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The Cochrane Database of Systematic... Mar 2017Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease, and hypersecretory conditions (e.g. Zollinger-Ellison syndrome), and as part of the eradication therapy for Helicobacter pylori bacteria. However, approximately 25% to 70% of people are prescribed a PPI inappropriately. Chronic PPI use without reassessment contributes to polypharmacy and puts people at risk of experiencing drug interactions and adverse events (e.g. Clostridium difficile infection, pneumonia, hypomagnesaemia, and fractures).
OBJECTIVES
To determine the effects (benefits and harms) associated with deprescribing long-term PPI therapy in adults, compared to chronic daily use (28 days or greater).
SEARCH METHODS
We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE, Embase, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The last date of search was November 2016. We handsearched the reference lists of relevant studies. We screened 2357 articles (2317 identified through search strategy, 40 through other resources). Of these articles, we assessed 89 for eligibility.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-randomized trials comparing at least one deprescribing modality (e.g. stopping PPI or reducing PPI) with a control consisting of no change in continuous daily PPI use in adult chronic users. Outcomes of interest were: change in gastrointestinal (GI) symptoms, drug burden/PPI use, cost/resource use, negative and positive drug withdrawal events, and participant satisfaction.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed and extracted data and completed the risk of bias assessment. A third review author independently confirmed risk of bias assessment. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information.
MAIN RESULTS
The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects.
AUTHORS' CONCLUSIONS
In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.
Topics: Aged; Deprescriptions; Esophagitis; Gastroesophageal Reflux; Humans; Inappropriate Prescribing; Middle Aged; Patient Satisfaction; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Withholding Treatment
PubMed: 28301676
DOI: 10.1002/14651858.CD011969.pub2 -
PloS One 2017To conduct a systematic review and meta-analysis of studies comparing the gastric-tube vs. whole-stomach for esophageal cancer in order to determine the optimal surgical... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To conduct a systematic review and meta-analysis of studies comparing the gastric-tube vs. whole-stomach for esophageal cancer in order to determine the optimal surgical technique of esophagectomy.
METHODS
A comprehensive literature search was performed using PubMed, EMBASE, ScienceDirect, Ovid MEDLINE, Cochrane Library, Web of Science, Google Scholar, and Scopus. Clinical trials that compared the gastric-tube versus whole-stomach for esophageal cancer were selected. The clinical endpoints included anastomotic leakage, anastomotic stenosis, reflux esophagitis, pneumonia, delayed gastric emptying, and thoracic stomach syndrome.
RESULTS
A total of 6 articles (1571 patients) were included. Compared to the whole-stomach approach, the gastric-tube approach was associated with a lower incidence of reflux esophagitis (95% confidence interval [CI]: 0.16 to 0.81, p = 0.01) and thoracic stomach syndrome (95% CI: 0.17 to 0.55, p < 0.0001). The rates of anastomotic leakage, anastomotic stenosis, pneumonia, and delayed gastric emptying did not significantly differ between the two groups.
CONCLUSIONS
The gastric-tube esophagectomy is superior to the whole-stomach approach, as it is associated with a lower incidence of postoperative reflux esophagitis and thoracic stomach syndrome. Our findings must be validated in large-scale randomized controlled trials.
Topics: Anastomotic Leak; Esophageal Neoplasms; Esophagectomy; Esophagitis, Peptic; Humans; Pneumonia; Publication Bias
PubMed: 28267808
DOI: 10.1371/journal.pone.0173416 -
PloS One 2017Proton pump inhibitors (PPIs) have been used for treatment of Barrett's esophagus (BE) for many years. However, the connection between PPIs and esophageal adenocarcinoma... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Proton pump inhibitors (PPIs) have been used for treatment of Barrett's esophagus (BE) for many years. However, the connection between PPIs and esophageal adenocarcinoma (EAC) in patients with BE has still been controversial. The current systematic review and meta-analysis was designed to evaluate the association between PPIs and the risk of EAC or high-grade dysplasia (HGD) in patients with BE.
METHODS
A systematic literature search of studies reporting the association between PPIs and the risk of EAC and/or HGD in patients with BE was conducted in PubMed, Embase, Web of Science and the Cochrane Library. Next, literature was screened using previously established criteria and relevant data were extracted from included studies. Finally, the software program Review Manage 5.2 was applied to aggregate data and analyze the results.
RESULTS
Nine observational studies, comprising five cohort and four case-control studies (including a total of 5712 patients with BE), were identified. Upon meta-analysis, PPIs were found to have no association with the risk of EAC and/or HGD in patients with BE (unadjusted OR 0.43, 95% CI 0.17-1.08). Analysis for duration response relationship revealed no significant trend toward protection against EAC or HGD with PPIs usage for >2~3 years (one study using 7-year cutoff) when compared to usage for shorter time periods (PPIs usage >2~3 years vs. <2~3 years: OR 0.91 (95% CI 0.25-3.31) vs. 0.91 (0.40-2.07)).There also was considerable heterogeneity between studies.
CONCLUSION
No dysplasia- or cancer-protective effects of PPIs usage in patients with BE were identified by our analysis. Therefore, we conclude that clinicians who discuss the potential chemopreventive effects of PPIs with their patients, should be aware that such an effect, if exists, has not been proven with statistical significance.
Topics: Adenocarcinoma; Barrett Esophagus; Disease Progression; Esophageal Neoplasms; Esophagitis, Peptic; Humans; Odds Ratio; Proton Pump Inhibitors; Risk
PubMed: 28072858
DOI: 10.1371/journal.pone.0169691 -
Journal of Gastroenterology and... Sep 2016Upper gastrointestinal endoscopic findings, such as esophagitis, Barrett's esophagus, peptic ulcer, and malignancy, represent a public health problem. This systematic... (Review)
Review
BACKGROUND AND AIM
Upper gastrointestinal endoscopic findings, such as esophagitis, Barrett's esophagus, peptic ulcer, and malignancy, represent a public health problem. This systematic review aimed to evaluate the prevalence of upper gastrointestinal endoscopic findings in the community.
METHODS
A systematic search was conducted in PUBMED and EMBASE to May 2015. Studies were eligible if they reported the prevalence of upper gastrointestinal endoscopic findings in unselected samples of the community.
RESULTS
Twelve articles were eligible, nine reported data from three endoscopic surveys (n = 3063 subjects), and three from national screening programs (n = 84 153). The overall prevalence of upper gastrointestinal endoscopic findings in the community was 30% in the Kalixanda study (Sweden), 24.9% in the Loiano-Monghidoro study (Italy), and 68.9% in the Systematic Investigation of Gastrointestinal Diseases study (China). The pooled prevalence of esophagitis, endoscopically suspected esophageal metaplasia (ESEM), peptic ulcer, and gastric cancer in all studies was 11.2, 5.1, 6.8, and 0.33%, respectively. The most frequent finding was esophagitis in Europe, with a prevalence of 15.5% in Sweden and 11.8% in Italy, and peptic ulcer in China (17.1%), both in asymptomatic and symptomatic individuals. The prevalence of Helicobacter pylori was positively associated with the prevalence of peptic ulcer (r = 0.91) but negatively associated with the prevalence of both esophagitis (r = -0.99) and ESEM (r = -0.95).
CONCLUSIONS
Upper gastrointestinal endoscopic findings are present in at least a quarter of subjects in the community with different patterns in Western and Eastern countries, both in asymptomatic and symptomatic subjects. H. pylori prevalence negatively impacts on the prevalence of reflux-related esophageal findings.
Topics: Barrett Esophagus; Endoscopy, Gastrointestinal; Gastroesophageal Reflux; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Prevalence; Stomach Neoplasms
PubMed: 26840528
DOI: 10.1111/jgh.13308 -
Journal of Clinical Pharmacy and... Aug 2015Proton pump inhibitors (PPIs) are one of the most widely used classes of drugs. However, the quantum clinical benefit of newer and more expensive PPIs over the older... (Comparative Study)
Comparative Study Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Proton pump inhibitors (PPIs) are one of the most widely used classes of drugs. However, the quantum clinical benefit of newer and more expensive PPIs over the older generation PPIs remains uncertain. This meta-analysis sought to assess the clinical and safety profiles of esomeprazole versus omeprazole at pharmacologically equivalent doses in healing gastroesophageal reflux disease (GERD), peptic ulcer disease and eradicating Helicobacter pylori (H. pylori) infection.
METHODS
PubMed and the Cochrane Library were searched for randomized controlled trials comparing esomeprazole with omeprazole at all doses up to February 2015. Trials were assessed by two reviewers for eligibility according to predefined study inclusion criteria. Meta-analysis was conducted using a random effects model, and heterogeneity in the estimated effects was investigated using meta-regression. Sensitivity analysis was performed to test the robustness of the findings.
RESULTS AND DISCUSSION
Fifteen trials were included and none of which compared esomeprazole with omeprazole in peptic ulcer disease. The included studies had not evaluated esomeprazole 20 mg versus omeprazole 40 mg. In GERD, esomeprazole 40 mg (relative risk (RR) = 1·07; 95% confidence interval (CI) 1·02 to 1·12) and 20 mg (RR=1·04; 95% CI 1·01 to 1·08) significantly improved esophagitis healing when compared with omeprazole 20 mg at week 8. The corresponding numbers needed to treat were 17 and 30, respectively. No significant difference was observed between esomeprazole 20 mg and omeprazole 20 mg at week 4. In H. pylori eradication, there was no difference in the treatment effects between esomeprazole 20 mg and omeprazole 20 mg (RR = 1·01;95% CI 0·96 to 1·05). Their safety profiles were comparable.
WHAT IS NEW AND CONCLUSION
Esomeprazole demonstrated better esophagitis healing rate in patients with GERD than omeprazole at week 8. However, this clinical advantage diminished when both drugs were given at the same doses at week 4. Superiority of esomeprazole was not observed in the H. pylori eradication rates.
Topics: Esomeprazole; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 25893507
DOI: 10.1111/jcpt.12277