RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial: Study rationale and design.

Out-of-hospital cardiac arrest (OHCA) occurs in nearly 350,000 people each year in the United States (US). Despite advances in pre and in-hospital care, OHCA survival remains low and is highly variable across systems and regions. The critical barrier to improving cardiac arrest outcomes is not a lack of knowledge about effective interventions, but rather the widespread lack of systems of care to deliver interventions known to be successful.

Commensal Oral Microbiota, Disease Severity, and Mortality in Fibrotic Lung Disease.

Oral microbiota associate with diseases of the mouth and serve as a source of lung microbiota. However, the role of oral microbiota in lung disease is unknown. To determine associations between oral microbiota and disease severity and death in idiopathic pulmonary fibrosis (IPF).

Comparison of Pirfenidone and Nintedanib: Post Hoc Analysis of the CleanUP-IPF Study.

Background: Antifibrotics are effective in slowing FVC decline in idiopathic pulmonary fibrosis (IPF). However, whether antifibrotic type is differentially associated with FVC decline remains inconclusive.

Research Question: Are there significant differences in 12-month FVC decline between pirfenidone and nintedanib?

Study Design And Methods: A post hoc analysis was performed using the Clinical Efficacy of Antimicrobial Therapy Strategy Using Pragmatic Design in IPF (CleanUP-IPF) trial (No.

Deferred Testing in Stable Outpatients With Suspected Coronary Artery Disease: A Prespecified Secondary Analysis of the PRECISE Randomized Clinical Trial.

Importance: Guidelines recommend deferral of testing for symptomatic people with suspected coronary artery disease (CAD) and low pretest probability. To our knowledge, no randomized trial has prospectively evaluated such a strategy.

Objective: To assess process of care and health outcomes in people identified as minimal risk for CAD when testing is deferred.

Clinical and cost implications of deferred testing in low-risk patients with stable chest pain: a simulation using the PROMISE trial.

Current guidelines recommend a deferred testing approach in low-risk patients presenting with stable chest pain. After simulating a deferred testing approach using the PROMISE Minimal Risk Score to identify 915 minimal risk participants with cost data from the PROMISE trial, a deferred testing strategy was associated with an adjusted cost savings of -$748.74 (95% CI: -1646.

Circulating Angiokines Are Associated With Reverse Remodeling and Outcomes in Chronic Heart Failure.

Background: We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF).

Methods: We measured 25 proteins related to endothelial function in 99 patients from the GUIDE-IT study. Protein levels were evaluated for association with echocardiographic parameters and the incidence of all-cause death and hospitalization for heart failure (HHF).

The prospective randomized trial of the optimal evaluation of cardiac symptoms and revascularization: Rationale and design of the PRECISE trial.

Background: Clinicians vary widely in their preferred diagnostic approach to patients with non-acute chest pain. Such variation exposes patients to potentially avoidable risks, as well as inefficient care with increased costs and unresolved patient concerns.

Methods: The Prospective Randomized Trial of the Optimal Evaluation of Cardiac Symptoms and Revascularization (PRECISE) trial (NCT03702244) compares an investigational "precision" diagnostic strategy to a usual care diagnostic strategy in participants with stable chest pain and suspected coronary artery disease (CAD).

Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults With Idiopathic Pulmonary Fibrosis: The CleanUP-IPF Randomized Clinical Trial.

Importance: Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis.

Objective: To assess the effect of antimicrobial therapy on clinical outcomes.

Design, Setting, And Participants: Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites.

Differences in NT-proBNP Response and Prognosis in Men and Women With Heart Failure With Reduced Ejection Fraction.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a prognostic biomarker in heart failure (HF) with reduced ejection fraction. However, it is unclear whether there is a sex difference in NT-proBNP response and whether the therapeutic goal of NT-proBNP ≤1000 pg/mL has equivalent prognostic value in men and women with HF with reduced ejection fraction. Methods and Results In a secondary analysis of the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial we analyzed trends in NT-proBNP and goal attainment by sex.

Antifibrotic Drug Use in Patients with Idiopathic Pulmonary Fibrosis. Data from the IPF-PRO Registry.

Two antifibrotic medications, nintedanib and pirfenidone, have been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in the United States. Few data have been published on the use of these medications in clinical practice. To investigate patterns of use of antifibrotic medications in the United States.

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial.

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns.

Percutaneous coronary intervention outcomes in patients with stable coronary disease and left ventricular systolic dysfunction.

Aims: We sought to better understand the role of percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) and moderate or severe left ventricular systolic dysfunction.

Methods And Results: Using data from the Duke Databank for Cardiovascular Disease, we analysed patients who underwent coronary angiography at Duke University Medical Center (1995-2012) that had stable CAD amenable to PCI and left ventricular ejection fraction ≤35%. Patients with acute coronary syndrome or Canadian Cardiovascular Society class III or IV angina were excluded.

NT-proBNP Goal Achievement Is Associated With Significant Reverse Remodeling and Improved Clinical Outcomes in HFrEF.

Objectives: This study aims to assess the association between biomarker-guided therapy and left ventricular (LV) remodeling.

Background: In patients with heart failure with reduced ejection fraction (HFrEF), it is unclear if lowering natriuretic peptides reflects structural and functional changes in the heart. This study aims to assess the association between biomarker-guided therapy and left ventricular (LV) remodeling.

Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial.

Background: Abnormal acid gastro-oesophageal reflux (GER) is hypothesised to play a role in progression of idiopathic pulmonary fibrosis (IPF). We aimed to determine whether treatment of abnormal acid GER with laparoscopic anti-reflux surgery reduces the rate of disease progression.

Methods: The WRAP-IPF trial was a randomised controlled trial of laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER recruited from six academic centres in the USA.

Analysis of relationships between 25-hydroxyvitamin D, parathyroid hormone and cathelicidin with inflammation and cardiovascular risk in subjects with paediatric systemic lupus erythematosus: an Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study.

Objectives: Previous studies demonstrated associations between reduced serum 25-hydroxyvitamin D (25OHD), inflammation and disease activity in paediatric systemic lupus erythematosus (pSLE). The goal of this study was to assess parathyroid hormone (PTH) in its relationship to vitamin D and inflammation, as well as to better understand the role of human cathelicidin (LL-37) in pSLE.

Methods: Frozen serum samples collected at baseline of the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study were assayed to determine 25OHD, PTH and LL-37 levels.

Echocardiography Core Laboratory Reproducibility of Cardiac Safety Assessments in Cardio-Oncology.

Background: As the potential for cancer therapy-related cardiac dysfunction is increasingly recognized, there is a need for the standardization of echocardiographic measurements and cut points to guide treatment. The aim of this study was to determine the reproducibility of cardiac safety assessments across two academic echocardiography core laboratories (ECLs) at the University of Pennsylvania and the Duke Clinical Research Institute.

Methods: To harmonize the application of guideline-recommended measurement conventions, the ECLs conducted multiple training sessions to align measurement practices for traditional and emerging assessments of left ventricular (LV) function.

Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide.

Background: Mitochondrial dysfunction and energy depletion in the failing heart are innovative therapeutic targets in heart failure management. Elamipretide is a novel tetrapeptide that increases mitochondrial energy; however, its safety, tolerability, and therapeutic effect on cardiac structure and function have not been studied in heart failure with reduced ejection fraction.

Methods And Results: In this double-blind, placebo-controlled, ascending-dose trial, patients with heart failure with reduced ejection fraction (ejection fraction, ≤35%) were randomized to either a single 4-hour infusion of elamipretide (cohort 1 [n=8], 0.

Reliability of the triple-timed up-and-go test.

Introduction: We report the reliability of a new measure, the triple-timed up-and-go (3TUG) test, for assessing clinical function in patients with Lambert-Eaton myasthenia (LEM).

Methods: Intrarater reproducibility and interrater agreement of the 3TUG test were assessed in 25 control participants, 24 patients with non-LEM neuromuscular disease, and 12 patients with LEM. The coverage probability (CP) method was the primary measure of reproducibility and agreement.

Comparison of visual assessment of coronary stenosis with independent quantitative coronary angiography: Findings from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial.

Background: The outcomes in patients by visual assessment and quantitative coronary angiography (QCA) for obstructive coronary artery disease (CAD) are not known. Our objectives were to compare visual and QCA estimates of obstructive CAD and to assess their relationship to outcomes in stable patients with symptoms of CAD.

Methods: The PROMISE trial randomized 10,003 patients with CAD symptoms to anatomical or functional testing.

Idiopathic Pulmonary Fibrosis: The Association between the Adaptive Multiple Features Method and Fibrosis Outcomes.

Rationale: Adaptive multiple features method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns.

Objectives: To evaluate AMFM and visual quantification of HRCT patterns and their relationship with disease progression in idiopathic pulmonary fibrosis.

Methods: Patients with idiopathic pulmonary fibrosis in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish.

Critical Review of Current Approaches for Echocardiographic Reproducibility and Reliability Assessment in Clinical Research.

Background: There is no broadly accepted standard method for assessing the quality of echocardiographic measurements in clinical research reports, despite the recognized importance of this information in assessing the quality of study results.

Methods: Twenty unique clinical studies were identified reporting echocardiographic data quality for determinations of left ventricular (LV) volumes (n = 13), ejection fraction (n = 12), mass (n = 9), outflow tract diameter (n = 3), and mitral Doppler peak early velocity (n = 4). To better understand the range of possible estimates of data quality and to compare their utility, reported reproducibility measures were tabulated, and de novo estimates were then calculated for missing measures, including intraclass correlation coefficient (ICC), 95% limits of agreement, coefficient of variation (CV), coverage probability, and total deviation index, for each variable for each study.

Laparoscopic anti-reflux surgery for idiopathic pulmonary fibrosis at a single centre.

We sought to assess whether laparoscopic anti-reflux surgery (LARS) is associated with decreased rates of disease progression in patients with idiopathic pulmonary fibrosis (IPF).The study was a retrospective single-centre study of IPF patients with worsening symptoms and pulmonary function despite antacid treatment for abnormal acid gastro-oesophageal reflux. The period of exposure to LARS was September 1998 to December 2012.

Echocardiographic agreement in the diagnostic evaluation for infective endocarditis.

Echocardiography is essential for the diagnosis and management of infective endocarditis (IE). However, the reproducibility for the echocardiographic assessment of variables relevant to IE is unknown. Objectives of this study were: (1) To define the reproducibility for IE echocardiographic variables and (2) to describe a methodology for assessing quality in an observational cohort containing site-interpreted data.