A randomized, double-blind, placebo-controlled trial of CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, in patients with corticosteroid-dependent Crohn's disease.

AIM: To evaluate CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for the treatment of corticosteroid-dependent Crohn's disease. METHODS: Patients with corticosteroid-dependent Crohn's disease (use of prednisolone 15-40 mg/day or budesonide 9 mg/day for at least 8 weeks, a previous failed attempt to discontinue corticosteroids within 8 weeks, and Crohn's Disease Activity Index score 150 points or less) were enrolled in a 16-week, randomized, double-blind, placebo-controlled trial. The patients received intravenous CDP571 (20 mg/kg at week 0 and 10 mg/kg at week 8) or placebo. Corticosteroid therapy was decreased following a predefined schedule. The primary efficacy end-point was the percentage of patients with corticosteroid-sparing [i.e. no disease flare (Crohn's Disease Activity Index score > or =220 points) and no longer requiring corticosteroid therapy] at week 10. The major secondary efficacy end-point was corticosteroid-sparing at week 16. RESULTS: Seventy-one patients received treatment. Corticosteroid-sparing was achieved by 19 of 39 (48.7%) CDP571 patients and 13 of 42 (40.6%) placebo patients (P = 0.452) at week 10, and by 18 of 39 (46.2%) CDP571 patients and seven of 32 (21.9%) placebo patients (P = 0.032) at week 16. CDP571 therapy was well-tolerated and the incidence of serious adverse events was similar to placebo. CONCLUSIONS: The CDP571 was effective for corticosteroid-sparing at week 16 but not week 10, and was well-tolerated in patients with corticosteroid-dependent Crohn's disease.

Gastrointestinal tissue cultures for HIV in HIV-infected/AIDS patients. The University of Calgary Gastrointestinal/HIV Study Group.

OBJECTIVE: To determine the prevalence of HIV in endoscopic biopsies from the esophagus, stomach, duodenum, and rectum of homosexual and bisexual men at various stages of HIV infection as part of a comprehensive study of gastrointestinal dysfunction in HIV infection. METHODS: After repeated washings and mechanical disruption, biopsies obtained from 58 volunteers were individually cocultured with pooled peripheral blood lymphocytes from healthy HIV-seronegative blood donors. RESULTS: HIV was isolated from at least one site in 40 out of 49 patients. Esophageal biopsies were most frequently found positive (46%), followed by duodenal biopsies (44%), rectal biopsies (43%), and gastric biopsies (27%). Recovery of HIV was not related to any gastrointestinal signs or symptoms. HIV was recovered in the biopsies both from asymptomatic patients with CD4 lymphocyte counts greater than 500 x 10(6)/l and also from patients with more advanced disease receiving zidovudine therapy. CONCLUSIONS: The entire gastrointestinal tract appears to be a target site throughout the course of HIV infection in homosexual and bisexual men.

Nutritional status and food intake in human immunodeficiency virus infection. GI/HIV Study Group.

Nutritional status and food intake of HIV+ and HIV- homosexual men that were free from enteric pathogens were compared. Food intake (7-day weighed record), anthropometry, and D-xylose excretion were measured in 44 patients (9 HIV-, 35 HIV+). HIV+ patients were found to be thinner, based on anthropometric measurements of skinfold thickness (p < 0.05) and percentage body fat (p < 0.05), and they also tended to be lighter than the HIV- patients. No differences were observed in the arm muscle mass or the food intake of the two groups. In the HIV+ patients, regression analysis was used to correlate changes in nutritional status with progression of the disease, using CD4+ lymphocyte count as a measure of severity. A decrease in CD4 count positively correlated with a decrease in weight (r = 0.48, p < 0.01), body mass index (r = 0.41, p < 0.05), and arm muscle area (r = 0.42, p < 0.01). Energy intake (r = 0.67, p < 0.01), serum albumin (r = 0.52, p < 0.01), and D-xylose excretion (r = 0.57, p < 0.0001) also positively correlated with CD4 count. Multiple regression analysis revealed a relationship between CD4 count, weight, and energy intake, indicating that as the disease progresses, a decline in weight is seen parallel to a reduction in food intake. These data indicate that changes in body composition and nutritional status are present throughout the stages of HIV disease, though no causal relationships can be interpreted from this study. The initial changes appear to be due to loss of fat stores, as determined by anthropometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of relapse of Crohn's disease.

Until a cure for Crohn's disease(s) is found, strategies that prolong the time spent in remission offer the greatest hope for reducing the morbidity and significant social costs associated with the disease. Medical therapy to date has been disappointing, and the search for a safe, effective therapy that could be offered at low cost continues. The aminosalicylates, so effective in ulcerative colitis, have shown, at best, minimal efficacy in maintaining remission in Crohn's disease. Conventional corticosteroids are not effective, and any reduction in time to relapse for budesonide-treated patients is measured in weeks not months. Azathioprine, 6-mercaptopurine, and methotrexate are effective in maintaining remission, but all three have significant side effects. Antibiotics may have a role to play. Biological therapy may be considered, but the issues of cost and long-term safety require evaluation. Future studies should segregate patients into two groups, those with a medically induced remission and patients whose concern is the prevention of postoperative recurrence.

Appraising the trial literature: checking randomization, controls, and blinding.

: The three essentials of any trial that has the potential to alter the practice of medicine are randomization, inclusion of a control, and the highest possible level of blinding. Spending a few moments reading the Methods Section will often provide information sufficient for the reader to perform a critical appraisal of the results of the clinical trial. A variety of factors encourage a positive result in any clinical trial. Randomization techniques produce uncertainty and should be viewed as techniques to prevent either patient or physician from acquiring advance knowledge as to which treatment assignment or allocation is about to occur. The control treatment is the drug, device, test, or procedure administered in a clinical trial that serves as the standard against which the test treatments are evaluated. Technically controls may be classified according to their place in time or the type of intervention offered. Blinding may occur at several levels. When reviewing a trial, the reader should discern whether blinding was achieved to the highest degree possible. Assuring onesself that the trial is of high standard is the first step towards implementing a change in the pattern of one's practice.

Alternatives to Sulfasalazine: A Meta-analysis of 5-ASA in the Treatment of Ulcerative Colitis.

SUMMARY: : The purpose of this study was to assess the efficacy and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared with placebo or sulfasalazine (SASP) for the treatment of active disease and the maintenance of remission in ulcerative colitis. A computer-assisted literature search for relevant studies (1981-1996) was performed using MEDLINE, BIOS, and Science Citation Index, followed by a manual search of reference lists from previously retrieved articles, review articles, symposia proceedings, and abstracts from major gastrointestinal conferences. Studies were accepted for analysis if they were randomized, double-blinded, and controlled clinical trials of parallel design, with treatment durations of a minimum of 4 weeks for the treatment of active disease (19 studies), and a minimum of 6 months for maintenance therapy (16 studies). Based on an intention-to-treat principle, the outcomes of interest in the treatment of active disease were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, or endoscopic improvement. For maintenance therapy, the primary measured outcome was the failure to maintain clinical or endoscopic remission. In active disease, 5-ASA was superior to placebo with regard to all measured outcome variables. For the failure to induce global/clinical improvement or remission, the pooled odds ratio was 0.39 [95% confidence interval (CI), 0.29-0.52]. A dose-response trend for 5-ASA was also observed. When 5-ASA was compared with SASP in active disease, the pooled odds ratio was 0.87 (CI, 0.63-1.20) for the failure to induce global/clinical improvement or remission, and 0.66 (CI, 0.42-1.04) for the failure to induce endoscopic improvement. In maintenance therapy, the pooled odds ratio for the failure to maintain clinical or endoscopic remission (withdrawals and relapses) for 5-ASA versus placebo was 0.48 (CI, 0.35-0.65) and versus SASP, 1.29 (CI, 1.06-1.57) at 6 months and 1.15 (0.89-1.50) at 12 months. SASP was not as well tolerated as 5-ASA in active disease despite their relatively similar tolerabilities in maintenance therapy. The newer 5-ASA preparations were superior to placebo for both active disease and maintenance of remission. In a patient population selected for tolerance to SASP, there is insufficient evidence to confirm their benefit over SASP for either active or maintenance therapy.

Intestinal permeability and postheparin plasma diamine oxidase activity in the prediction of Crohn's disease relapse.

A method of detecting presymptomatic relapse of Crohn's disease could allow for the selective use of maintenance or intensified medical therapy in those with an increased risk of relapse. The aim of this study was to evaluate three potential laboratory markers of relapse: intestinal and gastroduodenal permeability and plasma diamine oxidase activity. Intestinal permeability (lactulose/mannitol test), gastroduodenal permeability (urinary sucrose excretion), and postheparin plasma diamine oxidase activity were serially measured in 61 adults with Crohn's disease in remission (CDAI <150) for at least 30 days. Subjects were followed periodically for clinical relapse (CDAI >150 and increased by at least 100 points or the need for steroids or surgery). Fourteen patients (23%) relapsed. A cut-off of 0.030 for the lactulose/mannitol ratio was defined. Those with ratios above the cutoff had a 7.0 times greater risk of relapse (p<0.001). Three subjects who went from a normal ratio to an abnormal ratio relapsed, whereas none of 32 subjects with a repeatedly normal ratio relapsed. Sucrose excretion and plasma diamine oxidase activity did not predict relapse. Serial testing of intestinal permeability, but not of gastroduodenal permeability or plasma diamine oxidase activity, was useful in predicting relapse in asymptomatic patients.

Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.

A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998.

Crohn's disease is a heterogeneous entity. Previous attempts of classification have been based primarily on anatomic location and behavior of disease. However, no uniform definition of patient subgroups has yet achieved broad acceptance. The aim of this international Working Party was to develop a simple classification of Crohn's disease based on objective variables. Eight outcome-related variables relevant to Crohn's disease were identified and stepwise evaluated in 413 consecutive cases, a database survey, and by clinical considerations. Allocation of variables was conducted with well-defined Crohn's disease populations from Europe and North America. Cross-table analyses were performed by chi-square testing. Three variables were finally elected: Age at Diagnosis [below 40 years (A1), equal to or above 40 years (A2)], Location [terminal ileum (L1), colon (L2), ileocolon (L3), upper gastrointestinal (L4)], and Behavior [nonstricturing nonpenetrating (B1), stricturing (B2), penetrating (B3)]. The allocation of patients to these 24 subgroups proved feasible and resulted in specific disease clusters. Cross-table analyses revealed associations between Age at Diagnosis and Location, and between Behavior and Location (all p < 0.001). The Vienna classification of Crohn's disease provides distinct definitions to categorize Crohn's patients into 24 subgroups. Operational guidelines should be used for the characterization of patients in clinical trials as well as for correlation of particular phenotypes with putative biologic markers or environmental factors.

Review article: treatment of Clostridium difficile infection.

AIM: A systematic review of controlled trials of therapy of Clostridium difficile intestinal infection using methodology described by the Cochrane Collaboration. METHODS: Trials were identified by searching computer databases over the years 1978-1996. Trials were included if they were (a) prospective randomized, controlled trials and (b) included patients with symptomatic disease. The primary end-point was clinical resolution of diarrhoea. Secondary end-points were clinical relapse and stool clearance of C. difficile and C. difficile toxin. RESULTS: Nine trials (469 patients) satisfying the inclusion criteria were identified. Two trials were placebo controlled. Six trials compared vancomycin to other antibiotics (fusidic acid, bacitracin, teicoplanin and metronidazole). For clinical resolution response rates ranged from 21 (placebo) to 100% (vancomycin). On pooling the trials, no antibiotic showed clear therapeutic superiority. Rates of clinical relapse ranged from 5 to 42%. Only one trial showed significant advantage of one antibiotic over another for prevention of relapse (teicoplanin vs. fusidic acid). CONCLUSION: The published data are limited, and further studies are required.

Efficacy of bile acid therapy for gallstone dissolution: a meta-analysis of randomized trials.

To define better the efficacy of bile acid therapy for dissolution of radiolucent gallstones, we performed a meta-analysis of published trials from January 1966 to September 1992. Studies were identified using a MEDLINE computer search followed by an extensive manual search. The inclusion criteria used were: randomized trial, radiolucent gallstones in a visualizing gallbladder on oral cholecystography, and complete stone dissolution confirmed by oral cholecystography or ultrasound. Study results were pooled into 6 groups: placebo: high- and low-dose chenodeoxycholic acid (CDCA) (> or = 10 mg.kg/day and < 10 mg.kg/day); high- and low-dose ursodeoxycholic acid (UDCA) (> or = 7 mg.kg/day and < 7 mg.kg/day) and combined CDCA plus UDCA. Homogeneity calculations were performed and the percentage of complete stone dissolution calculated for each group with 95% confidence intervals. Of 66 trials identified, 23 comprising 1949 patients met the inclusion criteria. A total of 1062 patients were treated with CDCA, 819 with UDCA and 78 combination therapy. In studies > 6 months' duration, high-dose UDCA completely dissolved stones in 37.3% of patients (95% C.I. 33-42%), low-dose UDCA in 20.6%) and high-dose CDCA 18.2% (95% C.I. 15-21%). Based on only two studies, combination therapy achieved dissolution in 62.8% (95% C.I. 51-74%) of patients. Stones less than 10 mm dissolved significantly more frequently than stones larger than 10 mm. This analysis shows that UDCA in doses greater than 7 mg.kg/day taken for greater than 6 months will dissolve radiolucent gallstones in 38% of patients. The combination of UDCA and CDCA may be more efficacious but this observation is based upon only 78 patients and requires confirmation in further randomized trials.

Does medical antireflux therapy improve asthma in asthmatics with gastroesophageal reflux?: a critical review of the literature.

OBJECTIVE: Identify and critically review the peer-reviewed, English-language studies of the effects of medical antireflux therapy in asthmatics with gastroesophageal reflux (GER). DESIGN: Using the 1966 to 1996 MEDLINE database, asthma was combined with GER to identify all studies of the effects of medical antireflux therapy on asthma control. The articles' bibliographies were also reviewed. Studies were graded according to Sackett's criteria and grouped by levels of evidence. RESULTS: A total of 242 citations were found; 171 were published in English. Twelve studies of the effects of medical antireflux therapy on asthma control, with a total of 326 treated patients, were identified. Eight studies were placebo-controlled, three were open studies, and one used an untreated control. Eight studies treated 20 or fewer patients. Reflux symptoms either did not improve or the effects of antireflux therapy on them were not reported in four studies. The combined data from the controlled medical antireflux studies showed that: (1) asthma symptoms improved in 69% of the subjects; (2) asthma medication use was reduced in 62% of the subjects; (3) evening peak expiratory flow (PEF), but not PEF at other times, improved in 26% of the subjects; and (4) spirometry did not improve in any of the placebo-controlled antireflux studies. CONCLUSIONS: Analysis of the combined data suggests that medical antireflux therapy improves asthma symptoms, may reduce asthma medication use, but has minimal or no effect on lung function.

Topical treatment of ulcerative colitis.

It is clear that the therapeutic options available for the treatment of ulcerative proctosigmoiditis have increased over the last few years and in the future additional therapies will be available. Therapy will have to be individualized. Studies to date have generally failed to confirm the superiority of one form of treatment over another, although there is some evidence that high-dose 5-ASA enemas are superior to hydrocortisone enemas. Patients who fail to respond to one form of therapy may respond to another therapeutic modality. Continued evaluation of topical therapies provides not only an opportunity to improve the treatment prospects for patients but also allows for examination of potential mechanisms of action of therapeutically active compounds. Future research directions should also include assessment of combination therapy, the more widespread use of suppositories, and strategies to encourage patient compliance. Larger multicenter trials are needed to assess the effectiveness of some of the newer compounds. The role of topical therapy for patients with Crohn's disease confined to the left colon requires evaluation.

Determinants of abstract acceptance for the Digestive Diseases Week--a cross sectional study.

BACKGROUND: The Digestive Diseases Week (DDW) is the major meeting for presentation of research in gastroenterology. The acceptance of an abstract for presentation at this meeting is the most important determinant of subsequent full publication. We wished to examine the determinants of abstract acceptance for this meeting. METHODS: A cross-sectional study was performed, based on abstracts submitted to the DDW. All 17,205 abstracts submitted from 1992 to 1995 were reviewed for acceptance, country of origin and research type (controlled clinical trials (CCT), other clinical research (OCR), basic science (BSS)). A random sub-sample (n = 1,000) was further evaluated for formal abstract quality, statistical significance of study results and sample size. RESULTS: 326 CCT, 455 OCR and 219 BSS abstracts were evaluated in detail. Abstracts from N/W Europe (OR 0.4, 95% CI 0.3-0.6), S/E Europe (OR 0.4, 95% CI 0.2-0.6) and non-Western countries (OR 0.3, 95% CI 0.2-0.5) were less likely to be accepted than North-American contributions when controlling for research type. In addition, the OR for the acceptance for studies with negative results as compared to those with positive results was 0.4 (95% CI 0.3-0.7). A high abstract quality score was also weakly associated with acceptance rates (OR 1.4, 95% CI 1.0-2.0). CONCLUSIONS: North-American contributions and reports with statistically positive results have higher acceptance rates at the AGA. Formal abstract quality was also predictive for acceptance.

General practitioners' assessment of and interest in alternative medicine in Canada.

Canadian physicians' opinions about alternative medicine have, as yet, not been assessed. The objectives of this pilot study were to assess general practitioners': (1) desired involvement in alternative medicine; (2) perceived demand for alternative medicine; and (3) beliefs about the efficacy of different alternative approaches. The study design was a cross-sectional survey of 400 randomly selected Alberta and Ontario general practitioners. Of the 384 eligible physicians, 200 (52%) completed the questionnaire. Seventy-three percent of physicians felt that they should have some knowledge about the most important alternative treatments. However, with respect to other issues, physicians desired less involvement with alternative medicine. Sixty-five percent perceived a demand for alternative medicine from their patients, in particular chiropractic. Alternative medicine was perceived to be needed most for musculoskeletal problems and chronic pain or illness. Chiropractic, hypnosis and acupuncture (for chronic pain) were believed to be most efficacious, while homeopathy and reflexology were considered to be least efficacious. Undergraduate, graduate clinical and continuing medical education will need to address alternative treatments in order to provide physicians with up-to-date and relevant information.

Azathioprine for maintaining remission of Crohn's disease.

OBJECTIVES: To assess the effectiveness of azathioprine in maintaining remission of quiescent Crohn's disease. SEARCH STRATEGY: Pertinent studies were selected using the MEDLINE data base (1966 - May 1998), the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease Trials Register, as well as abstracts from major gastrointestinal research meetings and references from published articles and reviews. SELECTION CRITERIA: Five randomized, double-blind, placebo-controlled trials of azathioprine therapy were identified. Two of these trials consisted solely of patients with quiescent Crohn's disease. Three trials had multiple therapeutic arms for both induction of remission and maintenance of remission. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers (GRM, GF, LRS) based on the intention to treat principle. Peto odds ratios for the overall maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated, and from these, 95% confidence intervals were derived. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined. MAIN RESULTS: Azathioprine had a positive effect on maintaining remission. The Peto odds ratio for maintenance of remission was 2.16 (CI 1.35 - 3.47) with an NNT of 7. A higher dose improved response. A steroid sparing effect was noted, with a Peto odds ratio of 5.22 (CI 1.06 - 25.68) and NNT of 3 for quiescent disease. The Peto odds ratio for withdrawals due to adverse events was 4.36 (CI 1.63 - 11.67), the NNH (Number Needed to Harm) was 19. REVIEWER'S CONCLUSIONS: Azathioprine is effective in maintaining remission. There is evidence for a steroid sparing effect.

Maintenance therapy for inflammatory bowel disease: what really works.

The propensity of inflammatory bowel disease sufferers to experience recurrent episodes or disease flares is well documented. Until a cure can be found, strategies to lengthen the period of remission offer the greatest opportunity to reduce morbidity and enhance patient quality of life. Therapies that have been shown in randomized, controlled, double-blind clinical trials to either lengthen the time of remission or improve the odds of staying in remission during a set time interval are required.

Survey of current practices among members of CAG in the follow-up of patients diagnosed with gastric ulcer.

INTRODUCTION: Guidelines recommend a policy of endoscopic follow-up of all gastric ulcers until healing. Analysis of data from the Alberta Endoscopy Project indicates that fewer than 50% of patients diagnosed with benign gastric ulcer had undergone a repeat procedure. The practice and attitudes of physician members of the Canadian Association of Gastroenterology (CAG) on the follow-up of such patients were assessed. METHODS: A self-administered questionnaire was mailed to members of CAG. Respondents were asked to indicate their practice setting and to estimate the proportion of gastric ulcer patients in whom they perform follow-up endoscopy. They were also asked to indicate factors influencing this choice, including the role of Helicobacter pylori. RESULTS: Fifty-seven per cent of 220 respondents indicated that they perform repeat endoscopy in 95% to 100% of individuals with benign gastric ulcer. The most common reasons influencing this choice were to ensure healing (86.3%) and to confirm the benign nature of the lesion (79.5%). Nonsteroidal anti-inflammatory drug (NSAID) use (83.2%) and patient ill health (62.9%) were the most common reasons for not repeating the endoscopy. Twenty per cent of individuals indicated that H pylori had influenced a change in their practice. DISCUSSION: Physicians vary widely in their follow-up of benign gastric ulcer. Studies on the occurrence of gastric cancer in this setting are not unanimous in their conclusions. Subgroups of patients with NSAID exposure and successfully eradicated H pylori infection may have a lower risk of malignancy. Studies to confirm this are warranted, and modified guidelines may be appropriate.

Giant cell myocarditis, in a patient with Crohn's disease, treated with etanercept--a tumour necrosis factor-alpha antagonist.

Cardiac disease in association with inflammatory bowel disease (IBD) is uncommon. Reports include pericarditis, pericardial effusion, myocarditis, myocardial infarction, endocarditis and arrythmias. Myocardial inflammation related to IBD may be due to a drug hypersensitivity reaction or micronutrient deficiency, or may be secondary to the underlying IBD as an extraintestinal manifestation. In this setting, myocarditis usually presents as congestive heart failure and/or refractory arrhythmia. Prognosis varies among reported cases, including complete recovery, remission with recurrence and fatal disease. Treatment of myocarditis has included aminosalicylates and immunosuppressive medications. Recently, newer therapies for IBD have been developed, such as tumour necrosis factor-alpha (TNF-a) antagonists. The present report describes a case of a 46-year-old man with clinical and endoscopic evidence of moderately active colonic Crohn's disease who developed congestive heart failure due to giant cell myocarditis. Little clinical improvement occurred with immunosuppressive therapy. Only after the addition of etanercept, a TNF-a p75 receptor antagonist, did complete clinical resolution occur. These authors conclude that the use of TNF-a antagonists may be considered in the treatment of life-threatening extraintestinal manifestations of inflammatory bowel disease.

Endoscopists' opinions of indications for upper gastrointestinal endoscopy.

OBJECTIVE: To determine whether endoscopists and general internists agreed with the characterization of appropriateness for endoscopy of various clinical scenarios, as previously reported by the RAND Corporation. DESIGN: Mail survey. STUDY SAMPLE: All endoscopists in western Canada and a random sample of general internists who did not perform endoscopy. METHODS: Questionnaires were sent to 179 endoscopists in western Canada who were asked to rate the 53 scenarios for endoscopy on a nine-point scale ranging from most appropriate to most inappropriate. A similar questionnaire was sent to 39 general internists practising in the province of Alberta. RESULTS: Response rate was 72% of endoscopists (n = 128) and 64% of general internists (n = 25). Among the endoscopists, there was agreement with the RAND classification for 32 scenarios. All 18 indications previously thought to be appropriate were considered to be appropriate. However, endoscopists agreed with only six of 16 equivocal and eight of 19 indications considered inappropriate. Discrepancies were reviewed by five experienced endoscopists and most appeared to be related to a concern regarding possible malignancy linked in part with the definition of failure to respond to medical therapy; and to a refusal to request a barium meal before endoscopy. Among general internists, there was agreement with RAND in 26 scenarios. When the appropriateness rankings of endoscopists and general internists were compared, there was agreement in 40 of 53 scenarios. Significant discrepancies in ratings were identified in scenarios in which barium studies were described as being normal, known or not done. CONCLUSIONS: The equivocal and inappropriate ratings developed by the RAND Corporation are not uniformly accepted by the endoscopy community or general internists. Use of the RAND indications for assessing quality assurance can be challenged.