Irradiated Tree Nut Flours for Use in Oral Immunotherapy.

Background: Tree nut allergies affect an estimated 1% of the US population and is lifelong in 90% of allergic individuals. Oral immunotherapy (OIT) for food allergies is an effective method to induce desensitization in a majority of participants in trials of peanut, egg, and milk OIT. Limited trials using tree nut OIT have been reported, possibly due to the lack of standardized drug products.

Factors associated with opioid use after endoscopic sinus surgery.

Objectives/hypothesis: Responsible prescribing of postoperative pain medications is necessary in combatting the current opioid epidemic in the United States. The goal of this study was to determine which clinical factors affect opioid usage following functional endoscopic sinus surgery (FESS).

Study Design: Retrospective medical records study.

Characteristics of pediatric pulmonary hypertension trials registered on ClinicalTrials.gov.

The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high priority by the United States National Institutes of Health (NIH). Studying pediatric PH is challenging due to the rare and heterogeneous nature of the disease. We sought to define the pediatric PH clinical trials landscape, to evaluate areas of trial success or failure, and to identify potential obstacles to the study of pediatric PH drugs.

Clinical Acuity Shorthand System: a standardized classification tool to facilitate handoffs.

Background: The handoff of medical information from one provider to another can be inefficient and error prone, potentially undermining patient safety. Although several tools for structuring handoffs exist, none provide a brief, standardized framework for ensuring that patient acuity is efficiently and reliably communicated. We aim to introduce and perform initial testing of the Clinical Acuity Shorthand System (CLASS) (Copyright 2015, Duke University.

Gene products promoting remyelination are up-regulated in a cell therapy product manufactured from banked human cord blood.

Background Aims: DUOC-01, a cell product being developed to treat demyelinating conditions, is composed of macrophages that arise from CD14 monocytes in the mononuclear cell (MNC) population of banked cord blood (CB). This article demonstrates that expression of multiple gene products that promote remyelination is rapidly up-regulated during manufacturing of DUOC-01 from either MNC or purified CB CD14 monocytes.

Methods: Cell cultures were initiated with MNC or with immunoselected CD14 monocytes isolated from the same CB unit.

Preparation and Analysis of Peanut Flour Used in Oral Immunotherapy Clinical Trials.

Background: Oral immunotherapy (OIT) is an investigational therapeutic approach for the treatment of food allergies. Characterization of the drug product used in oral immunotherapy trials for peanut allergy has not been reported.

Objective: To quantify relative amounts of the major peanut allergens and microbial load present in peanut flour used in OIT trials and assess whether these parameters change over a 12-month period.

Evaluating common data models for use with a longitudinal community registry.

Objective: To evaluate common data models (CDMs) to determine which is best suited for sharing data from a large, longitudinal, electronic health record (EHR)-based community registry.

Materials And Methods: Four CDMs were chosen from models in use for clinical research data: Sentinel v5.0 (referred to as the Mini-Sentinel CDM in previous versions), PCORnet v3.

A cord blood monocyte-derived cell therapy product accelerates brain remyelination.

Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14 monocytes.

Assessing electronic health record phenotypes against gold-standard diagnostic criteria for diabetes mellitus.

Objective: We assessed the sensitivity and specificity of 8 electronic health record (EHR)-based phenotypes for diabetes mellitus against gold-standard American Diabetes Association (ADA) diagnostic criteria via chart review by clinical experts.

Materials And Methods: We identified EHR-based diabetes phenotype definitions that were developed for various purposes by a variety of users, including academic medical centers, Medicare, the New York City Health Department, and pharmacy benefit managers. We applied these definitions to a sample of 173 503 patients with records in the Duke Health System Enterprise Data Warehouse and at least 1 visit over a 5-year period (2007-2011).

Novel baseline predictors of adverse events during oral immunotherapy in children with peanut allergy.

Background: Though peanut oral immunotherapy (OIT) is a promising investigational therapy, its potential is limited by substantial adverse events (AEs), which are relatively understudied.

Objective: A retrospective analysis was conducted, pooling data from 3 pediatric peanut OIT trials, comprising the largest analysis of peanut OIT safety to date.

Methods: We pooled data from 104 children with peanut allergy from 3 peanut OIT studies.

Research Reproducibility in Longitudinal Multi-Center Studies Using Data from Electronic Health Records.

A fundamental premise of scientific research is that it should be reproducible. However, the specific requirements for reproducibility of research using electronic health record (EHR) data have not been sufficiently articulated. There is no guidance for researchers about how to assess a given project and identify provisions for reproducibility.

Effect of single and dual renin-angiotensin blockade on stroke in patients with and without diabetes in VALIANT.

Introduction: Concern has been raised about a possible increase in risk of stroke in patients with diabetes treated with the combination of the renin-inhibitor aliskiren and an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. We compared the rate of stroke in patients with and without diabetes treated with single or dual renin-angiotensin system blockade after acute myocardial infarction.

Patients And Methods: We performed a post hoc analysis of the Valsartan in Acute Myocardial Infarction trial in which 14,703 patients with heart failure, left ventricular systolic dysfunction or both, were randomised to captopril (C), valsartan (V) or both (C + V) after 0.

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: Data From ROCKET AF.

Background: Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions.

Methods And Results: In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin.

Native valve disease in patients with non-valvular atrial fibrillation on warfarin or rivaroxaban.

Objective: To compare the characteristics and outcomes of patients with atrial fibrillation (AF) and aortic stenosis (AS) with patients with AF with mitral regurgitation (MR) or aortic regurgitation (AR) and patients without significant valve disease (no SVD).

Methods: Using Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) data, we analysed efficacy and safety outcomes, adjusting hazard ratios (HRs) for potential confounders using Cox regression analysis.

Results: Among 14 119 intention-to-treat ROCKET AF trial patients, a trial that excluded patients with mitral stenosis or artificial valve prosthesis, 214 had AS with or without other valve abnormalities, 1726 had MR or AR and 12 179 had no SVD.

A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial.

Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats.

D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel immunotoxin that reacts with wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFRvIII proteins overexpressed in glioblastomas. This study assessed the toxicity of intracerebral administration of D2C7-IT to support an initial Food and Drug Administration Investigational New Drug application. After the optimization of the formulation and administration, two cohorts (an acute and chronic cohort necropsied on study days 5 and 34) of Sprague-Dawley (SD) rats (four groups of 5 males and 5 females) were infused with the D2C7-IT formulation at total doses of 0, 0.

Factors Affecting Accuracy of Data Abstracted from Medical Records.

Objective: Medical record abstraction (MRA) is often cited as a significant source of error in research data, yet MRA methodology has rarely been the subject of investigation. Lack of a common framework has hindered application of the extant literature in practice, and, until now, there were no evidence-based guidelines for ensuring data quality in MRA. We aimed to identify the factors affecting the accuracy of data abstracted from medical records and to generate a framework for data quality assurance and control in MRA.

Use of altered informed consent in pragmatic clinical research.

There are situations in which the requirement to obtain conventional written informed consent can impose significant or even insurmountable barriers to conducting pragmatic clinical research, including some comparative effectiveness studies and cluster-randomized trials. Although certain federal regulations governing research in the United States (45 CFR 46) define circumstances in which any of the required elements may be waived, the same standards apply regardless of whether any single element is to be waived or whether consent is to be waived in its entirety. Using the same threshold for a partial or complete waiver limits the options available to institutional review boards as they seek to optimize a consent process.

Exploring the ethical and regulatory issues in pragmatic clinical trials.

The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more "traditional" research methods promise to help close this gap.

Prevalence and Access of Secondary Source Medication Data: Evaluation of the Southeastern Diabetes Initiative (SEDI).

Medication non-adherence is a major public health issue, and measuring non-adherence is a crucial step toward improving it. A paucity of retrievable data prevents researchers from effectively measuring, tracking and sharing outcomes on medication management. High quality data derived from prescribing patterns, including behavioral and technology-based interventions, is necessary to support meaningful use, improve publicly reported quality metrics, and develop strategies to improve medication management.

Diuretic response in acute heart failure-an analysis from ASCEND-HF.

Background: Diuretic unresponsiveness often occurs during hospital admission for acute heart failure (AHF) and is associated with adverse outcome. This study aims to investigate determinants, clinical outcome, and the effects of nesiritide on diuretic response early after admission for AHF.

Methods: Diuretic response, defined as weight loss per 40 mg of furosemide or equivalent, was examined from hospital admission to 48 hours in 4,379 patients from the ASCEND-HF trial.

Worsening heart failure during hospitalization for acute heart failure: Insights from the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF).

Background: Despite initial in-hospital treatment of acute heart failure (HF), some patients experience worsening HF (WHF). There are limited data about the outcomes and characteristics of patients who experience in-hospital WHF.

Methods And Results: We assessed the characteristics and outcomes of patients with and without WHF in the ASCEND-HF trial.

Reprint of: Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases.

Background Aims: Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period.

Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study.

Objectives: While bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity.

Design: Observational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively.