Understanding inconsistency in the results from observational pharmacoepidemiological studies: the case of antidepressant use and risk of hip/femur fractures.

PURPOSE: Results from observational studies on the same exposure-outcome association may be inconsistent because of variations in methodological factors, clinical factors or health care systems. We evaluated the consistency of results assessing the association between antidepressant use and the risk of hip/femur fractures in three European primary care databases using two different study designs. METHODS: Cohort and nested case control studies were conducted in three European primary care databases (Spanish BIFAP, Dutch Mondriaan and UK THIN) to assess the association between use of antidepressants and hip/femur fracture. A common protocol and statistical analysis plan was applied to harmonize study design and conduct between data sources. RESULTS: Current use of antidepressants was consistently associated with a 1.5 to 2.5-fold increased risk of hip/femur fractures in all data sources with both designs, with estimates for SSRIs generally higher than those for TCAs. In general, risk estimates in Mondriaan, the smallest data source, were higher compared to the other data sources. This difference may be partially explained by an interaction between SSRI and age in Mondriaan. Adjustment for GP-recorded lifestyle factors and matching on general practice had negligible impact on adjusted relative risk estimates. CONCLUSION: We found a consistent increased risk of hip/femur fracture with current use of antidepressants across different databases and different designs. Applying similar pharmacoepidemiological study methods resulted in similar risks for TCA use and some variation for SSRI use. Some of these differences may express real (or natural) variance in the exposure-outcome co-occurrences.

Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database.

BACKGROUND: The risk of thromboembolic events in adults with primary immune thrombocytopenia has been little investigated despite findings of increased susceptibility in other thrombocytopenic autoimmune conditions. The objective of this study was to evaluate the risk of thromboembolic events among adult patients with and without primary immune thrombocytopenia in the UK General Practice Research Database. DESIGN AND METHODS: Using the General Practice Research Database, 1,070 adults (>or=18 years) with coded records for primary immune thrombocytopenia first referenced between January 1(st) 1992 and November 30(th) 2007, and having at least one year pre-diagnosis and three months post-diagnosis medical history were matched (1:4 ratio) with 4,280 primary immune thrombocytopenia disease free patients by age, gender, primary care practice, and pre-diagnosis observation time. The baseline prevalence and incidence rate of thromboembolic events were quantified, with comparative risk modelled by Cox's proportional hazards regression. RESULTS: Over a median 47.6 months of follow-up (range: 3.0-192.5 months), adjusted hazard ratios of 1.58 (95% CI, 1.01-2.48), 1.37 (95% CI, 0.94-2.00), and 1.41 (95% CI, 1.04-1.91) were found for venous, arterial, and combined (arterial and venous) thromboembolic events, respectively, when comparing the primary immune thrombocytopenia cohort with the primary immune thrombocytopenia disease free cohort. Further event categorization revealed an elevated incidence rate for each occurring venous thromboembolic subtype among the adult patients with primary immune thrombocytopenia. CONCLUSIONS: Patients with primary immune thrombocytopenia are at increased risk for venous thromboembolic events compared with patients without primary immune thrombocytopenia.

Retapamulin prescriptions and monitored off-label use.

INTRODUCTION: Retapamulin, a topical pleuromutilin that selectively inhibits bacterial protein synthesis, is approved for treatment of impetigo and secondarily infected traumatic lesions in adults and in children older than 9 months of age. OBJECTIVE: A 5-year study was conducted to monitor prescription use in children younger than 9 months of age. METHODS: Annual prescription events were monitored in the UK Clinical Practice Research Datalink (CPRD) and the Clinformatics™ DataMart Multiplan (IMPACT), a product of OptumInsight Life Sciences, Inc. (Eden Prairie, MN, USA), from the USA. RESULTS: In the CPRD, of 148 prescriptions, three (2 %) were identified in children aged less than 9 months between years 2008 and 2011. In IMPACT, of 59,210 claims for retapamulin in children, 1,951 (3.3 %) were categorized as definitive, or uncertain for, less than 9 months of age between 2007 and 2011. CONCLUSION: Retapamulin prescription events in children aged less than 9 months were relatively low compared with other recent estimations of off-label pediatric medicines. Our report provides a framework for future investigations and discussions that may facilitate off-label reporting schemes and promote pediatric drug safety.

Prevalence of diagnosed adult immune thrombocytopenia in the United Kingdom.

INTRODUCTION: Data regarding the prevalence of immune thrombocytopenia (ITP) is limited, and is derived from North American population-based analyses. Therefore, the authors conducted the first study outside the United States (US) using the United Kingdom (UK) General Practice Research Database (GPRD) to estimate the adult prevalence of ITP in the UK. METHODS: This study estimated the diagnosed prevalence of ITP in the adult population in UK using the GPRD from January 1, 1992 to December 31, 2009. RESULTS: The unadjusted, overall 18-year period prevalence was 50.29/100,000 (95% CI: 48.51, 52.06). The age- and gender-adjusted, overall 18-year period prevalence was 50.00/100,000 (95% CI: 49.20, 50.90). ITP prevalence was lower in adults aged 18-49 years of age (30.09/100,000, 95% CI: 28.27, 31.90) than in older adults aged 50-64 years of age (58.22/100,000, 95% CI: 53.88, 62.57) or ≥65 years of age (93.80/100,000, 95% CI: 88.76, 98.85). Prevalence was higher among females (59.32/100,000, 95% CI: 56.63, 62.01) than in males (40.66/100,000, 95% CI: 38.36, 42.96). Prevalence in the GPRD increased over time (1992 [16.33/100,000, 95% CI: 13.70, 19.00], 2000 [36.93/100,000, 95% CI: 34.50, 39.30], and 2009 [58.49/100,000, 95% CI: 55.80, 61.20]). CONCLUSION: This new analysis of general practice in the UK provides robust prevalence estimates of diagnosed ITP among adults in Europe. ITP prevalence is higher in women and increases with age and over time.