Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus.

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

A model of the long-term cost effectiveness of scheduled maintenance treatment with infliximab for moderate-to-severe ulcerative colitis.

BACKGROUND: Infliximab (IFX) has been shown to be efficacious in moderate-severe ulcerative colitis (UC). Aim To evaluate the cost-effectiveness of a scheduled maintenance treatment (SMT) with IFX in moderate-severe UC patients. METHODS: A Markov model was constructed to simulate the progression of a cohort of moderate-severe UC patients treated with IFX (5 mg/kg) SMT. Transitions were estimated from two phase III trials of IFX (ACT I and ACT II). Standard care, comprising immunomodulators and/or corticosteroids was used as a comparator. Two separate treatment strategies were evaluated - continued treatment in IFX responders and continued treatment in IFX patients achieving remission. The dose of IFX was estimated for a 73 kg typical UC patient in the UK. The results were calculated over 10 years using a discount rate of 3.5% for costs and outcomes. The outcome measure was quality-adjusted life years (QALYs) estimated using EQ-5D. Sensitivity analyses explored the uncertainty around the results. RESULTS: The incremental cost effectiveness ratio (ICER) for IFX was 27,424 pounds in the responder strategy and 19,696 pounds in the remission strategy at 10 years. In sensitivity analysis, the ICER for IFX in the responder strategy ranged from 21,066 pounds to 86,322 pounds and in the remission strategy ranged from 14,728 pounds to 46,765 pounds. The model time horizon and patient body weight were important factors affecting results. CONCLUSION: Eight-week SMT with IFX appears to be a cost-effective treatment option for adult patients suffering from moderate to severe UC.

Recall of informed consent information by healthy volunteers in clinical trials.

BACKGROUND: Information sheets for clinical research are becoming increasingly complex but the extent to which they are understood is uncertain. AIMS: To assess, as our primary outcome, recall by healthy volunteers of key facts in a patient information sheet in a phase 3 clinical trial. As secondary outcomes, we examined whether there was a difference between medical student and non-medically trained volunteers. DESIGN: Questionnaire to determine recall by healthy volunteers of informed consent information. METHODS: Eighty-two healthy volunteers participating in a capsule endoscopy study were given a 13 page written information sheet and allowed to asked questions. After indicating they were ready to give consent they were asked to complete a 6-item questionnaire covering the identity and adverse effects of trial treatments and of the procedure, the duration of the trial and value of the inconvenience allowance. RESULTS: All 82 healthy volunteers were questioned. Of the volunteers, 74 (90%) had university level education and 49 (60%) were clinical medical students. However, only 10 subjects (12%) could name the three trial drugs. The maximum number of risks remembered was 6 (n = 2) of 23. Only 14 (17%) could name three or more potential risks of the medication they might be exposed to, whilst 17 (20%) could identify none. Most subjects (77/82, 90%) identified capsule endoscopy as the trial procedure and impaction/obstruction as its main risk (52/82, 64%). All but one subject (98.8%) could recall the exact value of the inconvenience payment. CONCLUSION: A comprehensive information sheet resulted in limited recall of trial risks. Shorter information sheets with a test and feedback session should be trialled so that informed consent becomes valid informed consent.

Narrow-band imaging with magnification in Barrett's esophagus: validation of a simplified grading system of mucosal morphology patterns against histology.

BACKGROUND AND STUDY AIMS: Validation of a simplified classification of mucosal morphology in prediction of histology in Barrett's esophagus using narrow-band imaging with magnification (NBI-Z) and assessing its reproducibility by endoscopists experienced in the use of NBI (NBI-experts) and by endoscopists who were new to NBI (non-NBI-experts). PATIENTS AND METHODS: In a prospective cohort study of 109 patients with Barrett's esophagus at a single tertiary referral center, mucosal patterns visualized in Barrett's esophagus on NBI-Z were classified into four easily distinguishable types: A, round pits with regular microvasculature; B, villous/ridge pits with regular microvasculature; C, absent pits with regular microvasculature; D, distorted pits with irregular microvasculature. The NBI-Z grading was compared with the final histopathological diagnosis, and positive (PPV) and negative predictive values (NPV) were calculated. The reproducibility of the grading was then assessed by NBI-expert and non-NBI-expert endoscopists, and interobserver and intraobserver agreement were calculated using kappa statistics. RESULTS: Per-biopsy analysis: In 903 out of 1021 distinct areas (87.9%) the NBI-Z grading corresponded to the histological diagnosis. Per-patient analysis: The PPV and NPV for type A pattern (columnar mucosa without intestinal metaplasia) were 100% and 97% respectively; for types B and C (intestinal metaplasia) they were 88% and 91% respectively, and for type D (high-grade dysplasia) 81% and 99% respectively. Inter- and intraobserver agreement: The mean kappa values in assessing the various patterns were 0.71 and 0.87 in the non-expert group; 0.78 and 0.91 in the expert group. CONCLUSIONS: This study has validated a simplified classification of the various morphologic patterns visualized in Barrett's esophagus and confirmed its reproducibility when used by NBI-expert and non-NBI-expert endoscopists.

High-resolution magnification endoscopy can reliably identify normal gastric mucosa, Helicobacter pylori-associated gastritis, and gastric atrophy.

BACKGROUND AND STUDY AIMS: The aims of the study were to describe the magnified endoscopic findings in the gastric body, correlate these with histology, and evaluate their reproducibility in the assessment of the magnified endoscopic patterns seen. PATIENTS AND METHODS: A total of 95 consecutive dyspeptic patients underwent upper gastrointestinal endoscopy with a magnifying endoscope. The endoscopists classified the magnified endoscopic patterns and correlated them with the histological findings. In the second part of the study, 200 images were shown to five endoscopists in order to examine inter- and intraobserver variability in image assessment. RESULTS: The magnified endoscopic findings in the gastric body were categorized into four types: type 1, honeycomb-type subepithelial capillary network (SECN) with regular arrangement of collecting venules and regular, round pits; type 2, honeycomb-type SECN with regular, round pits, but loss of collecting venules; type 3, loss of normal SECN and collecting venules, with enlarged white pits surrounded by erythema; and type 4, loss of normal SECN and round pits, with irregular arrangement of collecting venules. The sensitivity, specificity, and positive and negative predictive values of the type 1 pattern for predicting normal gastric mucosa were 92.7% (95% confidence interval [CI] 93.2-97.3%), 100% (95% CI 83.9-100%), 100% (95% CI 92.9-100%), and 83.8% (95% CI 65.5-93.9%). The sensitivity, specificity, and positive and negative predictive values of types 2 and 3 patterns for predicting a Helicobacter pylori-infected stomach were 100% (95% CI 83.9-100%), 92.7% (95% CI 93.2-97.3%), 83.8% (95% CI 65.5-93.9%), and 100% (95% CI 92.9-100%). The sensitivity, specificity, and positive and negative predictive values of a type 4 pattern for predicting gastric atrophy were 90% (95% CI 66.8-98.2%), 96% (95% CI 87.9-98.9%), 85.7% (95% CI 62.6-96.2%), and 97.3% (95% CI 89.6-99.5%. The kappa values for inter- and intraobserver agreement in predicting normal gastric mucosa, H. pylori gastritis, and gastric atrophy were 0.864 and 0.913 respectively. CONCLUSION: High-resolution magnification endoscopy can reliably identify the normal gastric mucosa, H. pylori-associated gastritis, and gastric atrophy in a Western population.

Probiotics for maintenance of remission in Crohn's disease.

BACKGROUND: Crohn's disease (CD) is characterised by episodes of disease activity and symptom-free remission. Probiotics are microorganisms that can potentially benefit health, and have been evaluated as an alternate means of preventing relapse in patients with CD. OBJECTIVES: To assess the effectiveness of probiotics for the maintenance of remission in CD. SEARCH STRATEGY: The following databases were searched: the Cochrane Database of Systematic Reviews (2005, Issue 3); the Cochrane Central Register of Controlled Trials (2005, Issue 3); the Cochrane IBD/FBD Group Trials Register (2005), MEDLINE (1966-2005); EMBASE (1980-2005); ISI Web of Knowledge (BIDS) 1981-2005; On-line clinical trials databases (2005); and review articles. Experts in the field were contacted for unpublished data. SELECTION CRITERIA: Randomised controlled trials of probiotic therapy. DATA COLLECTION AND ANALYSIS: Two independent reviewers performed data extraction and assessment of methodological quality. The primary outcome was the relative risk (RR) of relapse after maintenance treatment (and 95% confidence intervals [CI]). MAIN RESULTS: Seven small studies were identified and varied according to probiotics tested, methodological quality and medication regimen. No studies were pooled for statistical analysis. There was no statistically significant benefit of E. coli Nissle for reducing the risk of relapse compared to placebo (RR 0.43, 95% CI 0.15 to 1.20), or Lactobacillus GG after surgically-induced remission (RR 1.58, 95% CI 0.30 to 8.40) or medically-induced remission (RR 0.83, 95% CI 0.25 to 2.80). There was no statistically significant benefit of probiotics for reducing the risk of relapse compared to maintenance therapy employing aminosalicylates or azathioprine (RR 0.67, 95% CI 0.13 to 3.30), and in this study the probiotic Lactobacillus GG was associated with adverse events. In children, there was there was no statistically significant difference between Lactobacillus GG and placebo for reducing the risk of relapse (RR 1.85, 95% CI 0.77 to 4.40). A small study using the yeast Saccharomyces boulardii demonstrated a difference that was not statistically significant in favour of probiotic combined with a reduced level of maintenance therapy over standard maintenance treatment alone (RR 0.17, 95% CI 0.02 to 1.23). AUTHORS' CONCLUSIONS: There is no evidence to suggest that probiotics are beneficial for the maintenance of remission in CD. All of the included studies enrolled small numbers of patients and may have lacked statistical power to show differences should they exist. Larger trials are required to determine if probiotics are of benefit in Crohn's disease.

Barrett's esophagus specialist clinic: what difference can it make?

A 'Barrett's specialist clinic' was set up in our institution consisting of a specialist nurse, research fellow, and a consultant gastroenterologist. The aim of our study was to examine the impact of this clinic in the management of patients with Barrett's esophagus (BE). Patients with the diagnosis of BE seen in the outpatient departments or in the endoscopy unit were referred to this clinic. Guidelines were introduced modelling the American College of Gastroenterology recommendation. Patients were assessed based on their comorbidity and willingness to undergo surveillance. Reflux symptom control and acid suppression was addressed. All patients were invited to undergo high-resolution enhanced magnification endoscopy (EME) and targeted biopsy to confirm the diagnosis and to form a management plan. During the appointment in the clinic, patients were given an option to fill a questionnaire that inquired about the information given to them regarding BE. One hundred and forty-three patients (92 men, mean age: 62 years) with a diagnosis of BE were seen in the specialist clinic. In 16 patients surveillance was stopped. In 25 patients treatment was changed due to poor control of reflux symptoms. Sixty-five patients (51%) answered the questionnaire. Seventy-five patients (58%) underwent high resolution EME. Twelve patients, had a histological upgrade after EME, in spite of a short mean screening interval (5.5 months). The 'Barrett's specialist clinic' introduced a more structured approach in our institution and changed the way these patients were managed. Our results indicate the need for local guidelines and Barrett's specialist clinics in the UK, and perhaps in the rest of the Western world, wherein the burden of this condition is increasing.

Acetic acid-enhanced magnification endoscopy in the diagnosis of specialized intestinal metaplasia, dysplasia and early cancer in Barrett's oesophagus.

BACKGROUND: Barrett's surveillance is prone to sampling error. Aim To determine whether enhanced magnification endoscopy using acetic acid instillation improves diagnostic accuracy of specialized intestinal metaplasia/dysplasia in Barrett's oesophagus. METHODS: We examined the detection rate of the specialized intestinal metaplasia/dysplasia in 64 consecutive patients with Barrett's oesophagus using acetic acid to enhance mucosal pit patterns. Histology was compared with the previous findings at recent conventional surveillance in 62 patients. We also examined the inter-/intra-observer agreement in the assessment of the enhanced magnification endoscopy pit pattern findings. RESULTS: Histology revealed columnar-lined oesophagus in six (9%) patients, specialized intestinal metaplasia in 49 (77%), low-grade dysplasia in five (8%), high-grade dysplasia in one (2%), and adenocarcinoma in three (5%). There was discordance between the histologic findings from conventional surveillance with random biopsy. Fifteen patients (24%) had a histological upgrade with enhanced magnification endoscopy. There was a high detection rate of specialized intestinal metaplasia even in short segment Barrett's oesophagus (74%), and additionally, there were two cancers, one with 2-cm Barrett's oesophagus and one ultra-short (1 cm). The mean kappa values for inter- and intra-observer agreement in assessing the pit patterns were 0.571 (0.041) and 0.709 (0.038), respectively. CONCLUSIONS: Enhanced magnification endoscopy allows clear visualization of the epithelial pit patterns within Barrett's oesophagus, and targeted biopsy results in a high yield of specialized intestinal metaplasia and dysplasia.

Does concurrent prescription of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?

BACKGROUND: A 15-fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people. AIM: To quantify the risk of gastrointestinal bleeding associated with current exposure to non-steroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently. METHODS: We conducted a case-control analysis of 11,261 cases with upper gastrointestinal bleeding and 53,156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self-controlled case series analysis. RESULTS: Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08-2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02-2.28 for non-steroidal anti-inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95% confidence interval 2.25-3.82). The self-controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non-steroidal anti-inflammatory drugs (2.71, 95% confidence interval 2.51-2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48-1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95-5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non-steroidal anti-inflammatory drugs and was similar when we looked at tricyclic anti-depressants. CONCLUSIONS: Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non-steroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.

Silent myocardial infarction and its prognosis in a community-based cohort of Type 2 diabetic patients: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: Our study investigated the prognosis of Type 2 diabetic patients with silent myocardial infarction in a community-based cohort. METHODS: We analysed data from 1269 patients with Type 2 diabetes mellitus from a community-based observational study of diabetes care, control and complications. Silent myocardial infarction was defined as Q waves (Minnesota codes 1.1, 1.2) on a baseline electrocardiogram in the absence of a history or symptoms of CHD. RESULTS: Silent myocardial infarction was present in 3.9% of patients, or 44% of all Q-wave myocardial infarctions. The patients were subdivided into those with (i). no clinical or Q-wave evidence of myocardial infarction (Group 1), (ii). silent myocardial infarction (Group 2), (iii). self-reported CHD but no Q waves (Group 3), and (iv) self-reported CHD and Q waves (Group 4). Compared to Groups 3 and 4, Group 2 patients were more likely to be women, less likely to have smoked, and had higher serum HDL-cholesterol concentrations and higher blood pressure. Over an average of seven years, and after adjusting for other independent predictors of death, all-cause and CHD mortality were similar in Groups 1 and 2 and greater (twofold for all-cause and fourfold for CHD mortality) in Groups 3 and 4. CONCLUSIONS/INTERPRETATION: Silent myocardial infarction is common in Type 2 diabetes and has a prognosis similar to that in patients without a history of CHD or Q waves.