A model for undertaking effectiveness and cost-effectiveness analyses of primary preventive strategies in cardiovascular disease.

BACKGROUND: Clinical trials generally provide strong evidence of the efficacy of cardiovascular preventive strategies, but poor evidence of their 'real-life' utility, in terms of effectiveness and cost-effectiveness. DESIGN AND METHODS: The Cardiovascular Disease Prevention Model is presented, which represents a means of extrapolating the results of clinical trials to a broader, more relevant context. The model is configured as a decision-analysis tree, and underpinned by life-course analysis and Markov processes. Uncertainty and sensitivity analyses are undertaken by Monte Carlo simulation. RESULTS: The results of effectiveness and cost-effectiveness analyses of a hypothetical preventive intervention are presented to demonstrate the outputs of the model. The potential impact and efficiency of the intervention are made obvious. CONCLUSIONS: The Cardiovascular Disease Prevention Model offers a means to translate the results of trials of cardiovascular preventive interventions, in order to inform clinical and public health practice, as well as health policy.     

加拿大PICU和NICU临床医生的道德困境

目的:量化NICU和PICU临床医生的道德困境,并确认相关因素。设计:对在NICU或PICU中工作的临床医生进行全国性横断面调查。采用道德困境量表修订版(Moral Distress Scale-Revised,MDS-R)和自我评定法评价道德困境程度。采用Maslach职业倦怠问卷子量表评定去人格化。受访者报告参加6...     

Homologous Recombination Deficiency: Concepts,Definitions, and Assays

BackgroundHomologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting.MethodsFriends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status.ResultsThis publication provides findings from the group’s discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community.ConclusionOverall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors.     

Associations of perceived prenatal stress and adverse pregnancy outcomes with perceived stress years after delivery

Archives of Women's Mental Health - Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal...     

Candesartan Normalizes Changes in Retinal Blood Flow and p22phox in the Diabetic Rat Retina

Angiotensin II has been implicated in the progression of diabetic retinopathy, which is characterized by altered microvasculature, oxidative stress, and neuronal dysfunction. The signaling induced by angiotensin II can occur not only via receptor-mediated calcium release that causes vascular constriction, but also through a pathway whereby angiotensin II activates NADPH oxidase to elicit the formation of reactive oxygen species (ROS). In the current study, we administered the angiotensin II receptor antagonist candesartan (or vehicle, in untreated animals) in a rat model of type 1 diabetes in which hyperglycemia was induced by injection of streptozotocin (STZ). Eight weeks after the STZ injection, untreated diabetic rats were found to have a significant increase in tissue levels of angiotensin converting enzyme (ACE; p < 0.05) compared to non-diabetic controls, a 33% decrease in retinal blood flow rate (p < 0.001), and a dramatic increase in p22phox (a subunit of the NADPH oxidase). The decrease in retinal blood flow, and the increases in retinal ACE and p22phox in the diabetic rats, were all significantly attenuated (p < 0.05) by the administration of candesartan in drinking water within one week. Neither STZ nor candesartan induced any changes in tissue levels of superoxide dismutase (SOD-1), 4-hydroxynonenal (4-HNE), or nitrotyrosine. We conclude that one additional benefit of candesartan (and other angiotensin II antagonists) may be to normalize retinal blood flow, which may have clinical benefits in diabetic retinopathy.