarely. PRO-2 recording in EHR was associated with a diagnosis of ulcerative colitis (OR: 2.09 (95% CI 1.15 to 3.80)) and nurse-led consultations (OR: 6.98 (95% CI 3.28 to 14.83)) and a three-way model suggested 26% of total variability lay between clinicians, 17% between patients but the remainder was unexplained. Most clinicians expressed preference for individualised health status evaluations versus standardised outcome assessments., Conclusions: There was little evidence for standardised assessment and recording of IBD outcomes and substantial intra-clinician and inter-clinician variation from one consultation to another. Nurses demonstrated a greater tendency to standardised practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19., Design: Population based study., Setting: 1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database., Participants: 456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803)., Main Outcome Measures: Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression., Results: Relative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18 059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease., Conclusions: GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from BREATHE for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)