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Journal of Gastroenterology Apr 2021The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an...
The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an English version. The revised guidelines consist of nine items: epidemiology, hemorrhagic gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcers, non-H. pylori, and nonsteroidal anti-inflammatory drug (NSAID) ulcers, remnant gastric ulcers, surgical treatment, and conservative therapy for perforation and stenosis. Therapeutic algorithms for the treatment of peptic ulcers differ based on ulcer complications. In patients with NSAID-induced ulcers, NSAIDs are discontinued and anti-ulcer therapy is administered. If NSAIDs cannot be discontinued, the ulcer is treated with proton pump inhibitors (PPIs). Vonoprazan (VPZ) with antibiotics is recommended as the first-line treatment for H. pylori eradication, and PPIs or VPZ with antibiotics is recommended as a second-line therapy. Patients who do not use NSAIDs and are H. pylori negative are considered to have idiopathic peptic ulcers. Algorithms for the prevention of NSAID- and low-dose aspirin (LDA)-related ulcers are presented in this guideline. These algorithms differ based on the concomitant use of LDA or NSAIDs and ulcer history or hemorrhagic ulcer history. In patients with a history of ulcers receiving NSAID therapy, PPIs with or without celecoxib are recommended and the administration of VPZ is suggested for the prevention of ulcer recurrence. In patients with a history of ulcers receiving LDA therapy, PPIs or VPZ are recommended and the administration of a histamine 2-receptor antagonist is suggested for the prevention of ulcer recurrence.
Topics: Humans; Anti-Bacterial Agents; Evidence-Based Practice; Japan; Peptic Ulcer; Proton Pump Inhibitors
PubMed: 33620586
DOI: 10.1007/s00535-021-01769-0 -
JAMA Internal Medicine Nov 2014Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with... (Comparative Study)
Comparative Study Meta-Analysis Review
IMPORTANCE
Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding ulcers. Substitution of intermittent PPI therapy, if similarly effective as bolus plus continuous-infusion PPI therapy, would decrease the PPI dose, costs, and resource use.
OBJECTIVE
To compare intermittent PPI therapy with the currently recommended bolus plus continuous-infusion PPI regimen for reduction of ulcer rebleeding.
DATA SOURCES
Searches included MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases through December 2013; US and European gastroenterology meeting abstracts from 2009 to 2013; and bibliographies of systematic reviews.
STUDY SELECTION
Randomized trials of patients with endoscopically treated high-risk bleeding ulcers (active bleeding, nonbleeding visible vessels, and adherent clots) comparing intermittent doses of PPIs and the currently recommended regimen (80-mg intravenous bolus dose of a PPI followed by an infusion of 8 mg/h for 72 hours).
DATA EXTRACTION AND SYNTHESIS
Duplicate independent data extraction and risk-of-bias assessment were performed. Data were pooled using a fixed-effects model or a random effects model if statistical heterogeneity was present.
MAIN OUTCOMES AND MEASURES
The primary outcome was rebleeding within 7 days; additional predefined outcomes included rebleeding within 3 and 30 days, need for urgent intervention, mortality, red blood cell transfusion, and length of hospital stay. The primary hypothesis, defined before initiation of the literature review, was that intermittent use of PPIs was noninferior to bolus plus continuous infusion of PPIs, with the noninferiority margin predefined as an absolute risk difference of 3%.
RESULTS
The risk ratio of rebleeding within 7 days for intermittent vs bolus plus continuous infusion of PPIs was 0.72 (upper boundary of 1-sided 95% CI, 0.97) and the absolute risk difference was -2.64% (upper boundary of 1-sided 95% CI, -0.28%, which is well below the predefined noninferiority margin of 3%). Risk ratios for rebleeding within 30 days and 3 days, mortality, and urgent interventions were less than 1 and mean differences for blood transfusion and hospital length of stay were less than 0, indicating that no summary estimate showed an increased risk with intermittent therapy. The upper boundaries of 95% CIs for absolute risk differences were less than 1.50% for all predefined rebleeding outcomes.
CONCLUSIONS AND RELEVANCE
Intermittent PPI therapy is comparable to the current guideline-recommended regimen of intravenous bolus plus a continuous infusion of PPIs in patients with endoscopically treated high-risk bleeding ulcers. Guidelines should be revised to recommend intermittent PPI therapy.
Topics: Humans; Infusions, Intravenous; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors
PubMed: 25201154
DOI: 10.1001/jamainternmed.2014.4056 -
Alimentary Pharmacology & Therapeutics Jan 2021Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown.
AIM
To perform a systematic review with network meta-analysis to resolve this uncertainty.
METHODS
We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.
RESULTS
We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.
CONCLUSIONS
TCAs, histamine- receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.
Topics: Adult; Dyspepsia; Histamine H2 Antagonists; Humans; Network Meta-Analysis; Pharmaceutical Preparations; Proton Pump Inhibitors
PubMed: 32936964
DOI: 10.1111/apt.16072 -
Journal of Gastroenterology and... Dec 2022Potassium-competitive acid blocker (PCAB) is a recent alternative to proton pump inhibitor (PPI) for potent acid suppression. The current systematic review and... (Meta-Analysis)
Meta-Analysis
A comparison of efficacy and safety of potassium-competitive acid blocker and proton pump inhibitor in gastric acid-related diseases: A systematic review and meta-analysis.
BACKGROUND AND AIM
Potassium-competitive acid blocker (PCAB) is a recent alternative to proton pump inhibitor (PPI) for potent acid suppression. The current systematic review and meta-analysis aimed to compare the efficacy and safety of PCAB versus PPI in treating gastric acid-related diseases.
METHODS
We searched up to June 5, 2022, for randomized controlled trials of gastric acid-related diseases that included erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD), peptic ulcers, and Helicobacter pylori infection. The pooled risk ratio (RR) was evaluated for the efficacy outcome and treatment-emergent adverse events (TEAEs) as the safety outcome. Sensitivity analyses were performed to test the robustness of the study findings.
RESULTS
Of the 710 screened studies, 19 studies including 7023 participants were analyzed. The RRs for the healing of erosive esophagitis with Vonoprazan versus PPI were 1.09 (95% confidence interval [CI] 1.03-1.14), 1.03 (95% CI 1.00-1.07), and 1.02 (95% CI 1.00-1.05) in Weeks 2, 4, and 8, respectively. There were no differences in the improvement of GERD symptoms and healing of gastric and duodenal ulcers between PCAB and PPI. The pooled eradication rates of H. pylori were significantly higher in Vonoprazan versus PPI first-line treatment (RR 1.13; 95% CI 1.04-1.22). The overall RR of TEAEs with Vonoprazan versus PPI was 1.08 (95% CI 0.89-1.31). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion.
CONCLUSION
Vonoprazan is superior to PPI in first-line H. pylori eradication and erosive esophagitis but non-inferior in other gastric acid-related diseases. Likewise, short-term safety is comparable in both treatment groups.
Topics: Humans; Gastric Acid; Proton Pump Inhibitors; Potassium; Helicobacter Infections; Helicobacter pylori
PubMed: 36181401
DOI: 10.1111/jgh.16017 -
World Journal of Gastroenterology Mar 2016To evaluate whether Helicobacter pylori (H. pylori) eradication therapy benefits patients with functional dyspepsia (FD). (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate whether Helicobacter pylori (H. pylori) eradication therapy benefits patients with functional dyspepsia (FD).
METHODS
Randomized controlled trials (RCTs) investigating the efficacy and safety of H. pylori eradication therapy for patients with functional dyspepsia published in English (up to May 2015) were identified by searching PubMed, EMBASE, and The Cochrane Library. Pooled estimates were measured using the fixed or random effect model. Overall effect was expressed as a pooled risk ratio (RR) or a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0.
RESULTS
This systematic review included 25 RCTs with a total of 5555 patients with FD. Twenty-three of these studies were used to evaluate the benefits of H. pylori eradication therapy for symptom improvement; the pooled RR was 1.23 (95%CI: 1.12-1.36, P < 0.0001). H. pylori eradication therapy demonstrated symptom improvement during long-term follow-up at ≥ 1 year (RR = 1.24; 95%CI: 1.12-1.37, P < 0.0001) but not during short-term follow-up at < 1 year (RR = 1.26; 95%CI: 0.83-1.92, P = 0.27). Seven studies showed no benefit of H. pylori eradication therapy on quality of life with an SMD of -0.01 (95%CI: -0.11 to 0.08, P = 0.80). Six studies demonstrated that H. pylori eradication therapy reduced the development of peptic ulcer disease compared to no eradication therapy (RR = 0.35; 95%CI: 0.18-0.68, P = 0.002). Eight studies showed that H. pylori eradication therapy increased the likelihood of treatment-related side effects compared to no eradication therapy (RR = 2.02; 95%CI: 1.12-3.65, P = 0.02). Ten studies demonstrated that patients who received H. pylori eradication therapy were more likely to obtain histologic resolution of chronic gastritis compared to those who did not receive eradication therapy (RR = 7.13; 95%CI: 3.68-13.81, P < 0.00001).
CONCLUSION
The decision to eradicate H. pylori in patients with functional dyspepsia requires individual assessment.
Topics: Adult; Anti-Bacterial Agents; Chi-Square Distribution; Drug Therapy, Combination; Dyspepsia; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Odds Ratio; Proton Pump Inhibitors; Remission Induction; Risk Factors; Treatment Outcome
PubMed: 27022230
DOI: 10.3748/wjg.v22.i12.3486 -
Gastroenterologia Y Hepatologia May 2022Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last...
Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.
Topics: Amoxicillin; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Peptic Ulcer; Proton Pump Inhibitors
PubMed: 34629204
DOI: 10.1016/j.gastrohep.2021.07.011 -
Journal of Pediatric Gastroenterology... Jun 2017Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for...
BACKGROUND
Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required.
METHODS
A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting.
RESULTS
The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests.
CONCLUSIONS
The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.
Topics: Adolescent; Antacids; Anti-Bacterial Agents; Child; Delphi Technique; Drug Administration Schedule; Drug Resistance, Bacterial; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors
PubMed: 28541262
DOI: 10.1097/MPG.0000000000001594 -
BMJ (Clinical Research Ed.) Mar 2019Upper gastrointestinal bleeding (UGIB) is a common medical emergency, with a reported mortality of 2-10%. Patients identified as being at very low risk of either needing...
Upper gastrointestinal bleeding (UGIB) is a common medical emergency, with a reported mortality of 2-10%. Patients identified as being at very low risk of either needing an intervention or death can be managed as outpatients. For all other patients, intravenous fluids as needed for resuscitation and red cell transfusion at a hemoglobin threshold of 70-80 g/L are recommended. After resuscitation is initiated, proton pump inhibitors (PPIs) and the prokinetic agent erythromycin may be administered, with antibiotics and vasoactive drugs recommended in patients who have cirrhosis. Endoscopy should be undertaken within 24 hours, with earlier endoscopy considered after resuscitation in patients at high risk, such as those with hemodynamic instability. Endoscopic treatment is used for variceal bleeding (for example, ligation for esophageal varices and tissue glue for gastric varices) and for high risk non-variceal bleeding (for example, injection, thermal probes, or clips for lesions with active bleeding or non-bleeding visible vessel). Patients who require endoscopic therapy for ulcer bleeding should receive high dose proton pump inhibitors after endoscopy, whereas those who have variceal bleeding should continue taking antibiotics and vasoactive drugs. Recurrent ulcer bleeding is treated with repeat endoscopic therapy, with subsequent bleeding managed by interventional radiology or surgery. Recurrent variceal bleeding is generally treated with transjugular intrahepatic portosystemic shunt. In patients who require antithrombotic agents, outcomes appear to be better when these drugs are reintroduced early.
Topics: Anti-Bacterial Agents; Blood Transfusion; Disease Management; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Portasystemic Shunt, Transjugular Intrahepatic; Practice Guidelines as Topic; Proton Pump Inhibitors; Resuscitation; Severity of Illness Index
PubMed: 30910853
DOI: 10.1136/bmj.l536 -
Diseases of the Esophagus : Official... May 2017In patients with gastroesophageal reflux disease (GERD) and erosive esophagitis, treatment with proton pump inhibitors (PPIs) is highly effective. However, in some... (Meta-Analysis)
Meta-Analysis Review
In patients with gastroesophageal reflux disease (GERD) and erosive esophagitis, treatment with proton pump inhibitors (PPIs) is highly effective. However, in some patients, especially those with nonerosive reflux disease or atypical GERD symptoms, acid-suppressive therapy with PPIs is not as successful. Alginates are medications that work through an alternative mechanism by displacing the postprandial gastric acid pocket. This study performed a systematic review and meta-analysis to examine the benefit of alginate-containing compounds in the treatment of patients with symptoms of GERD. PubMed/MEDLINE, Embase, and the Cochrane library electronic databases were searched through October 2015 for randomized controlled trials comparing alginate-containing compounds to placebo, antacids, histamine-2 receptor antagonists (H2RAs), or PPIs for the treatment of GERD symptoms. Additional studies were identified through a bibliography review. Non-English studies and those with pediatric patients were excluded. Meta-analyses were performed using random-effect models to calculate odds ratios (OR). Heterogeneity between studies was estimated using the I2 statistic. Analyses were stratified by type of comparator. The search strategy yielded 665 studies and 15 (2.3%) met inclusion criteria. Fourteen were included in the meta-analysis (N = 2095 subjects). Alginate-based therapies increased the odds of resolution of GERD symptoms when compared to placebo or antacids (OR: 4.42; 95% CI 2.45-7.97) with a moderate degree of heterogeneity between studies (I2 = 71%, P = .001). Compared to PPIs or H2RAs, alginates appear less effective but the pooled estimate was not statistically significant (OR: 0.58; 95% CI 0.27-1.22). Alginates are more effective than placebo or antacids for treating GERD symptoms.
Topics: Adult; Alginates; Antacids; Female; Gastroesophageal Reflux; Glucuronic Acid; Hexuronic Acids; Histamine H2 Antagonists; Humans; Male; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28375448
DOI: 10.1093/dote/dow020 -
Gastroenterology May 2016Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of benefit of H pylori eradication in populations with different levels of gastric cancer risk and in different clinical scenarios is unclear. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies to investigate the effects of H pylori eradication on the incidence of gastric cancer.
METHODS
We searched PubMed, Cochrane Library, and ClinicalTrials.gov, reviewing titles and abstracts of studies of the effects of eradication of H pylori infection on risk of gastric cancer, through May 2015. We also searched bibliographies of included studies, related reviews, and abstracts presented at Digestive Disease Week. Twenty-four eligible studies (22 research manuscripts and 2 abstracts) were included in our meta-analysis (715 incident gastric cancers among a total of 48,064 individuals/340,255 person-years). We assessed the effects, as well as their modification by baseline gastric cancer incidence, study design (randomized trial vs observational study), clinical scenario (asymptomatic infected individuals vs individuals after endoscopic resection of early gastric cancer), demographic characteristics of patients (age and sex), and duration of follow-up.
RESULTS
After adjustment for baseline gastric cancer incidence, individuals with eradication of H pylori infection had a lower incidence of gastric cancer than those who did not receive eradication therapy (pooled incidence rate ratio = 0.53; 95% confidence interval: 0.44-0.64). There was little heterogeneity among studies. Baseline gastric cancer incidence modified the benefit of H pylori eradication (P = .037 for interaction); the incidence rate ratio of gastric cancer decreased in a nonlinear fashion with increasing baseline incidence of gastric cancer (P = .018, in comparison with the linear model). The benefit also modestly increased with age (P = .023 for interaction), but this might be due to correlation between age and baseline gastric cancer incidence. Eradication provided significant benefit for asymptomatic infected individuals (pooled incidence rate ratio, 0.62; 95% CI: 0.49-0.79) and individuals after endoscopic resection of gastric cancers (pooled incidence rate ratio, 0.46; 95% CI: 0.35-0.60). The benefits of H pylori eradication did not differ with study design, sex, or follow-up period.
CONCLUSIONS
In a systematic review and meta-analysis, we associated eradication of H pylori infection with a reduced incidence of gastric cancer. The benefits of eradication vary with baseline gastric cancer incidence, but apply to all levels of baseline risk.
Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Odds Ratio; Protective Factors; Proton Pump Inhibitors; Risk Assessment; Risk Factors; Stomach Neoplasms; Treatment Outcome
PubMed: 26836587
DOI: 10.1053/j.gastro.2016.01.028