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Context: Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because of inhibition of cyclooxygenase (COX)-1. Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown.Objective: To determine whether celecoxib, a COX-2-specific inhibitor, is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs.Design: The Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind, randomized controlled trial conducted from September 1998 to March 2000.Setting: Three hundred eighty-six clinical sites in the United States and Canada.Participants: A total of 8059 patients (>/=18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received at least 1 dose of study drug. A total of 4573 patients (57%) received treatment for 6 months.Interventions: Patients were randomly assigned to receive celecoxib, 400 mg twice per day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987); ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per day (n = 1996). Aspirin use for cardiovascular prophylaxis (Main Outcome Measures: Incidence of prospectively defined symptomatic upper GI ulcers and ulcer complications (bleeding, perforation, and obstruction) and other adverse effects during the 6-month treatment period.Results: For all patients, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76% vs 1.45% (P =.09) and 2. 08% vs 3.54% (P =.02), respectively. For patients not taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44% vs 1.27% (P =.04) and 1.40% vs 2.91% (P =.02). For patients taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01% vs 2.12% (P =.92) and 4.70% vs 6.00% (P =.49). Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss, GI intolerance, hepatotoxicity, or renal toxicity. No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs, irrespective of aspirin use.Conclusions: In this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages. The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly. JAMA. 2000;284:1247-1255 [ABSTRACT FROM AUTHOR]

Objective: To determine more precise and accurate cancer risk estimates for achalasia that could be used to plan surveillance.Design: Cohort.Setting: Swedish population.Participants: All patients with achalasia listed in the population-based Swedish Inpatient Register from 1964 through 1989.Main Outcome Measures: The observed number of cancers in the cohort was compared with expected numbers of cancers (standardized incidence ratio [SIR]) for each 5-year age group and calendar year of observation, calculated using data from the Swedish Cancer Registry.Results: A total of 1062 patients with achalasia accumulated 9864 years of follow-up. The mean age at entry was 57.2 years, and the mean age at cancer diagnosis was 71.0 years. Esophageal cancer occurred in 24 patients. The risk of esophageal cancer in the first year after achalasia diagnosis was extremely high (SIR, 126.3; 95% confidence interval [CI], 63.0 to 226.1) as a consequence of prevalent cancers leading to distal esophageal obstruction simulating achalasia. During years 1 to 24, the risk was increased more than 16-fold (SIR, 16.6; 95% CI, 8.8 to 28.3). Annual surveillance after the first year would require 406 endoscopic examinations in men and 2220 in women to detect one cancer.Conclusions: Patients with achalasia are at markedly increased risk of developing esophageal cancer. A substantial number of surveillance examinations might be required to screen for cancers, especially in women. It is not known whether surveillance will result in improved survival. [ABSTRACT FROM AUTHOR]