Interventions to improve the quality of screening-related colonoscopy: protocol for a systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Colonoscopy quality can vary depending on endoscopist-related factors. Quality indicators, such as adenoma detection rate (ADR), have been adopted to reduce variations in care. Several interventions aim to improve ADR, but these fall into several domains that have traditionally been difficult to compare. We will conduct a systematic review and network meta-analysis of randomised controlled trials evaluating the efficacies of interventions to improve colonoscopy quality and report our findings according to clinically relevant interventional domains. METHODS AND ANALYSIS: We will search MEDLINE (Ovid), PubMed, EMBASE, CINAHL, Web of Science, Scopus and Evidence-Based Medicine from inception to September 2022. Four reviewers will screen for eligibility and abstract data in parallel, with two accordant entries establishing agreement and with any discrepancies resolved by consensus. The primary outcome will be ADR. Two authors will independently conduct risk of bias assessments. The analyses of the network will be conducted under a Bayesian random-effects model using Markov-chain Monte-Carlo simulation, with 10 000 burn-ins and 100 000 iterations. We will calculate the ORs and corresponding 95% credible intervals of network estimates with a consistency model. We will report the impact of specific interventions within each domain against standard colonoscopy. We will perform a Bayesian random-effects pairwise meta-analysis to assess heterogeneity based on the I2 statistic. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework for network meta-analyses. ETHICS AND DISSEMINATION: Our study does not require research ethics approval given the lack of patient-specific data being collected. The results will be disseminated at national and international gastroenterology conferences and peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021291814.

Declining Use of Corticosteroids for Crohn's Disease Has Implications for Study Recruitment: Results of a Pilot Randomized Controlled Trial.

BACKGROUND: Corticosteroids (CS) have been used extensively to induce remission in Crohn's disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We proposed to undertake a pilot study comparing EEN and CS therapy to CS alone to assess decrease symptoms and inflammatory markers over 6 weeks. AIM: The overall aim was to assess study feasibility based on recruitment rates and acceptability of treatment in arms involving EEN. METHODS: The pilot study intended to recruit 100 adult patients with active CD who had been prescribed CS to induce remission as part of their care. The patients were randomized to one of three arms: (i) standard-dose CS; (ii) standard-dose CS plus EEN (Modulen 1.5 kcal); or (iii) short-course CS plus EEN. RESULTS: A total of 2009 CD patients attending gastroenterology clinics were screened from October 2018 to November 2019. Prednisone was prescribed to only 6.8% (27/399) of patients with active CD attending outpatient clinics. Of the remaining 372 patients with active CD, 34.8% (139/399) started or escalated immunosuppressant or biologics, 49.6% (198/399) underwent further investigation and 8.8% (35/399) were offered an alternative treatment (e.g., antibiotics, surgery or investigational agents in clinical trials). Only three patients were enrolled in the study (recruitment rate 11%; 3/27), and the study was terminated for poor recruitment. CONCLUSION: The apparent decline in use of CS for treatment of CD has implications for CS use as an entry criterion for clinical trials.

Canadian association of gastroenterology clinical practice guideline for the management of Luminal Crohn's Disease

Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

BACKGROUND: Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. AIM: To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. METHODS: A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. RESULTS: A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. CONCLUSIONS: According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding.

Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus

BACKGROUND & AIMS:: The medical management of ulcerative colitis (UC) has improved through the development of new therapies and novel approaches that optimize existing drugs. Previous Canadian consensus guidelines addressed the management of severe UC in the hospitalized patient. We now present consensus guidelines for the treatment of ambulatory patients with mild to severe active UC. METHODS: A systematic literature search identified studies on the management of UC. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a working group of specialists. RESULTS: The participants concluded that the goal of therapy is complete remission, defined as both symptomatic and endoscopic remission without corticosteroid therapy. The consensus includes 34 statements focused on 5 main drug classes: 5-aminosalicylate (5-ASA), corticosteroids, immunosuppressants, anti-tumor necrosis factor (TNF) therapies, and other therapies. Oral and rectal 5-ASA are recommended first-line therapy for mild to moderate UC, with corticosteroid therapy for those who fail to achieve remission. Patients with moderate to severe UC should undergo a course of oral corticosteroid therapy, with transition to 5-ASA, thiopurine, anti-TNF (with or without thiopurine or methotrexate), or vedolizumab maintenance therapy in those who successfully achieve symptomatic remission. For patients with corticosteroid-resistant/dependent UC, anti-TNF or vedolizumab therapy is recommended. Timely assessments of response and remission are critical to ensuring optimal outcomes. CONCLUSIONS: Optimal management of UC requires careful patient assessment, evidence-based use of existing therapies, and thorough assessment to define treatment success.(AU)

Guide wire-assisted cannulation for the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis.

BACKGROUND AND STUDY AIMS: Cannulation techniques are recognized to be important in causing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, considerable controversy exists about the usefulness of the guide wire-assisted cannulation technique for the prevention of PEP. This systematic review of randomized controlled trials (RCTs) aimed to compare the guide wire-assisted cannulation technique with the contrast-assisted cannulation technique. METHODS: CENTRAL, MEDLINE, EMBASE, CINAHL, and abstracts from Digestive Disease Week and the United European Gastroenterology Week were searched up to February 2012 for RCTs comparing the guide wire-assisted ERCP cannulation technique with the conventional contrast-assisted ERCP cannulation technique. The risk of bias was assessed, and outcomes were pooled by meta-analysis (random-effects model). The primary outcome measure was PEP. Secondary outcome measures included severity of PEP, primary common bile duct (CBD) cannulation success, overall CBD cannulation success, precut sphincterotomy, and other ERCP-related complications. RESULTS: In total, 12 RCTs (3450 patients) were included. The guide wire-assisted cannulation technique significantly reduced PEP compared with the contrast-assisted cannulation technique (risk ratio [RR] 0.51, 95 % confidence interval [CI] 0.32 - 0.82). In addition, the guide wire-assisted cannulation technique was associated with greater primary cannulation success (RR 1.07, 95 %CI 1.00 - 1.15), fewer precut sphincterotomies (RR 0.75, 95 %CI 0.60 - 0.95), and no increase in other ERCP-related complications. Subgroup analyses indicated that this significant risk reduction in PEP with the guide wire-assisted cannulation technique existed only in "non-crossover" trials (RR 0.22, 95 %CI 0.12 - 0.42). The results were robust in sensitivity analyses. CONCLUSION: Compared with the contrast-assisted cannulation technique, the guide wire-assisted cannulation technique increases the primary cannulation rate and reduces the risk of PEP, and therefore appears to be the most appropriate first-line cannulation technique.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. DATA SOURCES: Electronic databases and major conference proceedings were searched up to February 2006. REVIEW METHODS: Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. RESULTS: PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. CONCLUSIONS: PPI treatment compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduces the proportion of patients with SRH at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.

Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding.

BACKGROUND: There is conflicting evidence regarding the clinical efficacy of proton pump inhibitors (PPI) initiated prior to endoscopy in patients with upper gastrointestinal bleeding. OBJECTIVES: We aimed to systematically review evidence from randomised controlled trials (RCTs) that studied PPI treatment initiated before endoscopy in patients with upper gastrointestinal bleeding. SEARCH STRATEGY: A search was undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases model using CENTRAL, (The Cochrane Library), MEDLINE, EMBASE and CINAHL databases and major conference proceedings up to September 2005. The literature search was re-run in February 2006. SELECTION CRITERIA: Types of studies: Randomised controlled trials (RCTs). TYPES OF PARTICIPANTS: Hospitalised patients with unselected upper gastrointestinal bleeding. Types of interventions: Active treatment with a PPI (oral or intravenous) and control treatment with either placebo or an histamine-(2) receptor antagonist (H(2)RA). Types of outcome measures: Assessed at 30 days: mortality, rebleeding and surgery. Also assessed were stigmata of recent haemorrhage at index endoscopy, length of hospital stay and blood transfusion requirements. DATA COLLECTION AND ANALYSIS: At least two reviewers assessed the eligibility criteria of each study and extracted data regarding outcomes and factors affecting methodological quality. MAIN RESULTS: Five RCTs were included for review. No further RCTS were identified in an updated literature search. Four trials comprising a total of 1512 patients in total reported data for all randomised patients. There was no statistical heterogeneity among trials for the outcomes of mortality, rebleeding and surgery. There were no statistically significant differences in rates of mortality, rebleeding or surgery between PPI and control treatment. Pooled mortality rates were 6.1% and 5.5% respectively (odds ratio (OR)1.12; 95% CI 0.72 to 1.73). Pooled rebleeding rates were 13.9% and 16.6% respectively (OR 0.81; 95%CI 0.61 to 1.09). Pooled rates for surgery were 9.9% and 10.2% respectively (OR 0.96 95% CI 0.68 to 1.35). PPI treatment compared to control significantly reduced the proportion of patients with stigmata of recent haemorrhage at index endoscopy; pooled rates were 37.2% and 46.5% respectively (OR 0.67; 95% CI 0.54 to 0.84). For the continuous outcomes, namely length of hospital stay and blood transfusion requirements, quantitative analysis could not be performed. AUTHORS' CONCLUSIONS: PPI treatment initiated prior to endoscopy in patients with upper gastrointestinal bleeding significantly reduces the proportion of patients with stigmata of recent haemorrhage at index endoscopy. However, there is no evidence that PPI treatment affects clinically important outcomes, namely mortality, rebleeding or need for surgery.

Proton pump inhibitor treatment for acute peptic ulcer bleeding.

BACKGROUND: Randomised controlled trials (RCTs) evaluating the clinical effect of proton pump inhibitors (PPIs) in peptic ulcer (PU) bleeding yield conflicting results. OBJECTIVES: To evaluate the efficacy of PPIs in acute bleeding from PU using evidence from RCTs. SEARCH STRATEGY: We searched CENTRAL, The Cochrane Library (Issue 4, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), proceedings of major meetings to November 2004, and reference lists of articles. We contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: RCTs of PPI treatment (oral or intravenous) compared with placebo or H(2)-receptor antagonist (H(2)RA) in acute bleeding from PU. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently, assessed study validity, summarised studies and undertook meta-analysis. The influence of study characteristics on the outcomes was examined by subgroup analyses and meta-regression. MAIN RESULTS: Twenty-four RCTs comprising 4373 participants in total were included. Statistical heterogeneity was found among trials for rebleeding (P = 0.04), but not for all-cause mortality (P = 0.24) or surgery (P = 0.45). There was no significant difference in all-cause mortality rates between PPI and control treatment; pooled rates were 3.9% on PPI versus 3.8% on control (odds ratio (OR) 1.01; 95% CI 0.74 to 1.40). PPIs significantly reduced rebleeding compared to control; pooled rates were 10.6% with PPI versus 17.3% with control treatment (OR 0.49; 95% CI 0.37 to 0.65). PPI treatment significantly reduced surgery compared with control; pooled rates were 6.1% on PPI versus 9.3% on control (OR 0.61; 95% CI 0.48 to 0.78). There was no evidence to suggest that results on mortality and rebleeding were dependent on study quality, route of PPI administration, type of control treatment or application of initial endoscopic haemostatic treatment. PPIs significantly reduced surgery compared with placebo but not when compared with H(2)RA. There was no evidence to suggest that study quality, route of PPI administration or application of initial endoscopic haemostatic treatment influenced results on surgery. PPI treatment appeared more efficacious in studies conducted in Asia compared to studies conducted elsewhere. All-cause mortality was reduced only in Asian studies; reductions in rebleeding and surgery were quantitatively greater in Asian studies. Among patients with active bleeding or non-bleeding visible vessel, PPI treatment reduced mortality (OR 0.53; 95% CI 0.31 to 0.91), rebleeding and surgery. AUTHORS' CONCLUSIONS: PPI treatment in PU bleeding reduces rebleeding and surgery compared with placebo or H(2)RA, but there is no evidence of an overall effect on all-cause mortality.

Systematic review and meta-analysis: proton-pump inhibitor treatment for ulcer bleeding reduces transfusion requirements and hospital stay--results from the Cochrane Collaboration.

BACKGROUND: Proton-pump inhibitors reduce re-bleeding and surgical intervention, but not mortality, after ulcer bleeding. AIM: To examine the effects of proton-pump inhibitor treatment on transfusion requirements and length of hospital stay in patients with ulcer bleeding. METHODS: For the Cochrane Collaboration meta-analysis of randomized-controlled trials of proton-pump inhibitor therapy for ulcer bleeding, outcomes of transfusion requirements and hospital stay were summarized, respectively, as mean (+/-s.d.) units transfused and hospital days. We calculated weighted mean difference with 95% confidence interval. We also performed subgroup analyses according to geographical origin of the randomized-controlled trials. RESULTS: There was significant heterogeneity among randomized-controlled trials for either outcome. Overall, proton-pump inhibitor treatment marginally reduced transfusion requirements (WMD = -0.6 units; 95% CI: -1.1 to 0; P = 0.05) and length of hospitalization (WMD = -1.1 days; 95% CI: -1.5 to -0.7; P < 0.0001). Most of the randomized-controlled trials did not state precise criteria for administering blood transfusion and discharging patients, thereby limiting the strength of conclusions on the pooled effects. CONCLUSIONS: Proton-pump inhibitor treatment for ulcer bleeding produces small, but potentially important, reductions in transfusion requirements and length of hospitalization.

Systematic review and meta-analysis: enhanced efficacy of proton-pump inhibitor therapy for peptic ulcer bleeding in Asia--a post hoc analysis from the Cochrane Collaboration.

BACKGROUND: Proton-pump inhibitors reduce re-bleeding rates after ulcer bleeding. However, there is significant heterogeneity among different randomized-controlled trials. AIM: To see whether proton-pump inhibitors for ulcer bleeding produced different clinical outcomes in different geographical locations. METHODS: This was a post hoc analysis of our Cochrane Collaboration systematic review and meta-analysis of proton-pump inhibitor therapy for ulcer bleeding. Sixteen randomized-controlled trials conducted in Europe and North America were pooled and re-analysed separately from seven conducted in Asia. We calculated pooled rates for 30-day all-cause mortality, re-bleeding and surgical intervention and derived odds ratios and numbers needed to treat with 95% confidence intervals. RESULTS: There was no significant heterogeneity for any outcome. Reduced all-cause mortality was seen in the Asian randomized-controlled trials (odds ratios = 0.35; 95% confidence interval: 0.16-0.74; number needed to treat = 33), but not in the others (odds ratios = 1.36; 95% confidence interval: 0.94-1.96; number needed to treat--incalculable). There were significant reductions in re-bleeding and surgery in both sets of randomized-controlled trials, but the effects were quantitatively greater in Asia. CONCLUSIONS: Proton-pump inhibitor therapy for ulcer bleeding has been more efficacious in Asia than elsewhere. This may be because of an enhanced pharmacodynamic effect of proton-pump inhibitors in Asian patients.

Proton pump inhibitor treatment for acute peptic ulcer bleeding.

BACKGROUND: Peptic ulcer (PU) bleeding is associated with substantial morbidity, mortality and healthcare cost. Randomised controlled trials (RCTs) evaluating the clinical effect of proton pump inhibitors (PPIs) in peptic ulcer bleeding have yielded conflicting results. OBJECTIVES: To evaluate the efficacy of PPIs in the management of acute bleeding from PU using evidence from RCTs. SEARCH STRATEGY: We performed a search of CENTRAL, The Cochrane Library (Issue 3, 2003), MEDLINE (1966 to February 2003) and EMBASE (1980 to February 2003) and proceedings of recent major meetings through to February 2003. We searched the reference lists of articles and contacted pharmaceutical companies and experts in the field for additional published or unpublished data. SELECTION CRITERIA: RCTs of PPI treatment (oral or intravenous) compared with either placebo or H(2)-receptor antagonist (H(2)RA) in patients with acute bleeding from PU were included if they met pre-defined criteria. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently on a purpose-designed data extraction form. Validity of included studies was assessed by adequacy of randomisation method and other pre-defined criteria. Studies were summarised and meta-analysis was undertaken. The influence of factors on the outcomes was assessed. MAIN RESULTS: Twenty-one RCTs with a total of 2915 participants were included. Statistical heterogeneity was found among trials for rebleeding (P = 0.05), but not for mortality (P = 0.26) or surgery (P = 0.42). There was no significant difference in mortality rates between PPI and control treatment; pooled rates were 5.2% on PPI versus 4.6% on control (odds ratio (OR) 1.11; 95% CI 0.79 to 1.57). PPI treatment significantly reduced rates of surgical intervention compared with control; pooled rates were 8.4% on PPI versus 13.0% on control (OR 0.59; 95% CI 0.46 to 0.76). PPIs significantly reduced rebleeding compared to control; pooled rates were 10.6% with PPI (range: 0% to 24.4%) versus 18.7% with control treatment (range: 2.3% to 39.1%), the OR was 0.46 (95% CI 0.33 to 0.64). Results on mortality and rebleeding rates were independent of route of PPI administration, type of control treatment or application of initial endoscopic haemostatic treatment. Surgical intervention rates varied with type of control (PPI significantly reduced surgical intervention rates compared with placebo and not when compared with H(2)RA) but not with route of PPI administration or application of initial endoscopic haemostatic treatment. REVIEWERS' CONCLUSIONS: PPI treatment in PU bleeding reduces rebleeding and surgical intervention rates in studies comparing treatment with placebo or H(2)RA, but there is no evidence of an effect on mortality.

Meta-analysis: the efficacy of intravenous H2-receptor antagonists in bleeding peptic ulcer.

BACKGROUND: Although a previous meta-analysis found that intravenous H2-receptor antagonists were only weakly beneficial in bleeding gastric ulcer and of no benefit in bleeding duodenal ulcer, patients with ulcer bleeding continue to receive such treatment. AIM: To re-evaluate the efficacy of intravenous H2-receptor antagonists in ulcer re-bleeding, surgery and mortality by updating the previous meta-analysis. METHODS: After two independent literature searches, randomized, placebo-controlled trials of intravenous H2-receptor antagonists in bleeding ulcer published between 1984 and 2000 were added to those from the initial meta-analysis. Pooled rates of re-bleeding, surgery and death were re-calculated, together with the relative risk reduction, absolute risk reduction, number needed to treat and Mantel-Haenszel odds ratio. RESULTS: Intravenous H2-receptor antagonists did not significantly reduce re-bleeding, surgery or death in bleeding duodenal ulcer. There were small but significant reductions in re-bleeding, surgery and death in bleeding gastric ulcer; the absolute risk reductions were 7.2%, 6.7% and 3.2%, respectively. CONCLUSIONS: Intravenous H2-receptor antagonists are of no value in bleeding duodenal ulcer, although they may be mildly beneficial in bleeding gastric ulcer. Because proton pump inhibitors have a greater inhibitory effect on gastric acid secretion than H2-receptor antagonists, they may be more effective in ulcer bleeding and should be further evaluated for that indication.