Ethical Issues Faced by Data Monitoring Committees: Results from an Exploratory Qualitative Study.

To protect research participants and ensure scientific integrity in clinical trials, independent data monitoring committees (DMCs, also known as data and safety monitoring boards) increasingly oversee randomized clinical trials and recommend modifying or stopping research. Little is known about the ethical issues DMCs face. We conducted semistructured interviews of DMC members using a qualitative description approach with low-inference interpretation.

Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia.

Background: Adrenal insufficiency in patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy. Control of adrenal-derived androgen excess usually requires supraphysiologic glucocorticoid dosing, which predisposes patients to glucocorticoid-related complications. Crinecerfont, an oral corticotropin-releasing factor type 1 receptor antagonist, lowered androstenedione levels in phase 2 trials involving patients with CAH.

Optimizing Blood Culture Collection Volumes.

Infection in an immunocompromised person can be a life-threatening emergency. Collection of blood culture specimens is an important method for detecting organisms when infection is suspected. One aspect of proper blood culture collection is obtaining an accurate blood volume in the sample in accordance with the blood culture bottle manufacturer's recommendation.

Objection or Obstacle: Applying Amartya Sen's Capability Approach to the Conscientious Refusal of Emergency Contraception.

The conscientious refusal to dispense emergency contraception (EC) is legally protected in fourteen states. While the ethical dimensions of these objections have been explored within moral and feminist philosophy, conscientious refusal to the over-the-counter sale of EC has not been significantly studied through an egalitarian lens, especially with attention to the existing reproductive healthcare landscape in which these refusals occur. This article argues, through Amartya Sen's capability approach, that conscientious refusal to EC creates a burdensome inequality for people wishing to prevent pregnancy that manifests within a background of historical injustices, elevating its importance in our weighing of capabilities.

Interleaved Assistance and Resistance for Exoskeleton Mediated Gait Training: Validation, Feasibility and Effects.

Strength and selective motor control are primary determinants of pathological gait in children with cerebral palsy (CP) and other neuromotor disorders. Emerging evidence suggests robotic application of task-specific resistance to functional movements may provide the opportunity to strengthen muscles and improve neuromuscular function during walking in children with CP. Such a strategy could be most beneficial to children who are more severely affected by the pathology but their ability to overcome such resistance and maintain functional ambulation remains unclear.

Excess 11-Oxygenated Androgens in Women With Severe Insulin Resistance Are Mediated by Adrenal Insulin Receptor Signaling.

Context: Syndromes of severe insulin resistance (SIR) include insulin receptoropathy, in which all signaling downstream of the insulin receptor is lost, and lipodystrophy, in which some signaling pathways are impaired and others preserved. Women with SIR commonly have ovarian hyperandrogenemia; adrenal-derived 11-oxygenated androgens, produced by CYP11B1, have not been studied.

Objective: We aimed to evaluate classic pathway androgens (androstenedione, testosterone) and 11-oxygenated androgens in women with SIR and hyperandrogenemia, and to elucidate the role of insulin receptor signaling for 11-oxygenated androgen production by comparing lipodystrophy and receptoropathy.

Evaluating the Ability to Consent to Research: A Twenty-Year Track Record.

Occasionally, the ability of prospective research participants to consent may be uncertain. Yet standardized capacity-assessment tools may not suffice to determine the ability to consent to a particular research protocol. This study consisted of a retrospective review of the outcomes of an alternative approach used by the Ability to Consent Assessment Team at the National Institutes of Health.

American Indian and Alaska Native Enrollment in Clinical Studies in the National Institutes of Health's Intramural Research Program.

Clinical studies conducted by the National Institutes of Health's Intramural Research Program (NIH-IRP) provide eligible individuals with access to innovative research treatments that may not otherwise be available. The NIH-IRP's mission is to include all Americans, including American Indians and Alaska Natives, in its clinical research. This study is the first to provide data about inclusion of American Indians/Alaska Natives in NIH-IRP clinical studies.

Akwenda intervention programme for children and youth with cerebral palsy in a low-resource setting in sub-Saharan Africa: protocol for a quasi-randomised controlled study.

Introduction: Cerebral palsy (CP) is the most common childhood-onset motor disorder accompanied by associated impairments, placing a heavy burden on families and health systems. Most children with CP live in low/middle-income countries with little access to rehabilitation services. This study will evaluate the Akwenda CP programme, a multidimensional intervention designed for low-resource settings and aiming at improving: (1) participation, motor function and daily activities for children with CP; (2) quality of life, stress and knowledge for caregivers; and (3) knowledge and attitudes towards children with CP in the communities.

Integrating Eye Tracking and Speech Recognition Accurately Annotates MR Brain Images for Deep Learning: Proof of Principle.

Purpose: To generate and assess an algorithm combining eye tracking and speech recognition to extract brain lesion location labels automatically for deep learning (DL).

Materials And Methods: In this retrospective study, 700 two-dimensional brain tumor MRI scans from the Brain Tumor Segmentation database were clinically interpreted. For each image, a single radiologist dictated a standard phrase describing the lesion into a microphone, simulating clinical interpretation.

The Competing Demands of Patient Privacy and Clinical Research.

Privacy and confidentiality of personal medical information are cornerstones of ethical clinical care and ethical research. But real-world research has challenged traditional ways of thinking about privacy and confidentiality of information. In today's world of "big data" and learning health care systems, researchers and others are combining multiple sources of information to address complex problems.

Exoskeleton Assistance Improves Crouch during Overground Walking with Forearm Crutches: A Case Study.

Research, development and testing of wearable robotic exoskeletons for gait training and improved mobility in children with cerebral palsy (CP) and other movement disorders has become increasingly prevalent in recent years. Broadly, these devices are split into two categories: fully wearable devices that are affixed to the lower limbs and/or pelvis and systems that include a mobile frame that moves with the user. The former systems have generally targeted more functional individuals who are independent walkers while the latter target more affected individuals who do not ambulate on their own.

A Phase 2, Multicenter Study of Nevanimibe for the Treatment of Congenital Adrenal Hyperplasia.

Context: Patients with classic congenital adrenal hyperplasia (CAH) often require supraphysiologic glucocorticoid doses to suppress adrenocorticotropic hormone (ACTH) and control androgen excess. Nevanimibe hydrochloride (ATR-101), which selectively inhibits adrenal cortex function, might reduce androgen excess independent of ACTH and thus allow for lower glucocorticoid dosing in CAH. 17-hydroxyprogesterone (17-OHP) and androstenedione are CAH biomarkers used to monitor androgen excess.

Advantages of Using Lotteries to Select Participants for High-Demand Covid-19 Treatment Trials.

As hospitals have experienced a surge of Covid-19 patients, investigators of Covid-19 treatment trials face a difficult problem: when an institution has more eligible and interested patients than trial slots, who should be enrolled? Defining a clear strategy for selecting participants for "high-demand" Covid-19 treatment trials is important to avoid ad hoc and potentially biased decision-making by local investigators, which could inadvertently compromise a trial's social value, participants' interests, or fairness. In this article, we propose a set of ethical criteria for evaluating participant-selection strategies for such trials. We argue that the pandemic context-in particular, great urgency to develop safe and effective treatments, uncertainty surrounding Covid-19, and strain on the health care system that limits the time and effort available for trial enrollment-favors participant-selection strategies that optimize the ease of enrollment and, ideally, social value.

Controversies in Perioperative Antimicrobial Prophylaxis.

Although clinical guidelines for antibiotic prophylaxis across a wide array of surgical procedures have been proposed by multidisciplinary groups of physicians and pharmacists, clinicians often deviate from recommendations. This is particularly true when recommendations are based on weak data or expert opinion. The goal of this review is to highlight certain common but controversial topics in perioperative prophylaxis and to focus on the data that does exist for the recommendations being made.

Adrenal morphology and associated comorbidities in congenital adrenal hyperplasia.

Objective: Adrenonodular hyperplasia and tumour formation are potential long-term complications of congenital adrenal hyperplasia (CAH) with little known regarding the clinical implications. Our aim was to describe volumetric adrenal morphology and determine the association between radiological findings and comorbidities in adults with classic CAH.

Design: This was a cross-sectional study of 88 patients (mean age 29.

Asymptotic convergence in distribution of the area bounded by prevalence-weighted Kaplan-Meier curves using empirical process modelling.

The Kaplan-Meier product-limit estimator is a simple and powerful tool in time to event analysis. An extension exists for populations stratified into cohorts where a population survival curve is generated by weighted averaging of cohort-level survival curves. For making population-level comparisons using this statistic, we analyse the statistics of the area between two such weighted survival curves.

Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.

Background: Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. The UDN, which is funded by the National Institutes of Health, was formed in 2014 as a network of seven clinical sites, two sequencing cores, and a coordinating center.

Respiratory magnetic resonance imaging biomarkers in Duchenne muscular dystrophy.

Objective: To examine the diaphragm and chest wall dynamics with cine breathing magnetic resonance imaging (MRI) in ambulatory boys with Duchenne muscular dystrophy (DMD) without respiratory symptoms and controls.

Methods: In 11 DMD boys and 15 controls, cine MRI of maximal breathing was recorded for 10 sec. The lung segmentations were done by an automated pipeline based on a Holistically-Nested Network model (HNN method).

Genetics of Congenital Adrenal Hyperplasia.

Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive disorders due to single-gene defects in the various enzymes required for cortisol biosynthesis. CAH represents a continuous phenotypic spectrum with more than 95% of all cases caused by 21-hydroxylase deficiency. Genotyping is an important tool in confirming the diagnosis or carrier state, provides prognostic information on disease severity, and is essential for genetic counseling.