Publications

Previously, we found that 4 weeks of treatment with lopinavir-ritonavir did not decrease insulin sensitivity but did increase adiponectin levels. In the present study, a single dose of lopinavir-ritonavir decreases insulin sensitivity but does not alter adiponectin levels. Insulin resistance from protease inhibitors may decrease with prolonged use; an increase in adiponectin levels may mediate this effect.

The aim of the present study was to predict which patients with severe or difficult-to-treat asthma are at highest risk for healthcare utilisation can be predicted so as to optimise clinical management. Data were derived from 2,821 adults with asthma enrolled in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Multiple potential predictors were assessed at baseline using a systematic algorithm employing stepwise logistic regression. Outcomes were asthma-related hospitalisations or emergency department (ED) visits within 6 months following baseline. Overall, 239 subjects (8.5%) reported hospitalisation or ED visits at follow-up. Predictors retained after multivariate analysis were as follows: younger age; female sex; non-white race; body mass index > or =35 kg x m(-2); post-bronchodilator per cent predicted forced vital capacity <70%; history of pneumonia; diabetes; cataracts; intubation for asthma; and three or more steroid bursts in the prior 3 months. A final risk score derived from the logistic regression model ranged from 0-18 and was highly predictive (c-index: 0.78) of hospitalisation or ED visits. This tool was re-tested in a prospective validation using outcomes at 12- to 18-months follow-up among the same cohort (c-index: 0.77). The risk score derived is a clinically useful tool for assessing the likelihood of asthma-related hospitalisation or emergency department visits in adults with severe and difficult-to-treat asthma.

Given the elevated risk of cardiovascular events and the higher prevalence of silent coronary artery disease (CAD) in diabetic versus non-diabetic patients, screening asymptomatic diabetic patients for CAD is an appealing concept. However, many factors argue against implementing a broad-based screening program at the present time. Foremost is the lack of any published data demonstrating that a prospectively applied screening program improves outcome in asymptomatic diabetic patients. The true prevalence of CAD, and in particular prognostically important CAD, in this population is uncertain. Consensus documents recommend more aggressive treatment of hypertension and hyperlipidemia solely on the basis of diabetes status, without differentiation based on the presence or absence of identifiable CAD. There is no evidence that use of anti-ischemic medication can alter the natural history of CAD in these patients. Retrospectively performed studies using stress single-photon emission computed tomography (SPECT) imaging have reported that approximately 50% and 20% of patients have abnormal and high-risk images, respectively. However, the only prospectively designed study, the DIAD (Detection of Ischemia in Asymptomatic Diabetics) study, reported a much lower percentage of abnormal SPECT images (16%) and images with a very large (>/=10% of the left ventricle) defect (1%). The financial implications of screening all asymptomatic diabetic patients determined to be at intermediate and high risk by clinical scoring systems is enormous. Clearly more data are needed to address this issue. Future studies should consider possible methods to enrich the patient subset that might benefit from screening and should include carefully performed cost-effective analyses.