124 research outputs found

    Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials

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    Objective: To evaluate differences in downstream testing, coronary revascularisation, and clinical outcomes following non-invasive diagnostic modalities used to detect coronary artery disease. Design: Systematic review and network meta-analysis. Data sources: Medline, Medline in process, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, SCOPUS, WHO International Clinical Trials Registry Platform, and Clinicaltrials.gov. Eligibility criteria for selecting studies: Diagnostic randomised controlled trials comparing non-invasive diagnostic modalities in patients presenting with symptoms suggestive of low risk acute coronary syndrome or stable coronary artery disease. Data synthesis: A random effects network meta-analysis synthesised available evidence from trials evaluating the effect of non-invasive diagnostic modalities on downstream testing and patient oriented outcomes in patients with suspected coronary artery disease. Modalities included exercise electrocardiograms, stress echocardiography, single photon emission computed tomography-myocardial perfusion imaging, real time myocardial contrast echocardiography, coronary computed tomographic angiography, and cardiovascular magnetic resonance. Unpublished outcome data were obtained from 11 trials. Results: 18 trials of patients with low risk acute coronary syndrome (n=11 329) and 12 trials of those with suspected stable coronary artery disease (n=22 062) were included. Among patients with low risk acute coronary syndrome, stress echocardiography, cardiovascular magnetic resonance, and exercise electrocardiograms resulted in fewer invasive referrals for coronary angiography than coronary computed tomographic angiography (odds ratio 0.28 (95% confidence interval 0.14 to 0.57), 0.32 (0.15 to 0.71), and 0.53 (0.28 to 1.00), respectively). There was no effect on the subsequent risk of myocardial infarction, but estimates were imprecise. Heterogeneity and inconsistency were low. In patients with suspected stable coronary artery disease, an initial diagnostic strategy of stress echocardiography or single photon emission computed tomography-myocardial perfusion imaging resulted in fewer downstream tests than coronary computed tomographic angiography (0.24 (0.08 to 0.74) and 0.57 (0.37 to 0.87), respectively). However, exercise electrocardiograms yielded the highest downstream testing rate. Estimates for death and myocardial infarction were imprecise without clear discrimination between strategies. Conclusions: For patients with low risk acute coronary syndrome, an initial diagnostic strategy of stress echocardiography or cardiovascular magnetic resonance is associated with fewer referrals for invasive coronary angiography and revascularisation procedures than non-invasive anatomical testing, without apparent impact on the future risk of myocardial infarction. For suspected stable coronary artery disease, there was no clear discrimination between diagnostic strategies regarding the subsequent need for invasive coronary angiography, and differences in the risk of myocardial infarction cannot be ruled out. Systematic review registration: PROSPERO registry no CRD42016049442

    Primary Cardiac Sarcoma: A Rare, Aggressive Malignancy with a High Propensity for Brain Metastases.

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    Introduction: Primary cardiac sarcoma (PCS) has a poor prognosis compared to other sarcomas due to late presentation, challenging resection, incidence of metastases, and limited efficacy of systemic therapies. Methods: A medical record search engine was queried to identify patients diagnosed with PCS from 1992 to 2017 at the University of Michigan. Results: Thirty-nine patients with PCS had a median age of 41 years (range 2-77). Common histologies were angiosarcoma (AS, 14), high-grade undifferentiated pleomorphic sarcoma (UPS, 10), and leiomyosarcoma (LMS, 5). Sites of origin were left atrium (18), right atrium (16), and pericardium (5). AS was the most common right-sided tumor; UPS was more common on the left. Eighteen patients presented with metastases involving lung (10), bone (7), liver (5), and brain (4). Twenty-five patients underwent resection, achieving 3 R Conclusions: PCS portends a poor prognosis, because of difficulty in obtaining complete resection of sarcoma, advanced stage at diagnosis, and high risk of brain metastases. Providers should be aware of the increased risk of brain metastases and consider brain imaging at diagnosis and follow-up

    Prediction of cardiovascular risk using Framingham, ASSIGN and QRISK2: how well do they predict individual rather than population risk?

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    BACKGROUND: The objective of this study was to evaluate the performance of risk scores (Framingham, Assign and QRISK2) in predicting high cardiovascular disease (CVD) risk in individuals rather than populations. METHODS AND FINDINGS: This study included 1.8 million persons without CVD and prior statin prescribing using the Clinical Practice Research Datalink. This contains electronic medical records of the general population registered with a UK general practice. Individual CVD risks were estimated using competing risk regression models. Individual differences in the 10-year CVD risks as predicted by risk scores and competing risk models were estimated; the population was divided into 20 subgroups based on predicted risk. CVD outcomes occurred in 69,870 persons. In the subgroup with lowest risks, risk predictions by QRISK2 were similar to individual risks predicted using our competing risk model (99.9% of people had differences of less than 2%); in the subgroup with highest risks, risk predictions varied greatly (only 13.3% of people had differences of less than 2%). Larger deviations between QRISK2 and our individual predicted risks occurred with calendar year, different ethnicities, diabetes mellitus and number of records for medical events in the electronic health records in the year before the index date. A QRISK2 estimate of low 10-year CVD risk (<15%) was confirmed by Framingham, ASSIGN and our individual predicted risks in 89.8% while an estimate of high 10-year CVD risk (≥ 20%) was confirmed in only 48.6% of people. The majority of cases occurred in people who had predicted 10-year CVD risk of less than 20%. CONCLUSIONS: Application of existing CVD risk scores may result in considerable misclassification of high risk status. Current practice to use a constant threshold level for intervention for all patients, together with the use of different scoring methods, may inadvertently create an arbitrary classification of high CVD risk

    Genetics of callous-unemotional behavior in children

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    Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU

    Association Between TAS2R38 Gene Polymorphisms and Colorectal Cancer Risk: A Case-Control Study in Two Independent Populations of Caucasian Origin

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    Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99–1.67; Pvalue = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06–1.75; Pvalue = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12–1.61; Pvalue = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin

    A systematic review of intervention effects on potential mediators of children\u27s physical activity

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    Background : Many interventions aiming to increase children&rsquo;s physical activity have been developed and implemented in a variety of settings, and these interventions have previously been reviewed; however the focus of these reviews tends to be on the intervention effects on physical activity outcomes without consideration of the reasons and pathways leading to intervention success or otherwise. To systematically review the efficacy of physical activity interventions targeting 5-12 year old children on potential mediators and, where possible, to calculate the size of the intervention effect on the potential mediator. Methods : A systematic search identified intervention studies that reported outcomes on potential mediators of physical activity among 5-12 year old children. Original research articles published between 1985 and April 2012 were reviewed. Results : Eighteen potential mediators were identified from 31 studies. Positive effects on cognitive/psychological potential mediators were reported in 15 out of 31 studies. Positive effects on social environmental potential mediators were reported in three out of seven studies, and no effects on the physical environment were reported. Although no studies were identified that performed a mediating analysis, 33 positive intervention effects were found on targeted potential mediators (with effect sizes ranging from small to large) and 73% of the time a positive effect on the physical activity outcome was reported. Conclusions : Many studies have reported null intervention effects on potential mediators of children&rsquo;s physical activity; however, it is important that intervention studies statistically examine the mediating effects of interventions so the most effective strategies can be implemented in future programs

    Setting priorities for knowledge translation of Cochrane reviews for health equity: Evidence for Equity

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    Background A focus on equity in health can be seen in many global development goals and reports, research and international declarations. With the development of a relevant framework and methods, the Campbell and Cochrane Equity Methods Group has encouraged the application of an ‘equity lens’ to systematic reviews, and many organizations publish reviews intended to address health equity. The purpose of the Evidence for Equity (E4E) project was to conduct a priority-setting exercise and apply an equity lens by developing a knowledge translation product comprising summaries of systematic reviews from the Cochrane Library. E4E translates evidence from systematic reviews into ‘friendly front end’ summaries for policy makers. Methods The following topic areas with high burdens of disease globally, were selected for the pilot: diabetes/obesity, HIV/AIDS, malaria, nutrition, and mental health/depression. For each topic area, a “stakeholder panel” was assembled that included policymakers and researchers. A systematic search of Cochrane reviews was conducted for each area to identify equity-relevant interventions with a meaningful impact. Panel chairs developed a rating sheet which was used by all panels to rank the importance of these interventions by: 1) Ease of Implementation; 2) Health System Requirements; 3)Universality/Generalizability/Share of Burden; and 4) Impact on Inequities/Effect on equity. The ratings of panel members were averaged for each intervention and criterion, and interventions were ordered according to the average overall ratings. Results Stakeholder panels identified the top 10 interventions from their respective topic areas. The evidence on these interventions is being summarized with an equity focus and the results posted online, at http://methods.cochrane.org/equity/e4e-series. Conclusions This method provides an explicit approach to setting priorities by systematic review groups and funders for providing decision makers with evidence for the most important equity-relevant interventions

    Erratum to: Methods for evaluating medical tests and biomarkers

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    [This corrects the article DOI: 10.1186/s41512-016-0001-y.]

    withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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