118 research outputs found

    Lessons learned while starting multi-institutional genetics research in diverse populations: A report from the Clinical Sequencing Evidence-Generating Research (CSER) consortium

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    Background: Increasing diversity in clinical trial participation is necessary to improve health outcomes and requires addressing existing social, structural, and geographic barriers. The Clinical Sequencing Evidence-Generating Research Consortium (CSER) included six research projects to enroll historically underrepresented/underserved (UR/US) populations in clinical genomics research. Delays and project re-designs emerged shortly after work began. Understanding common experiences of these projects may inform future trial implementation. Methods: Semi-structured interviews with six CSER principal investigators and seven project managers were performed. An interview guide included questions of research/clinical infrastructure, logistics across sites, language, communication, and allocation of grant-related resources. Interviews were recorded, transcribed verbatim; transcripts were analyzed using inductive coding, thematic analysis and consensus building. Results: All projects collaborating with new clinical sub-sites to recruit UR/US populations. Refining trial logistics continued long after enrollment for all projects. Themes of challenges included: sub-site customization for workflow and genetics support, conflicting input from participant advisory groups and approval bodies, developing research personnel, complex data management structures, and external changes (e.g. subcontractors ending contracts) that required redesign. Themes of beneficial lessons included: domains with prior experience were easier, develop project champions at each sub-site, structure communication within the research team, and simplify research design when possible. Conclusions: The operational aspects of expanding clinical research into novel sub-sites are significant and require investment of time and resources. The themes arising from these interviews suggest priority areas for more quantitative analyses in the future including multi-institutional approval policies and processes, data management structures, and incremental research complexity

    Performance of Framingham cardiovascular disease (CVD) predictions in the Rotterdam Study taking into account competing risks and disentangling CVD into coronary heart disease (CHD) and stroke

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    AbstractBackgroundTo evaluate the performance of Framingham predictions of cardiovascular disease (CVD) risk corrected for the competing risk of non-CVD death, in an independent European cohort of older individuals and subsequently extend the predictions by disentangling CVD into coronary heart disease (CHD) and stroke separately.MethodsWe used the Rotterdam Study data, a prospective cohort study of individuals aged 55years and older (N=6004), to validate the Framingham predictions of CVD, defined as first occurrence of myocardial infarction, coronary death or stroke during 15years of follow-up, corrected for the competing risk of non-CVD death. We subsequently estimated the risks of CHD and stroke separately, and used the sum as a predictor for the total CVD risk. Calibration plots and c-statistics were used to evaluate the performance of the models.ResultsPerformance of the Framingham predictions was good in the low- to intermediate risk (≤30%, 15-year CVD risk) (17.5% observed vs. 16.6% expected) but poorer in the higher risk (>30%) categories (36.3% observed vs. 44.1% expected). The c-statistic increased from 0.66 to 0.69 after refitting. Separately estimating CHD and stroke revealed considerable heterogeneity with regard to the contribution of CHD and stroke to total CVD risk.ConclusionsFramingham CVD risk predictions perform well in the low- to intermediate risk categories in the Rotterdam Study. Disentangling CVD into CHD and stroke separately provides additional information about the individual contribution of CHD and stroke to total individual CVD risk

    Which interventions offer best value for money in primary prevention of cardiovascular disease?

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    BackgroundDespite many decades of declining mortality rates in the Western world, cardiovascular disease remains the leading cause of death worldwide. In this research we evaluate the optimal mix of lifestyle, pharmaceutical and population-wide interventions for primary prevention of cardiovascular disease.Methods and FindingsIn a discrete time Markov model we simulate the ischaemic heart disease and stroke outcomes and cost impacts of intervention over the lifetime of all Australian men and women, aged 35 to 84 years, who have never experienced a heart disease or stroke event. Best value for money is achieved by mandating moderate limits on salt in the manufacture of bread, margarine and cereal. A combination of diuretic, calcium channel blocker, ACE inhibitor and low-cost statin, for everyone with at least 5% five-year risk of cardiovascular disease, is also cost-effective, but lifestyle interventions aiming to change risky dietary and exercise behaviours are extremely poor value for money and have little population health benefit.ConclusionsThere is huge potential for improving efficiency in cardiovascular disease prevention in Australia. A tougher approach from Government to mandating limits on salt in processed foods and reducing excessive statin prices, and a shift away from lifestyle counselling to more efficient absolute risk-based prescription of preventive drugs, could cut health care costs while improving population health.<br /

    Development and pilot of an internationally standardized measure of cardiovascular risk management in European primary care

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    Contains fulltext : 97806.pdf (publisher's version ) (Open Access)BACKGROUND: Primary care can play an important role in providing cardiovascular risk management in patients with established Cardiovascular Diseases (CVD), patients with a known high risk of developing CVD, and potentially for individuals with a low risk of developing CVD, but who have unhealthy lifestyles. To describe and compare cardiovascular risk management, internationally valid quality indicators and standardized measures are needed. As part of a large project in 9 European countries (EPA-Cardio), we have developed and tested a set of standardized measures, linked to previously developed quality indicators. METHODS: A structured stepwise procedure was followed to develop measures. First, the research team allocated 106 validated quality indicators to one of the three target populations (established CVD, at high risk, at low risk) and to different data-collection methods (data abstraction from the medical records, a patient survey, an interview with lead practice GP/a practice survey). Secondly, we selected a number of other validated measures to enrich the assessment. A pilot study was performed to test the feasibility. Finally, we revised the measures based on the findings. RESULTS: The EPA-Cardio measures consisted of abstraction forms from the medical-records data of established Coronary Heart Disease (CHD)-patients--and high-risk groups, a patient questionnaire for each of the 3 groups, an interview questionnaire for the lead GP and a questionnaire for practice teams. The measures were feasible and accepted by general practices from different countries. CONCLUSIONS: An internationally standardized measure of cardiovascular risk management, linked to validated quality indicators and tested for feasibility in general practice, is now available. Careful development and pilot testing of the measures are crucial in international studies of quality of healthcare

    Cell Walls of Saccharomyces cerevisiae Differentially Modulated Innate Immunity and Glucose Metabolism during Late Systemic Inflammation

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    BACKGROUND: Salmonella causes acute systemic inflammation by using its virulence factors to invade the intestinal epithelium. But, prolonged inflammation may provoke severe body catabolism and immunological diseases. Salmonella has become more life-threatening due to emergence of multiple-antibiotic resistant strains. Mannose-rich oligosaccharides (MOS) from cells walls of Saccharomyces cerevisiae have shown to bind mannose-specific lectin of Gram-negative bacteria including Salmonella, and prevent their adherence to intestinal epithelial cells. However, whether MOS may potentially mitigate systemic inflammation is not investigated yet. Moreover, molecular events underlying innate immune responses and metabolic activities during late inflammation, in presence or absence of MOS, are unknown. METHODS AND PRINCIPAL FINDINGS: Using a Salmonella LPS-induced systemic inflammation chicken model and microarray analysis, we investigated the effects of MOS and virginiamycin (VIRG, a sub-therapeutic antibiotic) on innate immunity and glucose metabolism during late inflammation. Here, we demonstrate that MOS and VIRG modulated innate immunity and metabolic genes differently. Innate immune responses were principally mediated by intestinal IL-3, but not TNF-α, IL-1 or IL-6, whereas glucose mobilization occurred through intestinal gluconeogenesis only. MOS inherently induced IL-3 expression in control hosts. Consequent to LPS challenge, IL-3 induction in VIRG hosts but not differentially expressed in MOS hosts revealed that MOS counteracted LPS's detrimental inflammatory effects. Metabolic pathways are built to elucidate the mechanisms by which VIRG host's higher energy requirements were met: including gene up-regulations for intestinal gluconeogenesis (PEPCK) and liver glycolysis (ENO2), and intriguingly liver fatty acid synthesis through ATP citrate synthase (CS) down-regulation and ATP citrate lyase (ACLY) and malic enzyme (ME) up-regulations. However, MOS host's lower energy demands were sufficiently met through TCA citrate-derived energy, as indicated by CS up-regulation. CONCLUSIONS: MOS terminated inflammation earlier than VIRG and reduced glucose mobilization, thus representing a novel biological strategy to alleviate Salmonella-induced systemic inflammation in human and animal hosts

    Improving the cost-effectiveness of cardiovascular disease prevention in Australia : a modelling study

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    Background : Cardiovascular disease is the leading cause of death worldwide. Like many countries, Australia is currently changing its guidelines for cardiovascular disease prevention from drug treatment for everyone with \u27high blood pressure\u27 or \u27high cholesterol\u27, to prevention based on a patient\u27s absolute risk. In this research, we model cost-effectiveness of cardiovascular disease prevention with blood pressure and lipid drugs in Australia under three different scenarios: (1) the true current practice in Australia; (2) prevention as intended under the current guidelines; and (3) prevention according to proposed absolute risk levels. We consider the implications of changing to absolute risk-based cardiovascular disease prevention, for the health of the Australian people and for Government health sector expenditure over the long term. Methods : We evaluate cost-effectiveness of statins, diuretics, ACE inhibitors, calcium channel blockers and beta-blockers, for Australian men and women, aged 35 to 84 years, who have never experienced a heart disease or stroke event. Epidemiological changes and health care costs are simulated by age and sex in a discrete time Markov model, to determine total impacts on population health and health sector costs over the lifetime, from which we derive cost-effectiveness ratios in 2008 Australian dollars per quality-adjusted life year. Results : Cardiovascular disease prevention based on absolute risk is more cost-effective than prevention under the current guidelines based on single risk factor thresholds, and is more cost-effective than the current practice, which does not follow current clinical guidelines. Recommending blood pressure-lowering drugs to everyone with at least 5% absolute risk and statin drugs to everyone with at least 10% absolute risk, can achieve current levels of population health, while saving 5.4billionfortheAustralianGovernmentoverthelifetimeofthepopulation.Butsavingscouldbeashighas5.4 billion for the Australian Government over the lifetime of the population. But savings could be as high as 7.1 billion if Australia could match the cheaper price of statin drugs in New Zealand. Conclusions : Changing to absolute risk-based cardiovascular disease prevention is highly recommended for reducing health sector spending, but the Australian Government must also consider measures to reduce the cost of statin drugs, over and above the legislated price cuts of November 2010. <br /
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