Risk of hip fractures associated with benzodiazepines: Applying common protocol to a multi-database nested case-control study. The protect project
Requena, Gema; Logie, John; González-González, Rocío; Gardarsdottir, Helga; Afonso, Ana; Souverein, Patrick C.; Merino, Elisa Martin; Boudiaf, Nada; Huerta, Consuelo; Bate, Andrew; Alvarez, Yolanda; García-Rodríguez, Luis A.; Reynolds, Robert; Schlienger, Raymond G.; De Groot, Mark C.H.; Klungel, Olaf H.; De Abajo, Francisco J.
(2014) Pharmacoepidemiology and Drug Safety, volume 23, pp.
(Abstract)
Abstract
Background: The association between benzodiazepines (BZD) and hip fractures has been estimated in several observational studies although diverse methodologies and definitions have hampered comparability. Objectives: To evaluate the discrepancies in the risk estimates of hip/femur fractures associated with BDZs across different databases and to assess the impact of different matching
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strategies. Methods: A case control study nested in a cohort of BZD users, examining their association with the risk of hip/ femur fracture between 2001 and 2009, was performed within 3 databases, the BIFAP (Spain), the CPRD (UK) and the Mondriaan (Netherlands) database. A risk set sampling matching was performed using two strategies: 1) controls matched by age (up to ± 2 years), sex and time in the cohort (up to ± 6 months) and 2) controls selected with the smallest Manhattan distance according same matching factors. Co-morbidity and co-medication adjusted OR and (95% confidence intervals) were estimated for current use (up to 30 days after last supply) vs. past (>60 days after current use) using conditional logistic regression models. Sensitivity analysis was performed in CPRD including matching by general practice (GP). Results: Adjusted ORs (matching 1) for current use were 1.14 (1.03-1.27) in BIFAP; 1.32 (1.22-1.42) in CPRD, and 1.34 (0.63-2.82) in Mondriaan. Matching 2 resulted in ORs of 1.09 (1.03-1.27), 1.29 (1.17-1.42) and 1.28 (0.60-2.71) in BIFAP, CPRD and Mondriaan respectively. In CPRD, adding GP-practice as a matching factor to matching strategy 1 increased the OR to 1.46 (1.35-1.59). Conclusions: By applying a common protocol, the estimated risk of hip/femur fractures associated to BZD was consistent between studies. The different matching strategies did not influence the risk estimates substantially, however the inclusion of GP-practice as matching factor should be carefully considered in further studies.
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Keywords: benzodiazepine derivative, hip fracture, data base, human, case control study, pharmacoepidemiology, risk management, risk, implantable cardioverter defibrillator, fracture, femur fracture, observational study, general practice, sensitivity analysis, model, logistic regression analysis, confidence interval, drug therapy, morbidity, sampling, methodology, Netherlands, Spain
ISSN: 1053-8569
Publisher: John Wiley and Sons Ltd