Osteoprotegerin, Osteopontin, and Osteocalcin Are Associated With Cardiovascular Events in Type 2 Diabetes: Insights From EXSCEL.

Objective: To evaluate the association of four bone metabolism biomarkers (osteoprotegerin, osteopontin, sclerostin, and osteocalcin) with cardiovascular events in people with type 2 diabetes (T2D).

Research Design And Methods: The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) was a randomized clinical trial evaluating the cardiovascular (CV) safety and efficacy of once-weekly exenatide for patients with T2D. Candidate biomarker data were selected from proteomic profiling performed at baseline and 12 months after randomization samples by SomaScan assay in 5,473 trial participants.

Using QALYs as an Outcome for Assessing Global Prediction Accuracy in Diabetes Simulation Models.

Objectives: (1) To demonstrate the use of quality-adjusted life-years (QALYs) as an outcome measure for comparing performance between simulation models and identifying the most accurate model for economic evaluation and health technology assessment. QALYs relate directly to decision making and combine mortality and diverse clinical events into a single measure using evidence-based weights that reflect population preferences. (2) To explore the usefulness of Q, the proportional reduction in error, as a model performance metric and compare it with other metrics: mean squared error (MSE), mean absolute error, bias (mean residual), and .

Younger-onset compared with later-onset type 2 diabetes: an analysis of the UK Prospective Diabetes Study (UKPDS) with up to 30 years of follow-up (UKPDS 92).

Background: Younger-onset type 2 diabetes is associated with accelerated complications. We assessed whether complications and mortality rates differed for younger age compared with older age at diagnosis over 30 years of follow-up.

Methods: In this study, we used data from the UKPDS, collected between 1977 and 2007, of participants aged 25-65 years with newly diagnosed type 2 diabetes with younger-onset (younger than 40 years) or later-onset (40 years or older), and without diabetes autoantibodies.

Great debate: pre-diabetes is not an evidence-based treatment target for cardiovascular risk reduction.

With the increasing burden of diabetes as a cause of macro- and microvascular disease linked to the epidemics of obesity, attention is being paid to dysglycaemic states that predict and precede the development of type 2 diabetes. Such conditions, termed pre-diabetes, are characterized by fasting plasma glucose, or plasma glucose levels on an oral glucose tolerance test, or values of glycated haemoglobin intermediate between 'normal' values and those characterizing diabetes. These last are by definition associated, in epidemiological terms, with a higher incidence of microvascular disease-mostly retinopathy.

Predictors of emergency medical transport refusal following opioid overdose in Washington, DC.

Background And Aims: Patient initiated transport refusal during Emergency Medical Service (EMS) opioid overdose encounters has become an endemic problem. This study aimed to quantify circumstantial and environmental factors which predict refusal of further care.

Design: In this cross-sectional analysis, a case definition for opioid overdose was applied retrospectively to EMS encounters.

Cardiovascular outcomes with exenatide in type 2 diabetes according to ejection fraction: The EXSCEL trial.

Aims: Glucagon-like peptide-1 receptor agonists reduce major adverse cardiovascular events (MACE) and cardiovascular mortality in people with type 2 diabetes (T2D). However, previous studies suggest the effects on heart failure outcomes vary according to left ventricular ejection fraction (LVEF). We aimed to evaluate the effects of exenatide on cardiovascular events according to LVEF in people with T2D.

Inflammatory proteins associated with Alzheimer's disease reduced by a GLP1 receptor agonist: a post hoc analysis of the EXSCEL randomized placebo controlled trial.

Background: Glucagon-like peptide-1 receptor agonists are a viable option for the prevention of Alzheimer's disease (AD) but the mechanisms of this potential disease modifying action are unclear. We investigated the effects of once-weekly exenatide (EQW) on AD associated proteomic clusters.

Methods: The Exenatide Study of Cardiovascular Event Lowering study compared the cardiovascular effects of EQW 2 mg with placebo in 13,752 people with type 2 diabetes mellitus.

Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial.

Aim: The decline in estimated glomerular filtration rate (eGFR), a significant predictor of cardiovascular disease (CVD), occurs heterogeneously in people with diabetes because of various risk factors. We investigated the role of eGFR decline in predicting CVD events in people with type 2 diabetes in both primary and secondary CVD prevention settings.

Materials And Methods: Bayesian joint modelling of repeated measures of eGFR and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to examine the association between the eGFR slope and the incidence of major adverse CV event/hospitalization for heart failure (MACE/hHF) (non-fatal myocardial infarction, non-fatal stroke, CV death, or hospitalization for heart failure).

Parent attitudes towards data sharing in developmental science.

Background: Data sharing in developmental science is increasingly encouraged, supported by funder and publisher mandates for open data access. Data sharing can accelerate discovery, link researchers with high quality analytic expertise to researchers with large datasets and democratise the research landscape to enable researchers with limited funding to access large sample sizes. However, there are also significant privacy and security concerns, in addition to conceptual and ethical considerations.

Estimating Risk Factor Time Paths Among People with Type 2 Diabetes and QALY Gains from Risk Factor Management.

Objectives: Most type 2 diabetes simulation models utilise equations mapping out lifetime trajectories of risk factors [e.g. glycated haemoglobin (HbA)].

Protocol for a double-blind placebo-controlled randomised controlled trial assessing the impact of oral semaglutide in amyloid positivity (ISAP) in community dwelling UK adults.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently marketed for type 2 diabetes and obesity, may offer novel mechanisms to delay or prevent neurotoxicity associated with Alzheimer's disease (AD). The impact of semaglutide in amyloid positivity (ISAP) trial is investigating whether the GLP-1 RA semaglutide reduces accumulation in the brain of cortical tau protein and neuroinflammation in individuals with preclinical/prodromal AD.

Methods And Analysis: ISAP is an investigator-led, randomised, double-blind, superiority trial of oral semaglutide compared with placebo.

Isohemagglutinin titration in pooled and apheresis platelets.

Background: Platelet inventory constraints necessitate ABO-incompatible platelet transfusion. Many minimize the hemolytic impact by confirming low titre (LT) donor isohemagglutinins. This process is costly.

A randomized controlled trial evaluating the effects of nurse-led triage of 911 calls.

To better connect non-emergent 911 callers to appropriate care, Washington, DC, routed low-acuity callers to nurses. Nurses could provide non-emergent transportation to a health centre, recommend self-care or return callers to the traditional 911 system. Over about one year, 6,053 callers were randomized (1:1) to receive a business-as-usual response (n = 3,023) or further triage (n = 3,030).

Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91).

Background: The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years.

Patient Education Materials for Immobilisation Masks in Radiation Therapy for Adult Head and Neck Cancer Patients: A Scoping Review.

Immobilisation masks (IMs) are used for people with head and neck cancer (HNC) undergoing radiation therapy (RT) treatment to ensure accuracy and reproducibility between treatments. Claustrophobia-related mask anxiety in HNC patients is common and can compromise treatment due to patient distress. This scoping review aimed to describe the content of publicly available Patient Education Materials (PEMs) for people with HNC undergoing RT.

Regional variation in cause of death in patients with type 2 diabetes: Insights from EXSCEL.

Aims: Type 2 diabetes (T2D) is a risk factor for cardiovascular and non-cardiovascular mortality. However, global distribution of cause-specific deaths in T2D is poorly understood. We characterized cause-specific deaths by geographic region among individuals with T2D at risk for cardiovascular disease (CVD).

Phenotype-based targeted treatment of SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes.

Aims/hypothesis: A precision medicine approach in type 2 diabetes could enhance targeting specific glucose-lowering therapies to individual patients most likely to benefit. We aimed to use the recently developed Bayesian causal forest (BCF) method to develop and validate an individualised treatment selection algorithm for two major type 2 diabetes drug classes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA).

Methods: We designed a predictive algorithm using BCF to estimate individual-level conditional average treatment effects for 12-month glycaemic outcome (HbA) between SGLT2i and GLP1-RA, based on routine clinical features of 46,394 people with type 2 diabetes in primary care in England (Clinical Practice Research Datalink; 27,319 for model development, 19,075 for hold-out validation), with additional external validation in 2252 people with type 2 diabetes from Scotland (SCI-Diabetes [Tayside & Fife]).

Three year outcomes in infants with a family history of autism and/or attention deficit hyperactivity disorder.

Background: Most research on early outcomes in infants with a family history (FH) of autism has focussed on categorically defined autism, although some have language and developmental delays. Less is known about outcomes in infants with a FH of attention deficit hyperactivity disorder (ADHD).

Methods: Infants with and without a FH of autism and/or ADHD, due to a first-degree relative with either or both conditions, were recruited at 5 or 10 months.

Comparison of medical resources and costs among patients with coronary heart disease and impaired glucose tolerance in the Acarbose Cardiovascular Evaluation trial.

Background: The Acarbose Cardiovascular Evaluation (ACE) trial (ISRCTN91899513) evaluated the alpha-glucosidase inhibitor acarbose, compared with placebo, in 6522 patients with coronary heart disease and impaired glucose tolerance in China and showed a reduced incidence of diabetes. We assessed the within-trial medical resource use and costs, and quality-adjusted life years (QALYs).

Methods: Resource use data were collected prospectively within the ACE trial.

Orthostatic Hypotension, Hypertension Treatment, and Cardiovascular Disease: An Individual Participant Meta-Analysis.

Importance: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension.

Objective: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension.

Data Sources: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022.

Timing of SGLT2i initiation after acute myocardial infarction.

Background: Pharmacological post-MI treatment is routinely initiated at intensive/cardiac care units. However, solid evidence for an early start of these therapies is only available for dual platelet therapy and statins, whereas data on beta blockers and RAAS inhibitors are heterogenous and mainly limited to STEMI and heart failure patients. Recently, the EMMY trial provided the first evidence on the beneficial effects of SGLT2 inhibitors (SGLT2i) when initiated early after PCI.