Placebo Adherence and Its Association with Morbidity and Mortality in the Studies of Left Ventricular Dysfunction

A provocative finding from several double-blind clinical trials has been the association between greater adherence to placebo study medication and better health outcomes. We used data from the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial (SOLVD-TT) and the SOLVD Prevention Trial (SOLVD-PT) to examine whether such associations could be validated and to examine several sources of bias and potential confounding. Survival analytic methods were used to estimate the association between placebo adherence and several health outcomes, employing a number of modeling techniques to test for the existence of alternative explanations for the association. Higher adherence was defined as having taken ≥75% of prescribed study medication. Higher placebo adherence was associated with improved overall survival in both SOLVD-TT and SOLVD-PT [hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.35 to 0.79 and HR = 0.52, 95%CI: 0.38 to 0.71, respectively]. Associations were similar for fatal or non-fatal cardiovascular or coronary heart disease events. Adjustment for both modifiable and non-modifiable cardiac risk factors (including age, gender, diabetes, blood pressure, smoking, weight, alcohol use, and levels of education) had minimal effect on the strength of the association. Little evidence of bias was found as an explanation for this relationship. In these two trials, better adherence to placebo was associated with markedly superior health outcomes, including total in-study mortality and incident cardiovascular events. No important confounders were identified. These data suggest there may exist strong but unrecognized determinants of health outcomes for which placebo adherence is a marker

Platelet activating factor stimulates arachidonic acid release in differentiated keratinocytes via arachidonyl non-selective phospholipase A2

Platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is known to be present in excess in psoriatic skin, but its exact role is uncertain. In the present study we demonstrate for the first time the role of group VI PLA2 in PAF-induced arachidonic acid release in highly differentiated human keratinocytes. The group IVα PLA2 also participates in the release, while secretory PLA2s play a minor role. Two anti-inflammatory synthetic fatty acids, tetradecylthioacetic acid and tetradecylselenoacetic acid, are shown to interfere with signalling events upstream of group IVα PLA2 activation. In summary, our major novel finding is the involvement of the arachidonyl non-selective group VI PLA2 in PAF-induced inflammatory responses

FRAX (R): Prediction of Major Osteoporotic Fractures in Women from the General Population: The OPUS Study

Purposes: The aim of this study was to analyse how well FRAXH predicts the risk of major osteoporotic and vertebral fractures over 6 years in postmenopausal women from general population. Patients and methods: The OPUS study was conducted in European women aged above 55 years, recruited in 5 centers from random population samples and followed over 6 years. The population for this study consisted of 1748 women (mean age 74.2 years) with information on incident fractures. 742 (43.1%) had a prevalent fracture; 769 (44%) and 155 (8.9%) of them received an antiosteoporotic treatment before and during the study respectively. We compared FRAXH performance with and without bone mineral density (BMD) using receiver operator characteristic (ROC) c-statistical analysis with ORs and areas under receiver operating characteristics curves (AUCs) and net reclassification improvement (NRI). Results: 85 (4.9%) patients had incident major fractures over 6 years. FRAXH with and without BMD predicted these fractures with an AUC of 0.66 and 0.62 respectively. The AUC were 0.60, 0.66, 0.69 for history of low trauma fracture alone, age and femoral neck (FN) BMD and combination of the 3 clinical risk factors, respectively. FRAXH with and without BMD predicted incident radiographic vertebral fracture (n = 65) with an AUC of 0.67 and 0.65 respectively. NRI analysis showed a significant improvement in risk assignment when BMD is added to FRAXH. Conclusions: This study shows that FRAXH with BMD and to a lesser extent also without FN BMD predict major osteoporotic and vertebral fractures in the general population

Effects of Happiness on All-Cause Mortality During 15 Years of Follow-Up: The Arnhem Elderly Study

Happiness, Longevity, Elderly subjects, Cohort study, Physical activity, Illnesses,