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Background: Cannulation techniques have been recognized as being important in causing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, considerable controversy exists about the usefulness of the guidewire-assisted cannulation technique for the prevention of PEP., Objectives: To assess the effectiveness and safety of the guidewire-assisted cannulation technique compared to the conventional contrast-assisted cannulation technique for the prevention of PEP in people undergoing diagnostic or therapeutic ERCP for biliary or pancreatic diseases., Search Methods: For the previous version of this review, we searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL and major conference proceedings, up to February 2012, with no language restrictions. An updated search was performed on 26 February 2021 for the current version of this review. Two clinical trial registries, clinicaltrials.gov and WHO ICTRP, were also searched in this update., Selection Criteria: Randomized controlled trials (RCTs) comparing the guidewire-assisted cannulation technique versus the contrast-assisted cannulation technique in people undergoing ERCP., Data Collection and Analysis: Two review authors conducted study selection, data extraction, and methodological quality assessment independently. Using intention-to-treat analysis with random-effects models, we combined dichotomous data to obtain risk ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using the Chi² test (P < 0.10) and I² statistic (> 50%). To explore sources of heterogeneity, we conducted a priori subgroup analyses according to trial design, publication type, risk of bias, use of precut sphincterotomy, inadvertent guidewire insertion or contrast injection of the pancreatic duct (PD), use of a PD stent, cannulation device, and trainee involvement in cannulation. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR versus odds ratio (OR)) and meta-analytic models (fixed-effect versus random-effects) and per-protocol analysis., Main Results: 15 RCTs comprising 4426 participants were included. There was moderate heterogeneity among trials for the outcome of PEP (P = 0.08, I² = 36%). Meta-analyses suggest that the guidewire-assisted cannulation technique probably reduces the risk of PEP compared to the contrast-assisted cannulation technique (RR 0.51, 95% CI 0.36 to 0.72, 15 studies, moderate-certainty evidence). In addition, the guidewire-assisted cannulation technique may result in an increase in primary cannulation success (RR 1.06, 95% CI 1.01 to 1.12, 13 studies, low-certainty evidence), and probably reduces the need for precut sphincterotomy (RR 0.79, 95% CI 0.64 to 0.96, 10 studies, moderate-certainty evidence). Compared to the contrast-assisted cannulation technique, the guidewire-assisted cannulation technique may result in little to no difference in the risk of post-sphincterotomy bleeding (RR 0.87, 95% CI 0.49 to 1.54, 7 studies, low-certainty evidence) and perforation (RR 0.93, 95% CI 0.11 to 8.23, 8 studies, very low-certainty evidence). Procedure-related mortality was reported by eight studies, and there were no cases of deaths in both arms (moderate-certainty evidence). Subgroup analyses suggest that the heterogeneity for the outcome of PEP could be explained by differences in trial design. The results were robust in sensitivity analyses., Authors' Conclusions: There is moderate-certainty evidence that the guidewire-assisted cannulation technique probably reduces the risk of PEP compared to the contrast-assisted cannulation technique. There is low-certainty evidence that the guidewire-assisted cannulation technique may result in an increase in primary cannulation success. There is low- and very low-certainty evidence that the guidewire-assisted cannulation technique may result in little to no difference in the risk of bleeding and perforation. No procedure-related deaths were reported. Therefore, the guidewire-assisted cannulation technique appears to be superior to the contrast-assisted cannulation technique considering the certainty of evidence and the balance of benefits and harms. However, the routine use of guidewires in biliary cannulation will be dependent on local expertise, availability, and cost. Future research should assess the effectiveness and safety of the guidewire-assisted cannulation technique in the context of other pharmacologic or non-pharmacologic interventions for the prevention of PEP., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding., Objectives: To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding., Search Methods: We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials., Selection Criteria: We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (H 2 RA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding., Data Collection and Analysis: At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane., Main Results: We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis., Authors' Conclusions: There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear., Objectives: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer., Search Methods: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1), MEDLINE (1946 to February 2020), and EMBASE (1974 to February 2020). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2019. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials., Selection Criteria: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology., Data Collection and Analysis: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy., Main Results: Six trials met all our eligibility criteria and provided extractable data in the previous version. Following our updated search, one new RCT was identified, meaning that seven trials were included in this updated review. In addition, one previously included trial provided fully published data out to 10 years, and another previously included trial provided fully published data out to 22 years of follow-up. Four trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Six trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (RR 0.54, 95% confidence interval (CI) 0.40 to 0.72, 7 trials, 8323 participants, moderate certainty evidence). Only two trials reported the effect of eradication of H. pylori on the development of subsequent oesophageal cancer. Sixteen (0.8%) of 1947 participants assigned to eradication therapy subsequently developed oesophageal cancer compared with 13 (0.7%) of 1941 participants allocated to placebo (RR 1.22, 95% CI 0.59 to 2.54, moderate certainty evidence). H. pylori eradication reduced mortality from gastric cancer compared with placebo or no treatment (RR 0.61, 95% CI 0.40 to 0.92, 4 trials, 6301 participants, moderate certainty evidence). There was little or no evidence in all-cause mortality (RR 0.97, 95% CI 0.85 to 1.12, 5 trials, 7079 participants, moderate certainty evidence). Adverse events data were poorly reported., Authors' Conclusions: We found moderate certainty evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Dyspepsia is a common condition associated with gastrointestinal (GI) disease. Prokinetics are the treatment of choice for functional dyspepsia (FD). However, the role of prokinetics in FD treatment is still controversial., Objectives: We conducted a systematic review and meta-analysis of randomised control trials (RCTs) examining the efficacy of prokinetics in the treatment of FD. The primary outcome was overall absence of or improvement of symptoms and symptom scores at the end of treatment. We also evaluated quality of life (QoL) and adverse events as secondary outcomes., Search Methods: We performed a systematic search of MEDLINE, Embase, the Cochrane Library, and CINAHL, from 1946 until September 2017. RevMan 5.3 was used to calculate pooled risk ratios (RR) of symptoms persisting or without improved QoL or adverse events, mean difference (MD) or standardised mean difference (SMD) of post-treatment symptoms scores, changes of symptom scores, and QoL, when appropriate with 95% confidence intervals (CI), using a random-effects model. Quality of evidence was evaluated using GRADE methodology., Selection Criteria: We included studies that were parallel group RCTs comparing one prokinetic with either placebo or another prokinetic of the same or different class for the treatment of FD. Studies involved adults who presented with dyspepsia symptoms and who had negative or insignificant findings on endoscopy as well as no other organic and metabolic disorders. Studies only including participants with primarily reflux or heartburn symptoms were excluded., Data Collection and Analysis: Two review authors independently assessed study eligibility, study quality and performed data extraction., Main Results: From an initial 1388 citations, we identified 43 studies in 40 papers. Of those, 29 studies with 10,044 participants compared six prokinetics with placebo for the outcome of absence of symptoms or symptom improvement. There was a statistically significant effect of prokinetic treatment in reducing global symptoms of FD (RR of remaining dyspeptic = 0.81, 95% CI 0.74 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) =7, very low-quality evidence) with considerable heterogeneity; I 2 = 91% (P < 0.00001). After removing cisapride from the analysis, the effect of prokinetics in global symptom improvement still persisted, compared to placebo (RR 0.87, 95% CI 0.80 to 0.94), but was still based on very low-quality evidence. The result showed persistence of significant improvement in subgroups of studies at unclear or at low risk of bias (RR 0.86, 95% CI 0.80-0.92), and in subgroups by molecules of cisapride (RR 0.71, 95% CI 0.54 to 0.93; NNTB = 4), acotiamide (RR 0.94, 95% CI 0.91 to 0.98; NNTB = 20) and tegaserod(RR 0.89, 95% CI 0.82 to 0.96; NNTB = 14).Ten studies compared different types of prokinetics with each other and the most commonly used comparator was domperidone, 10 mg three times a day (eight of the 10 studies). There was a significantly better post-treatment symptom score in other prokinetics, compared to domperidone (SMD -0.19, 95% CI -0.35 to -0.03, very low-quality evidence), but no difference in reducing global symptom (RR 0.94, 95% CI 0.83 to 1.07), and mean difference symptom scores (SMD -0.13, 95% CI -0.31 to 0.05). We found five studies that assessed quality of life, but there was no benefit in improving quality of life with prokinetic treatment (SMD 0.11, 95% CI -0.10 to 0.33; participants = 1774). The adverse events in individual prokinetics was not different from placebo (RR 1.09, 95% CI 0.95 to 1.25; participants = 3811; studies = 17). However, when we looked at the adverse effects by each prokinetic, there were overall greater adverse effects in the active treatment group with cisapride (RR 1.31, 95% CI 1.03 to 1.65; P = 0.03). The most common side effects were diarrhoea, abdominal discomfort and nausea. The funnel plot was asymmetric (Egger's test, P = 0.02) implying reporting bias or other small-study effects may be, in part, driving the benefit of prokinetics compared to placebo in this meta-analysis. The GRADE assessment of the quality of the evidence in each outcome are mostly low or very low due to concerns around risk of bias in study design, unexplained heterogeneity and possible publication bias., Authors' Conclusions: Due to low, or very low, quality of evidence, we are unable to say whether prokinetics are effective for the treatment of functional dyspepsia . We are uncertain which of the individual prokinetic drugs is the most effective as well as whether prokinetics can improve quality of life. Apart from cisapride, prokinetics are well-tolerated. Good quality RCTs are needed to verify the efficacy of prokinetics.

Background: Functional dyspepsia (FD or non-ulcer dyspepsia) is defined as continuous or frequently recurring epigastric pain or discomfort for which no organic cause can be found. Acid suppressive therapy, including proton pump inhibitors (PPIs), has been proposed as a therapeutic option in FD, but its efficacy remains controversial. While PPIs are generally considered safe and well tolerated, they have been associated with adverse events, especially in the long term. For this reason, decisions on whether to initiate or continue PPI therapy should be made based on an appropriate clinical indication. Therefore, we conducted a systematic review to evaluate whether PPI therapy provides symptomatic relief in FD., Objectives: To determine the efficacy of proton pump inhibitors in the improvement of global symptoms of dyspepsia and quality of life compared to placebo, H2 receptor antagonists or prokinetics, in people with functional dyspepsia., Search Methods: We searched in the following electronic databases: the Cochrane Library (to May 2017), MEDLINE (OvidSP; to May 2017), Embase (OvidSP; to May 2017), and SIGLE grey literature (up to May 2017) and clinical trial registries; we handsearched abstracts from conferences up to May 2017. We screened non-systematic reviews, systematic reviews and guidelines to identify any additional trials. We contacted trialists to obtain missing information., Selection Criteria: All randomized controlled trials (RCTs) comparing any PPI with placebo, H2 receptor antagonists (H2RAs) or prokinetics for the treatment of FD of at least two weeks' duration. Participants were adults (aged 16 years or greater) with an adequate diagnosis of FD (any validated criteria such as Rome I, II, III or Lancet Working Group)., Data Collection and Analysis: Two review authors independently assessed eligibility and trial quality, and extracted data. We collected data on dyspeptic symptoms, quality of life and number of overall adverse events. Specific adverse events were beyond the scope of this review., Main Results: We identified 25 RCTs from 27 papers (with 8453 participants) studying the effect of PPIs versus placebo, H2RAs or prokinetics for improvement of global symptoms of dyspepsia and quality of life in people with FD. Low-dose PPIs had similar efficacy as standard-dose PPIs, therefore we combined these subgroups for the analysis. PPI was more effective than placebo at relieving overall dyspepsia symptoms in people with FD (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.94; participants = 6172; studies = 18; number needed to treat for an additional beneficial outcome (NNTB) 11; moderate quality evidence). PPIs may have little or no effect compared with H2RAs (RR 0.88, 95% CI 0.74 to 1.04; participants = 740; studies = 2; low quality evidence), and may be slightly more effective than prokinetics (RR 0.89, 95% CI 0.81 to 0.99; participants = 1033; studies = 5; NNTB 16; low quality evidence) at relieving overall dyspepsia symptoms in people with FD. PPIs plus prokinetics have probably little or no effect compared with PPIs alone at relieving overall dyspepsia symptoms (RR 0.85, 95% CI 0.68 to 1.08; participants = 407; studies = 2; moderate quality evidence).There was no difference when subgrouped by Helicobacter pylori status, country of origin, or presence of reflux or Rome III subtypes. There were no differences in the number of adverse events observed between PPIs and any of the other treatments. There were fewer adverse events in the combination of PPI plus prokinetics compared to prokinetics alone (RR 0.60, 95% CI 0.39 to 0.93; participants = 407; studies = 2; moderate quality evidence)., Authors' Conclusions: There is evidence that PPIs are effective for the treatment of FD, independent of the dose and duration of treatment compared with placebo. PPIs may be slightly more effective than prokinetics for the treatment of FD; however, the evidence is scarce. The trials evaluating PPIs versus prokinetics are difficult to interpret as they are at risk of bias. Although the effect of these drugs seems to be small, the drugs are well tolerated.

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.

Background: Functional dyspepsia (FD or non-ulcer dyspepsia) is defined as continuous or frequently recurring epigastric pain or discomfort for which no organic cause can be found. Acid suppressive therapy, including proton pump inhibitors (PPIs), has been proposed as a therapeutic option in FD, but its efficacy remains controversial. While PPIs are generally considered safe and well tolerated, they have been associated with adverse events, especially in the long term. For this reason, decisions on whether to initiate or continue PPI therapy should be made based on an appropriate clinical indication. Therefore, we conducted a systematic review to evaluate whether PPI therapy provides symptomatic relief in FD., Objectives: To determine the efficacy of proton pump inhibitors in the improvement of global symptoms of dyspepsia and quality of life compared to placebo, H2 receptor antagonists or prokinetics, in people with functional dyspepsia., Search Methods: We searched in the following electronic databases: the Cochrane Library (to January 2016), MEDLINE (OvidSP; to February 2016), Embase (OvidSP; to February 2016), and SIGLE grey literature (up to February 2016) and clinical trial registries; we handsearched abstracts from conferences up to February 2016. We screened non-systematic reviews, systematic reviews and guidelines to identify any additional trials. We contacted trialists to obtain missing information., Selection Criteria: All randomized controlled trials (RCTs) comparing any PPI with placebo, H2 receptor antagonists (H2RAs) or prokinetics for the treatment of FD. Participants were adults (aged 16 years or greater) with an adequate diagnosis of FD (any validated criteria such as Rome I, II, III or Lancet Working Group)., Data Collection and Analysis: Two review authors independently assessed eligibility, trial quality and extracted data. We collected data on dyspeptic symptoms, quality of life and number of overall adverse events. Specific adverse events were beyond the scope of this review., Main Results: We identified 23 RCTs from 22 papers (with 8759 participants) studying the effect of PPIs versus placebo, H2RAs or prokinetics for improvement of global symptoms of dyspepsia and quality of life in people with FD. Low-dose PPIs had similar efficacy as standard-dose PPIs, therefore we combined these subgroups for the analysis. Two to eight weeks of therapy with PPI was slightly more effective than placebo at relieving overall dyspepsia symptoms in people with FD (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.94; participants = 5968; studies = 16; number needed to treat for an additional beneficial outcome (NNTB) 13; moderate quality evidence). PPIs may be slightly more effective than H2RAs (RR 0.88, 95% CI 0.74 to 1.04; participants = 740; studies = 2, NNTB 13; low quality evidence), and slightly more effective than prokinetics (RR 0.90, 95% CI 0.81 to 1.00; participants = 892; studies = 4; NNTB 20; low quality evidence) at relieving overall dyspepsia symptoms in people with FD. PPIs plus prokinetics were possibly slightly more effective than PPIs alone at relieving overall dyspepsia symptoms (RR 0.85, 95% CI 0.68 to 1.08; participants = 407; studies = 2; NNTB 18; moderate quality evidence).The was no difference when subgrouped by Helicobacter pylori status, country of origin, or presence of reflux or Rome III subtypes. There were no differences in the number of adverse events observed between PPIs and any of the other treatments., Authors' Conclusions: There is evidence that PPIs are effective for the treatment of FD, independent of the dose and duration of treatment compared with placebo. PPIs may be slightly more effective than H2RAs for the treatment of FD; however, the evidence is scarce. The trials evaluating PPIs versus prokinetics are difficult to interpret as they are at risk of bias. Although the effect of these drugs seems to be small, the drugs are well tolerated.

Background: Difficult cannulation is a risk factor for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). It has been postulated that the pancreatic duct guidewire (PGW) technique may improve biliary cannulation success and reduce the risk of PEP in people with difficult cannulation., Objectives: To systematically review evidence from randomised controlled trials (RCTs) assessing the effectiveness and safety of the PGW technique compared to persistent conventional cannulation (CC) (contrast- or guidewire-assisted cannulation) or other advanced techniques in people with difficult biliary cannulation for the prevention of PEP., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL databases, major conference proceedings, and for ongoing trials on the ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to March 2016, using the Cochrane Upper Gastrointestinal and Pancreatic Diseases model with no language restrictions., Selection Criteria: RCTs comparing the PGW technique versus persistent CC or other advanced techniques in people undergoing ERCP with difficult biliary cannulation., Data Collection and Analysis: Two review authors independently conducted study selection, data extraction, and methodological quality assessment. Using intention-to-treat analysis with random-effects models, we combined dichotomous data to obtain risk ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using the Chi(2) test (P < 0.15) and I(2) test (> 25%). To explore sources of heterogeneity, we conducted a priori subgroup analyses according to trial design, use of pancreatic duct (PD) stent, involvement of trainees in cannulation, publication type, and risk of bias. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR versus odds ratio (OR)) and meta-analytic models (fixed-effect versus random-effects)., Main Results: We included seven RCTs comprising 577 participants. There was no significant heterogeneity among trials for the outcome of PEP (P = 0.32; I(2) = 15%). The PGW technique significantly increased PEP compared to other endoscopic techniques (RR 1.98, 95% CI 1.14 to 3.42; low-quality evidence). The number needed to treat for an additional harmful outcome was 13 (95% CI 5 to 89). Among the three studies that compared the PGW technique with persistent CC, the incidence of PEP was 13.5% for the PGW technique and 8.7% for persistent CC (RR 1.58, 95% CI 0.83 to 3.01; low-quality evidence). Among the two studies that compared the PGW technique with precut sphincterotomy, the incidence of PEP was 29.8% in the PGW group versus 10.3% in the precut group (RR 2.92, 95% CI 1.24 to 6.88; low-quality evidence). Among the two studies that compared the PGW technique with PD stent placement, the incidence of PEP was 11.7% for the PGW technique and 5.0% for PD stent placement (RR 1.75, 95% CI 0.08 to 37.50; very low-quality evidence). There was no significant difference in common bile duct (CBD) cannulation success with the randomised technique (RR 1.04, 95% CI 0.87 to 1.24; low-quality evidence) or overall CBD cannulation success (RR 1.04, 95% CI 0.91 to 1.18; low-quality evidence) between the PGW technique and other endoscopic techniques. There was also no statistically significant difference in the risk of other ERCP-related complications (bleeding, perforation, cholangitis, and mortality). The results were robust in sensitivity analyses. The overall quality of evidence for the outcome of PEP was low or very low because of study limitations and imprecision., Authors' Conclusions: In people with difficult CBD cannulation, sole use of the PGW technique appears to be associated with an increased risk of PEP. Prophylactic PD stenting after use of the PGW technique may reduce the risk of PEP. However, the PGW technique is not superior to persistent attempts with CC, precut sphincterotomy, or PD stent in achieving CBD cannulation. The influence of co-intervention in the form of rectal peri-procedural nonsteroidal anti-inflammatory drug administration is unclear.

Background: Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4., Objectives: To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved., Search Methods: In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials., Selection Criteria: We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards., Data Collection and Analysis: We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible., Main Results: A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy., Authors' Conclusions: Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out.

Background: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear., Objectives: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer., Search Methods: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 11), MEDLINE (1946 to December 2013), and EMBASE (1974 to December 2013). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2013. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials., Selection Criteria: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology., Data Collection and Analysis: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy., Main Results: Six trials met all our eligibility criteria and provided extractable data. Three trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Five trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (6 trials, 6497 participants, risk ratio (RR) of developing subsequent gastric cancer 0.66; 95% confidence interval (CI) 0.46 to 0.95; moderate-quality evidence). Only one trial reported effect of eradication of H. pylori on development of subsequent oesophageal cancer (2 (0.2%) among 817 participants assigned to eradication therapy, compared with 1 (0.1%) of 813 participants allocated to placebo; RR 1.99; 95% CI 0.18 to 21.91). The effect of H. pylori eradication on preventing death from gastric cancer compared with placebo or no treatment was uncertain due to wide confidence intervals (3 trials, 4475 participants, RR 0.67; 95% CI 0.40 to 1.11; moderate-quality evidence). There was no evidence of an effect on all-cause mortality (4 trials, 5253 participants, RR 1.09; 95% CI 0.86 to 1.38; moderate-quality evidence). Adverse events data were poorly reported., Authors' Conclusions: We found limited, moderate-quality evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.

Background: The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens., Objectives: The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events., Search Methods: The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search., Selection Criteria: Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded., Data Collection and Analysis: Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori., Main Results: In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H₂RA) bismuth quadruple therapy (n = 3), H₂RA bismuth-based triple therapy (n = 2), H₂RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H₂RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data., Authors' Conclusions: Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.

Background: Cannulation techniques have been recognized to be important in causing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, considerable controversy exists about the usefulness of the guidewire-assisted cannulation technique for the prevention of PEP., Objectives: To systematically review evidence from randomised controlled trials (RCTs) assessing the effectiveness and safety of the guidewire-assisted cannulation technique compared to the conventional contrast-assisted cannulation technique for the prevention of PEP., Search Methods: We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and CINAHL databases and major conference proceedings, up to February 2012, using the Cochrane Upper Gastrointestinal and Pancreatic Diseases model with no language restrictions., Selection Criteria: RCTs comparing the guidewire-assisted cannulation technique versus the contrast-assisted cannulation technique in patients undergoing ERCP., Data Collection and Analysis: Two review authors conducted study selection, data extraction and methodological quality assessment independently. Using intention-to-treat analysis with random-effects models, we combined dichotomous data to obtain risk ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using the Chi² test (P < 0.15) and I² statistic (> 25%). To explore sources of heterogeneity, we conducted a priori subgroup analyses according to trial design, publication type, risk of bias, use of precut sphincterotomy, inadvertent guidewire insertion or contrast injection of the pancreatic duct (PD), use of a PD stent, cannulation device, and trainee involvement in cannulation. To assess the robustness of our results we carried out sensitivity analyses using different summary statistics (RR versus odds ratio (OR)) and meta-analytic models (fixed-effect versus random-effects), and per protocol analysis., Main Results: Twelve RCTs comprising 3450 participants were included. There was statistical heterogeneity among trials for the outcome of PEP (P = 0.04, I² = 45%). The guidewire-assisted cannulation technique significantly reduced PEP compared to the contrast-assisted cannulation technique (RR 0.51, 95% CI 0.32 to 0.82). In addition, the guidewire-assisted cannulation technique was associated with greater primary cannulation success (RR 1.07, 95% CI 1.00 to 1.15), less precut sphincterotomy (RR 0.75, 95% CI 0.60 to 0.95), and no increase in other ERCP-related complications. Subgroup analyses indicated that this significant risk reduction in PEP with the guidewire-assisted cannulation technique existed only in 'non-crossover' trials (RR 0.22, 95% CI 0.12 to 0.42). The results were robust in sensitivity analyses., Authors' Conclusions: Compared with the contrast-assisted cannulation technique, the guidewire-assisted cannulation technique increases the primary cannulation rate and reduces the risk of PEP, and it appears to be the most appropriate first-line cannulation technique.

Background: Studies have also shown that non-ulcer dyspepsia (NUD) patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis and tendency to be more pessimistic when compared with the community controls. However, the role of psychological interventions in NUD remains uncertain., Objectives: This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores in patients with NUD., Search Strategy: Trials were identified by searching the Cochrane Controlled Trials Register (Issue 3-1999), MEDLINE (1966-99), EMBASE (1988-99), PsycLIT (1987-1999) and CINAHL (1982-99). Bibliographies of retrieved articles were also searched and experts in the field were contacted. Searches were updated on 10 December 2002 and 21 January 2004. The searches were re-run on 24 January 2005 and 9 January 2006 and no new trials were found, Selection Criteria: All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia (NUD) were identified., Data Collection and Analysis: Data collected included both individual and global dyspepsia symptom scores and quality of life (QoL) scores., Main Results: We identified only four trials each using different psychological interventions; three presented results in a manner that did not allow synthesis of the data to form a meta-analysis. All trials suggested that psychological interventions benefit dyspepsia symptoms and this effect persists for one year. However, all trials used statistical techniques that adjusted for baseline differences between groups. This should not be necessary for a randomised trial that is adequately powered suggesting that the sample size was too small. Unadjusted data was not statistically significant. The other problems of psychological intervention included low recruitment and high drop out rate, which has been shown to be greater in patients receiving group therapy., Authors' Conclusions: There is insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD.

Background: The commonest cause of upper gastrointestinal symptoms is non-ulcer dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly characterised and the optimum treatment is uncertain. It is estimated that £450 million is spent on dyspepsia drugs in the UK each year., Objectives: This review aims to determine the effectiveness of six classes of drugs (antacids, histamine H2 antagonists, proton pump inhibitors, prokinetics, mucosal protecting agents and antimuscarinics) in the improvement of either the individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (1966 to January 2006), EMBASE (1988 to January 2006), CINAHL (1982 to January 2006), SIGLE, and reference lists of articles. We also contacted experts in the field and pharmaceutical companies. Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and text words, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and pharmaceutical companies., Selection Criteria: All randomised controlled trials (RCTs) comparing drugs of any of the six groups with each other or with placebo for non-ulcer dyspepsia (NUD)., Data Collection and Analysis: Two review authors independently assessed eligibility, trial quality and extracted data., Main Results: We included 73 trials: prokinetics (19 trials with dichotomous outcomes evaluating 3178 participants; relative risk reduction (RRR) 33%; 95% confidence intervals (CI) 18% to 45%), H(2)RAs (12 trials evaluating 2,183 participants; RRR 23%; 95% CI 8% to 35%) and PPIs (10 trials evaluating 3,347 participants; RRR 13%; 95% CI 4% to 20%) were significantly more effective than placebo. Bismuth salts (six trials evaluating 311 participants; RRR 40%; 95% CI -3 to 65%) were superior to placebo but this was of marginal statistical significance. Antacids (one trial evaluating 109 participants; RRR -2%; 95% CI -36% to 24%) and sucralfate (two trials evaluating 246 participants; RRR 29%; 95% CI -40% to 64%) were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic results could be due to publication bias or other small study effects., Authors' Conclusions: There is evidence that anti-secretory therapy may be effective in NUD. The trials evaluating prokinetic therapy are difficult to interpret as the meta-analysis result could have been due to publication bias. The effect of these drugs is likely to be small and many patients will need to take them on a long-term basis so economic analyses would be helpful and ideally the therapies assessed need to be inexpensive and well tolerated.

Background: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear., Objectives: To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia., Search Strategy: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies., Selection Criteria: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia., Data Collection and Analysis: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms., Main Results: Twenty one randomised controlled trials were included in the systematic review. Eighteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Seventeen of these trials gave results as dichotomous outcomes evaluating 3566 patients and there was no significant heterogeneity between the studies. There was a 10% relative risk reduction in the H pylori eradication group (95% CI = 6% to 14%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 14 (95% CI = 10 to 25). A further three trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia., Authors' Conclusions: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Background: Oesophagitis arises when reflux of acid from the stomach into the oesophagus causes mucosal inflammation. It is a common problem and a systematic review on the optimum treatment would be useful., Objectives: To assess the effectiveness of proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), prokinetic therapy, sucralfate and placebo in healing oesophagitis or curing reflux symptoms or both. To compare adverse effects with the different treatments., Search Strategy: We searched MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and the National Research Register until December 2004 and reference lists of articles. We also contacted manufacturers and researchers in the field., Selection Criteria: Randomised controlled trials assessing the healing of oesophagitis or reflux symptoms or both. Treatment involving PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo for 2 and 12 weeks., Data Collection and Analysis: Two reviews independently assessed trial quality and extracted data., Main Results: We included 134 trials involving 35,978 oesophagitis participants. Five RCTs evaluated standard dose of PPI versus placebo in 965 participants. There was a statistically significant benefit of taking standard dose PPI therapy compared to placebo in healing of oesophagitis (RR = 0.22; 95% CI 0.15 to 0.31). Ten RCTs reported on the outcome for H2RA versus placebo evaluating 1241 participants. There was statistically significant benefit of taking H2RA compared to placebo in healing of oesophagitis (RR 0.74,95% CI = 0.66 to 0.84). Three RCTs evaluated prokinetic therapy versus placebo in 198 participants. There was no statistically significant benefit of taking prokinetic therapy compared to placebo in healing of oesophagitis (RR 0.71, 95% CI 0.46 to 1.10). Twenty six RCTs reported the outcome for PPI versus H2RA or H2RA plus prokinetics, evaluating 4032 participants. There was statistically significant benefit of taking PPI therapy compared to H2RA or H2RA plus prokinetics in healing of oesophagitis (RR 0.51, 95% CI 0.44 to 0.59)., Authors' Conclusions: PPI therapy is the most effective therapy in oesophagitis but H2RA therapy is also superior to placebo. There is a paucity of evidence on prokinetic therapy but no evidence that it is superior to placebo.

Background: There is conflicting evidence regarding the clinical efficacy of proton pump inhibitors (PPI) initiated before endoscopy for upper gastrointestinal bleeding., Objectives: To systematically review evidence from randomised controlled trials (RCTs) of PPI treatment initiated before endoscopy for upper gastrointestinal bleeding., Search Strategy: We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE and CINAHL databases and major conference proceedings to September 2005, using the Cochrane Upper Gastrointestinal and Pancreatic Diseases model. Searches were re-run in February 2006 and October 2008., Selection Criteria: We selected randomised controlled trials (RCTs), of hospitalised participants with unselected upper gastrointestinal bleeding, undergoing active treatment with a proton pump inhibitor PPI (oral or intravenous) and control treatment with either placebo, histamine-2 receptor antagonist (H2RA) or no treatment prior to endoscopy. Outcomes were assessed at 30 days and included mortality, rebleeding and surgery. Also assessed were stigmata of recent haemorrhage (SRH; active bleeding, non bleeding visible vessel or adherent clot) at index endoscopy, length of hospital stay, blood transfusion requirements and requirement for endoscopic therapy at index endoscopy., Data Collection and Analysis: At least two review authors assessed eligibility criteria and extracted data regarding outcomes and factors affecting methodological quality., Main Results: Six RCTs comprising 2223 participants were included. There was no statistical heterogeneity among trials for dichotomous outcomes. There were no statistically significant differences in mortality, rebleeding or surgery between PPI and control treatment. Unweighted pooled mortality rates were 6.1% and 5.5% respectively (odds ratio (OR)1.12; 95% CI 0.72 to 1.73). Unweighted 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 participants with SRH at index endoscopy; unweighted pooled rates were 37.2% and 46.5% respectively (OR 0.67; 95% CI 0.54 to 0.84). However, this result was not robust to sensitivity analysis. PPI treatment compared to control significantly reduced endoscopic therapy at index endoscopy; unweighted pooled rates were 8.6% and 11.7% respectively (OR 0.68; 95% CI 0.50 to 0.93). For continuous outcomes (length of hospital stay and blood transfusion requirements), quantitative analysis could not be performed., Authors' Conclusions: PPI treatment initiated before endoscopy for upper gastrointestinal bleeding might reduce the proportion of participants with SRH at index endoscopy and significantly reduces requirement for endoscopic therapy during index endoscopy. However, there is no evidence that PPI treatment affects clinically important outcomes, namely mortality, rebleeding or need for surgery.

Background: Gastro-oesophageal reflux disease (GORD) - reflux of stomach contents +/- bile into the oesophagus causing symptoms such as heartburn and acid reflux - is a common relapsing and remitting disease which often requires long-term maintenance therapy. Patients with GORD may have oesophagitis (inflammation of the oesophagus) or a normal endoscopy (endoscopy negative reflux disease or ENRD)., Objectives: To assess the effects of continuous maintenance therapy in adults with GORD (both ENRD and healed oesophagitis)., Search Strategy: We searched Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), CINAHL (1982-2003), and the National Research Register (Issue 2, 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field., Selection Criteria: Randomised controlled studies comparing PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo in adults with reflux oesophagitis and ENRD., Data Collection and Analysis: One author extracted data from included trials and a second author carried out an unblinded check. Two authors independently assessed trial quality. Study authors were contacted for additional information., Main Results: Maintenance of patients with healed oesophagitis: For a healing dose of PPI (generally the standard dose given by the manufacturer) versus placebo, the relative risk (RR) for oesophagitis relapse was 0.26 (95% confidence interval (CI) 0.19 to 0.36); versus H2RAs the RR was 0.36 (95% CI 0.28 to 0.46) and versus maintenance PPIs the RR was 0.63 (95% CI 0.55 to 0.73). However overall adverse effects were also more common and headaches were more common when comparing healing PPIs to H2RAs.For a maintenance dose of PPI (half of the standard dose) versus placebo, the RR for oesophagitis relapse was 0.46 (95% CI 0.38 to 0.57) and versus H2RAs the RR was 0.57 (95% CI 0.47 to 0.69). Overall adverse effects were more common.H2RAs were of marginal help but beneficial for symptomatic relief. Prokinetics and sucralfate were also more effective than placebo.For ENRD patients: Limited data with one RCT showed benefit for omeprazole 10 mg once daily over placebo (RR 0.4; 95% CI 0.29 to 0.53)., Authors' Conclusions: The findings in this review support the long-term treatment of oesophagitis to prevent relapse, both endoscopically and symptomatically. Healing doses of PPIs are more effective than all other therapies, although there is an increase in overall adverse effects compared to placebo, and headache occurrence compared to H2RAs. H2RAs prevent relapse more effectively than placebo, demonstrating a role for PPI-intolerant patients. Prokinetics and sucralfate both show benefit over placebo, but the former is no longer licenced. There is only limited data for ENRD.

Background: This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients. Dyspepsia was defined to include both epigastric pain and heartburn., Objectives: To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia (a) Initial pharmacological therapy (including endoscopy for treatment failures). (b) Early endoscopy. (c) Testing for Helicobacter pylori (H. pylori )and endoscope only those positive. (d) H. pylori eradication therapy with or without prior testing., Search Strategy: Trials were located through electronic searches and extensive contact with trialists., Selection Criteria: All randomised controlled trials of dyspeptic patients presenting in primary care., Data Collection and Analysis: Data were collected on dyspeptic symptoms, quality of life and use of resources. An individual patient data meta-analysis of health economic data was conducted, Main Results: Twenty-five papers reporting 27 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (three trials) and histamine H2-receptor antagonists (H2RAs) (three trials), early endoscopy with initial acid suppression (five trials), H. pylori test and endoscope versus usual management (three trials), H. pylori test and treat versus endoscopy (six trials), and test and treat versus acid suppression alone in H. pylori positive patients (four trials), were pooled. PPIs were significantly more effective than both H2RAs and antacids. Relative risks (RR) and 95% confidence intervals (CI) were; for PPI compared with antacid 0.72 (95% CI 0.64 to 0.80), PPI compared with H2RA 0.63 (95% CI 0.47 to 0.85). Results for other drug comparisons were either absent or inconclusive. Initial endoscopy was associated with a small reduction in the risk of recurrent dyspeptic symptoms compared with H. pylori test and treat (OR 0.75, 95% CI 0.58 to 0.96), but was not cost effective (mean additional cost of endoscopy US$401 (95% CI $328 to 474). Test and treat may be more effective than acid suppression alone (RR 0.59 95% CI 0.42 to 0.83)., Authors' Conclusions: Proton pump inhibitor drugs (PPIs) are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease (GORD). The relative efficacy of histamine H2-receptor antagonists (H2RAs) and PPIs is uncertain. Early investigation by endoscopy or H. pylori testing may benefit some patients with dyspepsia but is not cost effective as part of an overall management strategy.

Background: Oesophagitis arises when reflux of acid from the stomach into the oesophagus causes mucosal inflammation. It is a common problem and a systematic review on the optimum treatment would be useful., Objectives: To assess the effectiveness of proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), prokinetic therapy, sucralfate and placebo in healing oesophagitis or curing reflux symptoms or both. To compare adverse effects with the different treatments., Search Strategy: We searched MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and the National Research Register until December 2004 and reference lists of articles. We also contacted manufacturers and researchers in the field., Selection Criteria: Randomised controlled trials assessing the healing of oesophagitis or reflux symptoms or both. Treatment involving PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo for 2 and 12 weeks., Data Collection and Analysis: Two reviews independently assessed trial quality and extracted data., Main Results: We included 134 trials involving 35,978 oesophagitis participants. Five RCTs evaluated standard dose of PPI versus placebo in 965 participants. There was a statistically significant benefit of taking standard dose PPI therapy compared to placebo in healing of oesophagitis (RR = 0.22; 95% CI 0.15 to 0.31). Ten RCTs reported on the outcome for H2RA versus placebo evaluating 1241 participants. There was statistically significant benefit of taking H2RA compared to placebo in healing of oesophagitis (RR 0.74,95% CI = 0.66 to 0.84). Three RCTs evaluated prokinetic therapy versus placebo in 198 participants. There was no statistically significant benefit of taking prokinetic therapy compared to placebo in healing of oesophagitis (RR 0.71, 95% CI 0.46 to 1.10). Twenty six RCTs reported the outcome for PPI versus H2RA or H2RA plus prokinetics, evaluating 4032 participants. There was statistically significant benefit of taking PPI therapy compared to H2RA or H2RA plus prokinetics in healing of oesophagitis (RR 0.51, 95% CI 0.44 to 0.59)., Authors' Conclusions: PPI therapy is the most effective therapy in oesophagitis but H2RA therapy is also superior to placebo. There is a paucity of evidence on prokinetic therapy but no evidence that it is superior to placebo.

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.

Background: The commonest cause of upper gastrointestinal symptoms is non-ulcer dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly characterised and the optimum treatment is uncertain. It is estimated that pound450 million is spent on dyspepsia drugs in the UK each year., Objectives: This review aims to determine the effectiveness of six classes of drugs (antacids, histamine H(2) antagonists, proton pump inhibitors, prokinetics, mucosal protecting agents and antimuscarinics) in the improvement of either the individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (1966 to January 2006), EMBASE (1988 to January 2006), CINAHL (1982 to January 2006), SIGLE, and reference lists of articles. We also contacted experts in the field and pharmaceutical companies. Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and text words, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and pharmaceutical companies., Selection Criteria: All randomised controlled trials (RCTs) comparing drugs of any of the six groups with each other or with placebo for non-ulcer dyspepsia (NUD)., Data Collection and Analysis: Two review authors independently assessed eligibility, trial quality and extracted data., Main Results: We included 73 trials: prokinetics (19 trials with dichotomous outcomes evaluating 3178 participants; relative risk reduction (RRR) 33%; 95% confidence intervals (CI) 18% to 45%), H(2)RAs (12 trials evaluating 2,183 participants; RRR 23%; 95% CI 8% to 35%) and PPIs (10 trials evaluating 3,347 participants; RRR 13%; 95% CI 4% to 20%) were significantly more effective than placebo. Bismuth salts (six trials evaluating 311 participants; RRR 40%; 95% CI -3 to 65%) were superior to placebo but this was of marginal statistical significance. Antacids (one trial evaluating 109 participants; RRR -2%; 95% CI -36% to 24%) and sucralfate (two trials evaluating 246 participants; RRR 29%; 95% CI -40% to 64%) were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic results could be due to publication bias or other small study effects., Authors' Conclusions: There is evidence that anti-secretory therapy may be effective in NUD. The trials evaluating prokinetic therapy are difficult to interpret as the meta-analysis result could have been due to publication bias. The effect of these drugs is likely to be small and many patients will need to take them on a long-term basis so economic analyses would be helpful and ideally the therapies assessed need to be inexpensive and well tolerated.

Background: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear., Objectives: To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia., Search Strategy: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies., Selection Criteria: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia., Data Collection and Analysis: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms., Main Results: Twenty one randomised controlled trials were included in the systematic review. Eighteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Seventeen of these trials gave results as dichotomous outcomes evaluating 3566 patients and there was no significant heterogeneity between the studies. There was a 10% relative risk reduction in the H pylori eradication group (95% CI = 6% to 14%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 14 (95% CI = 10 to 25). A further three trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia., Authors' Conclusions: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Background: Peptic ulcer disease is the cause for dyspepsia in about 10% of patients. 95% of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain., Objectives: The primary outcomes were the proportion of peptic ulcers healed initially and proportion of patients free from relapse following successful healing. Eradication therapy was compared to placebo or pharmacological therapies in H. pylori positive patients. Secondary aims included symptom relief and adverse effects., Search Strategy: Searches were conducted on the Cochrane Central register of Controlled Trials - CENTRAL (which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register) on The Cochrane Library (Issue 3 2002) MEDLINE (1966 to July 2002) and EMBASE (1980 to July 2002). Reference lists from trials selected by electronic searching were handsearched to identify further relevant trials. Published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) were handsearched. The search was updated in September 2003, November 2004 and November 2005. Members of the Cochrane UGPD Group, and experts in the field were contacted and asked to provide details of outstanding clinical trials and any relevant unpublished materials, Selection Criteria: Randomised controlled trials of short and long-term treatment of peptic ulcer disease in H. pylori positive adults were analysed. Patients received at least one week of H pylori eradication compared with ulcer healing drug, placebo or not treatment. Trials were included if they reported assessment from 2 weeks onwards., Data Collection and Analysis: Data were collected on ulcer healing, recurrence, relief of symptoms and adverse effects., Main Results: 63 trials were eligible. Data extraction was not possible in 7 trials, and 56 trials were included. In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95% confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients, RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant differences were detected between eradication therapy and UHD (14 trials, 1572 patients, RR = 1.25; 95% CI = 0.88, 1.76). In preventing duodenal ulcer recurrence no significant differences were detected between eradication therapy and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was superior to no treatment (27 trials 2509 patients, RR = 0.20; 95% CI = 0.15, 0.26). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (11 trials, 1104 patients, RR = 0.29; 95% CI 0.20, 0.42)., Authors' Conclusions: A 1 to 2 weeks course of H. pylori eradication therapy is an effective treatment for H. pylori positive peptic ulcer disease.

Background: This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients. Dyspepsia was defined to include both epigastric pain and heartburn., Objectives: To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia: (a) Initial pharmacological therapy (including endoscopy for treatment failures). (b) Early endoscopy. (c) Testing for Helicobacter pylori (H. pylori )and endoscope only those positive. (d) H. pylori eradication therapy with or without prior testing., Search Strategy: Trials were located through electronic searches and extensive contact with trialists., Selection Criteria: All randomised controlled trials of dyspeptic patients presenting in primary care., Data Collection and Analysis: Data were collected on dyspeptic symptoms, quality of life and use of resources. An individual patient data meta-analysis of health economic data was conducted, Main Results: Twenty-five papers reporting 27 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (three trials) and histamine H2-receptor antagonists (H2RAs) (three trials), early endoscopy with initial acid suppression (five trials), H. pylori test and endoscope versus usual management (three trials), H. pylori test and treat versus endoscopy (six trials), and test and treat versus acid suppression alone in H. pylori positive patients (four trials), were pooled. PPIs were significantly more effective than both H2RAs and antacids. Relative risks (RR) and 95% confidence intervals (CI) were; for PPI compared with antacid 0.72 (95% CI 0.64 to 0.80), PPI compared with H2RA 0.63 (95% CI 0.47 to 0.85). Results for other drug comparisons were either absent or inconclusive. Initial endoscopy was associated with a small reduction in the risk of recurrent dyspeptic symptoms compared with H. pylori test and treat (OR 0.75, 95% CI 0.58 to 0.96), but was not cost effective (mean additional cost of endoscopy US$401 (95% CI $328 to 474). Test and treat may be more effective than acid suppression alone (RR 0.59 95% CI 0.42 to 0.83)., Authors' Conclusions: Proton pump inhibitor drugs (PPIs) are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease (GORD). The relative efficacy of histamine H2-receptor antagonists (H2RAs) and PPIs is uncertain. Early investigation by endoscopy or H. pylori testing may benefit some patients with dyspepsia but is not cost effective as part of an overall management strategy.

Background: Studies have also shown that non-ulcer dyspepsia (NUD) patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis and tendency to be more pessimistic when compared with the community controls. However, the role of psychological interventions in NUD remains uncertain., Objectives: This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores in patients with NUD., Search Strategy: Trials were identified by searching the Cochrane Controlled Trials Register (Issue 3-1999), MEDLINE (1966-99), EMBASE (1988-99), PsycLIT (1987-1999) and CINAHL (1982-99). Bibliographies of retrieved articles were also searched and experts in the field were contacted. Searches were updated on 10 December 2002 and 21 January 2004. The searches were re-run on 24 January 2005 and no new trials were found, Selection Criteria: All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia (NUD) were identified., Data Collection and Analysis: Data collected included both individual and global dyspepsia symptom scores and quality of life (QoL) scores., Main Results: We identified only four trials each using different psychological interventions; three presented results in a manner that did not allow synthesis of the data to form a meta-analysis. All trials suggested that psychological interventions benefit dyspepsia symptoms and this effect persists for one year. However, all trials used statistical techniques that adjusted for baseline differences between groups. This should not be necessary for a randomised trial that is adequately powered suggesting that the sample size was too small. Unadjusted data was not statistically significant. The other problems of psychological intervention included low recruitment and high drop out rate, which has been shown to be greater in patients receiving group therapy., Authors' Conclusions: There is insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD.

Background: Gastro-oesophageal reflux disease (GORD) - reflux of stomach contents +/- bile into the oesophagus causing symptoms such as heartburn and acid reflux - is a common relapsing and remitting disease which often requires long-term maintenance therapy. Patients with GORD may have oesophagitis (inflammation of the oesophagus) or a normal endoscopy (endoscopy negative reflux disease or ENRD)., Objectives: To assess the effects of continuous maintenance therapy in adults with GORD (both ENRD and healed oesophagitis)., Search Strategy: We searched Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), CINAHL (1982-2003), and the National Research Register (Issue 2, 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field., Selection Criteria: Randomised controlled studies comparing PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo in adults with reflux oesophagitis and ENRD., Data Collection and Analysis: One author extracted data from included trials and a second author carried out an unblinded check. Two authors independently assessed trial quality. Study authors were contacted for additional information., Main Results: Maintenance of patients with healed oesophagitis: For a healing dose of PPI (generally the standard dose given by the manufacturer) versus placebo, the relative risk (RR) for oesophagitis relapse was 0.26 (95% confidence interval (CI) 0.19 to 0.36); versus H2RAs the RR was 0.36 (95% CI 0.28 to 0.46) and versus maintenance PPIs the RR was 0.63 (95% CI 0.55 to 0.73). However overall adverse effects were also more common and headaches were more common when comparing healing PPIs to H2RAs. For a maintenance dose of PPI (half of the standard dose) versus placebo, the RR for oesophagitis relapse was 0.46 (95% CI 0.38 to 0.57) and versus H2RAs the RR was 0.57 (95% CI 0.47 to 0.69). Overall adverse effects were more common.H2RAs were of marginal help but beneficial for symptomatic relief. Prokinetics and sucralfate were also more effective than placebo. For ENRD patients: Limited data with one RCT showed benefit for omeprazole 10 mg once daily over placebo (RR 0.4; 95% CI 0.29 to 0.53)., Authors' Conclusions: The findings in this review support the long-term treatment of oesophagitis to prevent relapse, both endoscopically and symptomatically. Healing doses of PPIs are more effective than all other therapies, although there is an increase in overall adverse effects compared to placebo, and headache occurrence compared to H2RAs. H2RAs prevent relapse more effectively than placebo, demonstrating a role for PPI-intolerant patients. Prokinetics and sucralfate both show benefit over placebo, but the former is no longer licenced. There is only limited data for ENRD.

Background: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear., Objectives: To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia., Search Strategy: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies. These searches were updated in October 2004., Selection Criteria: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia., Data Collection and Analysis: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms., Main Results: Seventeen randomised controlled trials were included in the systematic review. Fourteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Thirteen of these trials gave results as dichotomous outcomes evaluating 3186 patients and there was no significant heterogeneity between the studies. There was a 8% relative risk reduction in the H pylori eradication group (95% CI = 3% to 12%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 18 (95% CI = 12 to 48). A further three trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia., Authors' Conclusions: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Background: Peptic ulcer disease is the cause for dyspepsia in about 10% of patients. 95% of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain., Objectives: The primary outcomes were the proportion of peptic ulcers healed initially and proportion of patients free from relapse following successful healing. Eradication therapy was compared to placebo or pharmacological therapies in H. pylori positive patients. Secondary aims included symptom relief and adverse effects., Search Strategy: A search was undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group module using CCTR, MEDLINE, EMBASE and CINAHL databases. Experts in the field and pharmaceutical companies were contacted. Abstract books between 1994 and 2003 were hand-searched., Selection Criteria: Randomised controlled trials of short and long-term treatment of peptic ulcer disease in H. pylori positive adults were analysed. Patients received at least one week of H pylori eradication compared with ulcer healing drug, placebo or not treatment. Trials were included if they reported assessment from 2 weeks onwards., Data Collection and Analysis: Data were collected on ulcer healing, recurrence, relief of symptoms and adverse effects., Main Results: 60 trials were eligible. Data extraction was not possible in 7 trials, and 53 trials were included. In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95% confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients, RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant differences were detected between eradication therapy and UHD (13 trials, 1469 patients, RR = 1.32; 95% CI = 0.92, 1.90). In preventing duodenal ulcer recurrence no significant differences were detected between eradication therapy and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was superior to no treatment (27 trials 2509 patients, RR = 0.20; 95% CI = 0.15, 0.26). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (10 trials, 1029 patients, RR = 0.28; 95% CI 0.18, 0.43)., Reviewers' Conclusions: A 1 to 2 weeks course of H. pylori eradication therapy is an effective treatment for H. pylori positive peptic ulcer disease.

Background: The commonest cause of upper gastrointestinal symptoms is non-ulcer dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly characterised and the optimum treatment is uncertain. It is estimated that 450 million pounds is spent on dyspepsia drugs in the UK each year., Objectives: This review aims to determine the effectiveness of six classes of drugs (antacids, histamine H2 antagonists, proton pump inhibitors, prokinetics, mucosal protecting agents and antimuscarinics) in the improvement of either the individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia., Search Strategy: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and text words, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and pharmaceutical companies., Selection Criteria: All randomised controlled trials (RCTs) comparing drugs of any of the six groups with each other or with placebo for non-ulcer dyspepsia (NUD)., Data Collection and Analysis: Data were collected on dyspeptic symptom scores either individual or global symptom assessments and also quality of life scores and adverse effects., Main Results: A total of 11796 citations were obtained. 157 trials were retrieved and 98 trials fulfilled our eligibility criteria. However, subsequent data extraction was not possible in 31 trials. The final 67 trials were included in the meta-analysis. Prokinetics (14 trials with dichotomous outcomes generating 1053 patients; relative risk reduction [RRR] = 48%; 95% confidence intervals [CI] = 27% to 63%), H2RAs (11 trials generating 2,164 patients; RRR = 22%; 95% CI = 7% to 35%) and PPIs (8 trials generating 3,293 patients; RRR = 14%; 95% CI = 5% to 22%) were significantly more effective than placebo. Bismuth salts (6 trials generating 311 patients; RRR = 40%; 95% CI = -3 to 65%) were superior to placebo but this was of marginal statistical significance. Antacids (one trial generating 109 patients; RRR = -2%; 95% CI = -36% to 24%) and sucralfate (two trials generating 246 patients; RRR = 29%; 95% CI = -40% to 64%) were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and H2RA results could be due to publication bias., Reviewers' Conclusions: There is evidence that anti-secretory therapy may be effective in NUD. The trials evaluating prokinetic therapy are difficult to interpret as the meta-analysis result could have been due to publication bias. The effect of these drugs is likely to be small and many patients will need to take them on a long-term basis so economic analyses would be helpful and ideally the therapies assessed need to be inexpensive and well tolerated.

Background: Studies have also shown that NUD patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and tendency to be more pessimistic when compared with the community controls. However, the role of psychological interventions in NUD remains uncertain., Objectives: This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioral therapy, relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores patients with NUD., Search Strategy: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using very broad subject headings and text words. Bibliographies of retrieved articles were also searched and experts in the field were contacted., Selection Criteria: All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia (NUD) were identified., Data Collection and Analysis: Data collected included individual, global dyspepsia symptom scores and quality of life (QoL) scores., Main Results: We identified only four trials, each using different psychological interventions and three presenting results in a manner, that did not allow synthesis of the data to form a meta-analysis. All trials suggest that psychological interventions benefit dyspepsia symptoms and this effect persists for one year. However, all trials use statistical techniques that adjusted for baseline differences between groups. This should not be necessary for a randomised trial that is adequately powered suggesting that the sample size of these papers was too small. Unadjusted data was not statistically significant. The other problem of psychological intervention include low recruitment and high drop out rate which has been shown to be greater in patients receiving group therapy., Reviewer's Conclusions: There is currently insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD. There is also no evidence on the combined effects of pharmacological and psychological therapy. Nevertheless, if there are any benefits of psychological therapies, they are likely to persist long-term and NUD is a chronic relapsing and remitting disorder. Psychological therapies may therefore be offered to patients with severe symptoms that have not responded to pharmacological therapies.

Background: Studies have also shown that NUD patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and tendency to be more pessimistic when compared with the community controls. However, the role of psychological interventions in NUD remains uncertain., Objectives: This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioral therapy, relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores patients with NUD., Search Strategy: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using very broad subject headings and text words. Bibliographies of retrieved articles were also searched and experts in the field were contacted., Selection Criteria: All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia (NUD) were identified., Data Collection and Analysis: Data collected included individual, global dyspepsia symptom scores and quality of life (QoL) scores., Main Results: We identified only four trials, each using different psychological interventions and three presenting results in a manner, that did not allow synthesis of the data to form a meta-analysis. All trials suggest that psychological interventions benefit dyspepsia symptoms and this effect persists for one year. However, all trials use statistical techniques that adjusted for baseline differences between groups. This should not be necessary for a randomised trial that is adequately powered suggesting that the sample size of these papers was too small. Unadjusted data was not statistically significant. The other problem of psychological intervention include low recruitment and high drop out rate which has been shown to be greater in patients receiving group therapy., Reviewers' Conclusions: There is currently insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD. There is also no evidence on the combined effects of pharmacological and psychological therapy. Nevertheless, if there are any benefits of psychological therapies, they are likely to persist long-term and NUD is a chronic relapsing and remitting disorder. Psychological therapies may therefore be offered to patients with severe symptoms that have not responded to pharmacological therapies.

Background: Peptic ulcer disease is the cause for dyspepsia in about 10% of patients. 95% of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain., Objectives: The primary outcomes were the proportion of peptic ulcers healed initially and proportion of patients free from relapse following successful healing. Eradication therapy was compared to placebo or pharmacological therapies in H. pylori positive patients. Secondary aims included symptom relief and adverse effects., Search Strategy: A search was undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group module using CCTR, MEDLINE, EMBASE and CINAHL databases. Experts in the field and pharmaceutical companies were contacted. Abstract books between 1994 and 2002 were hand-searched., Selection Criteria: Randomised controlled trials of short and long-term treatment of peptic ulcer disease in H. pylori positive adults were analysed. Patients received at least one week of H pylori eradication compared with ulcer healing drug, placebo or not treatment. Trials were included if they reported assessment from 2 weeks onwards., Data Collection and Analysis: Data were collected on ulcer healing, recurrence, relief of symptoms and adverse effects., Main Results: 59 trials were eligible. Data extraction was not possible in 7 trials, and 52 trials were included. In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95% confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients, RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant differences were detected between eradication therapy and UHD (13 trials, 1469 patients, RR = 1.32; 95% CI = 0.92, 1.90). In preventing duodenal ulcer recurrence no significant differences were detected between eradication therapy and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was superior to no treatment (26 trials 2434 patients, RR = 0.19; 95% CI = 0.15, 0.26). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (9 trials, 774 patients, RR = 0.31; 95% CI 0.19, 0.48)., Reviewer's Conclusions: A 1 to 2 weeks course of H. pylori eradication therapy is an effective treatment for H. pylori positive peptic ulcer disease.

Background: This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients. Dyspepsia was defined to include both epigastric pain and heartburn., Objectives: To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia (a) initial pharmacological therapy (including endoscopy for treatment failures) (b) early endoscopy (c) testing for Helicobacter pylori and endoscope only those positive (d) H.pylori eradication therapy with or without prior testing., Search Strategy: Trials were located through electronic searches and extensive contact with trialists., Selection Criteria: All randomised controlled trials of dyspeptic patients presenting in primary care., Data Collection and Analysis: Data was collected on dyspeptic symptoms, quality of life and use of resources., Main Results: Twenty papers reporting 23 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (two trials) and H2 receptor antagonists (three trials), early endoscopy with initial acid suppression (five trials), H.pylori 'test and scope' v usual management (three trials), H.pylori test and treat v. endoscopy (four trials), and test and treat v. acid suppression alone in H.pylori positive patients (two trials), were pooled. PPIs were significantly more effective than both H2RAs and antacids. Relative risks (RR) and 95% CI were, for PPI: antacid 0.72 (0.64-0.80), PPI: H2RA 0.63 (0.47-0.85). Results for other drug comparisons were either absent or inconclusive. Initial endoscopy was associated with a small reduction in the risk of recurrent dyspeptic symptoms compared with initial prescribing (RR 0.89 (0.77-1.02). H.pylori test and endoscopy increases costs in primary care, but does not improve symptoms. H.pylori test and eradicate may be as effective as endoscopy- based management and reduces costs, by decreasing the proportion of patients that are endoscoped. 'Test and treat' may be more effective than acid suppression alone, RR 0.59 (0.42-0.83)., Reviewer's Conclusions: PPIs are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease. The relative efficacy of H2RA and PPI is uncertain. Early investigation by endoscopy or H.pylori testing may benefit some patients with dyspepsia. The review will be updated in 2004 with an individual patient data meta-analysis of the economic data, and a subgroup analysis by age and predominant dyspeptic symptom.

Background: The commonest cause of upper gastrointestinal symptoms is non-ulcer dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly characterised and the optimum treatment is uncertain. It is estimated that pound 450 million is spent on dyspepsia drugs in the UK each year., Objectives: This review aims to determine the effectiveness of six classes of drugs (antacids, histamine H2 antagonists, proton pump inhibitors, prokinetics, mucosal protecting agents and antimuscarinics) in the improvement of either the individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia., Search Strategy: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and text words, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and pharmaceutical companies., Selection Criteria: All randomised controlled trials (RCTs) comparing drugs of any of the six groups with each other or with placebo for non-ulcer dyspepsia (NUD)., Data Collection and Analysis: Data were collected on dyspeptic symptom scores either individual or global symptom assessments and also quality of life scores and adverse effects., Main Results: A total of 11796 citations were obtained. 155 trials were retrieved and 96 trials fulfilled our eligibility criteria. However, subsequent data extraction was not possible in 31 trials. The final 65 trials were included in the meta-analysis. Prokinetics (14 trials with dichotomous outcomes generating 1053 patients; relative risk reduction [RRR] = 48%; 95% confidence intervals [CI] = 27% to 63%), H2RAs (11 trials generating 2,164 patients; RRR = 22%; 95% CI = 7% to 35%) and PPIs (7 trials generating 3,031 patients; RRR = 14%; 95% CI = 5% to 23%) were significantly more effective than placebo. Bismuth salts (6 trials generating 311 patients; RRR = 40%; 95% CI = -3 to 65%) were superior to placebo but this was of marginal statistical significance. Antacids (one trial generating 109 patients; RRR = -2%; 95% CI = -36% to 24%) and sucralfate (two trials generating 246 patients; RRR = 29%; 95% CI = -40% to 64%) were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and H2RA results could be due to publication bias., Reviewer's Conclusions: There is evidence that anti-secretory therapy may be effective in NUD. The trials evaluating prokinetic therapy are difficult to interpret as the meta-analysis result could have been due to publication bias. The effect of these drugs is likely to be small and many patients will need to take them on a long-term basis so economic analyses would be helpful and ideally the therapies assessed need to be inexpensive and well tolerated.

Background: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear., Objectives: To determine the effect of H pylori eradication on dyspepsia symptoms and quality of life scores in patients with non-ulcer dyspepsia., Search Strategy: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies., Selection Criteria: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia., Data Collection and Analysis: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms., Main Results: Fifteen randomised controlled trials were included in the systematic review. Thirteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Twelve of these trials gave results as dichotomous outcomes evaluating 2,903 patients and there was no significant heterogeneity between the studies. There was a 9% relative risk reduction in the H pylori eradication group (95% CI = 5% to 14%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 15 (95% CI = 10 to 28). A further two trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia., Reviewer's Conclusions: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Background: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear., Objectives: To determine the effect of H pylori eradication on dyspepsia symptoms and quality of life scores in patients with non-ulcer dyspepsia., Search Strategy: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies., Selection Criteria: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia., Data Collection and Analysis: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms., Main Results: Twelve randomised controlled trials were included in the systematic review. Ten trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Nine of these trials gave results as dichotomous outcomes evaluating 2,541 patients and there was no significant heterogeneity between the studies. There was a 9% relative risk reduction in the H pylori eradication group (95% CI = 4% to 14%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 15 (95% CI = 10 to 31). A further two trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia., Reviewer's Conclusions: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Background: Studies have also shown that NUD patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and tendency to be more pessimistic when compared with the community controls., Objectives: This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioral therapy, relaxation therapy, guided imagery or hypnosis in the improvement of either individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia (NUD)., Search Strategy: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using appropriate subject headings and text words and searching bibliographies of retrieved articles., Selection Criteria: All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy, guided imagery or hypnosis) for non-ulcer dyspepsia (NUD)., Data Collection and Analysis: Data were collected on individual, global dyspepsia symptom scores, as well as measures of quality of life (QoL) scores and adverse effects., Main Results: The three trials identified showed that there was improvement in the dyspepsia symptom scores at the end of treatment and one trial showed improvement in the psychological parameters. However, meta-analysis was not possible as these trials used different psychological interventions and two of the trials only reported mean change in symptoms and did not give standard deviations of this change., Reviewer's Conclusions: Psychological intervention in the form of psychodynamic psychotherapy and cognitive behavioral therapy may be useful in the treatment of NUD. However, we need more trials to assess dyspepsia symptom scores and also psychological intervention in order to give us a clearer picture of the role of psychological intervention in NUD.

Background: This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients. Dyspepsia was defined to include both epigastric pain and heartburn., Objectives: To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia (a) initial pharmacological therapy (including endoscopy for treatment failures) (b) early endoscopy (c) testing for Helicobacter pylori and endoscope only those positive (d) H.pylori eradication therapy with or without prior testing., Search Strategy: Trials were located through electronic searches and extensive contact with trialists., Selection Criteria: All randomised controlled trials of dyspeptic patients presenting in primary care., Data Collection and Analysis: Data was collected on dyspeptic symptoms, quality of life and use of resources., Main Results: Eighteen papers reporting 20 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (two trials) and H2 receptor antagonists (three trials), early endoscopy with initial acid suppression (five trials), H.pylori 'test and scope' v usual management (three trials) and H.pylori test and treat v. endoscopy (three trials) were pooled. PPIs were significantly more effective than both H2RA s and antacids. Relative risks (RR) and 95% CI were, for PPI: antacid 0.72 (0.64-0.80), PPI: H2RA 0.63 (0.47-0.85). Results for other drug comparisons were either absent or inconclusive. Initial endoscopy was associated with a small reduction in the risk of recurrent dyspepstic symptoms compared with initial prescribing (RR 0.89 (0.77-1.02). H.pylori test and endoscopy increases costs in primary care, but does not improve symptoms. H.pylori test and eradicate may be as effective as endoscopy- based management and reduces costs, by decreasing the proportion of patients that are endoscoped. Further primary care-based trials are needed to compare 'test and treat' with empirical acid suppression., Reviewer's Conclusions: PPIs are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease. The relative efficacy of H2RA and PPI is uncertain. Early investigation by endoscopy or H.pylori testing may benefit some patients with dyspepsia. The review will be updated in 2002 with an individual patient data meta-analysis of the economic data, and a subgroup analysis by age and predominant dyspeptic symptom.

Background: The commonest cause of upper gastrointestinal symptoms is non-ulcer dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly characterised and the optimum treatment is uncertain. It is estimated that pound450 million is spent on dyspepsia drugs in the UK each year., Objectives: This review aims to determine the effectiveness of six classes of drugs (antacids, histamine H2 antagonists, proton pump inhibitors, prokinetics, mucosal protecting agents and antimuscarinics) in the improvement of either the individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia., Search Strategy: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and text words, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and pharmaceutical companies., Selection Criteria: All randomised controlled trials (RCTs) comparing drugs of any of the six groups with each other or with placebo for non-ulcer dyspepsia (NUD)., Data Collection and Analysis: Data were collected on dyspeptic symptom scores either individual or global symptom assessments and also quality of life scores and adverse effects., Main Results: A total of 11775 citations were obtained. 144 trials were retrieved and 94 trials fulfilled our eligibility criteria. However, subsequent data extraction was not possible in 37 trials. Fifty trials were excluded as they did not meet our eligibility criteria. The final 57 trials were included in the final meta-analysis. Prokinetics (12 trials with dichotomous outcomes generating 829 patients; relative risk reduction [RRR] = 50%; 95% confidence intervals [CI] = 30 to 65%) and H2RAs (8 trials generating 1,125 patients; RRR = 30%; 95% CI = 4 to 48%) were significantly more effective than placebo. Proton pump inhibitors (4 trials generating 1,248 patients; RRR = 12%; 95% CI = -1 to 24%) and Bismuth salts (6 trials generating 311 patients; RRR = 40%; 95% CI = -3 to 65%) were superior to placebo but this was of marginal statistical significance. Antacids (one trial generating 109 patients; RRR = -2%; 95% CI = -36% to 24%) and sucralfate (two trials generating 246 patients; RRR = 29%; 95% CI = -40% to 64%) were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic result could be due to publication bias. The funnel plot of H2RAs did not show any evidence of publication bias but the quality of the trials was generally poor., Reviewer's Conclusions: There is some evidence that anti-secretory therapy may be effective in NUD. The trials evaluating prokinetic therapy are difficult to interpret as the meta-analysis result could have been due to publication bias. Further research using prokinetics and anti-secretory therapy is required before any firm conclusions can be reached. The effect of these drugs is likely to be small and many patients will need to take them on a long-term basis so the therapies assessed need to be inexpensive and well tolerated.

Background: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear., Objectives: To determine the effect of H pylori eradication on dyspepsia symptoms and quality of life scores in patients with non-ulcer dyspepsia., Search Strategy: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies., Selection Criteria: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia., Data Collection and Analysis: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms., Main Results: Seven randomised controlled trials were included in the systematic review. Five trials compared proton pump inhibitor dual or triple therapy with a proton pump inhibitor + placebo antibiotics, and evaluated dyspepsia at 6-12 months in 1,385 patients. H pylori eradication was significantly superior to placebo in treating non ulcer dyspepsia (relative risk reduction = 7%; 95% CI = 1% to 12%; p=0.02) and there was no significant heterogeneity between the studies. The number needed to treat to cure one case of dyspepsia = 19 (95% CI = 11 to 132). A further two trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia., Reviewer's Conclusions: H pylori eradication may be an effective therapy for H pylori positive non-ulcer dyspepsia. This result is not robust and further evidence on the efficacy of H pylori eradication in non ulcer dyspepsia would be helpful. The effect is modest and economic models would help establish whether this approach is cost-effective. This review will be updated as results from other ongoing trials (Malfertheiner 2000) are made available.

Background: This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients., Objectives: To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia (a) initial pharmacological therapy (including endoscopy for treatment failures) (b) early endoscopy (c) testing for Helicobacter pylori and endoscope only those positive (d) H.pylori eradication therapy with or without prior testing., Search Strategy: Trials were located through electronic searches and extensive contact with trialists., Selection Criteria: All randomised controlled trials of dyspeptic patients presenting in primary care., Data Collection and Analysis: Data was collected on dyspeptic symptoms, quality of life and use of resources., Main Results: Ten papers reporting 12 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (2 trials) and H2 receptor antagonists (3 trials), and of early endoscopy compared with initial acid suppression (3 trials) were pooled. PPIs were significantly more effective than both H2RA s and antacids. Relative risks (RR) and 95% CI were, for PPI: antacid 0.72 (0.64-0.80), PPI: H2RA 0.63 (0.47-0.85). Results for other drug comparisons were either absent or inconclusive. Early endoscopy was not more effective than initial prescribing (RR 0.90 (0.77-1.04), but current studies lack power. No eligible trials of H.pylori test and endoscopy or test and eradicate were found., Reviewer's Conclusions: PPIs are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease. The relative efficacy of H2RA and PPI is uncertain. Early investigation may benefit some patients with dyspepsia. The review will be updated shortly with several large trials that have recently been completed.