title: Confounding in the association of proton pump inhibitor use with risk of community-acquired pneumonia.
abstract: BACKGROUND
  Use of proton pump inhibitors (PPIs) is associated with community-acquired pneumonia (CAP), an association which may be confounded by unobserved patient and prescriber characteristics.
  
  
  OBJECTIVE
  We assessed for confounding in the association between PPI use and CAP by using a 'falsification approach,' which estimated whether PPI use is also implausibly associated with other common medical conditions for which no known pathophysiologic link exists.
  
  
  METHODS
  Retrospective claims-based cohort study.
  
  
  METHODS
  Six private U.S. health plans.
  
  
  METHODS
  Individuals who filled at least one prescription for a PPI (N = 26,436) and those who never did (N = 28,054) over 11 years.
  
  
  METHODS
  Multivariate linear regression of the association between a filled prescription for a PPI and a diagnosis of CAP in each 3-month quarter. In falsification analyses, we tested for implausible associations between PPI use in each quarter and rates of osteoarthritis, chest pain, urinary tract infection (UTI), deep venous thrombosis (DVT), skin infection, and rheumatoid arthritis. Independent variables included an indicator for whether a prescription for a PPI was filled in a given quarter, and quarterly indicators for various co-morbidities, age, income, geographic location, and marital status.
  
  
  RESULTS
  Compared to nonusers, those ever using a PPI had higher adjusted rates of CAP in quarters in which no prescription was filled (68 vs. 61 cases per 10,000 persons, p < 0.001). Similar associations were noted for all conditions (e.g. chest pain, 336 vs. 282 cases, p < 0.001; UTI, 151 vs. 139 cases, p < 0.001). Among those ever using a PPI, quarters in which a prescription was filled were associated with higher adjusted rates of CAP (111 vs. 68 cases per 10,000, p < 0.001) and all other conditions (e.g. chest pain, 597 vs. 336 cases, p < 0.001; UTI, 186 vs. 151 cases, p < 0.001), compared to quarters in which no prescription was filled.
  
  
  CONCLUSIONS
  PPI use is associated with CAP, but also implausibly associated with common medical conditions. Observed associations between PPI use and CAP may be confounded.
authors.affiliation: Department of Health Care Policy, Harvard Medical School, 180 Longwood Avenue, Boston, MA 02115, USA. jena@hcp.med.harvard.edu
authors.forename: Anupam B
authors.initials: AB
authors.lastname: Jena
authors.forename: Eric
authors.initials: E
authors.lastname: Sun
authors.forename: Dana P
authors.initials: DP
authors.lastname: Goldman
mesh_terms: D000368:Aged; D002637:Chest Pain / Q000453:epidemiology; D017714:Community-Acquired Infections / Q000139:chemically induced / Q000453:epidemiology; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D004305:Dose-Response Relationship, Drug; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000453:epidemiology; D018410:Pneumonia, Bacterial / Q000139:chemically induced* / Q000453:epidemiology; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012959:Socioeconomic Factors; D014481:United States; D014552:Urinary Tract Infections / Q000453:epidemiology
chemical_list: D054328:Proton Pump Inhibitors