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      Proton pump inhibitor use increases the risk of peritonitis in peritoneal dialysis patients

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          Abstract

          Peritonitis is a major and the most significant complication of peritoneal dialysis (PD). Although some predictors of peritonitis in PD patients are known, the association between proton pump inhibitor (PPI) use and peritonitis has not been characterized. Here, we examined whether PPI use is a risk factor for the development of peritonitis, based on a single-center retrospective analysis of 230 consecutive Japanese PD patients at Narita Memorial Hospital. We assessed the association between PPI use and subsequent first episode of peritonitis using multivariate Cox proportional hazards models, following adjustment for clinically relevant factors. The median follow-up period was 36 months (interquartile range, 19–57 months). In total, 86 patients (37.4%) developed peritonitis. Analysis with multivariate Cox proportional hazards models revealed the following significant predictors of peritonitis: PPI use (adjusted hazard ratio [HR] = 1.72, 95% confidence interval [CI]: 1.11–2.66; P = 0.016) and low serum albumin level (per g/dl adjusted HR = 0.59, 95% CI: 0.39–0.90; P = 0.014). Thus, PPI use was independently associated with PD-related peritonitis. The results suggest that nephrology physicians should exercise caution when prescribing PPIs for PD patients.

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          Peritoneal dialysis-related peritonitis: towards improving evidence, practices, and outcomes.

          Peritonitis is a common serious complication of peritoneal dialysis that results in considerable morbidity, mortality, and health care costs. It also significantly limits the use of this important dialysis modality. Despite its importance as a patient safety issue, peritonitis practices and outcomes vary markedly and unacceptably among different centers, regions, and countries. This article reviews peritonitis risk factors, diagnosis, treatment, and prevention, particularly focusing on potential drivers of variable practices and outcomes, controversial or unresolved areas, and promising avenues warranting further research. Potential strategies for augmenting the existing limited evidence base and reducing the gap between evidence-based best practice and actual practice also are discussed.
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            Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis.

            In the past decade, there has been a growing epidemic of Clostridium difficile infection (CDI). During this time, use of proton pump inhibitors (PPIs) has increased exponentially. We evaluated the association between PPI therapy and the risk of CDI by performing a meta-analysis. We searched MEDLINE and 4 other databases for subject headings and text words related to CDI and PPI in articles published from 1990 to 2010. All observational studies that investigated the risk of CDI associated with PPI therapy and used CDI as an end point were considered eligible. Two investigators screened articles independently for inclusion criteria, data extraction, and quality assessment; disagreements were resolved based on consensus with a third investigator. Data were combined by means of a random-effects model and odds ratios were calculated. Subgroup and sensitivity analyses were performed based on study design and antibiotic use. Thirty studies (25 case-control and 5 cohort) reported in 29 articles met the inclusion criteria (n = 202,965). PPI therapy increased the risk for CDI (odds ratio, 2.15, 95% confidence interval, 1.81-2.55), but there was significant heterogeneity in results among studies (P < .00001). This association remained after subgroup and sensitivity analyses, although significant heterogeneity persisted among studies. PPI therapy is associated with a 2-fold increase in risk for CDI. Because of the observational nature of the analyzed studies, we were not able to study the causes of this association. Further studies are needed to determine the mechanisms by which PPI therapy might increase risk for CDI. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: a potential mechanism to explain the association between proton pump inhibitors and C. difficile-associated diarrhea?

              Proton pump inhibitors (PPIs) have been identified as a risk factor for Clostridium difficile-associated diarrhea (CDAD), though the mechanism is unclear because gastric acid does not kill C. difficile spores. We hypothesized that the vegetative form of C. difficile, which is killed by acid, could contribute to disease pathogenesis if it survives in room air and in gastric contents with elevated pH. We compared the numbers of C. difficile spores and vegetative cells in stools of patients prior to and during the treatment of CDAD. We assessed the survival of vegetative cells on moist or dry surfaces in room air versus anaerobic conditions and in human gastric contents, in pH-adjusted gastric contents, and in gastric contents from individuals receiving PPI therapy. Stool samples obtained from patients prior to the initiation of antibiotic treatment for C. difficile contained approximately 10-fold more vegetative cells than spores. On dry surfaces, vegetative C. difficile cells died rapidly, whereas they remained viable for up to 6 h on moist surfaces in room air. Vegetative C. difficile cells had only marginal survival in gastric contents at low pH; adjustment to a pH of >5 resulted in survival similar to that in the phosphate-buffered saline control. The survival of vegetative C. difficile in gastric contents obtained from patients receiving PPIs was also increased at a pH of >5. The ability of the vegetative form of C. difficile to survive on moist surfaces and in gastric contents with an elevated pH suggests a potential mechanism by which PPI therapy could increase the risk of acquiring C. difficile.
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                Author and article information

                Contributors
                Role: Data curationRole: Writing – original draft
                Role: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curationRole: Project administration
                Role: Formal analysis
                Role: Methodology
                Role: Supervision
                Role: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 November 2019
                2019
                : 14
                : 11
                : e0224859
                Affiliations
                [1 ] Department of Nephrology, Narita Memorial Hospital, Toyohashi, Japan
                [2 ] Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute, Japan
                [3 ] Division of Biostatistics, Clinical Research Center, Aichi Medical University, Nagakute, Japan
                Tokushima University Graduate School, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-9676-6961
                Article
                PONE-D-19-22245
                10.1371/journal.pone.0224859
                6837385
                31697753
                6ff7c1ef-e861-436f-b61a-e2846674a4bc
                © 2019 Maeda et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 August 2019
                : 23 October 2019
                Page count
                Figures: 2, Tables: 4, Pages: 11
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Peritonitis
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Peritonitis
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Biology and Life Sciences
                Biochemistry
                Proteins
                Albumins
                Serum Albumin
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Cell Membranes
                Membrane Proteins
                Proton Pumps
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Metaanalysis
                Physical Sciences
                Mathematics
                Statistics
                Statistical Methods
                Metaanalysis
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Ecology and Environmental Sciences
                Limnology
                Effluent
                Earth Sciences
                Marine and Aquatic Sciences
                Limnology
                Effluent
                Medicine and Health Sciences
                Nephrology
                Medical Dialysis
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

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