Non-steroidal anti-inflammatory drug-induced cardiovascular adverse events: a meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Although non-steroidal anti-inflammatory drugs (NSAIDs) have been studied in randomized, controlled trials and meta-analyses in an effort to determine their cardiovascular (CV) risks, no consensus has been reached. These studies continue to raise questions, including whether cyclooxygenase-2 (COX-2) selectivity plays a role in conferring CV risk. We performed a meta-analysis of current literature to determine whether COX-2 selectivity leads to an increased CV risk. METHODS: We utilized randomized, controlled trials and prospective cohort studies. We selected eight NSAIDs based on popularity and COX selectivity and conducted a search of the MEDLINE, EMBASE, and Cochrane databases. Primary endpoints included any myocardial infarction (MI), any stroke, CV death, and a combination of all three (composite CV outcomes). Twenty-six studies were found that met inclusion and exclusion criteria. Comparisons were made between all included drugs, against placebo, and against non-selective NSAIDs (nsNSAIDs). Drugs were also compared against COX-2 selective inhibitors (COXIBs) with and without inclusion of rofecoxib. RESULTS AND DISCUSSION: Incidence of MI was increased by rofecoxib in all comparison categories [all NSAIDs (OR: 1·811, 95% CI: 1·379-2·378), placebo (OR: 1·655: 95% CI: 1·029-2·661), nsNSAIDs (OR: 2·155, 95% CI: 1·146-4·053), and COXIBs (OR: 1·800, 95% CI: 1·217-2·662)], but was decreased by celecoxib and naproxen in the COXIB comparison [(OR: 0·583, 95% CI: 0·396-0·857) and (OR: 0·609, 95% CI: 0·375-0·989, respectively]. Incidence of stroke was increased by rofecoxib in comparisons with all NSAIDs and other COXIBs [(OR: 1·488, 95% CI: 1·027-2·155) and (OR: 1·933, 95% CI: 1·052-3·549), respectively]. Incidence of stroke was decreased by celecoxib when compared with all NSAIDs, nsNSAIDs, and COXIBs [(OR: 0·603, 95% CI: 0·410-0·887), (OR: 0·517, 95% CI: 0·287-0·929), and (OR: 0·509, 95% CI: 0·280-0·925), respectively]. No NSAID reached statistical significance in regard to CV death. Incidence of the composite endpoint was increased by rofecoxib when compared against all NSAIDs, placebo, and other COXIBs [(OR: 1·612, 95% CI: 1·313-1·981), (OR: 1·572, 95% CI: 1·123-2·201) and (OR: 1·838, 95% CI: 1·323-2·554), respectively]. Incidence of composite endpoint was decreased by celecoxib in the all NSAIDs and COXIBs comparisons [(OR: 0·805, 95% CI: 0·658-0·986) and (OR: 0·557, 95% CI: 0.404-0.767), respectively]. When rofecoxib was removed from the COXIBs group, no difference was found with any comparison, suggesting rofecoxib skewed the data. WHAT IS NEW AND CONCLUSION: This instead of the meta-analysis suggests that COX-2 selectivity may not play a role in the CV risk of NSAIDs. Rofecoxib was the only drug to demonstrate harm and skewed the data of the COX-2 selective group.

An evaluation of urinary measures of iodine and selenium status.

The aim of this study was to establish methodology for a survey of the iodine and selenium status of New Zealand residents, more specifically to investigate the correlation between fasting or random casual urine samples and 24 hour urines for iodine and selenium excretion. Sixty-two (31 M, 31 F) adults collected casual, fasting and 24 hour urine samples for analysis of iodide, selenium and creatinine. Plasma and serum samples were collected for analysis of selenium and glutathione peroxidase activity. Results indicated that fasting urine samples, but not casual urines, may give a reasonable estimate of urinary output of iodine and selenium on a population basis, but that 24 hour urines are necessary for diagnosis of iodine deficiency in an individual and for research purposes. The results for iodine also give no support for expressing iodine as the iodide-creatinine ratio, although there was some indication that the selenium-creatinine ratio might be useful. Significant correlations between total daily excretion of selenium and iodine and also for urinary concentrations of the two trace elements in fasting and in 24 hour urine specimens may reflect a relationship of selenium and iodine to body size which may have implications for dietary requirements of these trace elements. Alternatively the correlations may reflect a relationship between dietary intake of the two trace elements in a country in which food concentrations are low, and this needs further investigation.

Preliminary evaluation of a new curriculum--incorporation of problem based learning (PBL) into the traditional format.

An account of the establishment of a Problem Based Learning (PBL) curriculum at the Eric Williams Medical Science Complex Republic of Trinidad and Tobago provides the forum for a critical analysis of this process and for dialogue with current relevant literature on similar attempts elsewhere. Initial resistance to change and the assessment of the new system is discussed in the light of the fact that this is the first Caribbean territory to adopt Problem Based Learning as the major instrument to be employed in tertiary level medical education. The analysis uncovers a model of practitioner/researcher which provides a useful conceptual and operational framework for the articulation of the role of those engaged in effecting and studying the management of change.