Use of rosiglitazone and pioglitazone immediately after the cardiovascular risk warnings

BackgroundMeta-analyses of oral hypoglycemic agents (OHAs) revealed that rosiglitazone increased the risk of myocardial infarction (MI) and heart failure (HF) and that pioglitazone increased the risk of HF and decreased the risk of MI.ObjectiveTo characterize the change in the pattern of use of OHAs immediately after the publication of these meta-analyses on May 21, 2007.MethodsPharmacy and medical claims data for a managed care organization were analyzed for patients continuously enrolled from January 1, 2005, to November 30, 2007, with at least 1 pharmacy claim for OHA in the 13-month period between November 1, 2006, and November 30, 2007. A 5-month pre-publication period (November 1, 2006, through March 31, 2007) was compared with a 5-month post-publication period (July 1, 2007, through November 30, 2007) using a differences-in-differences multinomial logistic regression. This regression explored discontinuation; continuation with monotherapy or adding another drug; and switching to a drug different from the index monotherapy drug after adjusting for gender, age, type of insurance, past 1-year history of MI or HF, and risk factors for MI and HF in the past 1 year.ResultsThe relative rate of switching to nonindex drug in the postpublication relative to prepublication was 2.64 (P = .046) for monotherapy rosiglitazone users and 0.72 (P = .583) for monotherapy pioglitazone users. The differences-in-differences estimate of the rate of switching to nonindex drugs for monotherapy rosiglitazone users was 3.64 (P = .090) times higher relative to the estimate for monotherapy pioglitazone users.ConclusionThe pattern of use differed fundamentally between monotherapy rosiglitazone users and users of all other monotherapy OHAs in the postperiod. Not only were monotherapy rosiglitazone patients switching to non-rosiglitazone drugs at a higher rate, but the rate also was more than 3 times higher than similar switches among monotherapy pioglitazone users in the postperiod relative to the preperiod. This shows that the market response as observed by patient/prescriber decisions to the adverse news was interpreted narrowly to monotherapy rosiglitazone, and there is little or no spillover to the other drugs. Therefore, this study found that there was a differential effect of meta-analyses on the use of the 2 drugs.     

The Relation of Caregiver Demand to Adjustment Outcomes in Children With Cancer: The Moderating Role of Parenting Stress

This study investigated the relation of caregiver demand (CD) and parenting stress (PS) to child adjustment in a pediatric cancer sample. Mothers of children with cancer completed measures of PS and CD and rated their child's emotional, behavioral, and social adjustment. PS emerged as an independent predictor of the child's emotional, behavioral, and social adjustment; and moderated the relation between CD and child internalizing problems (IP). Contrary to expectations, children evidenced fewer IP under conditions of high CD and low PS, and more IP under conditions of low CD and low PS.     

Functional significance of prorenin internalization in the rat heart

Intracardiac renin is considered to be involved in the pathogenesis of cardiac hypertrophy, fibrosis, and myocardial infarction. Cardiac renin is predominantly derived from the circulation, because preprorenin is not expressed locally and uptake of renin has been demonstrated. One mechanism of internalization recently described involves the mannose-6-phosphate receptor and requires glycosylation of renin. Based on previous observations, we considered the existence of another pathway of uptake, not requiring glycosylation and predominantly involving prorenin. This hypothesis and its functional consequences were investigated in vitro and in vivo. We demonstrate that isolated adult cardiomyocytes internalize unglycosylated prorenin, which is followed by the generation of angiotensins. We further show that transgenic rats, expressing the ren-2(d) renin gene in an inducible manner, exhibit markedly enhanced levels of unglycosylated renin within intracellular compartments in the heart as a consequence of the induction of hepatic transgene expression and the rise of circulating unglycosylated prorenin levels. Because in this model severe cardiac damage occurs as a consequence of the rise of circulating prorenin levels, internalization of prorenin into cardiac cells is likely to play a key role in this process.