Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.

Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

Design: Double-blind, randomized, placebo-controlled, clinical trial.

Current use, training, and barriers in point-of-care ultrasound in hospital medicine: A national survey of VA hospitals.

Background: Point-of-care ultrasound (POCUS) can reduce procedural complications and improve the diagnostic accuracy of hospitalists. Currently, it is unknown how many practicing hospitalists use POCUS, which applications are used most often, and what barriers to POCUS use exist.

Objective: This study aimed to characterize current POCUS use, training needs, and barriers to use among hospital medicine groups (HMGs).

Harmonizing Magnetic Resonance Imaging Protocols for Veterans With Multiple Sclerosis.

Background: Magnetic resonance imaging (MRI) assists with the diagnosis of multiple sclerosis (MS), allows for timely therapeutic intervention, and for the evaluation of disease progression, treatment effect, and safety. An international task force including representatives from the Veterans Health Administration worked together to update guidelines for imaging the brain, spinal cord, and optic nerve in people with MS.

Observations: This commentary communicates the core message of the 2021 MAGNIMS-CMSC-NAIMS Consensus Recommendations on the Use of MRI in Patients With Multiple Sclerosis as part of the MS Center of Excellence effort to align with contemporary guidelines, apply the highest scientific standards, and achieve consistent outcomes for veterans with MS.

Screening High-Risk Women Veterans for Breast Cancer.

Background: Within the US Department of Veterans Affairs (VA), breast cancer prevalence has more than tripled from 1995 to 2012. Women veterans may be at an increased breast cancer risk based on service-related exposures and posttraumatic stress disorder (PTSD).

Methods: Women veterans aged ≥ 35 years with no personal history of breast cancer were enrolled at 2 urban VA medical centers.

Outcomes of Premature Ventricular Contraction-Cardiomyopathy in the Veteran Population: A Secondary Analysis of the CHF-STAT Study.

Objectives: This study sought to assess the rate and outcomes of premature ventricular contractions (PVC)-cardiomyopathy from the CHF-STAT (Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure) trial, a population with cardiomyopathy (left ventricular [LV] ejection fraction of <40%) and frequent PVCs (>10 PVCs per hour).

Background: PVCs are associated with heart failure and PVC-cardiomyopathy. The prevalence of PVC-cardiomyopathy and outcome benefits of PVC suppression are not clear.

Treatment of HF in an Era of Multiple Therapies: Statement From the HF Collaboratory.

The treatment of heart failure with reduced ejection fraction (HFrEF) has changed considerably over time, particularly with the sequential development of therapies aimed at antagonism of maladaptive biologic pathways, including inhibition of the sympathetic nervous system and the renin-angiotensin aldosterone system. The sequential nature of earlier HFrEF trials allowed the integration of new therapies tested against the background therapy of the time. More recently, multiple heart failure therapies are being evaluated simultaneously, and the number of therapeutic choices for treating HFrEF has grown considerably.

Standardized Definitions for Evaluation of Heart Failure Therapies: Scientific Expert Panel From the Heart Failure Collaboratory and Academic Research Consortium.

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation.

Conduct of Clinical Trials in the Era of COVID-19: JACC Scientific Expert Panel.

The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S.

Standardized definitions for evaluation of heart failure therapies: scientific expert panel from the Heart Failure Collaboratory and Academic Research Consortium.

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation.

Covariate adjusted reanalysis of the I-Preserve trial.

Background: The CHARM-Preserved trial suggested that the renin-angiotensin system (RAS) inhibitor candesartan might have been beneficial in heart failure with preserved ejection fraction (HFpEF); however, this hypothesis was not supported by the findings of I-Preserve with irbesartan.

Aims: To re-analyse the results of I-Preserve, adjusting for imbalances in baseline variables that may have influenced the trial outcomes.

Methods: Cox proportional hazards models with covariate adjustment for baseline variables, including age, sex, medical history, physiological and laboratory variables.

Heart Failure End Points in Cardiovascular Outcome Trials of Sodium Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Critical Evaluation of Clinical and Regulatory Issues.

Following regulatory guidance set forth in 2008 by the US Food and Drug Administration for new drugs for type 2 diabetes mellitus, many large randomized, controlled trials have been conducted with the primary goal of assessing the safety of antihyperglycemic medications on the primary end point of major adverse cardiovascular events, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Heart failure (HF) was not specifically mentioned in the US Food and Drug Administration guidance and therefore it was not a focus of these studies when planned. Several trials subsequently showed the impact of antihyperglycemic drugs on HF outcomes, which were not originally specified as the primary end point of the trials.

Platelet ATP, Thyroid Hormone Receptor on Integrin αvβ3 and Cancer Metastasis.

Activated platelets may contribute to the metastatic behavior of tumor cells when the cancer cells and platelets interact. The interaction requires cell and platelet surface integrin. Thyroid hormone as L-thyroxine (T4) is the principal ligand for a hormone receptor on integrin αvβ3 on tumor cells and platelets.

A randomized evaluation of on-site monitoring nested in a multinational randomized trial.

Background: Evidence from prospectively designed studies to guide on-site monitoring practices for randomized trials is limited. A cluster randomized study, nested within the Strategic Timing of AntiRetroviral Treatment (START) trial, was conducted to evaluate on-site monitoring.

Methods: Sites were randomized to either annual on-site monitoring or no on-site monitoring.

Design of a "Lean" Case Report Form for Heart Failure Therapeutic Development.

The development of treatments for heart failure (HF) is challenged by burdensome clinical trials. Reducing the need for extensive data collection and increasing opportunities for data compatibility between trials may improve efficiency and reduce resource burden. The Heart Failure Collaboratory (HFC) multi-stakeholder consortium sought to create a lean case report form (CRF) for use in HF clinical trials evaluating cardiac devices.

Prior Pacemaker Implantation and Clinical Outcomes in Patients With Heart Failure and Preserved Ejection Fraction.

Objectives: This study examined the relationship between prior pacemaker implantation and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF).

Background: Conventional right ventricular pacing causes electrical and mechanical left ventricular dyssynchrony and may worsen left ventricular systolic dysfunction and HF. Whether conventional pacing is also associated with worse outcomes in HFpEF is unknown.

N-Terminal Pro-B-Type Natriuretic Peptide Levels for Risk Prediction in Patients With Heart Failure and Preserved Ejection Fraction According to Atrial Fibrillation Status.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is useful in diagnosis and prognostication in heart failure (HF). We examined the relationship between NT-proBNP and outcomes in patients with HF and preserved ejection fraction, with and without atrial fibrillation (AF). Methods and Results Among 3835 HF with preserved ejection fraction patients enrolled in the I-Preserve (Irbesartan in Heart Failure With Preserved Systolic Function trial) or TOPCAT trial (Treatment of Preserved Cardiac Function in Heart Failure With an Aldosterone Antagonist), 719 (19%) patients had AF on their baseline ECG.

Burden of medical co-morbidities and benefit from surgical revascularization in patients with ischaemic cardiomyopathy.

Aims: The landmark STICH trial found that surgical revascularization compared to medical therapy alone improved survival in patients with heart failure (HF) of ischaemic aetiology and an ejection fraction (EF) ≤ 35%. However, the interaction between the burden of medical co-morbidities and the benefit from surgical revascularization has not been previously described in patients with ischaemic cardiomyopathy.

Methods And Results: The STICH trial (ClinicalTrials.

New Interfaces of Thyroid Hormone Actions With Blood Coagulation and Thrombosis.

Substantial clinical evidence indicates hyperthyroidism enhances coagulation and increases the risk of thrombosis. In vitro and clinical evidence implicate multiple mechanisms for this risk. Genomic actions of thyroid hormone as 3,5,3'-triiodo-L-thyronine (T) via a nuclear thyroid hormone receptor have been implicated, but recent evidence shows that nongenomic mechanisms initiated at the receptor for L-thyroxine (T) on platelet integrin αvβ3 are prothrombotic.

Which HIV-infected adults with high CD4 T-cell counts benefit most from immediate initiation of antiretroviral therapy? A post-hoc subgroup analysis of the START trial.

Background: Immediate initiation of antiretroviral therapy (ART) in asymptomatic adults with CD4 counts higher than 500 cells per μL, as recommended, might not always be possible in resource-limited settings. We aimed to identify subgroups of individuals who would benefit most from immediate treatment.

Methods: The START trial was a randomised controlled trial in asymptomatic, HIV-positive adults previously untreated with ART.

Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial.

Objective: To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT).

Research Design And Methods: This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL).

In-Hospital Mortality in Cirrhotic Patients with End-Stage Renal Disease Treated with Hemodialysis Versus Peritoneal Dialysis: A Nationwide Study.

Background: Cirrhotic patients often develop end-stage renal disease (ESRD) requiring renal replacement therapy in the form of hemodialysis (HD) or peritoneal dialysis (PD). Studies comparing the outcomes and difference in in-hospital mortality between these 2 groups, particularly among those with ascites, are sparse. We set our objective to determine the dialysis modality with a better in-hospital survival rate among cirrhotic patients with ESRD (ESRD-cirrhosis).

Device-Based Therapy for Drug-Resistant Hypertension: An Update.

Drug-resistant hypertension (RH) remains a significant and common cardiovascular risk despite the availability of multiple potent antihypertensive medications. Uncontrolled resistant hypertension contributes substantially to excessive cardiovascular and renal morbidity and mortality. Clinical and experimental evidence suggest that sympathetic nervous system over-activity is the main culprit for the development and maintenance of drug-resistant hypertension.