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Context: Cisapride, a gastrointestinal tract promotility agent, can cause life-threatening cardiac arrhythmias in patients susceptible either because of concurrent use of medications that interfere with cisapride metabolism or prolong the QT interval or because of the presence of other diseases that predispose to such arrhythmias. In June 1998, the US Food and Drug Administration (FDA) determined that use of cisapride was contraindicated in such patients and informed practitioners through additions to the boxed warning in the label and a "Dear Health Care Professional" letter sent by the drug's manufacturer.Objective: To evaluate the impact of the FDA's 1998 regulatory action regarding contraindicated use of cisapride.Design and Setting: Analysis of data for the 1-year periods before (July 1997-June 1998) and after (July 1998-June 1999) the regulatory action from the population-based, pharmacoepidemiology research databases of 2 managed care organizations (sites A and B) and a state Medicaid program (site C).Participants: Patients with at least 180 days of prior enrollment in 1 of the 3 sites who were prescribed cisapride at least once in the period before (n = 24 840) or after (n = 22 459) regulatory action. Patients could be included in both cohorts.Main Outcome Measures: Proportion of cisapride users in each period for whom cisapride use was contraindicated by the product label, based on computerized patient medical encounter records.Results: In the year prior to regulatory action, cisapride use was contraindicated for 26%, 30%, and 60% of users in study sites A, B, and C, respectively. In the year after regulatory action, use was contraindicated for 24%, 28%, and 58% of users, a reduction in contraindicated use of approximately 2 per 100 cisapride users at each site. When the analysis was restricted to new users of cisapride after regulatory action, only minor reductions in contraindicated use were found.Conclusion: The FDA's 1998 regulatory action regarding cisapride use had no material effect on contraindicated cisapride use. More effective ways to communicate new information about drug safety are needed. [ABSTRACT FROM AUTHOR]

Chelsea A Isom,1 Martha J Shrubsole,2,3 Qiuyin Cai,2 Walter E Smalley,4,5 Reid M Ness,5 Wei Zheng,2,3 Harvey J Murff3,6 1Department of General Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; 2Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA; 3GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA; 4Department of Health Policy, Vanderbilt University Medical Center, Nashville, TN, USA; 5Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN, USA; 6Division of General Internal Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, USA Background: Previous studies have shown a link between increased dietary intake of arachidonic acid (ARA) and colorectal neoplasms. It has been shown that erythrocyte phospholipid membrane concentrations of ARA are strongly determined by genetic variation. Fatty acid desaturase (FADS) controls the rate limiting step in ARA production, and FADS variant rs174537 has been shown to be responsible for up to 18.6% of the variation seen. To determine if a causal association exists between erythrocyte membrane ARA concentrations and colorectal adenomas, we conducted a Mendelian randomization (MR) analysis using rs174537 as an instrumental variable (IV). MR analysis was chosen because it is less susceptible to bias and confounding. Patients and methods: A case-control study was performed using the Tennessee Colorectal Polyps Study. Patients were matched on age, gender, race, facility site, and year of colonoscopy. Cases were defined as any colorectal adenoma on colonoscopy (n=909) and controls were polyp free (n=855). A two-stage logistic regression was conducted using rs174537 as the IV with the dependent variable being the presence of a colorectal adenoma on colonoscopy. Results: Cases were older (59 vs 57 years of age, P

Barrett's epithelium is a recognized premalignant condition for esophageal adenocarcinoma. Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the relative risk of colon cancer in humans and the esophageal tumor load in carcinogen-treated mice. Previous studies provided conflicting results for COX-2 activity in Barrett's mucosa. Pinch mucosal biopsies were collected from Barrett's and adjacent normal esophageal mucosa from 17 patients with Barrett's esophagus. Low-grade dysplasia was found in seven patients. COX-2 protein was undetectable in normal esophageal mucosa. COX-1 protein expression did not vary between normal and Barrett's epithelium. Increased COX-2 protein was detected in Barrett's epithelium in seven patients (41%) but did not differ with or without dysplasia (43% vs 40%). In conclusion, COX-2 protein is increased in 41% of patients with Barrett's epithelium compared to normal esophageal mucosa but did not differ with or without dysplasia. COX-2 induction may be an early event in the development of Barrett's esophagus. [ABSTRACT FROM AUTHOR]

Objective: To quantify medical care costs for the diagnosis and treatment of gastrointestinal disorders attributable to use of nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin in elderly persons.Design and Setting: Retrospective cohort study of 75,350 Tennessee Medicaid enrollees at least 65 years of age.Measurements: The cohort was classified by baseline NSAID use as nonusers (no use preceding 1988), occasional users (< 75% of days) or regular users (> or = 75% of days). For the follow-up year (1989), we calculated annual rates of utilization of and Medicare/Medicaid payments for: medical care for NSAID-associated gastrointestinal disorders; hospitalizations/emergency department visits for peptic ulcers, gastritis/duodenitis, and gastrointestinal bleeding; outpatient upper and lower gastrointestinal tract radiologic and endoscopic examinations; and histamine2 (H2)-receptor antagonist, sucralfate, and antacid prescriptions. Rates were adjusted for demographic characteristics and baseline health care utilization.Results: Among nonusers of NSAIDs, the adjusted mean annual payment for all types of medical care for study gastrointestinal disorders was $134. This increased to $180 among occasional users, an excess of $46 (p < .001); and to $244 among regular users, an excess of $111 (p < .001, comparison with both nonusers and occasional users). Cohort members with any baseline year NSAID use had an adjusted mean annual payment of $191, $57 (p < .001) higher than that for nonusers. In both users and nonusers of NSAIDs, medications and inpatient care accounted for the largest component of costs. Among regular NSAID users, excess payments increased with baseline NSAID dose: $56, $120, and $157 for less than 1, 1 to 2, and more than 2 standard units per day, respectively (p < .01, linear trend).Conclusions: Nonsteroidal anti-inflammatory drug (NSAID) use in elderly patients was associated with substantial excess costs and utilization of medical care for gastrointestinal disorders. [ABSTRACT FROM AUTHOR]