Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis.
01 May 2013-Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol)-Vol. 11, Iss: 5, pp 483-490
TL;DR: PPI use statistically was associated with SIBO risk, but only when the diagnosis was made by a highly accurate test (duodenal or jejunal aspirate culture) and differences in study results could arise from the use of different tests to diagnose SIBO.
About: This article is published in Clinical Gastroenterology and Hepatology.The article was published on 2013-05-01. It has received 255 citations till now.
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TL;DR: Recommendations on long-term use of proton pump inhibitors for three common indications: gastroesophageal reflux disease, Barrett's esophagus, and non-steroidal anti-inflammatory drug (NSAID) bleeding prophylaxis are reviewed.
532 citations
Cites background from "Proton pump inhibitor use and the r..."
...Overall, studies that have classified SIBO using aspirates have found an 8-fold relative risk associated with PPIs whereas studies using breath testing have found a 2-fold relative risk.(24) Non-typhoidal Salmonella and Campylobacter....
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TL;DR: Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night.
Abstract: Proton pump inhibitors (PPIs) were clinically introduced more than 25 years ago and have since proven to be invaluable, safe, and effective agents for the management of a variety of acid-related disorders. Although all members in this class act in a similar fashion, inhibiting active parietal cell acid secretion, there are slight differences among PPIs relating to their pharmacokinetic properties, metabolism, and Food and Drug Administration (FDA)-approved clinical indications. Nevertheless, each is effective in managing gastroesophageal reflux disease and uncomplicated or complicated peptic ulcer disease. Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night. Longer-acting PPIs and technology to prolong conventional PPI activity have been developed to specifically address these limitations and may improve clinical outcomes.
324 citations
TL;DR: Many of the proposed adverse consequences of PPI therapy are reviewed and established criteria for the determination of causation are applied and the potential contribution of residual confounding in many of the reported studies are considered.
318 citations
TL;DR: Overall, PPIs are irreplaceable drugs in the management of acid-related diseases, however, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects.
Abstract: The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Herein, we aim to review the current literature on PPI use and develop a position paper addressing the benefits and potential harms of acid suppression with the purpose of providing evidence-based guidelines on the appropriate use of these medications. The topics, identified by a Scientific Committee, were assigned to experts selected by three Italian Scientific Societies, who independently performed a systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were distilled, paying more attention to systematic reviews and meta-analyses (where available) representing the best evidence. The draft prepared on each topic was circulated amongst all the members of the Scientific Committee. Each expert then provided her/his input to the writing, suggesting changes and the inclusion of new material and/or additional relevant references. The global recommendations were then thoroughly discussed in a specific meeting, refined with regard to both content and wording, and approved to obtain a summary of current evidence. Twenty-five years after their introduction into clinical practice, PPIs remain the mainstay of the treatment of acid-related diseases, where their use in gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer disease and bleeding as well as, and Zollinger–Ellison syndrome is appropriate. Prevention of gastroduodenal mucosal lesions (and symptoms) in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or antiplatelet therapies and carrying gastrointestinal risk factors also represents an appropriate indication. On the contrary, steroid use does not need any gastroprotection, unless combined with NSAID therapy. In dyspeptic patients with persisting symptoms, despite successful H. pylori eradication, short-term PPI treatment could be attempted. Finally, addition of PPIs to pancreatic enzyme replacement therapy in patients with refractory steatorrhea may be worthwhile. Overall, PPIs are irreplaceable drugs in the management of acid-related diseases. However, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects. The overall benefits of therapy and improvement in quality of life significantly outweigh potential harms in most patients, but those without clear clinical indication are only exposed to the risks of PPI prescription. Adhering with evidence-based guidelines represents the only rational approach to effective and safe PPI therapy. Please see related Commentary: doi:
10.1186/s12916-016-0724-1
.
283 citations
Cites background from "Proton pump inhibitor use and the r..."
...difficile [456–458] and other pathogens [456, 459] • Increased Candida infections in the mouth, esophagus, stomach, and upper small intestine of PPI users have been documented [460] • PPI users are at increased risk of small intestinal bacterial overgrowth (SIBO) [461], while cirrhotic patients, taking these drugs, are at higher risk of spontaneous bacterial peritonitis [354, 355]...
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TL;DR: Endoscopic eradication therapy is the treatment of choice for high-grade dysplasia and is an option for low-grade Dysplasia, and endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett esophagus.
Abstract: Importance Barrett esophagus, a complication of gastroesophageal reflux disease (GERD), predisposes patients to esophageal adenocarcinoma, a tumor that has increased in incidence more than 7-fold over the past several decades. Controversy exists regarding the issues of endoscopic screening and surveillance for Barrett esophagus, treatment for the underlying GERD, and the role of endoscopic eradication therapy. Objectives To review current concepts on the pathogenesis, diagnosis, and treatment of Barrett esophagus; to discuss the importance of dysplasia and the role of endoscopic eradication therapy for its treatment; and to review current management guidelines. Evidence Review MEDLINE and the Cochrane Library were searched from 1984 to April 2013. Additional citations were obtained by reviewing references from selected research and review articles. Findings Risk factors for cancer in Barrett esophagus include chronic GERD, hiatal hernia, advanced age, male sex, white race, cigarette smoking, and obesity with an intra-abdominal body fat distribution. The annual risk of esophageal cancer is approximately 0.25% for patients without dysplasia and 6% for patients with high-grade dysplasia. High-quality studies have found no significant differences in cancer incidence for patients with Barrett esophagus whose GERD is treated medically or surgically. Endoscopic eradication therapy with radiofrequency ablation significantly reduces the frequency of progression to cancer for patients with high-grade dysplasia. Conclusions and Relevance Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett esophagus. For patients with Barrett esophagus without dysplasia, endoscopic surveillance at intervals of 3 to 5 years is recommended, and GERD is treated much as it is for patients without Barrett esophagus. Endoscopic eradication therapy is the treatment of choice for high-grade dysplasia and is an option for low-grade dysplasia. Endoscopic eradication therapy is not recommended for the general population of patients with nondysplastic Barrett esophagus.
248 citations
References
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TL;DR: A checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion should improve the usefulness ofMeta-an analyses for authors, reviewers, editors, readers, and decision makers.
Abstract: ObjectiveBecause of the pressure for timely, informed decisions in public health
and clinical practice and the explosion of information in the scientific literature,
research results must be synthesized. Meta-analyses are increasingly used
to address this problem, and they often evaluate observational studies. A
workshop was held in Atlanta, Ga, in April 1997, to examine the reporting
of meta-analyses of observational studies and to make recommendations to aid
authors, reviewers, editors, and readers.ParticipantsTwenty-seven participants were selected by a steering committee, based
on expertise in clinical practice, trials, statistics, epidemiology, social
sciences, and biomedical editing. Deliberations of the workshop were open
to other interested scientists. Funding for this activity was provided by
the Centers for Disease Control and Prevention.EvidenceWe conducted a systematic review of the published literature on the
conduct and reporting of meta-analyses in observational studies using MEDLINE,
Educational Research Information Center (ERIC), PsycLIT, and the Current Index
to Statistics. We also examined reference lists of the 32 studies retrieved
and contacted experts in the field. Participants were assigned to small-group
discussions on the subjects of bias, searching and abstracting, heterogeneity,
study categorization, and statistical methods.Consensus ProcessFrom the material presented at the workshop, the authors developed a
checklist summarizing recommendations for reporting meta-analyses of observational
studies. The checklist and supporting evidence were circulated to all conference
attendees and additional experts. All suggestions for revisions were addressed.ConclusionsThe proposed checklist contains specifications for reporting of meta-analyses
of observational studies in epidemiology, including background, search strategy,
methods, results, discussion, and conclusion. Use of the checklist should
improve the usefulness of meta-analyses for authors, reviewers, editors, readers,
and decision makers. An evaluation plan is suggested and research areas are
explored.
17,663 citations
01 Jan 2014
TL;DR: The Newcastle-Ottawa Scale (NOS) as discussed by the authors was developed to assess the quality of nonrandomised studies with its design, content and ease of use directed to the task of incorporating the quality assessments in the interpretation of meta-analytic results.
Abstract: Nonrandomised studies, including case-control and cohort studies, can be challenging to implement and conduct. Assessment of the quality of such studies is essential for a proper understanding of nonrandomised studies. The Newcastle-Ottawa Scale (NOS) is an ongoing collaboration between the Universities of Newcastle, Australia and Ottawa, Canada. It was developed to assess the quality of nonrandomised studies with its design, content and ease of use directed to the task of incorporating the quality assessments in the interpretation of meta-analytic results. A 'star system' has been developed in which a study is judged on three broad perspectives: the selection of the study groups; the comparability of the groups; and the ascertainment of either the exposure or outcome of interest for case-control or cohort studies respectively. The goal of this project is to develop an instrument providing an easy and convenient tool for quality assessment of nonrandomised studies to be used in a systematic review.
17,590 citations
TL;DR: In this paper, a rank-based data augmentation technique is proposed for estimating the number of missing studies that might exist in a meta-analysis and the effect that these studies might have had on its outcome.
Abstract: We study recently developed nonparametric methods for estimating the number of missing studies that might exist in a meta-analysis and the effect that these studies might have had on its outcome. These are simple rank-based data augmentation techniques, which formalize the use of funnel plots. We show that they provide effective and relatively powerful tests for evaluating the existence of such publication bias. After adjusting for missing studies, we find that the point estimate of the overall effect size is approximately correct and coverage of the effect size confidence intervals is substantially improved, in many cases recovering the nominal confidence levels entirely. We illustrate the trim and fill method on existing meta-analyses of studies in clinical trials and psychometrics.
9,163 citations
TL;DR: There is an association between acid suppression and an increased risk of enteric infection and further prospective studies on patients taking long-term acid suppression are needed to establish whether this association is causal.
584 citations
TL;DR: The data do not support an important role for SIBO according to commonly used clinical definitions, in irritable bowel syndrome, however, mildly increased counts of small-bowel bacteria seem to be more common in IBS, and needs further investigation.
Abstract: Background & aims: Small intestinal bacterial overgrowth
(SIBO) has been proposed to be common in irritable bowel
syndrome (IBS), with altered small bowel motility as a
possible predisposing factor. The aim of this
investigation was to assess the prevalence of SIBO,
using culture of small bowel aspirate, and its
correlation to symptoms and motility in IBS. Methods: We included 162 IBS patients who underwent
small bowel manometry. and culture of jejunal aspirate.
Cultures from 26 healthy subjects served as controls.
Two definitions of altered flora were used: standard
definition of SIBO (≥105 colonic type bacteria/mL), and
mildly elevated counts of small bowel bacteria (≥95th
percentile in controls). Results: SIBO (standard definition) was found in 4% of
both patients and controls. Signs of enteric dysmotility
were seen in 86% of patients with SIBO and 39% of
patients without SIBO (p=0.02). Patients with SIBO had
fewer phase IIIs (activity fronts) compared with
patients without SIBO (p=0.08), but otherwise no
differences in motility parameters were seen. Mildly
elevated bacterial counts (≥5x103/mL) were more common
in patients compared with controls (43% vs. 12%;
p=0.002), but this was unrelated to small intestinal
motility. No correlation between bacterial alterations
and symptom pattern could be observed. Conclusions: Our data do not support an important role
for SIBO according to commonly used clinical
definitions, in IBS. However, mildly elevated counts of
small bowel bacteria seem to be more common in IBS and
needs further investigation. Motility alterations could
not reliably predict altered small bowel bacterial flora.
473 citations