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A large number of observational studies, supported by animal and basic research studies, have shown a protective effect of hormone replacement therapy (HRT) on acute coronary outcomes. The recent large randomized Women's Health Initiative (WHI) study reported the opposite result, i.e. a small risk increase of 29% for acute coronary outcomes under estrogen-progestin treatment. Possible methodological reasons for these discrepancies are discussed. Despite randomization, the reported small increase in risk in the WHI study could be spurious because of differential unblinding of HRT users, which could have resulted in higher detection rates of otherwise clinically unrecognized acute myocardial infarction in these women. We show that altering diagnostic patterns because of unblinding could lower the crude rate ratio of 1.28 to 1.02. In the observational studies, the protective effect may have been exaggerated due to a healthy user bias and to the inappropriate choice of the reference group. Using an alternative reference group, the combined rate ratio of 0.67 was increased to 0.82. The diametrical effects of HRT on acute coronary outcomes found between the observational studies and the WHI Study may be a result not only of bias in the observational studies, but also of bias in the WHI Study. [ABSTRACT FROM AUTHOR]

Objectives. To assess the risk of severe infections associated with the use of traditional disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoid agents in rheumatoid arthritis (RA). Methods. Our study was a case-control design nested within a cohort of 23 733 RA patients studied between 1 January 1980 and 31 December 2003. Matching on age and gender, and adjusting for comorbidity and physician use, conditional logistic regression was used to estimate the effect of specific drugs on the rate ratio (RR) for infections requiring hospitalization. Results. The risk for all infections requiring hospitalization appeared to be most elevated with current exposures to cyclophosphamide [RR: 3.26, 95% confidence interval (CI): 2.28–4.67] and systemic glucocorticoid agents (RR: 2.56, 95% CI: 2.29–2.85); azathioprine was associated with a moderate increased risk (RR: 1.52, 95% CI: 1.18–1.97). There was a suggestion of increased risk of pneumonia due to methotrexate (RR: 1.16, 95% CI: 1.02–1.33). The results were similar for the period before and after the introduction of anti-tumour necrosis factor (TNF) agents. The RR point estimate for anti-TNF agents suggested about a 2-fold increased risk for all infections, but the estimate was imprecise. Conclusions. In this large cohort of RA patients, the most heightened risk of serious infections was seen with the use of glucocorticoid agents and immunosuppressive DMARDs. Assessments of infection risk related to newer and emerging therapies should carefully consider concomitant medication exposures, including traditional DMARDs and glucocorticoid therapy. [ABSTRACT FROM AUTHOR]