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INTRODUCTION: Antipsychotic drugs (APDs) are used to treat several mental illnesses. Some APDs have long been known to be associated with QT prolongation, potentially leading to torsades de pointes (TdP) and sudden cardiac death (SCD). In 2005, thioridazine was withdrawn because of the risk of SCD, bringing further attention to the arrhythmogenic potential of APDs.AIM: The aim of the current study was to evaluate the use of APDs in five European countries during the years 1996-2010.METHODS: A cohort study was conducted using prescription/dispensing data from seven healthcare databases [the AARHUS University Hospital Database (Denmark), the German Pharmacoepidemiological Research Database (GePaRD) (Germany), Health Search Database/Thales (HSD) and Emilia Romagna Regional Database (ERD) (Italy), PHARMO Database Network and Integrated Primary Care Information (IPCI) (the Netherlands) and The Health Improvement Network (THIN) (the UK), covering a population of 27 million individuals. The annual prescription rate of APDs was measured overall and for individual medications. APDs were classified as torsadogenic according to the Arizona-CERT list. All analyses were stratified by age, gender and calendar year.RESULTS: A total of 559 276 person-years (PYs) of exposure to APDs was captured. The crude annual prescription rate of APD use ranged from 3.0/1000 PYs in ERD to 7.7/1000 PYs in AARHUS. Among APDs with established torsadogenic potential, thioridazine was the most frequently used medication in the UK. Haloperidol was commonly prescribed in Italy and the Netherlands. The use of APDs with torsadogenic potential was much higher in elderly patients.CONCLUSIONS: Substantial use of APDs with torsadogenic potential has been reported in Europe in recent years, in spite of increasing concerns about their arrhythmogenic potential. This use was even greater in elderly patients, who are at higher risk of SCD.

Background: To describe the utilisation of antibiotics in children and adolescents across 5 European countries based on the same drug utilisation measures and age groups. Special attention was given to age-group-specific distributions of antibiotic subgroups, since comparison in this regard between countries is lacking so far.Methods: Outpatient paediatric prescriptions of systemic antibiotics during the years 2005-2008 were analysed using health care databases from the UK, the Netherlands, Denmark, Italy and Germany. Annual antibiotic prescription rates per 1,000 person years were estimated for each database and stratified by age (≤4, 5-9, 10-14, 15-18 years). Age-group-specific distributions of antibiotic subgroups were calculated for 2008.Results: With 957 prescriptions per 1000 person years, the highest annual prescription rate in the year 2008 was found in the Italian region Emilia Romagna followed by Germany (561), the UK (555), Denmark (481) and the Netherlands (294). Seasonal peaks during winter months were most pronounced in countries with high utilisation. Age-group-specific use varied substantially between countries with regard to total prescribing and distributions of antibiotic subgroups. However, prescription rates were highest among children in the age group ≤4 years in all countries, predominantly due to high use of broad spectrum penicillins.Conclusions: Strong increases of antibiotic prescriptions in winter months in high utilising countries most likely result from frequent antibiotic treatment of mostly viral infections. This and strong variations of overall and age-group-specific distributions of antibiotic subgroups across countries, suggests that antibiotics are inappropriately used to a large extent.

BACKGROUND: There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia.METHODS: We conducted a nested case-control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders.RESULTS: We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis.INTERPRETATION: Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.