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    Original Investigation
    Pharmacy and Clinical Pharmacology
    November 27, 2019

    Association Between Acute Gastroenteritis and Continuous Use of Proton Pump Inhibitors During Winter Periods of Highest Circulation of Enteric Viruses

    Author Affiliations
    • 1Sorbonne Université, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France
    • 2Real World Insight, IQVIA, La Défense Cedex, France
    • 3Service de Rhumatologie, Hôpital Lariboisière, Assistance Publique–Hôpitaux de Paris (APHP), Paris, France
    • 4Sorbonne Université, INSERM, Université Paris 13, Laboratoire d’informatique Médicale et d’Ingénierie des Connaissances en e-santé, LIMICS, Paris, France
    • 5Service de Médecine Interne, Hôpital Tenon, Assistance Publique–Hôpitaux de Paris (APHP), Paris, France
    • 6UVSQ, UFR de Médecine, Université de Versailles Saint-Quentin-en-Yvelines, Versailles, France
    • 7Service de Médecine Interne, Hôpital Ambroise Paré, Assistance Publique–Hôpitaux de Paris (APHP), Boulogne Billancourt, France
    JAMA Netw Open. 2019;2(11):e1916205. doi:10.1001/jamanetworkopen.2019.16205
    Key Points español 中文 (chinese)

    Question  Is continuous use of proton pump inhibitors (PPIs) associated with an increased risk of acute gastroenteritis during periods of highest circulation of enteric viruses?

    Findings  In this matched cohort study comparing 233 596 patients receiving continuous PPI therapy with 626 887 patients not receiving PPI therapy, the adjusted relative risk of occurrence of acute gastroenteritis during periods of highest circulation of enteric viruses was 1.81 times higher in patients receiving continuous PPI therapy than in those not receiving PPI therapy.

    Meaning  Continuous PPI use may be associated with an increased risk of enteric viral infections.


    Importance  An increased risk of acute bacterial enteric infections has been reported among patients receiving proton pump inhibitor (PPI) therapy. The risk of acute gastroenteritis (AGE) of viral origin associated with continuous PPI exposure has been less studied.

    Objective  To investigate the association between continuous PPI therapy and AGE occurrence during winter epidemic periods when the circulation of enteric viruses is the highest.

    Design, Setting, and Participants  A matched cohort study was performed using a prospectively collected drug dispensing database from a large panel of community pharmacies in continental France. All patients recorded in the database during the 2015 to 2016 winter season, with documented age, sex, and use of an identifiable regular panel pharmacy, were eligible for the study. Each patient exposed to continuous PPI therapy was matched to 3 unexposed patients, according to year of birth, sex, and identifiable regular panel pharmacy. Analyses were performed between January 2017 and December 2018.

    Exposure  Continuous PPI use during the 2015 to 2016 AGE winter epidemic.

    Main Outcomes and Measures  The occurrence of at least 1 AGE episode during the 2015 to 2016 AGE winter epidemic was the main outcome. Episodes of AGE were identified using a previously validated algorithm based on drug dispensing data. Relative risks of AGE were estimated using a multivariable log-binomial model adjusted for age, sex, and treatments for chronic conditions.

    Results  There were 233 596 patients receiving PPI therapy (median [interquartile range] age, 71 [62-81] years; 55.8% female) and 626 887 matched patients not receiving PPI therapy (median [interquartile range] age, 70 [61-80] years; 56.3% female) included in the analyses. At least 1 AGE epidemic episode was identified in 3131 patients (1.3%) receiving PPI therapy and in 4327 patients (0.7%) not receiving PPI therapy. The adjusted relative risk of AGE for those receiving PPI therapy was 1.81 (95% CI, 1.72-1.90) for all ages considered, 1.66 (95% CI, 1.54-1.80) among those aged 45 to 64 years, 2.19 (95% CI, 1.98-2.42) among those aged 65 to 74 years, and 1.98 (95% CI, 1.82-2.15) among those aged 75 years and older.

    Conclusions and Relevance  Continuous PPI therapy was associated with an increased risk of developing AGE during periods of highest circulation of enteric viruses. These findings support the hypothesis that PPI use is associated with an increased risk of enteric viral infections.