title: The risk of acute liver injury among users of antibiotic medications: a comparison of case-only studies.
abstract: OBJECTIVE
  The aims of this study were two-fold: (i) to investigate the effect of exposure to antibiotic agents on the risk of acute liver injury using a self-controlled case series and case-crossover study and (ii) to compare the results between the case-only studies.
  
  
  METHODS
  For the self-controlled case series study relative incidence ratios (IRR) were calculated by dividing the rate of acute liver injury experienced during patients' periods of exposure to antibiotics to patients' rate of events during non-exposed time using conditional Poisson regression. For the case-crossover analysis we calculated Odds Ratios (OR) using conditional logistic regression by comparing exposure during 14- and 30-day risk windows with exposure during control moments.
  
  
  RESULTS
  Using the self-controlled case series approach, the IRR was highest during the first 7 days after receipt of a prescription (10.01, 95% CI 6.59-15.18). Omitting post-exposure washout periods lowered the IRR to 7.2. The highest estimate in the case-crossover analysis was found when two 30-day control periods 1 year prior to the 30-day ALI risk period were retained in the analysis: OR = 6.5 (95% CI, 3.95-10.71). The lowest estimate was found when exposure in the 14-day risk period was compared to exposure in four consecutive 14-day control periods immediately prior to the risk period (OR = 3.05, 95% CI, 2.06-4.53).
  
  
  CONCLUSIONS
  An increased relative risk of acute liver injury was consistently observed using both self-controlled case series and case-crossover designs. Case-only designs can be used as a viable alternative study design to study the risk of acute liver injury, albeit with some limitations.
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Ruth
authors.identifier: http://orcid.org/0000-0001-8934-347X
authors.initials: R
authors.lastname: Brauer
authors.affiliation: Fundación Centro Español de Investigación Farmacoepidemiológica, (CEIFE), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ruigómez
authors.affiliation: Faculty of Science, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Olaf
authors.initials: O
authors.lastname: Klungel
authors.affiliation: Epidemiology, Pfizer Research and Development, New York, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Reynolds
authors.affiliation: Amgen NV, London, United Kingdom.
authors.forename: Maurille
authors.initials: M
authors.lastname: Feudjo Tepie
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Liam
authors.initials: L
authors.lastname: Smeeth
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Douglas
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents
keywords: CPRD; acute liver injury; antibiotic agents; case-crossover; pharmacoepidemiology; self-controlled case series