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There is increasing concern regarding a possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel that could lead to reduced cardiovascular protection by clopidogrel. We performed a literature search for relevant original studies and systematic reviews. PPIs likely affect the antiplatelet activity of clopidogrel as measured in vitro, and this may be a class effect. We conclude that the pharmacodynamic effect has not been translated into any clinically meaningful adverse effect. PPI cotherapy reduces the incidence of recurrent peptic ulcer and of upper gastrointestinal bleeding among patients on clopidogrel., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: Proton pump inhibitors (PPIs) are widely used in several acid-related gastrointestinal disorders. In vivo studies have suggested that gastric suppression by PPIs could result in decreased intestinal calcium absorption. Subsequently, there have been concerns that the chronic use of a PPI is associated with an increased risk of bone fracture. However, the results of clinical studies are conflicting., Methods: We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risks of PPI use on fracture outcome. All controlled observational studies that compared fracture outcome in patients with PPI therapy with a control group were included. We calculated pooled odds ratios (ORs) using a random-effects model., Results: Of 1,668 identified studies, 10 (4 cohort and 6 case-control) with 223,210 fracture cases were included in our analysis. In PPI users, compared with non/past users, the OR for hip fracture (n=9) was 1.25 (95% confidence interval (CI)=1.14-1.37). The OR for vertebral fracture (n=4) was 1.50 (95% CI=1.32-1.72) and for wrist/forearm fracture (n=3) was 1.09 (95% CI=0.95-1.24). In subgroup analysis of hip fracture, this association was observed in both high-dose and low-dose PPI exposure. When stratified by duration of exposure, the short duration of PPI use was associated with increased risk of developing hip fracture (OR=1.24; 95% CI=1.19-1.28), whereas there was no significant increase in risk of hip fracture in long-term PPI users (OR=1.30; 95% CI=0.98-1.70). There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the subgroup analyses., Conclusions: Our results should be interpreted with caution. We found a modest association between PPI use and increased risk of hip and vertebral fractures, but no evidence of duration effect in subgroup analysis. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding. Thus, randomized controlled studies are required to confirm or refute these results.

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.

Objectives: Capsule endoscopy (CE) has demonstrated superior performance compared with other modalities in its ability to detect early small-bowel (SB) Crohn's disease (CD), especially when ileoscopy is negative or unsuccessful. The aim of this study was to evaluate the diagnostic yield of CE compared with other modalities in patients with suspected and established CD using a meta-analysis., Methods: A thorough literature search for prospective studies comparing the diagnostic yield of CE with other modalities in patients with CD was undertaken. Other modalities included push enteroscopy (PE), colonoscopy with ileoscopy (C+IL), SB radiography (SBR), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). Data on diagnostic yield among various modalities were extracted, pooled, and analyzed. Data on patients with suspected and established CD were analyzed separately. Weighted incremental yield (IYW) (diagnostic yield of CE-diagnostic yield of comparative modality) and 95% confidence intervals (CIs) of CE over comparative modalities were calculated., Results: A total of 12 trials (n=428) compared the yield of CE with SBR in patients with CD. Eight trials (n=236) compared CE with C+IL, four trials (n=119) compared CE with CTE, two trials (n=102) compared CE with PE, and four trials (n=123) compared CE with MRE. For the suspected CD subgroup, several comparisons met statistical significance. Yields in this subgroup were CE vs. SBR: 52 vs. 16% (IYw=32%, P<0.0001, 95% CI=16-48%), CE vs. CTE: 68 vs. 21% (IYw=47%, P<0.00001, 95% CI=31-63%), and CE vs. C+IL: 47 vs. 25% (IYw=22%, P=0.009, 95% CI=5-39%). Statistically significant yields for CE vs. an alternate diagnostic modality in established CD patients were seen in CE vs. PE: 66 vs. 9% (IYw=57%, P<0.00001, 95% CI=43-71%), CE vs. SBR: 71 vs. 36% (IYw=38%, P<0.00001, 95% CI=22-54%), and in CE vs. CTE: 71 vs. 39% (IYw=32%, P=or<0.0001, 95% CI=16-47%)., Conclusions: Our meta-analysis demonstrates that CE is superior to SBR, CTE, and C+IL in the evaluation of suspected CD patients. CE is also a more effective diagnostic tool in established CD patients compared with SBR, CTE, and PE.

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

Should we interrupt antiplatelet therapy (acetylsalicylic acid [ASA] alone or in combination with clopidogrel) in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal (GI) procedures? The relevant evidence was critically appraised in a recent White Paper from the American College of Gastroenterology and the American College of Cardiology. Clinicians need to qualify and compare 2 competing risks: the increased risk of bleeding if antiplatelet therapy is maintained during the endoscopic GI procedure, vs. the increased risk of cardiovascular (CV) thrombosis if antiplatelet therapy is interrupted or modified in the periprocedural period. ASA treatment may be continued for all endoscopic GI procedures, provided that there is no pre-existing bleeding disorder. Clopidogrel administration could be maintained for low-risk endoscopic GI procedures, such as diagnostic endoscopy of the upper or lower GI tract with or without biopsies. For patients on clopidogrel undergoing high-risk endoscopic GI procedures, such as polypectomy or sphincterotomy, the individualized risk of CV complications from clopidogrel discontinuation should be assessed. During the first month following bare-metal stent implantation or the first 6 (possibly 12) months following drug-eluting stent placement the CV risk is particularly high, therefore elective high-risk endoscopic GI procedures should be deferred accordingly. In all other clinical situations requiring clopidogrel treatment, the risk of CV events is lower than above. Therefore, clopidogrel treatment could be interrupted for 7 to 10 days before the procedure (and restarted as soon as possible after the procedure), provided that ASA treatment is maintained.

Introduction: The principal effect of Helicobacter pylori infection is lifelong chronic gastritis, affecting up to 20% of younger adults but 50% to 80% of adults born in resource-rich countries before 1950., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of H pylori eradication treatment in people with a confirmed duodenal ulcer, a confirmed gastric ulcer, confirmed gastro-oesophageal reflux disease (GORD), confirmed non-ulcer dyspepsia, uninvestigated dyspepsia, localised B cell lymphoma of the stomach, and non-steroidal anti-inflammatory drug (NSAID)-related peptic ulcers? What are the effects of H pylori eradication treatment for preventing NSAID-related peptic ulcers in people with or without previous ulcers or dyspepsia? What are the effects of H pylori eradication treatment on the risk of developing gastric cancer? Do H pylori eradication treatments differ in their effects? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found 58 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: effects of H pylori eradication in different populations; relative effects of triple regimens, quadruple regimens, and sequential regimens.

Pre-endoscopic administration of PPIs in patients with nonvariceal upper GI bleeding is still of controversial efficacy. It downstages the severity of the endoscopic signs of recent bleeding and may reduce the requirement for endoscopic hemostatic therapy at index endoscopy. However, there is no evidence of an effect on mortality, rebleeding, or surgical intervention rates. In contrast, the efficacy of PPIs in endoscopically diagnosed peptic ulcer bleeding is supported by high-quality evidence from numerous RCTs and meta-analyses of RCTs. PPIs compared with H2RAs or placebo consistently reduce rebleeding rates regardless of dose, route of administration, application or not of endoscopic hemostatic treatment, and geographic location. Surgical intervention rates and the need for further endoscopic hemostatic treatment are also reduced by PPI treatment, although the results are not as robust as those for rebleeding. There is no evidence of an overall effect of PPI treatment on all-cause mortality. However, all-cause mortality is reduced among patients with high-risk endoscopic signs and among trials that had been conducted in Asia. The optimal dose and route of PPI administration has yet to be determined.

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

Over the last 3 decades, there has been extensive clinical research on the pharmacologic treatment of peptic ulcer bleeding. A critical review of randomized controlled trials and meta-analyses reveals insufficient evidence to recommend histamine-2 receptor antagonists (H(2)RAs), somatostatin, octreotide, or tranexamic acid in the routine management of patients with peptic ulcer bleeding. In contrast, there is good-quality evidence for recommending proton-pump inhibitor (PPI) treatment for patients with peptic ulcer bleeding. PPI treatment, compared with an H(2)RA or placebo, reduces rebleeding and the need for surgical intervention and, in patients with high-risk endoscopic stigmata, also reduces all-cause mortality. Patients with ulcers that demonstrate only low-risk endoscopic stigmata (clean base or flat pigmented spot) can be treated with an oral PPI at double the standard clinical dose. Patients with ulcers that demonstrate high-risk endoscopic stigmata (spurting, oozing, or nonbleeding visible vessel) should receive high-dose intravenous PPI treatment following appropriate endoscopic hemostatic treatment. The currently recommended dose is an initial intravenous bolus equivalent to 80 mg of omeprazole followed by an intravenous infusion equivalent to 8.0 mg/h of omeprazole for up to 72 hours. A switch to high-dose oral PPI treatment may be appropriate before completion of a 72-hour treatment period in some patients whose clinical status stabilizes early. Once the initial bleeding episode has been dealt with, patients will require standard pharmacologic treatment to heal the ulcer and prevent recurrence.

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

Proton pump inhibitor (PPI) therapy improves some outcomes after peptic ulcer bleeding. Recent meta-analyses have consistently found reduced rates of rebleeding and surgical intervention but there has been some discordance about effects on overall mortality. In general, more impressive results have been reported from trials conducted in Asia than elsewhere. PPI treatment for ulcer bleeding is not a substitute for appropriate endoscopic hemostatic treatment.

Objectives: Capsule endoscopy (CE) allows for direct evaluation of the small bowel mucosa in patients with Crohn's disease (CD). A number of studies have revealed significantly improved yield for CE over other modalities for the diagnosis of CD, but as sample sizes have been small, the true degree of benefit is uncertain. Additionally, it is not clear whether patients with a suspected initial presentation of CD and those with suspected recurrent disease are equally likely to benefit from CE. The aim of this study was to evaluate the yield of CE compared with other modalities in symptomatic patients with suspected or established CD using meta-analysis., Methods: We performed a recursive literature search of prospective studies comparing the yield of CE to other modalities in patients with suspected or established CD. Data on yield among various modalities were extracted, pooled, and analyzed. Incremental yield (IY) (yield of CE--yield of comparative modality) and 95% confidence intervals (95% CI) of CE over comparative modalities were calculated. Subanalyses of patients with a suspected initial presentation of CD and those with suspected recurrent disease were also performed., Results: Nine studies (n = 250) compared the yield of CE with small bowel barium radiography for the diagnosis of CD. The yield for CE versus barium radiography for all patients was 63% and 23%, respectively (IY = 40%, p < 0.001, 95% CI = 28-51%). Four trials compared the yield of CE to colonoscopy with ileoscopy (n = 114). The yield for CE versus ileoscopy for all patients was 61% and 46%, respectively (IY = 15%, p= 0.02, 95% CI = 2-27%). Three studies compared the yield of CE to computed tomography (CT) enterography/CT enteroclysis (n = 93). The yield for CE versus CT for all patients was 69% and 30%, respectively (IY = 38%, p= 0.001, 95% CI = 15-60%). Two trials compared CE to push enteroscopy (IY = 38%, p < 0.001, 95% CI = 26-50%) and one trial compared CE to small bowel magnetic resonance imaging (MRI) (IY = 22%, p= 0.16, 95% CI =-9% to 53%). Subanalysis of patients with a suspected initial presentation of CD showed no statistically significant difference between the yield of CE and barium radiography (p= 0.09), colonoscopy with ileoscopy (p= 0.48), CT enterography (p= 0.07), or push enteroscopy (p= 0.51). Subanalysis of patients with established CD with suspected small bowel recurrence revealed a statistically significant difference in yield in favor of CE compared with all other modalities (barium radiography (p < 0.001), colonoscopy with ileoscopy (p= 0.002), CT enterography (p < 0.001), and push enteroscopy (p < 0.001))., Conclusions: In study populations, CE is superior to all other modalities for diagnosing non-stricturing small bowel CD, with a number needed to test (NNT) of 3 to yield one additional diagnosis of CD over small bowel barium radiography and NNT = 7 over colonoscopy with ileoscopy. These results are due to a highly significant IY with CE over all other modalities in patients with established non-stricturing CD being evaluated for a small bowel recurrence. While there was no significant difference seen between CE and alternate modalities for diagnosing small bowel CD in patients with a suspected initial presentation of CD, the trend toward significance for a number of modalities suggests the possibility of a type II error. Larger studies are needed to better establish the role of CE for diagnosing small bowel CD in patients with a suspected initial presentation of CD.

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

We report the case of a 57-year old female patient with refractory to treatment pyoderma gangrenosum associated with clinically inactive Crohn's disease. Pyoderma gangrenosum was successfully treated with Infliximab, a chimeric monoclonal antibody that inhibits tumour necrosis factor alpha (TNF-alpha). Our case report suggests that Infliximab, a therapeutic agent for refractory and fistulizing Crohn's disease, may also be safe and effective in the treatment of Crohn's disease associated pyoderma gangrenosum, even though the inflammatory bowel disease is clinically inactive and repeated infusions may be required for successful treatment.

Objectives: Due to its superior ability to examine the entire small bowel mucosa, capsule endoscopy (CE) has broadened the diagnostic evaluation of patients with obscure gastrointestinal bleeding (OGIB). Published studies have revealed a numerically superior performance of CE in determining a source of OGIB compared with other modalities, but due to small sample sizes, the overall magnitude of benefit is unknown. Additionally, the types of lesions more likely to be found by CE versus alternate modalities are also unknown. The aim of this study was to evaluate the yield of small bowel findings with CE in patients with OGIB compared to other modalities using meta-analysis., Methods: We performed a recursive literature search of prospective studies comparing the yield of CE to other modalities in patients with OGIB. Data on yield and types of lesions identified among various modalities were extracted, pooled, and analyzed. Incremental yield (IY) (yield of CE-yield of comparative modality) and 95% confidence intervals (95% CI) of CE over comparative modalities were calculated., Results: A total of 14 studies (n = 396) compared the yield of CE with push enteroscopy for OGIB. The yield for CE and push enteroscopy was 63% and 28%, respectively (IY = 35%, p < 0.00001, 95% CI = 26-43%) and for clinically significant findings (n = 376) was 56% and 26%, respectively (IY = 30%, p < 0.00001, 95% CI = 21-38%). Three studies (n = 88) compared the yield of CE to small bowel barium radiography. The yield for CE and small bowel barium radiography for any finding was 67% and 8%, respectively (IY = 59%, p < 0.00001, 95% CI = 48-70%) and for clinically significant findings was 42% and 6%, respectively (IY = 36%, p < 0.00001, 95% CI = 25-48%). Number needed to test (NNT) to yield one additional clinically significant finding with CE over either modality was 3 (95% CI = 2-4). One study each compared the yield of significant findings on CE to intraoperative enteroscopy (n = 42, IY = 0%, p= 1.0, 95% CI =-16% to 16%), computed tomography enteroclysis (n = 8, IY = 38%, p= 0.08, 95% CI =-4% to 79%), mesenteric angiogram (n = 17, IY =-6%, p= 0.73, 95% CI =-39% to 28%), and small bowel magnetic resonance imaging (n = 14, IY = 36%, p= 0.007, 95% CI = 10-62%). Ten of the 14 trials comparing CE with push enteroscopy classified the types of lesions found on examination. CE had a 36% yield for vascular lesions versus 20% for push enteroscopy, with an IY of 16% (p < 0.00001, 95% CI = 9-23%). Inflammatory lesions were also found more often in CE (11%) than in push enteroscopy (2%), with an IY of 9% (p= 0.0001, 95% CI = 5-13%). There was no significant difference in the yield of tumors or "other" findings between CE and push enteroscopy., Conclusions: CE is superior to push enteroscopy and small bowel barium radiography for diagnosing clinically significant small bowel pathology in patients with OGIB. In study populations, the IY of CE over push enteroscopy and small bowel barium radiography for clinically significant findings is >or=30% with an NNT of 3, primarily due to visualization of additional vascular and inflammatory lesions by CE.

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

Background: Patients with systemic sclerosis may develop mild abnormalities of liver function tests. More serious hepatic involvement has been well documented but is rare. Idiopathic portal hypertension had been reported only in a few female patients with systemic sclerosis., Case Presentation: An 82-year-old man with known systemic sclerosis presented with melaena. Urgent gastroscopy revealed oesophageal varices, which re-started bleeding during the procedure and were treated ensocopically, with Sengstaken tube and glypressin. Liver function tests and coagulation were normal. Non-invasive liver screen (including hepatitis viral serology and autoantibodies) was negative. Ultrasound scan of the abdomen revealed a small liver with coarse texture and no focal lesion. Hepato-portal flow was demonstrated in the portal vein. The spleen was enlarged. A moderate amount of free peritoneal fluid was present. A CT scan confirmed the absence of portal vein thrombosis. One month following discharge the patient had a liver biopsy. Histological examination showed essentially normal liver tissue; there was no evidence of any excess inflammation and no features to suggest cirrhosis or drug-induced liver disease. Taking into account the above evaluation we concluded that the patient had idiopathic portal hypertension., Conclusion: Both male and female patients with systemic sclerosis may -- rarely -- develop idiopathic portal hypertension.

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

Objectives: To review randomised controlled trials of treatment with a proton pump inhibitor in patients with ulcer bleeding and determine the impact on mortality, rebleeding, and surgical intervention., Design: Systematic review and meta-analysis., Data Sources: Cochrane Collaboration's trials register, Medline, and Embase, handsearched abstracts, and pharmaceutical companies., Review Methods: Included randomised controlled trials compared proton pump inhibitor with placebo or H2 receptor antagonist in endoscopically proved bleeding ulcer and reported at least one of mortality, rebleeding, or surgical intervention. Trials were graded for methodological quality. Two assessors independently reviewed each trial, and disagreements were resolved by consensus., Results: We included 21 randomised controlled trials comprising 2915 patients. Proton pump inhibitor treatment had no significant effect on mortality (odds ratio 1.11, 95% confidence interval 0.79 to 1.57; number needed to treat (NNT) incalculable) but reduced rebleeding (0.46, 0.33 to 0.64; NNT 12) and surgery (0.59, 0.46 to 0.76; NNT 20). Results were similar when the meta-analysis was restricted to the 10 trials with the highest methodological quality: 0.96, 0.46 to 2.01, for mortality; 0.41, 0.25 to 0.68, NNT 10, for rebleeding; 0.62, 0.46 to 0.83, NNT 25, for surgery., Conclusions: Treatment with a proton pump inhibitor reduces the risk of rebleeding and the requirement for surgery after ulcer bleeding but has no benefit on overall mortality.

Aim: The pathogenesis of delayed gastric emptying in patients with non-ulcer dyspepsia (NUD) remains unclear. We aimed to examine whether gastric emptying rate in NUD patients was associated with Helicobacter pylori (H pylori) infection and whether it was affected by eradication of the infection., Methods: Gastric emptying rate of a mixed solid-liquid meal was assessed by the paracetamol absorption method in NUD patients and asymptomatic controls (n=17). H pylori status was assessed by serology and biopsy urease test. H pylori-positive NUD patients (n=23) received 10-day triple eradication therapy. H pylori status was re-assessed by biopsy urease test four weeks later, and if eradication was confirmed, gastric emptying rate was re-evaluated., Results: Thirty-three NUD patients and 17 controls were evaluated. NUD patients had significantly delayed gastric emptying compared with controls. The mean maximum plasma paracetamol concentration divided by body mass (Cmax/BM) was 0.173 and 0.224 mg/L.kg respectively (P=0.02), the mean area under plasma paracetamol concentration-time curve divided by body mass (AUC/BM) was 18.42 and 24.39 mg.min/L.kg respectively (P=0.01). Gastric emptying rate did not differ significantly between H pylori-positive and H pylori-negative NUD patients. The mean Cmax/BM was 0.172 and 0.177 mg/L.kg respectively (P=0.58), the mean AUC/BM was 18.43 and 18.38 mg.min/L.kg respectively (P=0.91). Among 14 NUD patients who were initially H pylori-positive, confirmed eradication of the infection did not significantly alter gastric emptying rate. The mean Cmax/BM was 0.171 and 0.160 mg/L.kg before and after Hp eradication, respectively (P=0.64), the mean AUC/BM was 17.41 and 18.02 mg.min/L.kg before and after eradication, respectively (P=0.93)., Conclusion: Although gastric emptying is delayed in NUD patients compared with controls, gastric emptying rate is not associated with H pylori status nor it is affected by eradication of the infection.

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

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

Although Helicobacter pylori infection remains the single most common cause of peptic ulcer, an increasing proportion of patients have H. pylori -negative ulcers. The proportion is higher in the USA--and possibly Australia--than elsewhere. Although the precise aetiology of these ulcers is often unknown, some are caused by the use of aspirin or non-steroidal anti-inflammatory drugs. In areas with a high prevalence of H. pylori -negative ulcers, the empirical treatment of H. pylori infection for newly diagnosed peptic ulcer disease should be discouraged. All such patients should have documentation of their H. pylori status before treatment. Patients with H. pylori -negative ulcers may have the more serious ulcer diathesis and are likely to require long-term management with acid-suppressing drugs. Proton pump inhibitors are likely to be the drugs of choice; patients may be relatively refractory to H(2)-receptor antagonists. The optimal duration of treatment is undefined but might be lifelong. There are no prospective studies of the efficacy of surgery or mucosal-protective agents in the treatment of H. pylori -negative ulcers.

Background: Omeprazole and lansoprazole are used to treat erosive oesophagitis in the respective daily doses of 20 and 30 mg., Aim: To investigate, by meta-analysis, whether treatment with lansoprazole 30 mg increases erosive oesophagitis healing rates over omeprazole 20 mg., Methods: We searched for randomized, double-blind trials comparing omeprazole 20 mg and lansoprazole 30 mg in endoscopically diagnosed erosive oesophagitis. After assessing for homogeneity, non-heterogeneous trials were combined and pooled healing rates derived. We calculated the relative benefit increase, absolute benefit increase and number needed to treat., Results: Six trials without significant heterogeneity met predetermined inclusion criteria. By per protocol analysis, pooled healing rates for omeprazole 20 mg and lansoprazole 30 mg were, respectively, 74.7% and 77.7% after 4 weeks and 87.0% and 88.7% after 8 weeks. The corresponding figures by intention-to-treat analysis were 70.8% and 72.7% after 4 weeks and 81.8% and 83.3% after 8 weeks. In each analysis the absolute benefit increase for lansoprazole was small and its 95% confidence interval encompassed zero., Conclusion: Lansoprazole 30 mg produces healing rates in erosive oesophagitis that are not statistically significantly different to those of omeprazole 20 mg.

Helicobacter pylori infection is linked to conditions of the upper gastrointestinal tract, including peptic ulcer and gastric adenocarcinoma. It has also been associated with a wide variety of non-gastrointestinal tract conditions. However, the evidence in support of H. pylori infection as a cause of the non-gastrointestinal tract conditions is not widely understood. We reviewed the medical literature for publications and abstracts dealing with putative non-gastrointestinal tract associations of H. pylori infection. We appraised the level of evidence and applied it to an established set of 9 criteria for determining causation. We found that many studies examining a possible causal relationship have been uncontrolled or inadequately controlled. Studies have often failed to control for socioeconomic status. Studies of treating H. pylori infection in patients with these disorders have been poorly designed and inappropriately controlled, and therefore add little to the evidence base. Attention should be focused on appropriate testing for and treatment of H. pylori infection in patients with conditions that are of proven association, notably peptic ulcer disease.