Declining Use of Corticosteroids for Crohn's Disease Has Implications for Study Recruitment: Results of a Pilot Randomized Controlled Trial.

BACKGROUND: Corticosteroids (CS) have been used extensively to induce remission in Crohn's disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We proposed to undertake a pilot study comparing EEN and CS therapy to CS alone to assess decrease symptoms and inflammatory markers over 6 weeks. AIM: The overall aim was to assess study feasibility based on recruitment rates and acceptability of treatment in arms involving EEN. METHODS: The pilot study intended to recruit 100 adult patients with active CD who had been prescribed CS to induce remission as part of their care. The patients were randomized to one of three arms: (i) standard-dose CS; (ii) standard-dose CS plus EEN (Modulen 1.5 kcal); or (iii) short-course CS plus EEN. RESULTS: A total of 2009 CD patients attending gastroenterology clinics were screened from October 2018 to November 2019. Prednisone was prescribed to only 6.8% (27/399) of patients with active CD attending outpatient clinics. Of the remaining 372 patients with active CD, 34.8% (139/399) started or escalated immunosuppressant or biologics, 49.6% (198/399) underwent further investigation and 8.8% (35/399) were offered an alternative treatment (e.g., antibiotics, surgery or investigational agents in clinical trials). Only three patients were enrolled in the study (recruitment rate 11%; 3/27), and the study was terminated for poor recruitment. CONCLUSION: The apparent decline in use of CS for treatment of CD has implications for CS use as an entry criterion for clinical trials.

Derivation and validation of a diagnostic test for irritable bowel syndrome using latent class analysis.

BACKGROUND: The accuracy of symptom-based diagnostic criteria for irritable bowel syndrome (IBS) is modest. AIMS: To derive and validate a new test that utilises latent class analysis. METHODS: Symptom, colonoscopy, and histology data were collected from 1981 patients and 360 patients in two cohorts referred to secondary care for investigation of their gastrointestinal symptoms in Canada and the UK, respectively. Latent class analysis was used to identify naturally occurring clusters in patient-reported symptoms in the Canadian dataset, and the latent class model derived from this was then applied to the UK dataset in order to validate it. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for the latent class models. RESULTS: In the Canadian cohort, the model had a sensitivity of 44.7% (95% CI 40.0-50.0) and a specificity of 85.3% (95% CI 83.4-87.0). Positive and negative LRs were 3.03 (95% CI 2.57-3.56) and 0.65 (95% CI 0.59-0.71) respectively. A maximum positive LR of 3.93 was achieved following construction of a receiver operating characteristic curve. The performance in the UK cohort was similar, with a sensitivity and specificity of 52.5% (95% CI 42.2-62.7) and 84.3% (95% CI 79.3-88.6), respectively. Positive and negative LRs were 3.35 (95% CI 2.38-4.70) and 0.56 (95% CI 0.45-0.68), respectively, with a maximum positive LR of 4.15. CONCLUSIONS: A diagnostic test for IBS, utilising patient-reported symptoms incorporated into a latent class model, performs as accurately as symptom-based criteria. It has potential for improvement via addition of clinical markers, such as coeliac serology and faecal calprotectin.

Poor predictive value of lower gastrointestinal alarm features in the diagnosis of colorectal cancer in 1981 patients in secondary care.

BACKGROUND: Clinicians are advised to refer patients with lower gastrointestinal (GI) alarm features for urgent colonoscopy to exclude colorectal cancer (CRC). However, the utility of alarm features is debated. AIM: To assess whether performance of alarm features is improved by using a symptom frequency threshold to trigger referral, or by combining them into composite variables, including minimum age thresholds, as recommended by the National Institute for Health and Care Excellence (NICE). METHODS: We collected data prospectively from 1981 consecutive adults with lower GI symptoms. Assessors were blinded to symptom status. The reference standard to define CRC was histopathological confirmation of adenocarcinoma in biopsy specimens from a malignant-looking colorectal lesion. Controls were patients without CRC. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values were calculated for individual alarm features, as well as combinations of these. RESULTS: In identifying 47 (2.4%) patients with CRC, individual alarm features had sensitivities ranging from 11.1% (family history of CRC) to 66.0% (loose stools), and specificities from 30.5% (loose stools) to 75.6% (family history of CRC). Using higher symptom frequency thresholds improved specificity, but to the detriment of sensitivity. NICE referral criteria also had higher specificities and lower sensitivity, with PPVs above 4.8%. More than 80% of those with CRC met at least one of the NICE referral criteria. CONCLUSIONS: Using higher symptom frequency thresholds for alarm features improved specificity, but sensitivity was low. NICE referral criteria had PPVs above 4.8%, but sensitivities ranged from 2.2% to 32.6%, meaning many cancers would be missed.

Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

An index with improved diagnostic accuracy for the diagnosis of Crohn's disease derived from the Lennard-Jones criteria.

BACKGROUND: The Lennard-Jones criteria are considered the gold standard for diagnosing Crohn's disease (CD) and include the items granuloma, macroscopic discontinuity, transmural inflammation, fibrosis, lymphoid aggregates and discontinuous inflammation on histology. The criteria have never been subjected to a formal validation process. AIM: To develop a validated and improved diagnostic index based on the items of Lennard-Jones criteria. METHODS: Included were 328 adult patients with long-standing CD (median disease duration 10 years) from three centres and classified as 'established', 'probable' or 'non-CD' by Lennard-Jones criteria at time of diagnosis. Controls were patients with ulcerative colitis (n = 170). The performance of each of the six diagnostic items of Lennard-Jones criteria was modelled by logistic regression and a new index based on stepwise backward selection and cut-offs was developed. The diagnostic value of the new index was analysed by comparing sensitivity, specificity and accuracy vs. Lennard-Jones criteria. RESULTS: By Lennard-Jones criteria 49% (n = 162) of CD patients would have been diagnosed as 'non-CD' at time of diagnosis (sensitivity/specificity/accuracy, 'established' CD: 0.34/0.99/0.67; 'probable' CD: 0.51/0.95/0.73). A new index was derived from granuloma, fibrosis, transmural inflammation and macroscopic discontinuity, but excluded lymphoid aggregates and discontinuous inflammation on histology. Our index provided improved diagnostic accuracy for 'established' and 'probable' CD (sensitivity/specificity/accuracy, 'established' CD: 0.45/1/0.72; 'probable' CD: 0.8/0.85/0.82), including the subgroup isolated colonic CD ('probable' CD, new index: 0.73/0.85/0.79; Lennard-Jones criteria: 0.43/0.95/0.69). CONCLUSION: We developed an index based on items of Lennard-Jones criteria providing improved diagnostic accuracy for the differential diagnosis between CD and UC.

Diagnosis and management of non-erosive reflux disease--the Vevey NERD Consensus Group.

BACKGROUND/AIMS: Although considerable information exists regarding gastroesophageal reflux disease with erosions, much less is known of non-erosive reflux disease (NERD), the dominant form of reflux disease in the developed world. METHODS: An expert international group using the modified Delphi technique examined the quality of evidence and established levels of agreement relating to different aspects of NERD. Discussion focused on clinical presentation, assessment of clinical outcome, pathobiological mechanisms, and clinical strategies for diagnosis and management. RESULTS: Consensus was reached on 85 specific statements. NERD was defined as a condition with reflux symptoms in the absence of mucosal lesions or breaks detected by conventional endoscopy, and without prior effective acid-suppressive therapy. Evidence supporting this diagnosis included: responsiveness to acid suppression therapy, abnormal reflux monitoring or the identification of specific novel endoscopic and histological findings. Functional heartburn was considered a separate entity not related to acid reflux. Proton pump inhibitors are the definitive therapy for NERD, with efficacy best evaluated by validated quality-of-life instruments. Adjunctive antacids or H(2) receptor antagonists are ineffective, surgery seldom indicated. CONCLUSIONS: Little is known of the pathobiology of NERD. Further elucidation of the mechanisms of mucosal and visceral hypersensitivity is required to improve NERD management.

Meta-analysis: yield of diagnostic tests for coeliac disease in dyspepsia.

BACKGROUND: The prevalence of coeliac disease (CD) may be increased in individuals with dyspepsia, but evidence is conflicting. AIMS: To conduct a systematic review and meta-analysis of studies reporting prevalence of CD in dyspepsia. METHODS: MEDLINE, EMBASE, and CINAHL were searched up to February 2009. Case series and case-control studies applying serological tests and/or distal duodenal biopsy for CD to unselected adults with dyspepsia were eligible. Prevalence of positive coeliac serology and biopsy-proven CD were pooled for all studies and compared between cases and controls using an odds ratio (OR) and 95% confidence interval (CI). RESULTS: Fifteen studies were identified. Prevalence of positive coeliac serology was higher in cases with dyspepsia (7.9%) compared with controls (3.9%), but not significantly so (OR for positive endomysial antibodies or tissue transglutaminase 1.89; 95% CI 0.90-3.99). Prevalence of biopsy-proven CD following positive serology was also higher (3.2% in cases vs. 1.3% in controls), but again this was not statistically significant (OR 2.85; 95% CI 0.60-13.38). Prevalence of biopsy-proven CD was 1% in ten studies performing duodenal biopsy first-line. CONCLUSION: Prevalence of biopsy-proven CD in subjects with dyspepsia was 1% and was higher than in controls, although this difference was not statistically significant.

Diagnostic utility of alarm features for colorectal cancer: systematic review and meta-analysis.

OBJECTIVE: Colorectal cancer is the second most common cause of cancer death in Europe and North America. Alarm features are used to prioritize access to urgent investigation, but there is little information concerning their utility in the diagnosis of colorectal cancer. METHODS: A systematic review and meta-analysis of the published literature was carried out to assess the diagnostic accuracy of alarm features in predicting colorectal cancer. Primary or secondary care-based studies in unselected cohorts of adult patients with lower gastrointestinal symptoms were identified by searching MEDLINE, EMBASE and CINAHL (up to October 2007). The main outcome measures were accuracy of alarm features or statistical models in predicting the presence of colorectal cancer after investigation. Data were pooled to estimate sensitivity, specificity, and positive and negative likelihood ratios. The quality of the included studies was assessed according to predefined criteria. RESULTS: Of 11 169 studies identified, 205 were retrieved for evaluation. Fifteen studies were eligible for inclusion, evaluating 19 443 patients, with a pooled prevalence of colorectal carcinoma of 6% (95% CI 5% to 8%). Pooled sensitivity of alarm features was poor (5% to 64%) but specificity was >95% for dark red rectal bleeding and abdominal mass, suggesting that the presence of either rules the diagnosis of colorectal cancer in. Statistical models had a sensitivity of 90%, but poor specificity. CONCLUSIONS: Most alarm features had poor sensitivity and specificity for the diagnosis of colorectal carcinoma, whilst statistical models performed better in terms of sensitivity. Future studies should examine the utility of dark red rectal bleeding and abdominal mass, and concentrate on maximising specificity when validating statistical models.

Meta-analysis: Helicobacter pylori'test and treat' compared with empirical acid suppression for managing dyspepsia.

BACKGROUND: Which of Helicobacter pylori'test and treat' or empirical acid suppression should be preferred for the initial management of uncomplicated dyspepsia is controversial. Aim To conduct an individual patient data meta-analysis of randomized controlled trials (RCTs) of 'test and treat' vs. empirical acid suppression in adults with uncomplicated dyspepsia in primary care. METHODS: Investigators provided original data sets for analysis. Effect of management strategy on symptom status and dyspepsia-related resource use at 12-month follow-up was examined by pooling symptom and cost data to obtain relative risk (RR) of remaining symptomatic at 12 months and weighted mean difference (WMD) in costs between the two strategies with 95% confidence intervals (CI). RESULTS: We identified three eligible RCTs containing 1547 patients, 791 (51%) of whom were assigned to 'test and treat'. There was no difference detected in symptom-cure at 12 months (RR = 0.99; 95% CI: 0.95-1.03). There was a nonsignificant trend towards cost-savings with 'test and treat' (WMD in costs = - 28.91 pound; 95% CI: - 68.48 pound to 10.65 pound). CONCLUSIONS: There was little difference in symptom-resolution or costs between the two strategies. A combination of patient and physician preference should determine the initial approach to the management of uncomplicated dyspepsia.

Mortality rates in patients with Barrett's oesophagus.

BACKGROUND: Patients with Barrett's oesophagus are at increased risk of oesophageal adenocarcinoma. Observational studies have suggested increase in overall mortality also but data are conflicting. AIM: To assess the cause of death in patients with Barrett's oesophagus compared with the general population. METHODS: Patients with Barrett's oesophagus were identified retrospectively in four hospitals in Leicestershire, UK using electronic endoscopy and histopathology records from 1997 to 2003. Data on deaths from this cohort of patients were identified through the Office of National Statistics and compared with age- and gender-adjusted mortality in the Leicestershire region. RESULT: In all, 1272 Barrett's patients were identified with 245 deaths in this cohort. Overall mortality was found to be increased [male standardized mortality ratio (SMR) = 552, 95% CI = 466-638; female SMR 455, 95% CI = 357-552]. The main disease areas that were responsible for this increase were oesophageal adenocarcinoma (n = 25, male SMR = 2171, 95% CI = 991-3351; female SMR = 1300, 95% CI = 26-2574), bronchopneumonia (n = 70, male SMR = 146, 95% CI = 55-236; female SMR = 436, 95% CI = 272-601) and ischaemic heart disease (n = 51, male SMR = 186, 95% CI = 97-2748; female SMR = 205, 95% CI = 105-306). CONCLUSIONS: Patients with Barrett's oesophagus die more commonly of bronchopneumonia and ischaemic heart disease compared with oesophageal adenocarcinoma, and overall mortality in this group may be increased.

Who provides gastrointestinal endoscopy in Canada?

PURPOSE: To determine who provides gastrointestinal endoscopy in Canada and to understand provincial and regional differences in endoscopy providers. METHODS: Aggregate physician sociodemographic and activity data for 2002 were obtained from the Canadian Institute of Health Information's National Physician Database. Physicians were classified as gastroenterologists, general surgeons and others. RESULTS: In 2002, 1444 physicians, including 735 surgeons, 551 gastroenterologists and 158 others, performed at least 100 colonoscopies or 100 gastroscopies. Gastroenterologists performed 53% of all colonoscopies and 59% of all gastroscopies. Gastroenterologists were the primary providers of colonoscopies in large urban areas, whereas surgeons were the primary providers in smaller urban and rural areas. An average of 317 colonoscopies were performed by surgeons, 516 by gastroenterologists and 203 by other physicians. The proportion of surgeon colonoscopists in each province ranged from 47% to 71%. CONCLUSIONS: Surgeons and gastroenterologists are the major providers of gastrointestinal endoscopy in Canada, but the distribution of these providers among provinces and urban and rural areas varies. Although surgeon endoscopists are more numerous, on average, they perform fewer procedures annually than internists.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

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.

Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding.

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.

Cough in the community: a cross sectional survey and the relationship to gastrointestinal symptoms.

BACKGROUND: The prevalence and severity of chronic cough in the community is uncertain. In a large population of representative normal subjects, we explored the relationship between self-reported cough severity and frequency, and factors known to be related to the aetiology of chronic cough. In particular, we have examined the relative association between cough and symptoms of gastrointestinal disease. METHODS: A cross-sectional survey was undertaken in 36 general practices with subjects randomly selected from practice computer databases. Baseline lifestyle and demographic characteristics were recorded. Participants were asked how often in the previous 2 months they had experienced bouts or spasms of coughing. Cough symptom status was dichotomised into symptomatic using a cut off of bouts or spasms of coughing at a frequency of between once a week and once a day or above. Gastrointestinal data were collected using validated methodology. RESULTS: Questionnaires were sent to 6416 subjects and 4003 (62%) responded. The prevalence of chronic cough was 12%, and was severe in 7%. Following multivariate analysis, regurgitation (OR 1.71; 99% CI 1.20 to 2.45) and irritable bowel syndrome (OR 2.00; 99% CI 1.47 to 2.72) were strong predictors of cough. Smoking (OR 1.61; 99% CI 1.18 to 2.19), declining social class (OR 1.63; 99% CI 1.04 to 2.57), and quality of life at baseline (OR 1.63; 99% CI 1.13 to 2.35) were also significantly associated. CONCLUSION: Chronic cough is a common symptom in the general population. Its strong association with gastrointestinal disease may have aetiological significance.

Initial management strategies for dyspepsia.

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

Gastro-oesophageal reflux is more prevalent in Western dyspeptics: a prospective comparison of British and South-East Asian patients with dyspepsia.

BACKGROUND: There is a paucity of data directly comparing dyspepsia in Western and Eastern populations. AIM: To compare clinical symptoms, epidemiological factors and endoscopic diagnoses in two sample populations with dyspepsia from the United Kingdom and South-East Asia in a cross-sectional study. METHODS: Patients with uncomplicated dyspepsia attending endoscopy units in Leeds, UK, and Kuala Lumpur, Malaysia, were prospectively interviewed and underwent subsequent endoscopy. RESULTS: A total of 1003 Malaysian patients (January 2002 to August 2003) and 597 Caucasian British patients (January 2000 to October 2002) were studied. The mean age was 48.7 +/- 15.8 and 47.5 +/- 13.8 years for the Malaysian and British patients respectively (P = NS). There was a higher proportion of cigarette smoking (35.7% vs. 12.4%, P < 0.0001) and alcohol consumption (34.4% vs. 2.0%, P < 0.0001) amongst British patients, but no difference in non-steroidal anti-inflammatory drug use nor having Helicobacter pylori infection. Gastro-oesophageal reflux disease (GERD) symptoms were more common in British compared with South-East Asian patients [heartburn (72% vs. 41%), regurgitation (66% vs. 29.8%) and dysphagia (21.1% vs. 7.3%), P < 0.0001]. This correlated with an increased endoscopic finding of oesophagitis (26.8% vs. 5.8%) and columnar-lined oesophagus (4.4% vs. 0.9%) amongst British patients (P < 0.001). A logistic regression model revealed that British Caucasian race (OR 9.7; 95% CI = 5.0-18.8), male gender (OR 2.0; 95% CI = 1.4-2.9) and not having H. pylori infection (OR 0.5; 95% CI = 0.3-0.7) were independent predictors for oesophagitis. CONCLUSION: GERD is more common in British compared with South-East Asian dyspeptic patients suggesting that race and/or western lifestyle are important risk factors.

Managing dyspepsia without alarm signs in primary care: new national guidance for England and Wales.

AIM: To report new recommendations for the primary care management of dyspepsia without alarm signs in England and Wales. METHOD: An independent, representative group of health care professionals, patient representatives and researchers developed the guideline using evidence-based and small group-working principles, and incorporated extensive peer-reviewing and feedback from stakeholder organizations. RESULTS: Referral to investigate dyspepsia should be made for alarm signs and not on the basis of age alone, reflecting the balance of benefit and harm from endoscopy. Empirical management without formal diagnosis is appropriate for most patients: reviewing patient history, lifestyle, over-the-counter medicines, and providing a course of proton-pump inhibitors and/or Helicobacter pylori test and treatment. Patients with ongoing symptoms require at least annual review to discuss symptoms and lifestyle, and as appropriate, encourage stepping down prescribed medication and returning to self-care. A new strategy included in the step down process is the use of therapies 'on-demand'. CONCLUSION: The guideline provides structured and supported recommendations for both undiagnosed and endoscopically investigated dyspepsia. Some favour increased investigation to detect Barrett's oesophagus and carcinoma. However, there is inconclusive evidence that patients without alarm signs will benefit subsequently from endoscopy, while investigation involves a small but real risk of harm.

Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease.

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