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Some pharmacokinetic studies have reported that proton pump inhibitors (PPIs) reduce the activity of clopidogrel, but the results of studies assessing clinical outcomes in patients receiving both drugs are inconsistent. We have therefore carried out a population-based cohort study with nested case-control analysis, in order to evaluate changes in the risk of cardiovascular and peptic ulcer bleeding (PUB) events associated with PPI use in patients receiving clopidogrel. A total of 42,542 patients aged 50-84 years in 2000-2007 who survived an acute coronary event were identified in two UK-based primary care databases (The Health Improvement Network and the General Practice Research Database). Individuals were followed up to identify incident cases of non-fatal myocardial infarction/coronary death (n = 2,546) and PUB (n = 194). Controls were frequency matched to cases by age, sex and calendar year. Compared with PPI non-use, current continuous PPI use was not associated with a significant change in risk of non-fatal myocardial infarction/coronary death among current continuous users of clopidogrel monotherapy (relative risk [RR], 1.06; 95% confidence interval [95% CI], 0.47 to 2.36) or dual antiplatelet therapy (DAT; RR, 0.80; 95% CI, 0.47 to 1.37) who initiated their antiplatelet therapy shortly after their coronary event. Among patients prescribed DAT at the start date, the RR of PUB events associated with current PPI use initiated at the start date was 0.66 (95% CI, 0.27 to 1.60).

BACKGROUND: Basal cell carcinoma (BCC) is one of the most common types of nonmelanoma skin cancer affecting the white population; however, little is known about how the incidence varies across the U.K. OBJECTIVES: To determine the variation in BCC throughout the U.K. METHODS: Data from 2004 to 2010 were obtained from The Health Improvement Network database. European and world age-standardized incidence rates (EASRs and WASRs, respectively) were obtained for country-level estimates and levels of socioeconomic deprivation, while strategic health-authority-level estimates were directly age and sex standardized to the U.K. standard population. Incidence-rate ratios were estimated using multivariable Poisson regression models. RESULTS: The overall EASR and WASR of BCC in the U.K. were 98.6 per 100,000 person-years and 66.9 per 100,000 person-years, respectively. Regional-level incidence rates indicated a significant geographical variation in the distribution of BCC, which was more pronounced in the southern parts of the country. The South East Coast had the highest BCC rate followed by South Central, Wales and the South West. Incidence rates were substantially higher in the least deprived groups and we observed a trend of decreasing incidence with increasing levels of deprivation (P < 0.001). Finally, in terms of age groups, the largest annual increase was observed among those aged 30-49 years. CONCLUSIONS: Basal cell carcinoma is an increasing health problem in the U.K.; the southern regions of the U.K. and those in the least deprived groups had a higher incidence of BCC. Our findings indicate an increased incidence of BCC for younger age groups below 49 years.

BACKGROUND: Data on utilization patterns and safety of non-steroidal anti-inflammatory drugs (NSAIDs) in children are scarce. The purpose of this study was to investigate the utilization of NSAIDs among children in four European countries as part of the Safety Of non-Steroidal anti-inflammatory drugs (SOS) project. METHODS: We used longitudinal patient data from seven databases (GePaRD, IPCI, OSSIFF, Pedianet, PHARMO, SISR, and THIN) to calculate prevalence rates of NSAID use among children (0-18 years of age) from Germany, Italy, Netherlands, and United Kingdom. All databases contained a representative population sample and recorded demographics, diagnoses, and drug prescriptions. Prevalence rates of NSAID use were stratified by age, sex, and calendar time. The person-time of NSAID exposure was calculated by using the duration of the prescription supply. We calculated incidence rates for serious adverse events of interest. For these adverse events of interest, sample size calculations were conducted (alpha = 0.05; 1-beta = 0.8) to determine the amount of NSAID exposure time that would be required for safety studies in children. RESULTS: The source population comprised 7.7 million children with a total of 29.6 million person-years of observation. Of those, 1.3 million children were exposed to at least one of 45 NSAIDs during observation time. Overall prevalence rates of NSAID use in children differed across countries, ranging from 4.4 (Italy) to 197 (Germany) per 1000 person-years in 2007. For Germany, United Kingdom, and Italian pediatricians, we observed high rates of NSAID use among children aged one to four years. For all four countries, NSAID use increased with older age categories for children older than 11. In this analysis, only for ibuprofen (the most frequently used NSAID), enough exposure was available to detect a weak association (relative risk of 2) between exposure and asthma exacerbation (the most common serious adverse event of interest). CONCLUSIONS: Patterns of NSAID use in children were heterogeneous across four European countries. The SOS project platform captures data on more than 1.3 million children who were exposed to NSAIDs. Even larger data platforms and the use of advanced versions of case-only study designs may be needed to conclusively assess the safety of these drugs in children.

BACKGROUND: Recent changes to diagnostic criteria for depression in DSM-5 remove the bereavement exclusion, allowing earlier diagnosis following bereavement. Evaluation of the potential effect of this change requires an understanding of existing psychotropic medication prescribing by non-specialists after bereavement. AIMS: To describe initiation of psychotropic medication in the first year after partner bereavement. METHODS: In a UK primary care database, we identified 21,122 individuals aged 60 and over with partner bereavement and no psychotropic drug use in the previous year. Prescribing (anxiolytic/hypnotic, antidepressant, antipsychotic) after bereavement was compared to age, sex and practice matched controls. RESULTS: The risks of receiving a new psychotropic prescription within two and twelve months of bereavement were 9.5% (95% CI 9.1 to 9.9%) and 17.9% (17.3 to 18.4%) respectively; an excess risk of initiation in the first year of 12.4% compared to non-bereaved controls. Anxiolytic/hypnotic and antidepressant initiation rates were highest in the first two months. In this period, the hazard ratio for initiation of anxiolytics/hypnotics was 16.7 (95% CI 14.7 to 18.9) and for antidepressants was 5.6 (4.7 to 6.7) compared to non-bereaved controls. 13.3% of those started on anxiolytics/hypnotics within two months continued to receive this drug class at one year. The marked variation in background family practice prescribing of anxiolytics/hypnotics was the strongest determinant of their initiation in the first two months after bereavement. CONCLUSION: Almost one in five older people received a new psychotropic drug prescription in the year after bereavement. The early increase and trend in antidepressant use after bereavement suggests some clinicians did not adhere to the bereavement exclusion, with implications for its recent removal in DSM-5. Family practice variation in use of anxiolytics/hypnotics suggests uncertainty over their role in bereavement with the potential for inappropriate long term use.