Ruth Brauer1,2, Ian Douglas1, Luis Alberto Garcia Rodriguez3, Gerald Downey2, Consuelo Huerta4, Francisco de Abajo5, Andrew Bate6, Maurille Feudjo Tepie2, Mark C H de Groot7, Raymond Schlienger8, Robert Reynolds9, Liam Smeeth1, Olaf Klungel7, Ana Ruigómez3. 1. London School of Hygiene and Tropical Medicine, Faculty of Epidemiology and Population Health, London, UK. 2. Amgen Limited, London, UK. 3. Fundación Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain. 4. Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), Medicines for Human Use Department, Division of Pharmacoepidemiology and Pharmacovigilance, Madrid, Spain. 5. Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Department of Biomedical Sciences, University of Alcala, Alcalá de Henares, Spain. 6. Epidemiology, Pfizer Ltd, Tadworth, UK. 7. Utrecht University, Faculty of Science, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht, The Netherlands. 8. Novartis Pharma AG, Basel, Switzerland. 9. Epidemiology, Pfizer Research and Development, New York, NY, USA.
Abstract
PURPOSE: To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use. METHODS: The source population comprised of patients registered in two primary care databases, in the UK and in Spain. We identified a cohort consisting of new users of antibiotics during the study period (2004-2009) and non-users during the study period or in the previous year. Cases with ALI were identified within this cohort and classified as definite or probable, based on recorded medical information. The relative risk (RR) of ALI associated with antibiotic use was computed using Poisson regression. For the nested case-control analyses, up to five controls were matched to each case by age, sex, date and practice (in CPRD) and odds ratios (OR) were computed with conditional logistic regression. RESULTS: The age, sex and year adjusted RRs of definite ALI in the current antibiotic use periods was 10.04 (95% CI: 6.97-14.47) in CPRD and 5.76 (95% CI: 3.46-9.59) in BIFAP. In the case-control analyses adjusting for life-style, comorbidities and use of medications, the OR of ALI for current users of antibiotics was and 5.7 (95% CI: 3.46-9.36) in CPRD and 2.6 (95% CI: 1.26-5.37) in BIFAP. CONCLUSION: Guided by a common protocol, both cohort and case-control study designs found an increased risk of ALI associated with the use of antibiotics in both databases, independent of the exposure and case definitions used. However, the magnitude of the risk was higher in CPRD compared to BIFAP.
PURPOSE: To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use. METHODS: The source population comprised of patients registered in two primary care databases, in the UK and in Spain. We identified a cohort consisting of new users of antibiotics during the study period (2004-2009) and non-users during the study period or in the previous year. Cases with ALI were identified within this cohort and classified as definite or probable, based on recorded medical information. The relative risk (RR) of ALI associated with antibiotic use was computed using Poisson regression. For the nested case-control analyses, up to five controls were matched to each case by age, sex, date and practice (in CPRD) and odds ratios (OR) were computed with conditional logistic regression. RESULTS: The age, sex and year adjusted RRs of definite ALI in the current antibiotic use periods was 10.04 (95% CI: 6.97-14.47) in CPRD and 5.76 (95% CI: 3.46-9.59) in BIFAP. In the case-control analyses adjusting for life-style, comorbidities and use of medications, the OR of ALI for current users of antibiotics was and 5.7 (95% CI: 3.46-9.36) in CPRD and 2.6 (95% CI: 1.26-5.37) in BIFAP. CONCLUSION: Guided by a common protocol, both cohort and case-control study designs found an increased risk of ALI associated with the use of antibiotics in both databases, independent of the exposure and case definitions used. However, the magnitude of the risk was higher in CPRD compared to BIFAP.
Authors: Francisco J de Abajo; Sara Rodríguez-Martín; Antonio Rodríguez-Miguel; Miguel J Gil Journal: J Am Heart Assoc Date: 2017-05-18 Impact factor: 5.501
Authors: Carmen Ferrajolo; Katia M C Verhamme; Gianluca Trifirò; Geert W 't Jong; Gino Picelli; Carlo Giaquinto; Giampiero Mazzaglia; Bruno H Stricker; Francesco Rossi; Annalisa Capuano; Miriam C J M Sturkenboom Journal: Drug Saf Date: 2017-04 Impact factor: 5.606
Authors: Ruth Brauer; Ana Ruigómez; Olaf Klungel; Robert Reynolds; Maurille Feudjo Tepie; Liam Smeeth; Ian Douglas Journal: Pharmacoepidemiol Drug Saf Date: 2015-08-06 Impact factor: 2.890