Introduction of the Concept of Diagnostic Sensitivity and Specificity of Normothermic Perfusion Protocols to Assess High-Risk Donor Livers.

Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess 3 such protocols, namely, those introduced by the teams from Birmingham (BP), Cambridge (CP), and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ use and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with 1 and 0 organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs but that the balance of risk of underuse and overuse varies by protocol.

The effects of proton pump inhibition on patient-reported severity of dyspepsia when receiving dual anti-platelet therapy with clopidogrel and low-dose aspirin: analysis from the Clopidogrel and the Optimization of Gastrointestinal Events Trial.

BACKGROUND: Dual anti-platelet therapy with clopidogrel and low-dose aspirin increases the risk for gastrointestinal clinical events. Omeprazole has been shown to significantly reduce these events without compromising cardiovascular safety in patients treated with dual anti-platelet therapy. Whether or not omeprazole improves patient-reported outcomes is undetermined. AIM: To assess the impact of prophylactic omeprazole with background dual anti-platelet therapy on patient-reported symptoms of dyspepsia compared to placebo. METHODS: We analysed results of the Severity of Dyspepsia Assessment questionnaires collected in the Clopidogrel and the Optimization of Gastrointestinal Events Trial. RESULTS: Patient-reported outcome data from 3759 subjects were available for analysis. At 4 weeks, the mean scores of pain intensity and nonpain symptoms were lower in the omeprazole group (5.61 ± 0.17 vs. 6.40 ± 0.17, P = 0.001, and 10.61 ± 0.07 vs. 11.00 ± 0.07, P < 0.001 respectively). These differences were maintained at 24 weeks (5.91 ± 0.35 vs. 7.10 ± 0.37, P = 0.020 for pain intensity; 10.36 ± 0.12 vs. 10.93 ± 0.13, P = 0.001 for nonpain symptoms). After adjusting for covariates there were no statistically significant differences between the groups in the percent of patients with dyspepsia during follow-up. CONCLUSIONS: In addition to reducing the risk of gastrointestinal bleeding, statistically significant benefits with prophylactic omeprazole use on both pain and nonpain symptoms were evident at 4 weeks and sustained through 24 weeks. The clinical significance of these overall results is unclear, but greater in patients with pain at baseline.

Delayed endoscopic retrograde cholangiopancreatography is associated with persistent organ failure in hospitalised patients with acute cholangitis.

BACKGROUND: Predictors of organ failure and the impact of early endoscopic retrograde cholangiopancreatography (ERCP) on outcomes in patients with acute cholangitis are unclear. AIM: To identify factors associated with persistent organ failure and assess the impact of early ERCP on outcomes in hospitalised patients with cholangitis. METHODS: Consecutive hospitalised patients who received ERCP at two centres for cholangitis from 4/2005-3/2013 were retrospectively reviewed. Delayed ERCP was defined as ERCP ≥ 48 h after hospitalisation. Primary outcome was persistent organ failure at >48 h after hospitalisation (≥ 1.5 times rise in creatinine levels from baseline values to ≥ 1.5 mg/dL or need for dialysis, mechanical ventilation and/or hypotension requiring vasopressor). RESULTS: 203 patients (mean age 59 ± 19 years) had ERCP for cholangitis: 115 with choledocholithiasis, 48 with other benign obstructions and 40 with malignant strictures. Forty-five (22%) patients had persistent organ failure at >48 h and 11 (5%) died. On multivariate analysis, Charlson Comorbidity Index >2 (OR = 4.6, 95% CI = 1.5-13.8), systemic inflammatory response syndrome (SIRS; OR = 3.2, 95% CI = 1.1-9.8), hypoalbuminemia (OR = 3.3, 95% CI = 1.4-7.9), bacteremia (OR = 2.8, 95% CI 1.3-6.2) and delayed ERCP(OR = 3.1, 95% CI: 1.4-7.0) were associated with persistent organ failure. Every 1-day delay in ERCP was associated with a 17% (95% CI = 5-29%) relative risk increase in persistent organ failure after adjusting for significant factors. CONCLUSIONS: Delay in ERCP beyond 48 h was associated with persistent organ failure in hospitalised patients with acute cholangitis. Other factors included increased comorbidities, SIRS, hypoalbuminemia and bacteremia. Early ERCP performed within 48 h after presentation in patients with cholangitis may improve outcomes.

The yield and cost of colonoscopy in patients with metastatic cancer of unknown primary.

BACKGROUND: Although gastroenterologists are asked to perform colonoscopy in patients with metastatic cancer of unknown primary (MCUP), studies evaluating this practice are lacking. AIM: To determine the yield and cost of colonoscopy in patients referred for colonoscopy with an indication of MCUP. METHODS: We prospectively and retrospectively assessed colonoscopies performed from 2000 to 2011 at a county, a university, and a Veterans Administration medical centre to identify patients referred for colonoscopy for the indication of MCUP. Exclusion criteria included overt or occult bleeding, iron-deficiency anaemia, familial-colon-cancer syndrome, prior colon cancer, imaging suggesting colorectal lesion, and palpable rectal mass. Outcomes were the number of primary colon cancers and costs based on 2012 Medicare reimbursements. RESULTS: Two (1%) of the 160 patients meeting enrollment criteria had a primary colon cancer identified, and both died within 1 month after diagnosis without receiving therapy targeted at colon cancer. One patient without colon cancer had a perforation because of colonoscopy, which required surgery and colostomy. The cost of a strategy of routinely performing colonoscopy in patients referred with MCUP was $84 736 per colon primary identified. CONCLUSIONS: Primary colon cancer was rarely identified at colonoscopy in patients with MCUP and no standard indications for diagnostic colonoscopy. Furthermore, the cost to diagnose one additional colon primary was very high. Those with colon cancer had advanced disease and were unable to benefit from targeted therapy. Routine colonoscopy for MCUP cannot be recommended at present.

Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials.

BACKGROUND: The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. METHODS: We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124,513 participants, 68,342 person-years) and 474 trials of one NSAID versus another NSAID (229,296 participants, 165,456 person-years). The main outcomes were major vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, obstruction, or bleed). FINDINGS: Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1·37, 95% CI 1·14-1·66; p=0·0009) or diclofenac (1·41, 1·12-1·78; p=0·0036), chiefly due to an increase in major coronary events (coxibs 1·76, 1·31-2·37; p=0·0001; diclofenac 1·70, 1·19-2·41; p=0·0032). Ibuprofen also significantly increased major coronary events (2·22, 1·10-4·48; p=0·0253), but not major vascular events (1·44, 0·89-2·33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0·93, 0·69-1·27). Vascular death was increased significantly by coxibs (1·58, 99% CI 1·00-2·49; p=0·0103) and diclofenac (1·65, 0·95-2·85, p=0·0187), non-significantly by ibuprofen (1·90, 0·56-6·41; p=0·17), but not by naproxen (1·08, 0·48-2·47, p=0·80). The proportional effects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17-2·81, p=0·0070; diclofenac 1·89, 1·16-3·09, p=0·0106; ibuprofen 3·97, 2·22-7·10, p<0·0001; and naproxen 4·22, 2·71-6·56, p<0·0001). INTERPRETATION: The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs. Although NSAIDs increase vascular and gastrointestinal risks, the size of these risks can be predicted, which could help guide clinical decision making. FUNDING: UK Medical Research Council and British Heart Foundation.

Natural history of acute upper GI bleeding due to tumours: short-term success and long-term recurrence with or without endoscopic therapy.

BACKGROUND: Scant information is available regarding patients with upper gastrointestinal bleeding (UGIB) from tumours. AIM: To determine the presentation, endoscopic findings, treatment and outcomes in patients with UGIB from malignant tumours and identify risk factors associated with rebleeding. METHODS: Consecutive patients who were hospitalised with haematemesis, melena or haematochezia and underwent upper endoscopy were identified retrospectively by reviewing an endoscopy database. Patients with UGIB due to biopsy-proven malignant tumours were studied. RESULTS: Tumours were the source of bleeding in 106 (5%) of 2,166 patients with UGIB. Tumours were oesophageal in 17 (16%), gastric in 77 (73%) and duodenal in 12 (11%). At presentation, 84 (79%) did not have known cancer previously, and 79 (75%) had metastatic disease. Seventy-seven (73%) received transfusions at index hospitalisation. At endoscopy, 32 (30%) had active bleeding (31 oozing, 1 spurting). Among actively bleeding patients, haemostasis was achieved in 12 (86%) of 14 receiving endoscopic therapy and all 18 not receiving endoscopic treatment. Hospitalisation for rebleeding occurred in 50 (49%) of 103 at a median of 30 days (3-885). On multivariate analysis, age ≤60 years (OR = 2.49, 95% CI 1.06-5.81) and haemodynamic instability (OR = 2.42, 95% CI 1.08-5.46) were associated with rebleeding. CONCLUSIONS: Patients presenting with tumour-associated UGIB have substantial blood loss, with three-quarters requiring transfusion at presentation. Initial haemostasis occurs in almost all patients, with or without endoscopic therapy, but rebleeding requiring repeat hospitalisation occurs in approximately half the patients and is more common in patients who are ≤60 years of age and have haemodynamic instability at presentation.

Gastroprotection in low-dose aspirin users for primary and secondary prevention of ACS: results of a cost-effectiveness analysis including compliance.

PURPOSE: Low-dose aspirin (ASA) increases the risk of upper gastrointestinal (GI) complications. Proton pump inhibitors (PPIs) reduce these upper GI side effects, yet patient compliance to PPIs is low. We determined the cost-effectiveness of gastroprotective strategies in low-dose ASA users considering ASA and PPI compliance. METHODS: Using a Markov model we compared four strategies: no medication, ASA monotherapy, ASA+PPI co-therapy and a fixed combination of ASA and PPI for primary and secondary prevention of ACS. The risk of acute coronary syndrome (ACS), upper GI bleeding and dyspepsia was modeled as a function of compliance and the relative risk of developing these events while using medication. Costs, quality adjusted life years and number of ACS events were evaluated, applying a variable risk of upper GI bleeding. Probabilistic sensitivity analyses were performed. RESULTS: For our base case patients using ASA for primary prevention of ACS no medication was superior to ASA monotherapy. PPI co-therapy was cost-effective (incremental cost-effectiveness ratio [ICER] €10,314) compared to no medication. In secondary prevention, PPI co-therapy was cost-effective (ICER €563) while the fixed combination yielded an ICER < €20,000 only in a population with elevated risk for upper GI bleeding or moderate PPI compliance. PPI co-therapy had the highest probability to be cost-effective in all scenarios. PPI use lowered the overall number of ACS. CONCLUSIONS: Considering compliance, PPI co-therapy is likely to be cost-effective in patients taking low dose ASA for primary and secondary prevention of ACS, given low PPI prices. In secondary prevention, a fixed combination seems cost-effective in patients with elevated risk for upper GI bleeding or in those with moderate PPI compliance. Both strategies reduced the number of ACS compared to ASA monotherapy.

Differentiation of eight phenotypes and discovery of potential biomarkers for a single plant organ class using laser electrospray mass spectrometry and multivariate statistical analysis.

Laser electrospray mass spectrometry (LEMS) coupled with offline multivariate statistical analysis is used to discriminate eight phenotypes from a single plant organ class and to find potential biomarkers. Direct analysis of the molecules from the flower petal is enabled by interfacing intense (10(13) W/cm(2)), nonresonant, femtosecond laser vaporization at ambient pressure with electrospray ionization for postionization of the vaporized analytes. The observed mass spectral signatures allowed for the discrimination of various phenotypes using principal component analysis (PCA) and either linear discriminant analysis (LDA) or K-nearest neighbor (KNN) classifiers. Cross-validation was performed using multiple training sets to evaluate the predictive ability of the classifiers, which showed 93.7% and 96.8% overall accuracies for the LDA and KNN classifiers, respectively. Linear combinations of significant mass spectral features were extracted from the PCA loading plots, demonstrating the capability to discover potential biomarkers from the direct analysis of tissue samples.

Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia.

BACKGROUND: Factors other than acid may play a role in gastro-oesophageal reflux disease (GERD) and its complications. AIM: To assessed the role of bile acids in the pathogenesis of GERD, Barrett's oesophagus and Barrett's-related neoplasia. METHODS: We conducted a systematic review of computerised bibliographic databases for original articles involving humans or human oesophageal tissue or cells that assessed exposure to or manipulation of bile acids. Outcomes assessed included GERD symptoms; gross oesophageal injury; Barrett's oesophagus and related neoplasia; and intermediate markers of inflammation, proliferation or neoplasia. RESULTS: Eighty-three original articles were included. In in vivo studies, bile acids concentrations were higher in the oesophageal aspirates of patients with GERD than controls, and bile acids infusions triggered GERD symptoms, especially in high concentrations or in combination with acid. In ex vivo/in vitro studies, bile acids stimulated squamous oesophageal cells and Barrett's epithelial cells to produce inflammatory mediators (e.g., IL-8 and COX-2) and caused oxidative stress, DNA damage and apoptosis. They also induced squamous cells to change their gene expression pattern to resemble intestinal-type cells and caused Barrett's cells to increase expression of intestinal-type genes. CONCLUSIONS: In aggregate, these studies suggest that bile acids may contribute to the pathogenesis of symptoms, oesophagitis and Barrett's metaplasia with related carcinogenesis in patients with GERD. However, all study results are not uniform and substantial differences in study parameters may explain at least some of this variation.

Randomised clinical trial: a novel rabeprazole extended release 50 mg formulation vs. esomeprazole 40 mg in healing of moderate-to-severe erosive oesophagitis - the results of two double-blind studies.

BACKGROUND: Current PPIs may not achieve desired outcomes in some GERD patients due to limited duration of acid inhibition. AIM: To evaluate a novel rabeprazole extended release (ER), which provides longer duration of drug exposure and acid suppression, in healing and symptomatic resolution of moderate-severe erosive oesophagitis. METHODS: Patients with LA grade C or D oesophagitis were randomised to rabeprazole-ER 50 mg or esomeprazole 40 mg once daily in two identical 8-week double-blind trials (N = 2130). Two primary endpoints were tested sequentially: (1) healing by 8 weeks [hypothesis: rabeprazole-ER non-inferior to esomeprazole (non-inferiority margin = 8%)], (2) healing by 4 weeks [hypothesis: rabeprazole-ER superior to esomeprazole (P < 0.05)]. The secondary endpoint was sustained heartburn resolution at 4 weeks. RESULTS: Rabeprazole-ER was non-inferior to esomeprazole in week-8 healing (80.0% vs. 75.0%; 77.5% vs. 78.4%). Week-4 healing (54.8% vs. 50.3%; 50.9% vs. 50.7%) and sustained heartburn resolution (48.3% vs. 48.2%; 53.2% vs. 52.5%) were not significantly different. Post hoc combined results for grade D revealed rabeprazole-ER vs. esomeprazole differences in week-8 healing = 10.4% (95% CI: -1.4%, 22.2%) and week-4 healing = 12.0% (P = 0.048). CONCLUSIONS: Rabeprazole-ER is as effective as esomeprazole in healing moderate-severe oesophagitis and achieves similar rates of heartburn resolution. Subgroup analysis suggests the possibility of benefit in severe oesophagitis, but this requires further evaluation (ClinicalTrials.gov: NCT00658528 and NCT00658775).

Risk factors for NSAID-associated upper GI clinical events in a long-term prospective study of 34 701 arthritis patients.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID)-related GI effects vary based on patient characteristics. AIMS: To assess risk factors for NSAID-associated upper GI clinical events and dyspepsia. METHODS: Patients ≥50 years with osteoarthritis or rheumatoid arthritis were randomized to etoricoxib or diclofenac in a prespecified intent-to-treat analysis of three double-blind randomized trials. Potential risk factors for upper GI clinical events (bleeding, perforation, obstruction, or ulcer), complicated events (perforation, obstruction, bleeding) and discontinuations due to dyspepsia were assessed with Cox proportional hazard models. RESULTS: Significant predictors of clinical events and complicated events included age ≥65 years [hazards ratios (HRs) = 2.25 (1.84-2.76), 4.09 (2.82-5.92)], prior event [HRs = 2.57 (1.94-3.39), 3.23 (2.09-5.00)], low-dose aspirin [HRs = 2.34 (1.87-2.92), 3.41 (2.33-5.00)] and corticosteroid [HRs = 1.85 (1.41-2.43), 2.09 (1.29-3.38)]. Predictors of discontinuation due to dyspepsia included prior dyspepsia [HR = 1.78 (1.44-2.00)], prior event [HR = 1.78 (1.40-2.27)] and age ≥65 years [HR = 1.35 (1.16-1.57)]. CONCLUSIONS: Assessment for age ≥65 years, prior upper GI clinical events and low-dose aspirin use are key in identifying patients who should either avoid NSAIDs or employ management strategies to reduce NSAID-associated upper GI events. Prior dyspepsia or upper GI clinical events and age ≥65 years also predict an increased risk of developing dyspepsia severe enough to necessitate discontinuation of NSAIDs.

Can museum egg specimens be used for proteomic analyses?

BACKGROUND: Mass spectrometry and proteomic analyses have become powerful tools for the analysis of proteins and peptides. Investigation of proteins contained in the various layers of the avian eggshell has focused entirely on domesticated species. It has been widely assumed that this existing research can inform the study of wild bird species despite the fact that the vast majority of the diversity in avian species (~95%) exists outside the Orders to which domestic and poultry species belong. Museum collections offer a potentially valuable source of material for studying composition of wild avian eggshell matrix proteins. We used museum and fresh eggshells of common quails Coturnix coturnix to compare the protein composition of their organic matrices. Four eggs of domestic chickens were analysed simultaneously as a control for comparison to the fresh and museum quail eggs. The determination of the proteins was carried out using enzymatic cleavage followed by high-performance mass spectrometry. RESULTS: We found that some of the expected key eggshell proteins (3 out of 11) were not present in the samples of museum quail egg. These proteins were either entirely absent from the museum eggs or the technique was unable to detect them. There was no pattern in the absent proteins in the sense of protein function or where they are located within the eggshell. CONCLUSION: We conclude it is likely that such studies on museum specimens using a proteomic approach will be limited in coverage of proteins and may, therefore, be misleading.

Prescription rates of protective co-therapy for NSAID users at high GI risk and results of attempts to improve adherence to guidelines.

BACKGROUND: Protective co-therapy is recommended in NSAID users with GI risk factors, but adherence is poor. AIM: To assess the proportion of NSAID users receiving co-therapy and strategies to improve adherence. METHODS: Arthritis patients > or =50 years of age received etoricoxib or diclofenac in a double-blind randomized trial. Reminders that high-risk patients (age > or = 65; previous ulcer/haemorrhage; corticosteroid, anticoagulant, aspirin use) should receive co-therapy were given at study initiation. Free PPI was provided. An intervention midway through the study included a written reminder and required written response regarding co-therapy. RESULTS: 16,244/23,504 (69%) patients had GI risk factors. Pre-intervention, co-therapy was most common with previous ulcer/haemorrhage [706/1107 (64%)] and 3-4 risk factors [331/519 (64%)]. In the 10,026 patients enrolled pre-intervention and remaining in the study > or =6 months after, co-therapy in high-risk patients increased from 2958/6843 (43%) to 4177/6843 (61%) (difference = 18%; 95% CI 16%,19%). The increase was greater outside the US (22%; 19%,24%) than in the US (15%; 13%,17%). CONCLUSIONS: Less than 50% of NSAID users with GI risk factors are given protective co-therapy--even if prescribers are given reminders and cost is not an issue. Direct communication requiring written response significantly increased adherence to guidelines, but achieving higher levels of adherence will require additional strategies.

Adherence to best practice guidelines in dyspepsia: a survey comparing dyspepsia experts, community gastroenterologists and primary-care providers.

BACKGROUND: Although 'best practice' guidelines for dyspepsia management have been disseminated, it remains unclear whether providers adhere to these guidelines. AIM: To compare adherence to 'best practice' guidelines among dyspepsia experts, community gastroenterologists and primary-care providers (PCPs). METHODS: We administered a vignette survey to elicit knowledge and beliefs about dyspepsia including a set of 16 best practices, to three groups: (i) dyspepsia experts; (ii) community gastroenterologists and (iii) PCPs. RESULTS: The expert, community gastroenterologist and PCP groups endorsed 75%, 73% and 57% of best practices respectively. Gastroenterologists were more likely to adhere with guidelines than PCPs (P < 0.0001). PCPs were more likely to define dyspepsia incorrectly, overuse radiographic testing, delay endoscopy, treat empirically for Helciobacter pylori without confirmatory testing and avoid first-line proton pump inhibitors (PPIs). PCPs had more concerns about adverse events with PPIs [e.g. osteoporosis (P = 0.04), community-acquired pneumonia (P = 0.01)] and higher level of concern predicted lower guideline adherence (P = 0.04). CONCLUSIONS: Gastroenterologists are more likely than PCPs to comply with best practices in dyspepsia, although compliance remains incomplete in both groups. PCPs harbour more concerns regarding long-term PPI use and these concerns may affect therapeutic decision making. This suggests that best practices have not been uniformly adopted and persistent guideline-practice disconnects should be addressed.

Evaluating the process of care in nonvariceal upper gastrointestinal haemorrhage: a survey of expert vs. non-expert gastroenterologists.

BACKGROUND: When faced with the same facts, physicians often make different decisions. Aim To perform a survey to measure the process of care and variations in decision-making in nonvariceal upper gastrointestinal tract haemorrhage (NVUGIH) and compare results between experts and non-experts. METHODS: We administered a vignette survey to elicit knowledge and beliefs about NVUGIH, including 13 'best practice' guidelines. We compared guideline compliance between experts and non-experts. RESULTS: One hundred and eighty-eight gastroenterologists responded (46%). Experts endorsed more 'best practices' than non-experts (93% vs. 85%; P = 0.002). Non-experts were more likely to endorse incorrectly bolus dosing vs. continuous infusion of intravenous proton pump inhibitors (PPIs; 92% vs. 64%; P = 0.005) and to select standard-channel vs. large-channel endoscopes in high-risk bleeding (100% vs. 85%; P = 0.04). There were wide variations within groups regarding the timing of nasogastric lavage, use of promotility agents, use of hemoclips and appropriateness of snaring clots overlying ulcers. CONCLUSIONS: Experts are more likely to comply with NVUGIH guidelines. Non-experts diverge from experts in the dosing of PPIs and choice of endoscope in high-risk bleeding. Moreover, there are wide variations in key practices even within groups. This suggests that best practices have been generally well disseminated, but that persistent disconnects exist that should be further investigated.