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Summary: Background: The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations. Methods: A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We defined two cohorts for the main analyses: a SARS-CoV-2 infection cohort [positive polymerase chain reaction (PCR) or rapid lateral flow test (LFT) result or clinical COVID-19 diagnosis] and a general population cohort. Individuals with less than 365 days of prior history or 120 days of follow-up were excluded. We estimated incidence rates (IRs) of the 25 WHO-proposed post-acute COVID-19 symptoms, considering symptoms that occurred ≥90 and ≤365 days after index date, excluding individuals with the respective symptoms 180 days prior to the index event. Stratified analyses were conducted by age and sex. Incidence rate ratios (IRRs) were calculated comparing rates in the infected cohort versus the general population. Results from the different databases were combined using random-effects meta-analyses. Findings: 3,019,408 individuals were included in the infection cohort. 1,585,160 of them were female and 1,434,248 of them male. 929,351,505 individuals were included in the general population group. 461,195,036 of them were female and 466,022,004 of them male. The 1-year IR of any post-acute COVID-19 symptom in the COVID-19 infection cohort varied significantly across databases, from 4.4 (95% CI 3.8–5.1) per 100 person-years to 103.9 (95% CI 103.2–104.7). The five most common symptoms were joint pain (from 1.6 (95% CI 1.3–1.9) to 14.3 (95% CI 14.1–14.6)), abdominal pain (from 0.3 (95% CI 0.1–0.5) to 9.9 (95% CI 9.7–10.1)), gastrointestinal issues (from 0.6 (95% CI 0.4–0.9) to 13.3 (95% CI 13.1–13.6)), cough (from 0.3 (95% CI 0.2–0.5) to 9.1 (95% CI 8.9–9.3)), and anxiety (from 0.8 (95% CI 0.6–1.2) to 11.4 (95% CI 11.2–11.6)); whereas muscle spasms (from 0.01 (95% CI 0.008–0.2) to 1.7 (95% CI 1.6–1.8)), pins and needles (from 0.05 (95% CI 0.03–0.0.9) to 1.5 (95% CI 1.4–1.6)), memory issues (from 0.03 (95% CI 0.02–0.06) to 0.8 (95% CI 0.7–0.8)), cognitive dysfunction (from 0.007 (95% CI 0.004–0.01) to 0.6 (95% CI 0.4–0.8)), and altered smell and/or taste (from 0.04 (95% CI 0.03–0.04) to 0.7 (95% CI 0.6–0.8)) were least common. Incidence rates of any post-acute COVID-19 symptoms generally increased with age, with certain symptoms peaking in middle-aged adults (anxiety, depressive disorders, headache, altered smell and taste) and others in pre-school children (gastrointestinal issues and cough). Females had higher incidence rates for most symptoms. Based on the random-effects model, the infected cohort had a higher incidence of any post-acute COVID-19 symptom than the general population, with a meta-analytic incidence rate ratio (meta-IRR) of 1.4 (1–2). A similar pattern was seen for all individual symptoms. The highest meta-IRRs were depressive disorder, 2.6 (1.7–3.9); anxiety, 2.3 (1.4–3.8); allergy, 2.1 (1.7–2.8) and sleep disorders, 2.1 (1.5–2.6). The meta-IRR for altered smell and/or taste was 1.9 (1.3–2.8). Interpretation: Post-acute COVID-19 symptoms, as listed by the WHO, were commonly observed following COVID-19 infection. However, even after standardising research methods, there was significant heterogeneity in the incidence rates from different healthcare settings and geographical locations. This is the first international study of the epidemiology of post-acute COVID-19 symptoms using the WHO-listed symptoms. Its findings contibute to understand the epidemiology of this condition from a multinational approach. Limitations of this study include the lack of consensus of the post-acute COVID-19 definition, as well as the difficulty to capture the impact on daily life of the post-acute COVID-19 symptoms in the available datasets. Funding: This work has been funded by the European Health Data Evidence Network (EHDEN) through an Evidence Generation Fund Grant and by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC).

Objectives To explore whether UK primary care databases arising from two different software systems can be feasibly combined, by comparing rates of Huntington’s disease (HD, which is rare) and 14 common cancers in the two databases, as well as characteristics of people with these conditions.Design Descriptive study.Setting Primary care electronic health records from Clinical Practice Research Datalink (CPRD) GOLD and CPRD Aurum databases, with linked hospital admission and death registration data.Participants 4986 patients with HD and 1 294 819 with an incident cancer between 1990 and 2019.Primary and secondary outcome measures Incidence and prevalence of HD by calendar period, age group and region, and annual age-standardised incidence of 14 common cancers in each database, and in a subset of ‘overlapping’ practices which contributed to both databases. Characteristics of patients with HD or incident cancer: medical history, recent prescribing, healthcare contacts and database follow-up.Results Incidence and prevalence of HD were slightly higher in CPRD GOLD than CPRD Aurum, but with similar trends over time. Cancer incidence in the two databases differed between 1990 and 2000, but converged and was very similar thereafter. Participants in each database were most similar in terms of medical history (median standardised difference, MSD 0.03 (IQR 0.01–0.03)), recent prescribing (MSD 0.06 (0.03–0.10)) and demographics and general health variables (MSD 0.05 (0.01–0.09)). Larger differences were seen for healthcare contacts (MSD 0.27 (0.10–0.41)), and database follow-up (MSD 0.39 (0.19–0.56)).Conclusions Differences in cancer incidence trends between 1990 and 2000 may relate to use of a practice-level data quality filter (the ‘up-to-standard’ date) in CPRD GOLD only. As well as the impact of data curation methods, differences in underlying data models can make it more challenging to define exactly equivalent clinical concepts in each database. Researchers should be aware of these potential sources of variability when planning combined database studies and interpreting results.

Abstract Introduction This retrospective database study explored treatment patterns and potential off-label prescribing among patients newly prescribed fluticasone furoate/vilanterol (FF/VI) in a UK primary care setting. Methods In Europe, FF/VI is approved in two strengths: 100/25 µg for adults with chronic obstructive pulmonary disease (COPD) and 100/25 µg or 200/25 µg for treatment of asthma in patients aged 12 or older. Using electronic health records from the Clinical Practice Research Datalink, new users of FF/VI or other inhaled corticosteroid/long-acting beta-agonist fixed-dose combination products were identified and classified into one of three groups: COPD diagnosis, asthma diagnosis, and other diagnosis (not COPD or asthma). Results During 2014–2015, 4373 patients initiated FF/VI: 3380 on FF/VI 100/25 (65% in the COPD diagnosis group) and 993 on FF/VI 200/25 (51% in the asthma diagnosis group). During up to 12 months of follow-up, the median number (interquartile range) of prescriptions of the index strength issued per patient was 7 (2–8) for FF/VI 100/25 and 5 (2–8) for FF/VI 200/25; most new users did not change from the index strength prescribed (93.0% COPD; 89.7% asthma, of all patients initiating treatment with FF/VI). Potential off-label FF/VI prescribing in children

Background: Bisphosphonates are contraindicated in patients with stage 4+ chronic kidney disease. However, they are widely used to prevent fragility fractures in stage 3 chronic kidney disease, despite a lack of good-quality data on their effects. Objectives: The aims of each work package were as follows. Work package 1: to study the relationship between bisphosphonate use and chronic kidney disease progression. Work package 2: to study the association between using bisphosphonates and fracture risk. Work package 3: to determine the risks of hypocalcaemia, hypophosphataemia, acute kidney injury and upper gastrointestinal events associated with using bisphosphonates. Work package 4: to investigate the association between using bisphosphonates and changes in bone mineral density over time. Design: This was a new-user cohort study design with propensity score matching. Setting and data sources: Data were obtained from UK NHS primary care (Clinical Practice Research Datalink GOLD database) and linked hospital inpatient records (Hospital Episode Statistics) for work packages 1–3 and from the Danish Odense University Hospital Databases for work package 4. Participants: Patients registered in the data sources who had at least one measurement of estimated glomerular filtration rate of

Objective To identify observational studies which used data from more than one primary care electronic health record (EHR) database, and summarise key characteristics including: objective and rationale for using multiple data sources; methods used to manage, analyse and (where applicable) combine data; and approaches used to assess and report heterogeneity between data sources.Design A systematic review of published studies.Data sources Pubmed and Embase databases were searched using list of named primary care EHR databases; supplementary hand searches of reference list of studies were retained after initial screening.Study selection Observational studies published between January 2000 and May 2018 were selected, which included at least two different primary care EHR databases.Results 6054 studies were identified from database and hand searches, and 109 were included in the final review, the majority published between 2014 and 2018. Included studies used 38 different primary care EHR data sources. Forty-seven studies (44%) were descriptive or methodological. Of 62 analytical studies, 22 (36%) presented separate results from each database, with no attempt to combine them; 29 (48%) combined individual patient data in a one-stage meta-analysis and 21 (34%) combined estimates from each database using two-stage meta-analysis. Discussion and exploration of heterogeneity was inconsistent across studies.Conclusions Comparing patterns and trends in different populations, or in different primary care EHR databases from the same populations, is important and a common objective for multi-database studies. When combining results from several databases using meta-analysis, provision of separate results from each database is helpful for interpretation. We found that these were often missing, particularly for studies using one-stage approaches, which also often lacked details of any statistical adjustment for heterogeneity and/or clustering. For two-stage meta-analysis, a clear rationale should be provided for choice of fixed effect and/or random effects or other models.

An algorithm that detects errors in diagnosis, classification or coding of diabetes in primary care computerised medial record (CMR) systems is currently available. However, this was developed on CMR systems that are “Episode orientated” medical records (EOMR); and don’t force the user to always code a problem or link data to an existing one. More strictly problem orientated medical record (POMR) systems mandate recording a problem and linking consultation data to them.

Aim To obtain insight into the perceived quality of electronic records received by GP2GP transfer, from the perspective of staff within the receiving practice. Methods A pilot study using a self-completion online survey.We used textual analysis and descriptive statistics to report the findings. Results Respondents considered a significantly higher proportion of their own records to be accurate, complete and useful compared with records transferred from other practices (PConclusion The results suggest that respondents value the GP2GP record transfer system. They perceive issues with record quality, which require significant resources to rectify. Textual analysis suggests that difficulties in mapping data structures between systems may underlie some of the perceived issues. Further research is needed to confirm these initial findings on differential perception and explore their underlying causes.