title: Proton pump inhibitors and risk of Clostridium difficile infection: a multi-country study using sequence symmetry analysis.
abstract: OBJECTIVE
  To determine the association between incident proton pump inhibitor (PPI) use and Clostridium difficile infections across multiple countries Method: National data covering the total population in Australia and Korea, the Canadian population over 65 years and a 3 million person random sample data set from Taiwan were assessed, as were data from a worker insurance population and a hospital inpatient/outpatient population in Japan. Sequence symmetry analysis was used to assess the association with oral vancomycin dispensing as the outcome of interest.
  
  
  RESULTS
  54,957 patients were included. Positive associations were observed in Australia; adjusted sequence ratio (ASR) 2.48 (95% CI 1.90, 3.12), Korea ASR 2.15 (95%CI 2.11, 2.19), Canada ASR 1.45 (95% CI 1.16, 1.79), Japan hospital dataset ASR 3.21 (95%CI 2.12, 4.55) and Japan worker insurance dataset ASR 5.40 (95% CI 2.73, 8.75). The pooled result was ASR 2.40 (95%CI 1.88, 3.05) and 3.16 (95%CI 1.95, 5.10) when limited to Japan, Korean and Taiwan. Results did not vary by individual PPI. The temporal analysis showed effects within the first two weeks of PPI initiation.
  
  
  CONCLUSIONS
  Our study confirms the association between PPI initiation and C. difficile infections across countries in the Asia-Pacific region.
authors.affiliation: a Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research , University of South Australia , Adelaide , Australia.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Roughead
authors.affiliation: b Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy , The University of Hong Kong , Hong Kong , Hong kong.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Chan
authors.affiliation: c Institute of Environmental Medicine, Medical Research Center , Seoul National University , Seoul , Korea.|d Division of Pharmacoepidemiology and Pharmacoeconomics , Brigham and Women's Hospital and Harvard Medical School , Boston , MA , USA.
authors.forename: Nam-Kyong
authors.initials: NK
authors.lastname: Choi
authors.affiliation: e Marketed Health Products Directorate , Health Products and Food Branch, Health Canada , Ottawa , ON , Canada.
authors.forename: Jenna
authors.initials: J
authors.lastname: Griffiths
authors.affiliation: f Department of Preventive Medicine , Seoul National University College of Medicine , Seoul , Korea.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Jin
authors.affiliation: g Medical Research Collaborating Centre , Seoul National University College of Medicine, Seoul National University Hospital , Seoul , Korea.
authors.forename: Joongyub
authors.initials: J
authors.lastname: Lee
authors.affiliation: h Department of Medical Informatics , Hamamatsu University, School of Medicine , Shizuoka , Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Kimura
authors.affiliation: i Medical Affairs , Astellas Pharma Inc , Tokyo , Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: j Department of Pharmacoepidemiology , University of Tokyo Graduate School of Medicine , Tokyo , Japan.|k NPO Drug Safety Research Unit , Tokyo , Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kubota
authors.affiliation: l School of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences, Health Outcome Research Centre , National Cheng Kung University , Tainan , Taiwan.
authors.forename: Edward Chia-Cheng
authors.initials: EC
authors.lastname: Lai
authors.affiliation: b Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy , The University of Hong Kong , Hong Kong , Hong kong.
authors.forename: Kenneth Kc
authors.initials: KK
authors.lastname: Man
authors.affiliation: a Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research , University of South Australia , Adelaide , Australia.
authors.forename: Tuan Anh
authors.initials: TA
authors.lastname: Nguyen
authors.affiliation: j Department of Pharmacoepidemiology , University of Tokyo Graduate School of Medicine , Tokyo , Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ooba
authors.affiliation: f Department of Preventive Medicine , Seoul National University College of Medicine , Seoul , Korea.
authors.forename: Byung-Joo
authors.initials: BJ
authors.lastname: Park
authors.affiliation: k NPO Drug Safety Research Unit , Tokyo , Japan.
authors.forename: Tsugumichi
authors.initials: T
authors.lastname: Sato
authors.affiliation: m Department of Epidemiology, Biostatistics, and Occupational Health , McGill University , Montreal , Canada.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Shin
authors.affiliation: e Marketed Health Products Directorate , Health Products and Food Branch, Health Canada , Ottawa , ON , Canada.
authors.forename: TongTong
authors.initials: T
authors.lastname: Wang
authors.affiliation: b Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy , The University of Hong Kong , Hong Kong , Hong kong.|n Research Department of Practice and Policy , UCL School of Pharmacy , London , England.
authors.forename: Ian Ck
authors.initials: IC
authors.lastname: Wong
authors.affiliation: l School of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences, Health Outcome Research Centre , National Cheng Kung University , Tainan , Taiwan.
authors.forename: Yea-Huei Kao
authors.initials: YK
authors.lastname: Yang
authors.affiliation: a Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research , University of South Australia , Adelaide , Australia.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Pratt
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology; D016208:Databases, Factual; D006801:Humans; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D014640:Vancomycin
keywords: Asia; Clostridium difficile; Proton pump inhibitors; adverse event; sequence symmetry analysis