Terry Ponich

Omega-3 Free Fatty Acids for the Maintenance of Remission in Crohn Disease: The EPIC Randomized Controlled Trials

CONTEXT Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority. OBJECTIVE To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease. DESIGN, SETTING, AND PATIENTS Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohns Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively. INTERVENTIONS Patients with a Crohns Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted. MAIN OUTCOME MEASURE Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease. RESULTS For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease. CONCLUSION In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease. TRIAL REGISTRATION clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.

Vedolizumab for the treatment of active ulcerative colitis: A randomized controlled phase 2 dose‐ranging study

Background: Vedolizumab is a gut‐selective biologic that has shown efficacy in ulcerative colitis (UC) and Crohns disease (CD). We studied the pharmacokinetics, pharmacodynamics, safety, tolerability, and efficacy of a new formulation of vedolizumab produced by an improved manufacturing process. Methods: UC patients were randomized to receive vedolizumab (2, 6, or 10 mg/kg) or placebo on days 1, 15, 29, and 85. Safety, pharmacokinetics, pharmacodynamics, and immunogenicity evaluations were performed at multiple timepoints through day 253. Partial Mayo Scores and fecal calprotectin levels were used to assess efficacy. Results: In all, 46 patients (9 placebo, 37 vedolizumab) received at least one dose of study medication. The vedolizumab serum concentration declined monoexponentially until concentrations reached 1–10 &mgr;g/mL, and then fell nonlinearly. Vedolizumab maximum serum concentration (Cmax) and area under the curve (AUC) increased approximately proportionally as a function of dose. Vedolizumab maximally saturated &agr;4&bgr;7 receptors on peripheral serum lymphocytes at all measurable serum concentrations. Vedolizumab was well tolerated, with no deaths and no adverse events leading to discontinuation. At every assessment from day 29 through day 253, over 50% of vedolizumab‐treated patients were in clinical response, while placebo response rates generally ranged between 22% and 33%. Vedolizumab treatment reduced fecal calprotectin levels compared with placebo. Conclusions: Vedolizumab demonstrated dose‐proportional pharmacokinetics and maximally saturated &agr;4&bgr;7 receptors over the tested dose range. Multiple dosing up to 10 mg/kg was well tolerated. Over the course of follow‐up a greater proportion of patients treated with vedolizumab were in clinical response than those who were assigned to placebo. (Inflamm Bowel Dis 2012)

Canadian credentialing guidelines for colonoscopy

A series of credentialing guidelines for gastrointestinal endoscopic procedures performed in the management of adult patients has been developed by the Canadian Association of Gastroenterology (CAG) Endoscopy Committee, approved by the Clinical Affairs Committee, and reviewed and endorsed by the Executive Board. In the present article, the CAG suggests specific guidelines for credentialing colonoscopy. It is intended to be read in conjunction with the introductory article that outlines the principles of credentialing (1). Dr Joseph Romagnuolo The CAG does not credential individuals for colonoscopy; that is the responsibility of the endoscopist’s local institution or facility. The purpose of these guidelines is to provide a framework that will allow organizations to assess the training and competence of applicants to perform colonoscopy as part of the credentialing process for the granting of privileges. Colonoscopy is performed to visualize the colonic mucosa, and can be both a diagnostic and therapeutic procedure; it requires the passage of a specialized endoscope – a colonoscope – via the anus or a colostomy to the cecum and, in some cases, to the terminal ileum. The purpose of the procedure is to document any abnormalities, to take biopsies and perform photographic documentation when appropriate, to remove polyps, or to perform therapy such as stricture dilation or hemostasis, if necessary, while minimizing procedure-related risks such as excessive sedation, cardiorespiratory compromise, bleeding and colonic perforation.

Should ERCP be routine after an episode of idiopathic pancreatitis ? A cost-utility analysis

BACKGROUND Patients often recover from an episode of acute pancreatitis with conservative therapy and without an identified cause. The options include proceeding with ERCP to identify and treat an occult common bile duct stone or performing the procedure only after a second episode of idiopathic pancreatitis occurs. METHODS Decision analysis (SMLTREE software) was used to determine incremental cost-utility. Variables were estimated from a search of the literature, a utility analysis involving health professionals familiar with the question, and a retrospective review of hospital charts and costs. RESULTS This model estimates an incremental utility gain for the prompt ERCP approach of 1.0 quality-adjusted life weeks per patient at an incremental cost of

Diaphragm-like strictures of the right colon induced by indomethacin suppositories : evidence of a systemic effect

245 (Canadian). This yields a cost-utility ratio of

Bismuth-based quadruple therapy with bismuth subcitrate, metronidazole, tetracycline and omeprazole in the eradication of Helicobacter pylori.

12,740 (Canadian) per quality-adjusted life year. The result was highly sensitive to the probability of finding an occult common bile duct stone. CONCLUSION Routine ERCP is of marginal overall benefit, but is of more substantial benefit and is more cost-effective in a subgroup of patients with a greater probability of having an occult common duct stone.

Screening for colorectal cancer: the cost to find an advanced adenoma

REFERENCES 1. R5sch T, Classen M. Gastroenterologic endosonography. Stuttgart: Georg Thieme Verlag, 1992:94-105. 2. Gensler S, Seidengerg B, Rifkin H, Rubinstein B. Ciliated lined intramural cyst of the stomach: case report and suggested embryogenesis. Ann Surg 1966;163:954-6. 3. Van Dam J, Rice TW, Sivak MV. Endoscopic ultrasonography and endoscopically guided needle aspiration for the diagnosis of upper gastrointestinal tract foregut cysts. Am J Gastroenterol 1992;87:762-5. 4. Rodgers BM, Harman PK, Johnson AM. Bronchopulmonary foregut malformations: the spectrum of anomalies. Ann Surg 1986;203:517-24. 5. Coselli MP, de Ipolyi P, Bloss RS, et al. Bronchogenic cysts above and below the diaphragm: report of eight cases. Ann Thorac Surg 1987;44:491-4. 6. Wieczorek RL, Seidman I, Ranson J, Ruoff M. Congenital duplication of the stomach: case report and review of the English literature. Am J Gastroenterol 1984;79:597-601. 7. Kochman ML, Hawes RH. Endosonographic evaluation of submucosal lesions of the gastrointestinal tract. In: Barkin JS, Phelan CA, eds. Advanced therapeutic endoscopy. 2nd ed. New York: Raven Press, Ltd, 1994:133-45.

Canadian credentialing guidelines for endoscopic retrograde cholangiopancreatography

BACKGROUND A previous study showed that 14 days of qid bismuth-based triple therapy with tetracycline 500 mg, metronidazole 250 mg and colloidal bismuth subcitrate 120 mg resulted in excellent Helicobacter pylori eradication rates (89.5%). The present study looked at a shorter treatment period by adding omeprazole and by reducing the dose of tetracycline. METHODS One hundred sixty-one patients with H pylori confirmed by histology and (13)carbon urea breath test were included in the study. They were treated for seven days with bismuth subcitrate 120 mg plus metronidazole 250 mg plus tetracycline 250 mg qid plus omeprazole 20 mg bid (OBMT). Patients were 18 to 75 years of age and had dyspepsia with or without a history of peptic ulcer. Patients with irritable bowel syndrome, active ulcer or previous attempt at eradication, or those who had used antibiotics or antiulcer drugs in the previous 30 days were excluded. Eradication was determined by two (13)carbon urea breath tests done one and three months, respectively, after treatment. Strains with minimal inhibitory concentrations of 8 microg/mL or higher were considered to be resistant to metronidazole. RESULTS The overall per protocol eradication rate was 84%-89.5% in metronidazole-sensitive and 70.8% in metronidazole-resistant strains. Modified intent-to-treat analysis resulted in a 80% eradication rate--82.5% in metronidazole-sensitive and 66.7% in metronidazole-resistant strains. Only one patient discontinued treatment because of adverse events. CONCLUSIONS The OBMT regimen used in this study is safe and effective against metronidazole-sensitive H pylori strains.

Predictive factors associated with immunosuppressive agent use in ulcerative colitis: a case–control study

OBJECTIVE:Cancer Care Ontario has recommended a program to screen for colorectal cancer using fecal occult blood testing (FOBT). Patients who test positive on FOBT will require further investigation. We examined the cost of finding an advanced adenoma in these patients using four different strategies.METHODS:Using decision analysis software (DATA 3.5, TreeAge Software, Boston, MA), we considered four strategies for evaluating patients referred for a positive FOBT: 1) flexible sigmoidoscopy to the splenic flexure, 2) flexible sigmoidoscopy with air contrast barium enema (ACBE), 3) virtual colonoscopy, and 4) colonoscopy. If an adenoma was found in any of the first three methods, colonoscopy and polypectomy were performed. An advanced adenoma was defined as a villous adenoma, tubular adenoma ≥10 mm, high grade dysplasia, or cancer. Values for probabilities, test characteristics and costs (

Canadian Credentialing Guidelines for Endoscopic Privileges: An Overview

CDN) were estimated from a MEDLINE literature review, local costs, and OHIP fee codes. Patients with adenomas identified as well as direct medical costs from a third party payer perspective were calculated.RESULTS:Assuming a probability of adenoma of 16.9%, the cost for each strategy (compared to no investigation) was as follows: flexible sigmoidoscopy to the splenic flexure,