Risultati per: Come il corpo produce i trigliceridi

Circulation, Volume 150, Issue Suppl_1, Page A4141151-A4141151, November 12, 2024. Background:Dozens of polygenic risk scores (PRSs) have been developed to estimate coronary artery disease (CAD) risk. Some are available clinically. PRS performances are traditionally evaluated and compared at the population level. Whether they provide similar individual-level assessments of disease liability is a critical consideration for clinical implementation that remains uncharacterized.Research Question:How does individual-level risk prediction compare across CAD PRSs?Methods:Published CAD PRSs were curated from the PGS Catalog, and two novel PRSs were created from the results of a large GWAS meta-analysis. For each score, normalized individual risk scores were calculated for All of Us Research Program (AOU) participants. PRSs with equal population-level performance were identified by using Bayesian analysis of variance to compare calibration and discrimination (Brier score and AUROC) of generalized linear models of prevalent CAD. Among equivalently performing scores, the individual-level agreement between risk percentile estimates was tested with intraclass correlation (ICC) and Light’s Kappa. This approach was replicated in the Penn Medicine Biobank (PMBB) and UCLA ATLAS Biobank.Results:50 PRSs were calculated for 171,095 AOU participants. When included in a model of prevalent CAD, 48 scores had practically equivalent Brier scores and AUROCs (region of practical equivalence = 0.02). Across these scores, 84% of AOU participants had at least one score in both the top and bottom risk quintile. Continuous agreement of individual risk predictions from the 48 scores was poor, with an ICC of 0.351 (95% CI; 0.349, 0.352). Agreement between two statistically equivalent scores was moderate, with an ICC of 0.646 (95% CI 0.643, 0.649). Light’s Kappa, used to evaluate consistency of assignment to high-risk percentile cutoffs, did not exceed 0.56 (interpreted as ‘fair’) across statistically and practically equivalent scores. Repeating the analysis among 41,193 PMBB and 50,748 UCLA participants yielded different sets of statistically and practically equivalent scores which also lacked strong individual agreement.Conclusions:When tested across three diverse biobanks, CAD PRSs that performed equivalently at the population level produced highly variable individual estimates of risk. Approaches to clinical implementation of CAD PRSs need to consider the potential for discordant individual risk estimates from otherwise indistinguishable scores.

New England Journal of Medicine, Ahead of Print.

Introduction
US Department of Agriculture (USDA) Gus Schumacher Nutrition Incentive Programme (GusNIP) produce prescription programme (PPR) ‘prescriptions’ provide eligible participants with low income, risk for diet-related chronic disease and food insecurity a healthcare issued incentive to purchase lower to no cost fruits and vegetables (FVs). However, GusNIP requirements specify that PPR prescriptions can only be redeemed for fresh (not frozen, canned or dried) FVs. This requirement may prevent participants from fully engaging in or benefiting from GusNIP PPR, given communities with lower healthy food access may have reduced fresh FV accessibility.

Methods and analysis
We will use the nationally representative 2012–2013 National Household Food Acquisition and Purchase Survey (FoodAPS) and complementary FoodAPS Geography Component data in a secondary data analysis to examine how household GusNIP PPR eligibility relates to the quantity and variety of fresh, frozen, canned and dried FV purchases and to what extent individual, household and food environment factors shape the relationship. FoodAPS data include household food purchasing and acquisition information across a 7 day period from 14 317 individuals among 4826 households and was collected between April 2012 and January 2013. The FoodAPS Geography Component provides information about the local community/environment relative to FoodAPS households. This study will examine the correlation or association of selected variables between different quantities and varieties of fresh, frozen, canned and dried FVs, as well as correlations among multilevel predictors.

Ethics and dissemination
We are following data integrity standards as outlined by agreements with the USDA Economic Research Service. All results of analyses will undergo a thorough disclosure review to ensure no identifiable data are shared. Results will be disseminated to research, practice and policy communities using an Open Access peer-reviewed manuscript(s), scientific and practice presentations, and a public facing report and infographic.

Introduction
An association between deep sedation and adverse short-term outcomes has been demonstrated although this evidence has been inconsistent. The A2B (alpha-2 agonists for sedation in critical care) sedation trial is designed to determine whether the alpha-2 agonists clonidine and dexmedetomidine, compared with usual care, are clinically and cost-effective. The A2B intervention is a complex intervention conducted in 39 intensive care units (ICUs) in the UK. Multicentre organisational factors, variable cultures, perceptions and practices and the involvement of multiple members of the healthcare team add to the complexity of the A2B trial. From our pretrial contextual exploration it was apparent that routine practices such as type and frequency of pain, agitation and delirium assessment, as well as the common sedative agents used, varied widely across the UK. Anticipated challenges in implementing A2B focused on the impact of usual practice, perceptions of risk, ICU culture, structure and the presence of equipoise. Given this complexity, a process evaluation has been embedded in the A2B trial to uncover factors that could impact successful delivery and explore their impact on intervention delivery and interpretation of outcomes.

Methods and analysis
This is a mixed-methods process evaluation guided by the A2B intervention logic model. It includes two phases of data collection conducted during and at the end of trial. Data will be collected using a combination of questionnaires, stakeholder interviews and routinely collected trial data. A framework approach will be used to analyse qualitative data with synthesis of data within and across the phases. The nature of the relationship between delivery of the A2B intervention and the trial primary and secondary outcomes will be explored.

Ethics and dissemination
All elements of the A2B trial, including the process evaluation, are approved by Scotland A Research Ethics Committee (Ref. 18/SS/0085). Dissemination will be via publications, presentations and media engagement.

Trial registration number
NCT03653832.

Primo ospedale pubblico pediatrico in Italia

Primo ospedale pubblico pediatrico in Italia

Introduction
Almost all patients receiving mechanical ventilation (MV) in intensive care units (ICUs) require analgesia and sedation. The most widely used sedative drug is propofol, but there is uncertainty whether alpha2-agonists are superior. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial aims to determine whether clonidine or dexmedetomidine (or both) are clinically and cost-effective in MV ICU patients compared with usual care.

Methods and analysis
Adult ICU patients within 48 hours of starting MV, expected to require at least 24 hours further MV, are randomised in an open-label three arm trial to receive propofol (usual care) or clonidine or dexmedetomidine as primary sedative, plus analgesia according to local practice. Exclusions include patients with primary brain injury; postcardiac arrest; other neurological conditions; or bradycardia. Unless clinically contraindicated, sedation is titrated using weight-based dosing guidance to achieve a Richmond-Agitation-Sedation score of –2 or greater as early as considered safe by clinicians. The primary outcome is time to successful extubation. Secondary ICU outcomes include delirium and coma incidence/duration, sedation quality, predefined adverse events, mortality and ICU length of stay. Post-ICU outcomes include mortality, anxiety and depression, post-traumatic stress, cognitive function and health-related quality of life at 6-month follow-up. A process evaluation and health economic evaluation are embedded in the trial.
The analytic framework uses a hierarchical approach to maximise efficiency and control type I error. Stage 1 tests whether each alpha2-agonist is superior to propofol. If either/both interventions are superior, stages 2 and 3 testing explores which alpha2-agonist is more effective. To detect a mean difference of 2 days in MV duration, we aim to recruit 1437 patients (479 per group) in 40–50 UK ICUs.

Ethics and dissemination
The Scotland A REC approved the trial (18/SS/0085). We use a surrogate decision-maker or deferred consent model consistent with UK law. Dissemination will be via publications, presentations and updated guidelines.

Trial registration number
ClinicalTrials.gov NCT03653832.

Impegno per Holostem. La petizione su Change.org ha raccolto oltre 45.300 firme

Si chiama “La memoria del nemico” il libro di Anrnaldo D’Amico sulla scoperta del vero eroe dei nostri giorni: il sistema immunitario

Da studi preliminari su topi dubbi su sucralosio

Total ankle replacement and ankle fusion were equally effective for improving end-stage ankle osteoarthritis and had a similar number of harms, trialists reported in the Annals of Internal Medicine.