Bmc Med
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Observational Study
Polygenic risk score improves the accuracy of a clinical risk score for coronary artery disease.
The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations. METHODS: An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case-control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine the risk prediction performance of pooled cohort equations, integrated polygenic risk score, and PRS-enhanced pooled cohort equation for incident CAD cases. The performance of each model was analyzed by discrimination and risk reclassification using a 7.5% threshold. ⋯ Addition of the integrated polygenic risk score for CAD to the pooled cohort questions improves the predictive accuracy for incident CAD and clinical risk classification in the White British from the UK Biobank. These findings suggest that an integrated polygenic risk score may enhance CAD risk prediction and screening in the White British population.
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The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic review aims to evaluate the availability, inclusivity, and quality of pandemic influenza CMGs, to identify gaps that can be addressed to strengthen pandemic preparedness in this area. ⋯ Our data highlights the limited availability of up-to-date pandemic influenza CMGs globally. Of those identified, many were limited in scope and quality and several lacked recommendations for specific at-risk populations. Recommendations on supportive care, the mainstay of treatment, were limited and heterogeneous. The most recent guideline highlighted that the evidence-base to support antiviral treatment recommendations is still limited. There is an urgent need for trials into treatment and supportive care strategies including for different risk populations. New evidence should be incorporated into globally accessible guidelines, to benefit patient outcomes. A 'living guideline' framework is recommended and further research into guideline implementation in different resourced settings, particularly low- and middle-income countries.
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The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five pregnancy-related conditions, including pre-eclampsia. In parallel, we published target product profiles (TPPs) that describe optimal characteristics of medicines for use in preventing/treating pre-eclampsia. The study objective was to use systematic double screening and extraction to identify all candidate medicines being investigated for pre-eclampsia prevention/treatment and rank their potential based on the TPPs. ⋯ This is a novel, evidence-informed approach to identifying promising candidates for pre-eclampsia prevention and treatment - a vital step in stimulating R&D of new medicines for pre-eclampsia suitable for real-world implementation.
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Women with gestational diabetes (GDM) have an elevated lifetime incidence of cardiovascular disease (CVD), but the basis of this excess risk remains to be established. In this context, we hypothesized that chronic exposure to adverse cardiovascular risk factors may contribute to their elevated risk of CVD. We thus sought to quantify the determinants of CVD risk in women with a history of GDM by performing mediation analyses. ⋯ Adverse glycemic and lipid measures mediate the elevated risk of CVD in women with previous GDM, with the impact of lipids particularly evident in those who do not develop diabetes. These findings thus identify potential targets for risk factor monitoring and ultimately early intervention towards the goal of primary prevention of CVD in this at-risk patient population.
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Randomized Controlled Trial
Methylene blue for intractable pain from oral mucositis related to cancer treatment: a randomized phase 2 clinical trial.
Oral mucositis (OM) in patients receiving cancer therapy is thus far not well managed with standard approaches. We aimed to assess the safety and effectiveness of methylene blue (MB) oral rinse for OM pain in patients receiving cancer therapy. ⋯ MB oral rinse showed significant pain reduction and improved oral functioning with minimal adverse effects.