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-acquiredpneumonia (CAP), an association which may be confounded by unobserved patient and prescribercharacteristics. 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. DESIGN: Retrospective claims-based cohort study. SETTING: Six private U.S. health plans. SUBJECTS: Individuals who filled at least one prescription for a PPI (N = 26,436) and those who never did (N = 28,054) over 11 years. INTERVENTIONS: 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. KEY 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