Applying two approaches to detect unmeasured confounding due to time-varying variables in a self-controlled risk interval design evaluating COVID-19 vaccine safety signals, using myocarditis as a case example.

We test the robustness of the self-controlled risk interval (SCRI) design in a setting where time between doses may introduce time-varying confounding, using both negative control outcomes (NCOs) and quantitative bias analysis (QBA). All vaccinated cases identified from 5 European databases between 1 September 2020 and end of data availability were included. Exposures were doses 1-3 of the Pfizer, Moderna, AstraZeneca, and Janssen COVID-19 vaccines; outcomes were myocarditis and otitis externa (NCO).

Effectiveness of homologous/heterologous booster COVID-19 vaccination schedules against severe illness in general population and clinical subgroups in three European countries.

Using 4 data-sources (Spain, Italy, United Kingdom) data and a 1:1 matched cohort study, we aimed to estimate vaccine effectiveness (VE) in preventing SARS-CoV-2 infections with hospitalisations (±30 days) and death (±56 days) in general population and clinical subgroups with homologous/heterologous booster schedules (Comirnaty-BNT and Spikevax-MOD original COVID-19 vaccines) by comparison with unboosted individuals, during Delta and beginning of Omicron variants. Hazard Ratio (HR, by Cox models) and VE ([1-HR]*100) were calculated by inverse probability weights. Between December 2020-February 2022, in adults without prior SARS-CoV-2 infection, we matched 5.

Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis.

In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy.

Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Prescribing Trends of Medicinal Products Containing Valproate: An Interrupted Time Series Study.

Introduction: Due to established teratogenicity of valproates, the EU risk minimisation measures (RMMs) with a pregnancy prevention programme (PPP) for valproate were updated in March 2018.

Objectives: To investigate the effectiveness of the 2018 EU RMMs on valproate utilisation in five European countries/regions.

Methods: A multi-database, times series study of females of childbearing potential (12-55 years) was conducted using electronic medical records from five countries/regions (01.

Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries.

Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest).

Assessment of thyroiditis risk associated with HPV vaccination among girls aged 9-18 years: A time-varying cohort study.

Background: Previous studies have suggested a relationship between human papillomavirus vaccine and autoimmune diseases, including thyroiditis. Thus, we aimed to evaluate the risk of thyroiditis associated with HPV vaccination among girls using the Primary Care Database For Pharmacoepidemiological Research (BIFAP) in Spain.

Methods: In this retrospective cohort study, girls in BIFAP aged 9-18 years from 2007 to 2016, free of past thyroiditis and HPV vaccination, were included.

Papillomavirus vaccination and Guillain-Barre Syndrome among girls: A cohort study in Spain.

Background: Studies of the association of Guillain-Barré Syndrome (GBS) with papillomavirus vaccination (HPVv; scheduled from 2007) have provided contradicting results, probably due to the low frequency of this disease. We aimed at estimating that risk relative to non-vaccination among girls, by using the Spanish Primary Care Database for Pharmacoepidemiological Research (BIFAP).

Methods: A cohort study of girls aged 9-18 years during 2007-2016 free of GBS or HPVv was selected and followed up to GBS diagnosis.

Evaluation of the Risk of Inflammatory Bowel Disease after the HPV Vaccination in Primary Care in Spain: A Time-Varying Cohort Analysis of Around 390,000 Girls.

Introduction: A link between the human papillomavirus vaccination (HPVv) and inflammatory bowel disease (IBD) has been suggested.

Objective: We aimed to estimate the risk of IBD following HPVv compared with periods not exposed to the vaccines.

Methods: Primary healthcare records (Spanish Primary Care Database For Pharmacoepidemiological Research [BIFAP]) were used in a cohort study of girls in Spain aged 9-18 years between 2007 and 2016 free of IBD or HPVv at study entrance.

An Estimation of the Incidence of Thyroiditis Among Girls in Primary Care in Spain.

Objective: As for other auto-immune processes, thyroiditis is monitored after vaccinations. The aim was to estimate the baseline incidence of thyroiditis among girls, before investigating papillomavirus vaccination as a potential risk factor.

Methods: Observational cohort study including girls aged 9-18 years and registered between 2002-2016 in the Spanish Primary Care Database for Pharmacoepidemiological Research.

The recording and prevalence of Inflammatory bowel disease in girls' primary care medical Spanish records.

Purpose: Inflammatory bowel disease (IBD) recording validation among girls in the Spanish Primary Care Database For Pharmacoepidemiological Research (BIFAP).

Methods: In this observational study, girls aged 9 to 18 years registered in BIFAP between 2002 and 2016, were followed up until there was a recorded IBD diagnosis or a referral to specialist indicating IBD. Anonymized profiles were reviewed to retrieve diagnosis confirmation (a positive colonoscopy or biopsy, specialist, or physician's comments mentioning the IBD diagnosis) or discarding (negative procedure results, alternative diagnosis, or family history).

Appropriateness of initial dose of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation in the UK.

Objective: To evaluate the appropriateness of the initial prescribed daily dose of non-vitamin K antagonist oral anticoagulants (NOACs) according to label in patients with non-valvular atrial fibrillation (NVAF) in the UK.

Design: Population-based cross-sectional study.

Setting: UK primary care.

Development of hypotension in patients newly diagnosed with heart failure in UK general practice: retrospective cohort and nested case-control analyses.

Objectives: Hypotension is of particular relevance for patients with heart failure (HF), since almost all HF drugs cause lowering of blood pressure (BP) and it is associated with a poor prognosis. We aimed to investigate hypotension incidence and risk factors in patients with incident HF in the UK.

Design: Retrospective cohort study including nested case-control analyses.

Predictors of Over-Anticoagulation in Warfarin Users in the UK General Population: A Nested Case-Control Study in a Primary Health Care Database.

Background:  Many patients on warfarin therapy often present with supratherapeutic international normalized ratio (INR) levels, resulting from the influence of several patient-specific factors, which have been associated with adverse outcomes.

Objective:  This article aims to identify risk factors for over-anticoagulation (INR levels ≥4) in a cohort of patients taking warfarin.

Methods:  A cohort of warfarin users aged 18 to 85 years from January 2005 to April 2013 was identified in The Health Improvement Network U.

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies.

Background: Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations.

Methods: Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75-325 mg/day).

Heart failure hospitalization: An important prognostic factor for heart failure re-admission and mortality.

Background: Few studies have evaluated incidence rates and risk factors for heart failure hospitalization (HFH) and mortality starting at initial heart failure (HF) diagnosis.

Methods: Patients with a first ever recorded diagnosis of HF between January 2000 and December 2005 (N=3516) were identified from The Health Improvement Network primary care database and followed until April 2011 to identify HFHs (through linked hospitalization data) and deaths. HF patients were stratified by hospitalization status at HF diagnosis (start date), and hazard ratios (HRs) for HFH and death were estimated using Cox regression.

Incidence and risk factors for atrial fibrillation in patients with newly diagnosed heart failure.

Aims: We aimed to identify the incidence and risk factors for first ever atrial fibrillation among patients with newly diagnosed heart failure following initial heart failure diagnosis.

Methods: A heart failure inception cohort of patients aged 20-89 years without atrial fibrillation or cancer (N = 14 457) from 2000 to 2005 was identified from The Health Improvement Network primary care database in the United Kingdom and followed for a mean of 2.67 years.

Impact of hyperkalaemia definition on incidence assessment: implications for epidemiological research based on a large cohort study in newly diagnosed heart failure patients in primary care.

Background: Various definitions of hyperkalaemia have been used in clinical research, and data from routine clinical practice on its incidence are sparse. We aimed to establish the incidence of hyperkalaemia in patients with newly diagnosed heart failure in the UK general population using different definitions for the condition.

Methods: We conducted a large retrospective cohort study using data from The Health Improvement Network primary care database.

Parental administration of over-the-counter medication to Spanish children: A population-based national study.

Purpose: To determine the prevalence and predictors of parental administration of over-the-counter (OTC) medications to children in Spain.

Design And Methods: This was a cross-sectional study performed with data from the 2011 to 2012 Spanish National Health Survey among children (birth to 14 years old) of both sexes.

Results: Of the 5,495 children analyzed, 8.