title: Case-crossover design: an alternative strategy for detecting drug-induced liver injury.
abstract: OBJECTIVE
  Our observational study was conducted to assess if the case--crossover design could be applied to detect the risk of hepatoxic drugs on liver injury in the automated databases.
  
  
  METHODS
  The study was conducted on approximately 22 million people enrolled in Taiwan's National Health Insurance database from 1997 to 2004. We applied case--crossover and case--control designs to assess the estimated risks of liver injury related to well-known hepatoxic drugs, including isoniazid, rifampicin, erythromycin, and diclofenac. Using case--crossover and case--control designs, we analyzed to explore the association between hospitalization and our target drugs through a conditional logistic regression model.
  
  
  RESULTS
  The adjusted odds ratios (ORs) of isoniazid, rifampicin, erythromycin, and diclofenac showed 24.4 (confidence interval [CI] =10.7-55.5), 30.8 (CI=14.1-67.1), 2.1 (CI=1.4-3.1), and 2.9 (CI=2.4-3.5) among 4,413 hospitalized liver injury patients during the 30-day exposure window by the case--crossover designs. Most adjusted ORs by case--crossover design were more conservative than ORs by case--control design.
  
  
  CONCLUSIONS
  In addition to a case--control design, the case--crossover design is a suitable method, for detecting the potential hepatotoxicity of drugs.
authors.affiliation: Department of Public Health, Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Room 733, 17 Syujhou Road, Taipei, Taiwan.
authors.forename: Chang-Hsing
authors.initials: CH
authors.lastname: Lee
authors.forename: Jung-Der
authors.initials: JD
authors.lastname: Wang
authors.forename: Pau-Chung
authors.initials: PC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000453:epidemiology*; D015897:Comorbidity; D018592:Cross-Over Studies; D019992:Databases as Topic; D004008:Diclofenac / Q000009:adverse effects; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology*; D004917:Erythromycin / Q000009:adverse effects; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011247:Pregnancy; D012107:Research Design; D012293:Rifampin / Q000009:adverse effects; D018570:Risk Assessment; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D004917:Erythromycin; D007538:Isoniazid; D012293:Rifampin