Alan N. Barkun

International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding

DESCRIPTION A multidisciplinary group of 34 experts from 15 countries developed this update and expansion of the recommendations on the management of acute nonvariceal upper gastrointestinal bleeding (UGIB) from 2003. METHODS The Appraisal of Guidelines for Research and Evaluation (AGREE) process and independent ethics protocols were used. Sources of data included original and published systematic reviews; randomized, controlled trials; and abstracts up to October 2008. Quality of evidence and strength of recommendations have been rated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RECOMMENDATIONS Recommendations emphasize early risk stratification, by using validated prognostic scales, and early endoscopy (within 24 hours). Endoscopic hemostasis remains indicated for high-risk lesions, whereas data support attempts to dislodge clots with hemostatic, pharmacologic, or combination treatment of the underlying stigmata. Clips or thermocoagulation, alone or with epinephrine injection, are effective methods; epinephrine injection alone is not recommended. Second-look endoscopy may be useful in selected high-risk patients but is not routinely recommended. Preendoscopy proton-pump inhibitor (PPI) therapy may downstage the lesion; intravenous high-dose PPI therapy after successful endoscopic hemostasis decreases both rebleeding and mortality in patients with high-risk stigmata. Although selected patients can be discharged promptly after endoscopy, high-risk patients should be hospitalized for at least 72 hours after endoscopic hemostasis. For patients with UGIB who require a nonsteroidal anti-inflammatory drug, a PPI with a cyclooxygenase-2 inhibitor is preferred to reduce rebleeding. Patients with UGIB who require secondary cardiovascular prophylaxis should start receiving acetylsalicylic acid (ASA) again as soon as cardiovascular risks outweigh gastrointestinal risks (usually within 7 days); ASA plus PPI therapy is preferred over clopidogrel alone to reduce rebleeding.

Consensus Recommendations for Managing Patients with Nonvariceal Upper Gastrointestinal Bleeding

Upper gastrointestinal (GI) bleeding represents a substantial clinical and economic burden. It has a prevalence of approximately 170 cases per 100 000 adults per year (1), at an estimated total cost of

The Canadian Registry on Nonvariceal Upper Gastrointestinal Bleeding and Endoscopy (RUGBE): Endoscopic Hemostasis and Proton Pump Inhibition are Associated with Improved Outcomes in a Real-Life Setting

750 million in U.S. dollars (2). Peptic ulcer disease accounts for 50% to 70% of cases of acute nonvariceal upper GI bleeding (3, 4). Despite recent advances in therapy, mortality rates have remained essentially unchanged at 6% to 8% (1, 2, 5). This could be explained by the fact that patients are older and have more concurrent illnesses; it may also be due to underuse of endoscopic hemostatic techniques. The Canadian Registry in Upper Gastrointestinal Bleeding and Endoscopy (RUGBE) initiative and international data have demonstrated wide variations in the utilization and timing of different diagnostic and therapeutic technologies, as well as disparate management approaches (4-10). In this context, it is surprising that, except for the recent British Society of Gastroenterology guidelines (9), the last widely disseminated consensus conference and publication of practice guidelines occurred more than 10 years ago (11, 12). Since publication of the British Society of Gastroenterology guidelines, new data have become available and are strengthened by a series of evidence-based systematic reviews and meta-analyses performed for this consensus (13, 14). The current guidelines are a consensus paper with multisociety representation. Methods The recommendation statements were developed according to generally accepted standards (15, 16). A 7-step approach addressing most of 37 pertinent criteria of validity was followed (16-20). The process of guideline development is described in the Figure. Figure. The adopted process of guideline development . Determination of Need for Guidelines The need for clinical practice guidelines on the management of patients with nonvariceal upper GI bleeding was identified by an initial review of the existing literature, current recommendations, and the timing of previously published guidelines. Recommendations are directed primarily to the management of nonvariceal bleeding largely due to peptic ulcers. Membership of the Consensus Group An organizing committee selected a multidisciplinary group of 25 voting participants for their expertise in the management of patients with acute nonvariceal upper GI bleeding, evidence-based medicine, and continuing medical education. The group included Canadian and international gastroenterologists, endoscopists, surgeons, family physicians, emergency medicine physicians, pharmacologists, epidemiologists (with methodologic and health economic expertise), and a hospital pharmacist. The attendees represented 11 national societies (Appendix). A representative from the Canadian Association of General Surgeons reviewed the consensus guidelines a posteriori. Nonvoting observers included representatives from government (Health Canada), the pharmaceutical industry, and distributors and manufacturers of endoscopic equipment (Appendix). Determination of Clinically Relevant Issues The issues were determined according to perceived clinical importance, likelihood of being resolved with the existing knowledge base, applicability to current practice, and perceived need for change (16). The RUGBE data were critical to this process (4). The conference organizer and a small working group generated a list of topics and circulated it electronically in advance (21, 22). For each topic, a statement was proposed to the consensus conference participants for discussion, revision, and voting. Nature and Extent of Background Preparation Literature review methods for relevant articles included MEDLINE searches and manual searches of bibliographies of key articles published in English between 1966 and June 2002. Search terms included upper GI bleeding, non-variceal, guidelines, meta-analysis, naso-gastric tube, risk stratification, re-bleeding, mortality, surgery, endoscopy, second-look, clot, stigmata, injection, thermal coaptive, laser, hemostatic clips, proton pump inhibitor, histamine-receptor antagonist, somatostatin, and octreotide. We referred to past reviews, meta-analyses, and published consensus conferences to summarize data up to 1992. New systematic reviews were conducted on data from the past 10 years on the prevalence and natural history of nonvariceal GI bleeding, risk stratification, and various management strategies. Economic considerations were recognized, but the country-specific nature of most cost data limited the review. Data were formally reviewed, including previous consensus opinions (for recommendations 1, 2, 3, and 18), narrative reviews (for recommendations 4, 11, 12, 13, 14, and 19), systematic reviews (for recommendations 5.1, 5.2, 6, and 20), and meta-analyses (for recommendations 7, 8, 9, 10, 15, 16, and 17). Data available only in abstract form were not considered, with the exception of results from 2 meta-analyses by Bardou and colleagues from McGill University (13, 14) and the RUGBE initiative (4), which had been submitted for publication at the time of writing of this manuscript. In addition, for recommendations 7 and 10, data from pivotal abstracts were discussed in detail and were published within 3 months following the conference (23, 24). Consequently, a postconference Delphi process was carried out and results from this final vote were included. More than 875 articles were initially reviewed, and the Delphi process identified 20 issues for discussion. A series of original meta-analyses, including 71 articles and nearly 9000 patients, were performed (13, 14). The key results of specific meta-analyses follow individual statements when appropriate, and full methods and results are available in separate publications (13, 14). Delphi Consensus Process Each statement was graded to indicate the level of evidence available and the strength of the recommendation by using the classification system of the Canadian Task Force on the Periodic Health Examination (Table 1) (25). This scheme was developed to assess therapeutic literature, not literature addressing prognosis (25). Table 1. Categorization of Evidence, Classification of Recommendations, and Voting Schema General Organization A 2-day consensus conference was held in June 2002 under the auspices of the Canadian Association of Gastroenterology. The conference was conducted according to generally accepted standards for the development of clinical practice guidelines (15, 16). At the consensus conference, data were presented and the statements and the grades attributed to evidence were discussed, modified if necessary, and voted on by each participant according to the recognized criteria shown in Table 1 (26). The Canadian Association of Gastroenterology, which administered all aspects of the meeting, secured multipartner funding from industry sponsors. Additional funds were obtained through a peer-review grant received by the Canadian Institutes of Health Research and an internal award from the Research Institute of the McGill University Health Centre. Statements of conflicts of interest were obtained from all voting participants, and additional ethical information was collected (27). Preparation Process and Format of the Report A working group drafted the manuscript, which was then reviewed by all voting conference participants and the nonvoting chair, who approved the final draft. A brief narrative summary regarding the pediatric patient was prepared and can be accessed at www.cag-acg.org/cag_at_glance/positions.htm. An algorithm specifically designed for use in Canada is also under development. Role of the Funding Sources The funding sources had no role in the design, conduct, and reporting of the study or in the decision to submit the results for publication. Recommendation Statements A summary of all of the recommendations is provided in Table 2. Table 2. Summary of Consensus Recommendations for the Management of Patients with Nonvariceal Upper Gastrointestinal Bleeding Initial Management Recommendation 1: Hospitals should develop institution-specific protocols for multidisciplinary management, which should include access to an endoscopist with training in endoscopic hemostasis. Recommendation: C (vote: a, 100%); Evidence: III Previous consensus groups have recommended a multidisciplinary approach with early involvement of a gastroenterologist and surgeon (9, 11, 12, 28). Hospitals with endoscopy services should have a multidisciplinary team in place with a prespecified chain of notification. Not all institutions have immediate access to these specialists, and not all patients require urgent endoscopy; thus, institution-specific protocols should be developed and updated. Endoscopy privileges should be reserved for practitioners who are properly trained according to established credentialing recommendations (29, 30). Recommendation 2: Support staff trained to assist in endoscopy should be available for urgent endoscopy. Recommendation: C (vote: a, 92%; b, 8%); Evidence: III Support staff, including appropriately trained endoscopy assistants, should be available to assist with urgent endoscopies. Any patient identified as high risk for rebleeding ideally should be admitted to a monitored setting for at least the first 24 hours (9). If intensive care beds are unavailable, wards with more intensive monitoring than standard units can be considered. Recommendation 3: Immediate evaluation and appropriate resuscitation are critical to proper management. Recommendation: C (vote: a, 96%; b, 4%); Evidence: III Patients with acute bleeding should be evaluated immediately on presentation. Resuscitation, including stabilization of blood pressure and restoration of intravascular volume (9, 11, 12, 28), should precede further diagnostic and therapeutic measures. Recommendation 4: In selected patients, the placement of a nasogastric tube can be considered because the findings may have prognostic value. Recomme

Magnetic Resonance Cholangiopancreatography: A Meta-Analysis of Test Performance in Suspected Biliary Disease

OBJECTIVES:From the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), we determined clinical outcomes and explored the roles of endoscopic and pharmacologic therapies in a contemporary real-life setting.METHODS:Analysis of randomly selected patients endoscoped for nonvariceal upper gastrointestinal bleeding at 18 community and tertiary care institutions between 1999 and 2002. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression models identified predictors of outcomes.RESULTS:One thousand eight-hundred and sixty-nine patients were included (66 ± 17 yr, 38% female, 2.5 ± 1.6 comorbid conditions, hemoglobin, 96 ± 27 g/L, 54% received a mean of 2.9 ± 1.7 units of blood). Endoscopy was performed within 24 h in 76%, with ulcers (55%) most commonly noted. High-risk endoscopic stigmata and endoscopic therapy were reported in 37%. Rebleeding, surgery, and mortality rates were 14.1%, 6.5%, and 5.4%, respectively. Decreased rebleeding was significantly and independently associated with PPI use (85% of patients, mean daily dose 56 ± 53 mg) in all patients regardless of endoscopic stigmata, (odds ratio (OR):0.53, 95% confidence interval, 95% CI:0.37–0.77) and endoscopic hemostasis in patients with high-risk stigmata (OR:0.39, 95% CI:0.25–0.61). PPI use (OR:0.18, 95% CI:0.04–0.80) and endoscopic therapy (OR:0.31, 95% CI:0.11–0.91) were also each independently associated with decreased mortality in patients with high-risk stigmata.CONCLUSIONS:These results appear to confirm the protective role of endoscopic therapy in patients with high-risk stigmata, and suggest that acute use of PPIs may be associated with a reduction of rebleeding in all patients, and lower mortality in patients with high-risk stigmata. Independent prospective validation of these observational findings is now required.

Useful predictors of bile duct stones in patients undergoing laparoscopic cholecystectomy

Context Noninvasive imaging of the biliary tree with magnetic resonance cholangiopancreatography (MRCP) may detect certain abnormalities better than others. Contribution This meta-analysis summarized 67 studies that compared MRCP with other gold standard tests for diagnosing biliary obstruction (for example, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, and intraoperative or intravenous cholangiography). Magnetic resonance cholangiopancreatography compared well with most other tests, but it seemed slightly less sensitive for diagnosing stones (92%) and for differentiating benign from malignant obstruction (85%) than it was for identifying the presence (99%) and level (96%) of biliary obstruction. Cautions Study quality varied, and some sensitivity estimates had wide confidence intervals. The Editors Biliary diseases and conditions associated with biliary obstruction are a major cause of morbidity and mortality in North America. The accurate diagnosis of the presence and cause of biliary obstruction is key to the cost-effective work-up of patients with suspected biliary disease. Since its introduction in 1968, endoscopic retrograde cholangiopancreatography (ERCP) has become the gold standard in this setting. However, 1.3% to 9% of patients undergoing ERCP will have clinically significant pancreatitis, and 0.2% to 0.5% of patients will die of procedural complications (1-5). In a larger series, diagnostic ERCP was associated with a mortality rate of 0.2% and a moderate to severe pancreatitis rate of 0.7% (1). In 1992, the development of magnetic resonance cholangiopancreatography (MRCP), which used heavy T2-weighting and rapid image acquisition (thus avoiding breathing artifact), allowed the accurate noninvasive imaging of the biliary and pancreatic trees. The weighting involved in selected MRCP sequences is unique because it allows relatively stagnant fluids, such as bile and pancreatic juice, to have a high-signal intensity. Without use of a contrast agent, these fluids appear bright compared with the dark, low-signal intensity of adjacent solid hepatic and pancreatic tissue and fast-flowing fluids (such as circulating blood). Concurrently performed enhanced T1-weighted magnetic resonance imaging (MRI) of the liver and pancreatic parenchyma can complement MRCP by adding important staging information when a malignant disorder is suspected. Although MRCP offered the potential of avoiding ERCP and its attendant risks, evidence for this is lacking because some patients undergoing MRCP will also require ERCP for invasive diagnostic tests (for example, bile sampling or cytologic testing) or for therapy (sphincterotomy, stone removal, or stenting) (6). The possible morbid implication of false-positive and false-negative results also needs to be considered. The identification of clinical scenarios for which MRCP may have limitations is therefore important for the development of adapted clinical guidelines and work-up algorithms in this area. Over the past decade, a plethora of reports have dealt with the accuracy of MRCP in biliary imaging. Most have shown excellent performance in comparison to ERCP or composite gold standards that have included computed tomography (CT), percutaneous transhepatic cholangiography, intraoperative cholangiography, intravenous cholangiography, endoscopic ultrasonography, and surgery, with or without subsequent clinical follow-up (772). However, individually, the studies are too small to allow precise comment on the performance of MRCP in selected diagnostic subgroups, such as patients with suspected stone disease or biliary cancer. In addition, because of variation in study quality, patient samples, MRI technology, and gold standards used, simple pooling of performance characteristics would be inappropriate and potentially misleading. Therefore, we undertook a meta-analysis to better characterize MRCP performance, stratified by clinically important diagnostic scenarios. Methods Search Strategy We searched MEDLINE (from January 1987 to March 2003) and bibliographies using magnetic resonance imaging and biliary tract diseases as Medical Subject Headings terms. The search was a priori restricted to English- and French-language articles. Because of the nature of the articles and subject matter of interest, we believed that MEDLINE would contain all relevant articles and that the use of other databases would be unlikely to reveal additional published studies. We manually screened and assessed abstracts to identify comparative studies with a single or composite gold standard. Most abstracts described articles that were reviews, comparisons of MRI techniques, or case series without comparison with any gold standard (Figure 1). Figure 1. Flowchart of study and abstract exclusions. Inclusion Criteria We included the following types of articles: 1) comparative studies with a defined single or composite gold standard and 2) articles that contained sufficient detail to reconstruct 2 2 tables expressing MRCP results by disease status. Acceptable gold standards included ERCP, intraoperative cholangiography, percutaneous transhepatic cholangiography, intravenous cholangiography, endoscopic ultrasonography, and surgical exploration. We also allowed composite gold standards, including CT and clinical follow-up until clinical and biological abnormalities had resolved or until a diagnosis had been made. If the study type was unclear from the abstract or if no abstract was available but the title suggested a comparative study, the full manuscript was manually reviewed. For bibliographic screening, we also examined relevant reviews. Two international experts were also contacted in an attempt to identify any additional relevant unpublished reports; however, no such reports were found. Exclusion Criteria We excluded case series of patients with a particular diagnosis who were undergoing MRCP and studies in which only patients with positive results on MRCP had other imaging techniques or ERCP to confirm the diagnosis. If a comparative study preselected only patients with a positive test result by using a gold standard to see how MRCP could visualize the abnormalities, we judged the study to be inadequate (even if a group of healthy control persons had been added for comparison). In addition to an artificially set prevalence of disease in such studies and somewhat artificial corresponding predictive values, hand selection of clearly positive and clearly healthy cases may lead to bias. This spectrum bias can occur when a diagnostic test seems to have better performance because more easily diagnosed extremes have been chosen (73, 74). If more than 1 study was included from the same author, we carefully assessed the absence of overlap by using the recruitment periods noted in the manuscript or by contacting the author if the report did not provide these data. Quality Assessment Two authors independently assessed the quality of acceptable manuscripts, and a third author independently settled discrepancies. Studies were graded by using 4 criteria for quality, defined a priori, as described by Irwig and colleagues [75, 76]: 1) blinding, 2) consecutive recruitment of patients, 3) single [versus composite] gold standards, and 4) the nonselective use of the gold standard (that is, the gold standard was performed in all patients). The latter criterion was used to avoid verification bias, which occurs when only abnormal results on the index test lead to the performance of the gold standard to verify the diagnosis (77, 78). To compare the result of MRCP versus that of the gold standard, we then reconstructed 2 2 tables from each study to determine the presence, level, and cause of biliary obstruction, as well as to distinguish benign from malignant obstruction and to detect common bile duct stones. In a particular study, if 22 tables could be reconstructed for more than 1 radiologist, we used the overall results reported in this study, as determined by consensus or a third-party arbitrator, depending on the protocol of the study. Data Stratification and Definition of Imaging End Points We extracted data from the studies and categorized the imaging end points into 4 groupings to diagnose 1) the presence of obstruction; 2) the level of obstruction (here, a diseased patient in terms of the 2 2 table was considered to have hilar or intrahepatic disease, except for the study by Zidi and colleagues [35], which exclusively studied hilar tumors and considered intrahepatic extension to be diseased]; and the presence of either 3) biliary lithiasis or 4) malignancy. Only studies that had more than 5 patients with common bile duct stones were considered in the stone detection subcategory. Potential Confounders We considered 4 other variables, apart from study quality, to be of potential importance for explaining heterogeneity and interstudy variability: 1) imaging end point of the study [presence of obstruction, level of obstruction, presence of common bile duct stones, or presence of malignancy]; 2) clinical context [suspicion of stone, suspicion of malignancy, suspicion of either stone or malignancy, or suspicion of a wide variety of pancreaticobiliary diseases]; 3) MRCP technology era [dichotomized at December 1996, 5 years after its introduction in 1991]; 4) frequency of direct visualization (79-81) of the common bile duct by a conventional gold standard [dichotomized at greater or less than 90% of patients having had ERCP, intraoperative cholangiography, or percutaneous transhepatic cholangiography]; and 4) prevalence of disease. For the MRCP technology era variable, we divided patients into the post-1996 category if most patients seemed to have been recruited after 1 January 1997. Meta-Analytic Statistical Methods and Modeling We assessed the sensitivity and specificity of MRCP by noting the number of true-positive, false-positive, true-negative, and false-negative results. The overall observed sensit

Management of Acute Bleeding from a Peptic Ulcer

ObjectiveThe authors determined the most useful predictors of common bile duct (CBD) stones as diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) in patients who underwent laparoscopic cholecystectomy (LC). MethodsProspective and retrospective collection of historical, biochemical and ultrasonographic data was used. Receiver operating characteristics curve analysis was used to determine optimal biochemical cut-off values. Multivariate analysis using logistic regression with generation of the best model identifying independent predictors of CBD stones also was employed. Prospective validation of the model was performed on an independent group of patients. ResultsEndoscopic retrograde cholangiopancreatographies were performed before LC in 106 patients, and after LC in 33. Only four of ten clinical variables evaluated independently predicted the presence of CBD stones. The optimal model predicted a 94% probability of CBD stones in a patient older than 55 years of age who presented with an elevated biliubin (over 30 μmol/L) and positive ultrasound findings (a dilated CBD, and a CBD stone seen on ultrasound). This model was validated prospectively in a subsequent series of 49 patients in which the probability of CBD stone was only 8% when all four predictors were absent. ConclusionsThe identified independent clinical predictors of a CBD stone helps select a population of symptomatic gallstone bearers who benefit most from cholangiographic assessment.

Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding: A Randomized Trial

The mortality associated with acute bleeding from a peptic ulcer remains high (5 to 10%), and the condition accounts for more than 400,000 hospital admissions per year in the United States. This review summarizes the approach to patient triage and risk stratification, the goals of early endoscopy, the options for medical therapy, and the role of surgery and interventional radiology.

Patterns of antibiotic use and risk of hospital admission because of Clostridium difficile infection

BACKGROUND Use of proton-pump inhibitors in the management of peptic ulcer bleeding is controversial because discrepant results have been reported in different ethnic groups. OBJECTIVE To determine whether intravenous esomeprazole prevents recurrent peptic ulcer bleeding better than placebo in a multiethnic patient sample. DESIGN Randomized trial conducted between October 2005 and December 2007; patients, providers, and researchers were blinded to group assignment. SETTING 91 hospital emergency departments in 16 countries. PATIENTS Patients 18 years or older with peptic ulcer bleeding from a single gastric or duodenal ulcer showing high-risk stigmata. INTERVENTION Intravenous esomeprazole bolus, 80 mg, followed by 8-mg/h infusion, over 72 hours or matching placebo, each given after successful endoscopic hemostasis. Intervention was allocated by computer-generated randomization. After infusion, both groups received oral esomeprazole, 40 mg/d, for 27 days. MEASUREMENTS The primary end point was rate of clinically significant recurrent bleeding within 72 hours. Recurrent bleeding within 7 and 30 days, death, surgery, endoscopic re-treatment, blood transfusions, hospitalization, and safety were also assessed. RESULTS Of 767 patients randomly assigned, 764 provided data for an intention-to-treat analysis (375 esomeprazole recipients and 389 placebo recipients). Fewer patients receiving intravenous esomeprazole (22 of 375) had recurrent bleeding within 72 hours than those receiving placebo (40 of 389) (5.9% vs. 10.3%; difference, 4.4 percentage points [95% CI, 0.6% to 8.3%]; P = 0.026). The difference in bleeding recurrence remained significant at 7 days and 30 days (P = 0.010). Esomeprazole also reduced endoscopic re-treatment (6.4% vs. 11.6%; difference, 5.2 percentage points [95% CI of difference, 1.1 percentage points to 9.2 percentage points]; P = 0.012), surgery (2.7% vs. 5.4%), and all-cause mortality rates (0.8% vs. 2.1%) more than placebo, although differences for the latter 2 comparisons were not significant. About 10% and 40% of patients in both groups reported serious and nonserious adverse events, respectively. LIMITATION Endoscopic therapy was not completely standardized; some patients received epinephrine injection, thermal coagulation, or hemoclips alone, whereas others received combination therapy, but there were similar proportions with single therapy in each group. CONCLUSION High-dose intravenous esomeprazole given after successful endoscopic therapy to patients with high-risk peptic ulcer bleeding reduced recurrent bleeding at 72 hours and had sustained clinical benefits for up to 30 days. PRIMARY FUNDING SOURCE AstraZeneca Research and Development.

Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses

Background: Previous observations have indicated that infection with Clostridium difficile occurs almost exclusively after exposure to antibiotics, but more recent observations have suggested that prior antibiotic exposure may be less frequent among cases of community-acquired disease. Methods: We used 2 linked health databases to perform a matched, nested case–control study of elderly patients admitted to hospital with community-acquired C. difficile infection. For each of 836 cases among people 65 years of age or older, we selected 10 controls. We determined the proportion of cases that occurred without prior antibiotic exposure and estimated the risk related to exposure to different antibiotics and the duration of increased risk. Results: Of the 836 cases, 442 (52.9%) had no exposure to antibiotics in the 45-day period before the index date, and 382 (45.7%) had no exposure in the 90-day period before the index date. Antibiotic exposure was associated with a rate ratio (RR) of 10.6 (95% confidence interval [CI] 8.9–12.8). Clindamycin (RR 31.8, 95% CI 17.6–57.6), cephalosporins (RR 14.9, 95% CI 10.9–20.3) and gatifloxacin (RR 16.7, 95% CI 8.3–33.6) were associated with the highest risk. The RR for C. difficile infection associated with antibiotic exposure declined from 15.4 (95% CI 12.2–19.3) by about 20 days after exposure to 3.2 (95% CI 2.0–5.0) after 45 days. Use of a proton pump inhibitor was associated with increased risk (RR 1.6, 95% CI 1.3–2.0), as were concurrent diagnoses of inflammatory bowel disease (RR 4.1, 95% CI 2.6–6.6), irritable bowel syndrome (RR 3.4, 95% CI 2.3–5.0) and renal failure (RR 1.7, 95% CI 1.2–2.2). Interpretation: Community-acquired C. difficile infection occurred in a substantial proportion of individuals with no recent exposure to antibiotics. Among patients who had been exposed to antibiotics, the risk declined markedly by 45 days after discontinuation of use.

Is Helicobacter pylori eradication associated with gastroesophageal reflux disease

BACKGROUND AND OBJECTIVE Optimal endoscopic hemostasis remains undetermined. This was a systematic review of contemporary methods of endoscopic hemostasis for patients with bleeding ulcers that exhibited high-risk stigmata. SETTING Randomized trials that evaluated injection, thermocoagulation, clips, or combinations of these were evaluated from MEDLINE, EMBASE, and CENTRAL (1990-2006). PATIENTS A total of 4261 patients were evaluated. OUTCOMES Outcomes were rebleeding (primary), surgery, and mortality (secondary). Summary statistics were determined; publication bias and heterogeneity were sought by using funnel plots or by subgroup analyses and meta-regression. RESULTS Forty-one trials assessed 4261 patients. All endoscopic therapies decreased rebleeding versus pharmacotherapy alone, including sole intravenous (IV) proton pump inhibition (PPI) (OR 0.56 [95% CI, 0.34-0.92]); only one trial assessed high-dose IV PPI. Injection alone was inferior compared with other methods, except for thermal hemostasis (OR 1.02 [95% CI, 0.74-1.40]), with a strong trend of increased rebleeding if 1 injectate is used rather than 2 (OR 1.40 [95% CI, 0.95-2.05]). Injection followed by thermal therapy did not decrease rebleeding compared with clips (OR 0.82 [95% CI, 0.28-2.38]) or thermal therapy alone (OR 0.79 [95% CI, 0.24-2.62]). Subgroup analysis, however, suggested that injection followed by thermal therapy was superior to thermal therapy alone. Clips were superior to thermal therapy (OR 0.24 [95% CI, 0.06-0.95]) but, when followed by injection, were not superior to clips alone (OR 1.30 [95% CI, 0.36-4.76]). Surgery or mortality was not altered in most comparisons. CONCLUSIONS All endoscopic treatments are superior to pharmacotherapy alone; only 1 study assessed high-dose IV PPI. Optimal endoscopic therapies include thermal therapy or clips, either alone or in combination with other methods. Additional data are needed that compare injection followed by thermal therapy to clips alone or clips combined with another method.