Gastrointestinal adverse effects of short-term aspirin use: a meta-analysis of published randomized controlled trials.

BACKGROUND AND OBJECTIVES: Aspirin is widely used for short-term treatment of pain, fever or colds, but there are only limited data regarding the safety of this use. To summarize the available data on this topic, we conducted a meta-analysis of the published clinical trial literature regarding the gastrointestinal adverse effects of short-term use of aspirin in comparison with placebo and other medications commonly used for the same purpose. DATA SOURCES AND METHODS: An extensive literature search identified 119,310 articles regarding possible adverse effects of aspirin, among which 23,131 appeared to possibly include relevant data. An automated text-mining procedure was used to score the references for potential relevance for the meta-analysis. The 3,983 highest-scoring articles were reviewed individually to identify those with data that could be included in this analysis. Ultimately, 78 relevant articles were identified that contained gastrointestinal adverse event data from clinical trials of aspirin versus placebo or an active comparator. Odds ratios (ORs) computed using a Mantel-Haenszel estimator were used to summarize the comparative effects on dyspepsia, nausea/vomiting, and abdominal pain, considered separately and also aggregated as 'minor gastrointestinal events'. Gastrointestinal bleeds, ulcers, and perforations were also investigated. RESULTS: Data were obtained regarding 19,829 subjects (34 % treated with aspirin, 17 % placebo, and 49 % an active comparator). About half of the aspirin subjects took a single dose. Aspirin was associated with a higher risk of minor gastrointestinal events than placebo or active comparators: the summary ORs were 1.46 (95 % confidence interval [CI] 1.15-1.86) and 1.81 (95 % CI 1.61-2.04), respectively. Ulcers, perforation, and serious bleeding were not seen after use of aspirin or any of the other interventions. CONCLUSIONS: During short-term use, aspirin is associated with a higher frequency of gastrointestinal complaints than other medications commonly used for treatment of pain, colds, and fever. Serious adverse events were not observed with aspirin or any of the comparators.

Combinatorial synthetic design. Solution and polymer-supported synthesis of heterocycles via intramolecular aza Diels-Alder and imino alcohol cyclizations.

A flexible synthetic strategy for combinatorial chemical applications has been developed on the basis of an aldehyde-bridge-alkene motif as the key component in several intramolecular cycloaddition reactions. This strategy was explored most extensively with the formal aza Diels-Alder cyclization, which affords a series of configurationally and functionally diverse heterocyclic compounds. The substrates included substituted salicylaldehydes, glyoxylic esters and amides, and N-acyl-alpha-aminoaldehydes; all reacted with a variety of anilines to yield different tetrahydroquinoline products. The cyclization of the aminoaldehydes was also translated from solution and optimized for solid phase. The stepwise mechanism of this cycloaddition suggested that the cationic intermediate from initial ring closure could be trapped by a variety of nucleophiles. This suggestion was confirmed by cyclization of amino alcohols and related compounds.