We conducted a nested case-control study of 1,377 cases of upper gastrointestinal bleeding or perforation (UGIB) and 10,000 controls to evaluate the association of individual nonsteroidal antiinflammatory drugs (NSAIDs), utilization characteristics, and other risk factors for these conditions. Age was the strongest risk factor for UGIB. Male gender, history of complicated peptide ulcer disease, and current use of steroids were also risk factors for UGIB. The adjusted odds ratio (OR) for current NSAID use was 4.3 [95% confidence interval (CI) = 3.7-5.0]. The ORs for current NSAID use were similar for fatal cases and for the gastric, duodenal, prepyloric, and multiple sites of lesion, but the OR was substantially increased for perforations (OR = 16.9;95% CI = 9.1-31.5). Women age 80 years and older experienced the greater effect of NSAID use. Current users of multiple NSAIDs and recent switchers showed ORs of 9.0 and 6.2, respectively. Ibuprofen showed the lowest OR and diflunisal, the highest. ORs for low, medium, and high NSAID daily dose were 2.9, 4.2, and 5.8, respectively. This trend was present among new, short-term, and long-term users. Simultaneous use of multiple NSAIDs as well as use of a single individual NSAID at high doses greatly increases the risk of complicated peptic ulcer disease.
We examined the positive predictive value of the International Classification of Diseases, 9th revision (ICD-9), codes used to identify cases of complicated peptic ulcer disease from the Saskatchewan Hospital automated database. Nonspecific and site- and lesion-specific codes were used in case detection to increase the sensitivity of the initial computer search. Review of the hospital records of 1,762 potential cases resulted in 1,375 confirmed cases. The positive predictive value of site and lesion-specific codes was about 90% and was about 70% for the nonspecific codes. Almost 50% of cases, however, would have been missed if the nonspecific codes had not been used.
To facilitate the availability of important new therapeutic agents, the Food and Drug Administration (FDA) in the mid-1970s began assigning therapeutic ratings to investigational new drugs and holding end-of-phase II conferences with drug sponsors. To determine whether these initiatives are associated with faster approvals, we examined new drug application (NDA) review times of new chemical entities (NCEs) approved during the 12-year period 1978 through 1989. Mean NDA review time for 1A drugs (22.5 months) was 22% shorter than that for 1B drugs (28.7 months), which in turn was 25% shorter than that for 1C drugs (38.4 months). For drugs approved during the recent 4-year period 1986 through 1989, however, the gap between 1A and 1C review times has narrowed considerably from 19 to 9 months. When drugs were grouped by FDA reviewing division, 1A drugs had the shortest mean review time in each division except the Cardio-Renal Division; in that division, 1B drugs had the shortest mean review time. Mean NDA review time for drugs that had end-of-phase II conferences (28.6 months) was 15% shorter than that for drugs without such conferences (33.7 months). These results suggest that NCEs that receive 1A or 1B ratings and are the subject of end-of-phase II conferences benefit by having shorter review times.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.