Based on a UK primary care dataset, patients with Multiple Myeloma (MM) experience a significantly higher index fracture rate from 1 year prior to MM diagnosis onwards and a higher subsequent vertebral fracture rate, compared to non-MM controls. There is potential for earlier MM diagnosis and reducing subsequent fracture risk. Whilst multiple myeloma (MM) is known to increase fracture risk, the incidence of subsequent fractures is poorly described. Here, we describe the incidence of index and subsequent fractures in a real-world cohort of MM patients, compared to non-MM controls. Using the UK Clinical Practice Research Datalink GOLD, we identified a MM cohort with age-, sex-, and GP-practice-matched controls from 1995 to 2017. The primary outcome was the incidence of fracture at major osteoporotic sites (i.e. hip, vertebral, wrist, or humerus) within 2 years before and after MM diagnosis. The cumulative incidence of subsequent fractures up to 2 years post-index fracture was estimated using Cox proportional hazards models. A total of 1972 patients (54.7

BACKGROUND:Real-world data studies suggest that the vaccine effectiveness (VE) of a fourth mRNA vaccine dose against SARS-CoV2 infection related hospitalisation wanes after a few months, potentially warranting consideration of additional booster doses. METHODS:A multi-data source cohort study was conducted through the Data Analysis and Real World Interrogation Network (DARWIN EU®) using routinely collected electronic health records from the UK (CPRD GOLD), the Netherlands (IPCI), and Spain (SIDIAP) from January 2021 to June 2023. The study included individuals aged 12 and above, vaccinated with at least three doses. We matched fourth-dose to third-dose vaccinated individuals using a weekly sequential approach, defining the date of the last dose received by the exposed individual as the index date. Primary outcomes were SARS-CoV2 infection related death and hospitalisation. Hazard ratios (HR) were estimated using Cox proportional hazard models, with VE defined as the percentage of 1 minus HR. Waning of VE was assessed at monthly intervals. FINDINGS:A total number of 975,496 matched pairs were identified from the three data sources, with a median age of 63-78. The pooled VE of a fourth vaccine dose against SARS-CoV2 infection related death compared to three vaccine doses was 30% (95%CI 9 to 46, I2=0). VE against SARS-CoV2 infection related hospitalisation was 26% (19% to 33%) in Spain (SIDIAP, median follow-up 8 weeks), and 46% (15% to 66%), in the Netherlands (IPCI, median follow-up 21 weeks) respectively. VE of a fourth dose started waning at 4-8 weeks after vaccination. INTERPRETATION:A fourth dose of a mRNA COVID-19 vaccination was effective against SARS-CoV2 infection related death and hospitalisation. However, effectiveness waned over time. Periodic revaccination should be considered, with recommendations regarding booster timing taking into account circulating variants, patterns of viral transmission, and population uptake. FUNDING:European Medicines Agency.

BACKGROUND:Acetylcholinesterase inhibitors (AChEIs), are commonly prescribed for dementia and can cause adverse drug events that may lead to new prescriptions, known as prescription cascades. We aimed to identify potential AChEI-induced prescription cascades using high-throughput sequence symmetry analysis (SSA). METHODS:Patients aged ≥18 years with 365 days of prior observation initiating AChEIs (donepezil, rivastigmine, or galantamine) were identified from the Clinical Practice Research Datalink GOLD (2002-2022). We screened 510 drug classes and 1213 individual ingredients initiated within ±180 days of AChEI initiation (365 days in sensitivity analyses). Crude and adjusted sequence ratios (ASRs) were calculated, and positive signals were reviewed for clinical plausibility. RESULTS:We identified 66 155 AChEI initiators (median age 81 years [IQR 76-85]; 62.8% female). Among ATC classes and individual ingredients, 51 and 46 signals were positive with 28 (55%) and 22 (48%) classified as potential prescription cascades after review. Gastrointestinal drugs showed positive signals including antipropulsives (ASR 1.50 [99% CI 1.28-1.75]), loperamide (ASR 1.52 [1.30-1.77]) and cyclizine (ASR 2.10 [1.72-2.59]). Positive signals were also observed nervous system drugs such as benzodiazepine derivatives (ASR 1.83 [1.55-2.16]) and respiratory drugs including corticosteroids (ASR 1.66 [1.33-2.08]) and glucocorticoids (ASR 1.54 [1.30-1.83]). Most positive signals remained in sensitivity analysis. CONCLUSIONS:These findings suggest potential AChEI-related prescription cascades consistent with gastrointestinal, neuropsychiatric, dermatological and respiratory adverse effects. While findings require further validation, this study demonstrates the utility of high-throughput signal detection to support pharmacovigilance in high-risk populations.

Since its establishment in the late 1980s, the UK Clinical Practice Research Datalink (CPRD) has become one of the most widely utilised data resources in both national and international research. Its value lies in the richness, scale and quality of its routinely collected primary care data, as well as the availability of numerous linkable datasets. This study provides comprehensive scientometric analyses of CPRD-related research output, impact, and data usage from 1988 to 2024. A total of 3779 peer-reviewed publications were identified, and for 98.78% of them, enriched bibliometric metadata were retrieved through Scopus and Web of Science. The UK emerged as the leading contributing country, with the United States and Canada ranking second and third. 'McGill University' was the most frequently affiliated institution, followed by the 'University of Manchester' and the 'University of Oxford', with seven UK universities among the top ten. The three journals most frequently publishing CPRD-based research overall, and since 2020, were 'BMJ Open', 'Pharmacoepidemiology and Drug Safety' and 'British Journal of General Practice'. Analyses of primary care data sources utilisation revealed that overall, 86.35% of manuscripts used CPRD GOLD exclusively, 8.39% used both CPRD GOLD and CPRD Aurum, and 4.76% used CPRD Aurum alone, although recent years showed an increased use of CPRD Aurum. Between 2016 and 2024, most articles (80.26%) were associated with CPRD research applications that referenced linked or CPRD algorithm-derived datasets. The three most frequently used were 'Hospital Episode Statistics' (69.77%), 'Small Area Linkages' (62.27%) and 'Office for National Statistics' mortality data (53.28%).

Primary liver cancer (PLC) remains a global health challenge. Understanding trends in the disease burden and survival is crucial to inform decisions regarding screening, prevention, and treatment. Population-based cohort study using UK primary care data from the Clinical Practice Research Datalink (CPRD) GOLD (2000–2021), replicated in CPRD Aurum. Crude and age-standardized incidence rates (IRs), crude period prevalence (PP), and survival at 1, 5, and 10 years were calculated, and stratified by age, sex, and diagnosis year. The crude IR of PLC was 4.56 (95% CI 4.42–4.70) per 100 000 person-years between 2000 and 2021, with an increase over time across age and sex strata. Sex-specific IR for males was higher than females, 6.60 (95% CI 6.36–6.85) vs. 2.58 (95% CI 2.44–2.74) per 100 000 person-years. Age-standardized IR showed identical trends. Crude PP showed a seven-fold increase over the study period, with PP 0.02% (95% CI 0.019%–0.022%) in 2021, and a 2.8-fold higher PP in males. Survival at 1, 5, and 10 years after diagnosis was 41.7%, 13.2%, and 7.1%, respectively, for both sexes. One-year survival increased only in men, from 33.2% in 2005–2009 to 49.3% in 2015–2019. Over the past two decades, there has been a substantial increase in the number of patients diagnosed with PLC. Despite a slight improvement in median and one-year survival in men, prognosis remains poor. To improve the survival of PLC patients, it is necessary to understand the epidemiological changes and address preventable risk factors associated with liver disease and promote early detection and access to care.

Background and purpose: Chondrosarcoma is a rare bone malignancy with a poor response to systemic therapy in advanced stages. European-level epidemiological data remain scarce. This study aimed to characterise patient demographics, treatments and survival using real-world data to inform regulatory decisions about the feasibility and design of new trials for the systemic treatment of chondrosarcoma. Patient/material and methods: This cohort study, part of the DARWIN EU® initiative, analysed data from six healthcare databases in Finland, France, the Netherlands, Spain and the UK. Patients diagnosed with chondrosarcoma between 2010 and 2022 were identified. Standardised analyses were performed within a federated network using the Observational Medical Outcomes Partnership (OMOP) Common Data Model. Results: A total of 2,498 chondrosarcoma patient records were identified, covering at least 2,356 unique patients. Median age at diagnosis was 52–55 years, with a balanced sex distribution. Surgical treatment was the most common intervention, recorded in 15.2% to 88.9% of patients, depending on the database. Fewer than 5% received systemic anticancer therapy, and radiotherapy was reported in fewer than 7%. The 10-year overall survival (OS) ranged from 58% (95% confidence interval [CI]: 43–78) to 80% (95% CI: 78–82), with restricted mean survival between 7.4 and 8.7 years. In the Netherlands, patients with late-stage, metastatic or high-grade disease showed significantly poorer outcomes. Interpretation: This study demonstrates the feasibility of using real-world data across Europe to describe chondrosarcoma patients. Most had early-stage, low-grade disease amenable to surgery, with limited use of systemic therapies. Survival was generally favourable, except in advanced disease. Clinical trials remain difficult due to the rarity of advanced chondrosarcoma and the lack of standards.

To evaluate secular trends of incidence and prevalence of Parkinson's Disease (PD), Vascular Parkinsonism (VP), and Drug-induced Parkinsonism from 2007 to 2021 in the UK. We used primary care data, Clinical Practice Research Datalink GOLD, from the UK. Individuals were included if they were registered from January 2007 to December 2021 with at least one year of prior observation. Age-standardized and crude incidence and prevalence were calculated annually; age-standardized rates were stratified by sex, and crude rates by age and sex. From 2007 to 2019, the age-standardized incidence of PD decreased from 35.61 (95% confidence interval: 33.97-37.30) to 31.27 (29.27-33.37) per 100 000 person-years. The prevalence of PD increased from 0.21% (0.21%-0.22%) in 2007, peaking in 2016 at 0.23% (0.23%-0.24%). The number of VP diagnoses has increased since 2010, whereas the incidence and prevalence of DIP remained stable. Incidence and prevalence increased with age and were generally higher in males, except for DIP, which was slightly higher in females. Crude rates showed similar trends. Though Parkinson Disease incidence has declined, prevalence has risen, suggesting improved survival. VP rates have increased, possibly due to improvements in diagnostic screening. Drug-induced Parkinsonism rates remained stable. With an aging UK population, Parkinsonism subtypes pose a growing burden.

Purpose To develop and describe DrugUtilisation, an open-source R package that facilitates drug utilisation studies using data mapped to the OMOP Common Data Model (CDM).Methods Core functionalities include creating drug user cohorts, identifying and summarising indications, describing the duration and dose of medication/s and assessing treatment adherence. The package works with packages developed within the DARWIN EU initiative to support study-specific workflows. We show the package's workflow by analysing the use of simvastatin in three European real-world databases.Results This paper outlines the DrugUtilisation package's functions and demonstrates their application with a clinical example of simvastatin use in databases from the United Kingdom, Estonia and the Netherlands. We generated results including cohort counts, indication summaries, measures of dose and duration, as well as publication-ready tables and figures. We implemented comprehensive unit tests and standardised output format, which ensured consistency across databases and minimised coding errors.Conclusion The development of this software allows for researchers to quickly perform common drug utilisation analyses, while also providing the foundation for additional, bespoke study-specific analyses.

ABSTRACT:Despite effective control of inflammation in rheumatoid arthritis (RA), persistent and severe pain remains a challenge. Dysregulated pain processing in the central nervous system may underlie this disconnect. The PainDETECT questionnaire, originally developed to identify neuropathic pain, may capture features of central sensitization. We hypothesized that neuropathic-like pain at diagnosis predicts worse pain prognosis in early RA, independent of baseline pain severity and inflammation. We also explored brain activation patterns using neuroimaging. In this prospective cohort study, adults with newly diagnosed RA completed the PainDETECT questionnaire at baseline. Bodily pain was measured using the SF-36 Bodily Pain Subscale at baseline, 3, 6, and 12 months. C-reactive protein (CRP) was monitored. Linear mixed-effects models examined associations between PainDETECT, as a continuous measure, and bodily pain and CRP over time, adjusting for baseline outcome values. A neuroimaging substudy (n = 27) used task-based functional MRI to assess brain responses to evoked pressure pain. Among 158 participants (mean age 58.4 years; 35% male), 24.7% had likely neuropathic-like pain (PainDETECT ≥19) at baseline. Higher baseline PainDETECT scores were associated with worse bodily pain throughout follow-up in fully adjusted models (β = -0.43; 95% CI: -0.84 to -0.02; P = 0.043), independent of socio-demographics and comorbidities. No association was found between PainDETECT and CRP. On neuroimaging, higher PainDETECT scores correlated with increased activation in the left insula, dorsal anterior cingulate cortex, and left amygdala during evoked wrist pain. Neuropathic-like pain at diagnosis predicts a worse pain prognosis in early RA, independently of inflammation. Early identification may support more targeted and effective pain management.

Objectives:To characterise the use of intra-articular corticosteroid injections (IACIs) in a large patient cohort with OA in UK primary care from 2005 to 2020. We sought to evaluate IACI practices, identify patterns of administration across different joints, assess regional variation and examine potential demographic factors influencing IACI utilisation for managing OA. Methods:This retrospective cohort study used data from the UK Clinical Practice Research Datalink GOLD, a database of primary care health records. Data from other healthcare settings were not included. Patients ≥20 years of age with a first diagnosis of OA between 2005 and 2019 were included. OA and IACIs were identified through Read and Gemscript codes, respectively. Results:Of 220 125 patients with OA, 11% received at least one IACI. The anatomical location was only specified in 56% of IACI records. The highest proportion of injections occurred in patients with multiple joints diagnosed with OA (19.0%), followed by the shoulder (14.9%) and knee (12.5%). The median time from OA diagnosis to first injection was 0.9 years and was shortest for the shoulder (0.3 years) and longest for the elbow (2.1 years). We observed substantial regional variation, with incidence rates ranging from 1.2 injections per 100 patient-years in the South East Coast to 3.8 in Yorkshire and the Humber. Conclusion:This study observed notable variation in the median time from OA diagnosis to injection, across different joints, with substantial heterogeneity in the incidence of IACIs across UK regions.

Abstract Patients with earlier SARS-CoV-2 variants are at increased risk of venous and arterial thromboembolic (VTE, ATE) events. Here we aimed to contextualise the incidence of thromboembolic events among patients with COVID-19 during the Omicron period. We conducted a population-based cohort study using electronic health records from the UK (CPRD GOLD), the Netherlands (IPCI), and Spain (SIDIAP) within the DARWIN EU ® network. Two cohorts were included: a pre-pandemic population (2017–2019) and individuals infected with SARS-CoV-2 during the Omicron-dominant period. We estimated incidence rates (IRs) of VTE, ATE, and other cardiovascular events at 30-, 60-, 90-, and 180-days post-infection. Crude incidence rate ratios (IRRs) and age-sex standardized incidence ratios (SIRs) were calculated relative to the pre-pandemic cohort. Analyses were stratified by prior infection, vaccination status, and immunocompromised status. In total, we included over 7.6 million individuals (CPRD GOLD: 5.28 M; IPCI: 1.59 M; SIDIAP: 0.75 M) in the general population cohort, and about 0.8 million individuals (CPRD GOLD: 248,847; IPCI: 330,200; SIDIAP: 200,563) in the COVID-19 Omicron cohort. Crude IRs varied by outcome and data source. For VTE, IRs per 100,000 person-years were 136 [95%CI 131–141] in SIDIAP, 167 [164–169] in CPRD GOLD, and 264 [259–270] in IPCI. Elevated SIRs for VTE and ATE were observed following SARS-CoV-2 infection, highest within 30 days and persisting up to 180 days. In CPRD GOLD, the VTE SIR was 3.61 [2.45–5.53] at 30 days, decreasing to 1.88 [1.52–2.34] at 180 days. Higher SIRs were observed among immunocompromised individuals and those without prior infection. Our findings indicate that among individuals diagnosed with SARS-CoV-2 infection during the Omicron-dominant period, observed rates of thromboembolic events exceeded expected background incidence, particularly in the early post-infection period.

BACKGROUND AND AIMS:Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. However, large-scale epidemiological evidence remains scarce due to challenges in real-world disease recognition. This study aimed to characterise clinically recognised HCM and obstructive HCM (oHCM) across six European countries regarding prevalence, demographics, and clinical characteristics. METHODS:We conducted a retrospective cohort study using routinely collected healthcare data from six European countries, all mapped to the Observational Medical Outcomes Partnership (OMOP) Common Data Model within the DARWIN EU® network: CPRD-GOLD (UK), DK-DHR (Denmark), InGef RDB (Germany), NAJS (Croatia), NLHR (Norway), and SIDIAP (Spain). Clinically recognised HCM was defined based on recorded diagnoses captured in routine healthcare data, rather than on imaging-, haemodynamic-, or genotype-confirmed population screening. Adults (≥18 years) with a first recorded HCM or oHCM diagnosis after 2010 were included. We estimated annual period prevalence and described recorded comorbidities, diagnostic measurements, and treatments before, at, and after diagnosis. RESULTS:Among 40,277 individuals with HCM, 12,363 (31%) were first diagnosed with oHCM. Females were older than males at diagnosis (median 67-78 vs 57-68 years). Annual period prevalence increased over time, ranging from 0.04% (95% Confidence interval: 0.04-0.05) to 0.24% (0.23-0.24) in recent years. Prevalence was higher in males, but differences diminished among those aged ≥80 and with oHCM. Cardiovascular comorbidities were frequently recorded before and at the time of first diagnosis, especially hypertension, cardiac arrhythmias, ischaemic heart disease, and heart failure. Beta-blockers, diuretics, and angiotensin-converting enzyme inhibitors were the most common treatments. Most comorbidities and treatments were recorded over a year before HCM diagnosis. CONCLUSIONS:An increase in the prevalence of clinically recognised HCM across Europe was observed over time. This trend is likely multifactorial and may reflect changes in disease recognition, clinical practice, demographics, database-related factors, and potentially the underlying disease burden. Cardiovascular comorbidities and treatments were frequently recorded prior to diagnosis, which may suggest that some patients would benefit from increased diagnostic awareness.

BACKGROUND:Understanding the changing burden of head and neck cancers (HNC) is essential to guide public health interventions and inform cancer care strategies. METHODS:We conducted a cohort study using routinely collected primary care data Clinical Practice Research Datalink (CPRD) GOLD from the United Kingdom. Adults aged ≥ 18 years with ≥ 1 year of prior history were included. We estimated crude and age-standardised incidence rates (IRs) and one-, five-, and ten-year survival from 2000 to 2021, stratified by age and calendar year. Findings from CPRD GOLD were compared with primary care data from CPRD Aurum (England only). RESULTS:There were 12,455 patients with a diagnosis of HNC from CPRD GOLD (69.2 % male; median age 64 years). Crude incidence in GOLD increased from 9.08 (95 % CI: 7.88-10.42) per 100,000 person-years in 2000-15.59 (14.07-17.23) in 2021, with similar trends observed in CPRD Aurum. Age-standardised incidence trends were attenuated overall but remained elevated for oropharyngeal and tongue cancers. Five-year survival improved modestly, from 53.8 % (95 % CI: 51.4-56.3 %) in 2000-2004-58.7 % (56.5-60.9 %) in 2015-2019. CONCLUSIONS:Incidence increases for HNC were attenuated after age standardisation, suggesting a contribution of demographic ageing, although elevations persisted for specific subsites. Small improvements in long term survival highlights more research is needed to improve earlier diagnosis which will lead to better patient outcomes.

Objectives We aimed to assess the risk of incident autoimmune and inflammatory conditions during the post-acute period of COVID-19.Design Descriptive network cohort study.Setting Electronic health records from the UK and Dutch primary care, Norwegian linked health registry, hospital records of specialist centres in Spain, France and Korea and healthcare claims from Estonia and the USA.Participants We followed individuals between September 2020 and the latest available data from day 91 after a SARS-CoV-2 negative test (comparator) or a COVID-19 record (exposed patients, ie assessing patients during the post-acute phase). We further established a reinfection cohort (any further COVID-19 record among the exposed patients). We followed patients until an outcome, end of study period, death, day 365 or an infection (comparator only) or reinfection (exposed patients only).Main outcome measures We assessed postural orthostatic tachycardia syndrome (POTS) diagnoses/symptoms, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnoses/symptoms, multi-inflammatory syndrome (MIS) and several autoimmune diseases (rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) and type 1 diabetes mellitus (T1DM)).Meta-analysed crude incidence rate ratios (IRRs) of outcomes after COVID-19 versus negative testing and after reinfection versus a previous COVID-19 record yield the ratios of respective absolute risks of each assessed outcome. We performed subgroup analyses by age, sex and predominant variant periods.Results We included 2 521 812 individuals with a first COVID-19 record, 4 233 145 with a first negative test and 135 551 with a reinfection. Age and sex were largely comparable between exposure groups with a shorter follow-up for the reinfection cohorts. After COVID-19 compared with test-negative patients and equally after reinfection compared with previous COVID-19 patients, we did not observe increased rates for all outcomes and all subgroup analyses. Counts of MIS and JIA were too small for meta-analyses.Conclusions In our descriptive meta-analyses of crude IRRs among databases from various countries and settings, we did not observe increased rates of incident POTS, ME/CFS, RA, IBD, SLE and T1DM in COVID-19 versus test-negative or reinfection versus COVID-19 during the first 9 months of the post-acute phase of COVID-19 or reinfection (>90 days postinfection until month 12). Since causal interpretation cannot be made from this study, further causal research is warranted.

Background Human Papillomavirus (HPV) vaccines prevent HPV infection and related disease. 15 years after the first HPV vaccination programmes were launched in Europe, their long-term effectiveness can now start to be assessed. We designed a target trial emulation study to estimate the effectiveness of HPV vaccination in preventing invasive cervical cancer and high-grade precancerous lesions using three primary care databases. Methods In this target trial emulation study, we analysed primary care records from the UK (Clinical Practice Research Datalink; data from Sept 9, 1987 to Dec 15, 2023), primary care records linked to hospital records from Catalonia, Spain (Sistema d’Informació per al Desenvolupament de la Investigació en Atenció Primària; Jan 1, 2006 to June 30, 2023), and nationwide linked health registry (including primary care, secondary care, and other health data) in Norway (Norwegian Linked Health Registry; Jan 1, 2018 to Dec 31, 2023), all standardised to the Observational Medical Outcomes Partnership common data model. We included women aged 15 years or younger in 2008, coinciding with the start of public vaccination programmes. Exposure was defined as receiving one or more HPV vaccine doses by age 15 years. The main outcomes included high-grade cervical intraepithelial neoplasia (CIN2+), invasive cervical cancer, and conisation (as a proxy for CIN2+ diagnosis). Vaccinated and unvaccinated cohorts were sequentially matched on an annual basis by year of birth, location, and propensity scores, with up to five vaccinated people matched to an unvaccinated individual. Vaccine effectiveness, based on incidence rate ratios after 15 years of follow-up, were calculated using Poisson regression. Results across databases were meta-analysed using fixed-effects. The specified primary analysis in the original protocol was designed to assess exposure by HPV brand versus unvaccinated populations; however, due to the low number of events by brand, the study was underpowered and the primary analysis was amended to assess HPV vaccination exposure overall (any brand) versus unvaccinated. Findings After two-step matching, our analysis included 81 863 vaccinated and 46 357 unvaccinated women from the UK; 148 214 vaccinated and 39 952 unvaccinated from Spain; and 14 885 vaccinated and 4073 unvaccinated from Norway. Fewer than five cervical cancers were observed per cohort, precluding vaccine effectiveness estimation for this outcome. Meta-analytic vaccine effectiveness at 15 years was 42% (95% CI 6–64) against CIN2+ and 58% (6–82) against conisation. Interpretation Our estimates of vaccine effectiveness against CIN2+ and conisation in Europe align with estimates from previous systematic reviews of randomised controlled trials. We also observed an increased health-seeking behaviour among vaccinated individuals, suggesting that our study might have underestimated vaccine effectiveness. Further studies with longer follow-up are needed to estimate vaccine effectiveness against cervical cancer. Funding European Medicines Agency.

Describing cohort characterisation ensures comparability and reproducibility in multi-database observational studies. To address this need, we developed CohortCharacteristics, an open-source R package that facilitates standardised cohort characterisation in datasets mapped to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). This study aims to explain the development of the package and demonstrate its core functionality. We developed CohortCharacteristics, an open-source R package that can perform cohort characterisation for various types of databases. To demonstrate its functionality, we then used CohortCharacteristics to generate descriptive statistics on demographics, comorbidities, medication exposures, cohort overlap, and timing of cohort entries. The study included data from CPRD GOLD (UK), DK-DHR (Denmark), IPCI (Netherlands), IQVIA Longitudinal Patient Database Belgium (IQVIA LPD Belgium), IQVIA DA Germany, NAJS (Croatia), and SIDIAP (Spain), all mapped to the OMOP CDM. The CohortCharacteristics R package is freely available on CRAN with detailed vignettes and documentation on its functionality. Cohort characteristics were generally consistent across databases, with similar age distributions and female representation. CPRD GOLD, NAJS, and SIDIAP exhibited higher prescribing rates for respiratory, cardiovascular, and nervous system medications, while IQVIA databases and DK-DHR reported lower rates. Timing analysis showed that dementia diagnoses typically followed insomnia diagnoses in several databases, supporting existing literature. Antipsychotic prescriptions often occurred after dementia diagnosis, reflecting prescribing practices aligned with clinical guidelines. CohortCharacteristics enables consistent cohort characterisation across a network of data mapped to the OMOP CDM, thereby improving transparency in multi-database research. The package’s functionality, demonstrated in this study, illustrates its applicability in observational studies with OMOP CDM data.

Background:An increase in the use of medications for Attention-Deficit Hyperactivity Disorder (ADHD) has been reported globally. This study aims to estimate the trends of ADHD medications use among children and adults across Europe from 2010 to 2023. Methods:We conducted a population-level observational study using electronic health records from five European countries: Belgium, Germany, the Netherlands, Spain, and the UK. We estimated the prevalence and incidence of methylphenidate, dexamphetamine, lisdexamfetamine, atomoxetine and guanfacine use among individuals aged 3 years and older. We used the proportion of patients covered to measure treatment adherence. All analyses were reported by country and stratified by age group and sex. Findings:The prevalence of ADHD medication use increased across all five countries during the study period. Between 2010 and 2023, prevalence rose more than threefold in the UK (from 0.12% to 0.39%) and more than doubled in the Netherlands (from 0.67% to 1.56%). Adult use increased substantially in all countries, particularly among females. In the UK, prevalence among adults aged over 25 increased from 0.01% in 2010 to approximately 0.20% in 2023, representing a more than twenty-fold increase in females and fifteen-fold in males. Although ADHD medication use remained higher among males, the sex gap in treatment narrowed over time and with increasing age. After 1-year of medication initiation, 14.9%, 16.0%, 43.9%, and 30.8% of participants were covered by treatment in Germany, the Netherlands, Spain, and the UK respectively. Among initiators, the prevalence of psychiatric conditions and prior use of psycholeptic medications was higher in females and in older age groups. Interpretation:Over 14 years, ADHD medication prevalence increased across Europe, with varying incidence trends by country, age, and sex. Understanding the utilisation of ADHD medications can provide useful information in monitoring use, as well as for anticipation and planning to minimise potential shortages. Funding:European Medicines Agency.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain, inflammation, and fever; however, real-world evidence on the cardiovascular risks of individual NSAIDs remains limited. Sequence symmetry analysis (SSA) is a signal detection method for identifying adverse drug events (ADEs) in large electronic health record datasets. This study applied SSA to identify cardiovascular ADE signals associated with oral NSAIDs. Methods: This cohort study used primary care records from the UK Clinical Practice Research Datalink (CPRD GOLD). Adults ≥18 years with ≥1 year of prior observation and a new NSAID prescription between 2013-2023 were included. Incidence of seven cardiovascular events (acute myocardial infarction [MI], arrhythmia, deep vein thrombosis [DVT], heart failure, hemorrhagic stroke, ischemic stroke, pulmonary embolism [PE]) was assessed within 180 days before versus after NSAID initiation. Adjusted sequence ratios (aSR) with 95% confidence intervals were calculated for each NSAID-event pair, with aSR>1 indicating a positive ADE signal and aSR<1 indicating protective effect. Positive (NSAID-edema) and negative (NSAID-cataract) controls assessed validity. Sensitivity analyses included stratification by age and sex, alternate windows (90 and 365 days), and stratification by prior proton pump inhibitor (PPI) use. Results: 77,570 patients met inclusion criteria (median age 66 [IQR 54-76]; 53.9% male). Positive and negative controls aligned with expectations. Naproxen showed positive signals across all events, with the highest for PE (3.03 [2.63-3.51]). Ibuprofen showed six positive signals, with PE being highest (2.2 [1.88-2.59]). Diclofenac and etoricoxib each had five positive signals, with MI (3.30 [2.42-4.57]) and ischemic stroke (3.84 [2.11-7.43]) as the highest, respectively. Celecoxib and meloxicam showed four positive signals, with the highest being heart failure (2.15 [1.17-4.11]) and PE (2.66 [1.30-5.82]), respectively. MI and arrhythmia were common across all aforementioned medications. Aspirin showed negative signals across all events except PE (1.08 [0.96-1.22]). Age, sex, and window sensitivity analyses were consistent, while prior PPI stratification showed aSR attenuation in prior users. Conclusions: Individual NSAIDs exhibit varied cardiovascular ADE signals, underscoring the need for personalized risk evaluation. SSA in real-world data enhances pharmacovigilance by identifying rare ADE trends.