A New Perspective on Drugs for Duchenne Muscular Dystrophy: Proposals for Better Respiratory Outcomes and Improved Regulatory Pathways.

New drugs for Duchenne muscular dystrophy (DMD) are emerging rapidly. However, we and others believe these drugs are achieving regulatory approval prematurely. It is the cardiorespiratory complications of DMD that cause the disease's major morbidities and that determine survival.

Evaluation of SARS-CoV-2 RNA Rebound After Nirmatrelvir/Ritonavir Treatment in Randomized, Double-Blind, Placebo-Controlled Trials - United States and International Sites, 2021-2022.

Rebound of SARS-CoV-2 shedding or COVID-19 signs and symptoms has been described after treatment with nirmatrelvir/ritonavir (Paxlovid). The direct association of nirmatrelvir/ritonavir to COVID-19 rebound remains unclear because most reports are based on individual cases or nonrandomized studies. Viral RNA shedding data from two phase 2/3, randomized, double-blind, placebo-controlled clinical trials of nirmatrelvir/ritonavir (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients [EPIC-HR] and Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients [EPIC-SR]) were analyzed to investigate the role of nirmatrelvir/ritonavir treatment in COVID-19 rebound.

Considerations and Challenges in the Remdesivir COVID-19 Pediatric Development Program.

The US Food and Drug Administration is committed to the development of effective antiviral regimens for pediatric patients with coronavirus disease 2019 (COVID-19), including infants and neonates. On April 25, 2022, the approved indication of remdesivir (RDV) was expanded to include pediatric patients 28 days and older and weighing at least 3 kg with positive results of direct severe acute respiratory syndrome coronavirus 2 viral testing, who are: Hospitalized, or Not hospitalized and have mild to moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death. Given the similar course of COVID-19 in adults and pediatric patients, the approval of RDV for use in pediatric patients is supported by the safety and efficacy data from adequate and well-controlled phase 3 trials in adults and adolescents; and by the safety and pharmacokinetic data from a single-arm, open-label, phase 2/3 pediatric clinical trial of 53 pediatric patients at least 28 days of age and weighing at least 3 kg with confirmed severe acute respiratory syndrome coronavirus 2 infection and mild, moderate, or severe COVID-19.

Cardiorespiratory management of Duchenne muscular dystrophy: emerging therapies, neuromuscular genetics, and new clinical challenges.

The life-limiting complications of Duchenne muscular dystrophy (DMD) include loss of lung function and progressive cardiomyopathy; when patients are treated with assisted ventilation, cardiac function becomes the main determinant of survival. Therapy for DMD is changing rapidly, with the emergence of new genetic and molecular therapeutic options, the proliferation of which has fostered the perception that DMD is a potentially curable disease. However, data for respiratory and cardiac outcomes are scarce and available evidence is not uniformly positive.

Benefit-risk assessment for brincidofovir for the treatment of smallpox: U.S. Food and Drug Administration's Evaluation.

The development and approval of brincidofovir for the treatment of smallpox, a disease that was eradicated from the world over 40 years ago, has resulted in the second antiviral approved via the Medical Countermeasure Initiative (MCMi) to combat this disease. Approval of brincidofovir required a unique regulatory approach based on the FDA Animal Rule, and development was supported by many years of research and collaboration among academic investigators, the pharmaceutical industry and multiple government agencies. This article summarizes the FDA regulatory pathway and describes the challenges involved.

A systematic review of pharmacologic therapies for the cardiomyopathy of Duchenne muscular dystrophy.

Objective: To perform a systematic review of studies evaluating pharmacologic therapies for the cardiomyopathy of Duchenne muscular dystrophy (DMD).

Methods: PubMed, Google Scholar, and Embase were searched through October 8, 2020. Articles were selected using pre-determined criteria; 26 underwent detailed review by two co-authors.

Cardiopulmonary phenotypic variability and discordance in Duchenne muscular dystrophy: Implications for new therapies.

Neuromuscular respiratory medicine has traditionally focused on assisted lung ventilation and mucus clearance. These therapies have prolonged survival for patients with Duchenne muscular dystrophy (DMD). However, the field is rapidly evolving in a new direction: it is being revolutionized by molecular and genetic therapies.

Year in review 2019: Neuromuscular diseases.

Neuromuscular cardiopulmonary medicine is entering a new and exciting phase, with studies that assess the respiratory effect of emerging genetic and molecular therapies. In this year's neuromuscular Year in Review, we focus on Duchenne muscular dystrophy (DMD), reviewing studies that evaluate the respiratory effect of eteplirsen, the cardiopulmonary effects of ataluren, and a study comparing the use of spironolactone with eplerenone for the treatment of DMD-related cardiomyopathy.

Albeit ever more technological, there's no place like home.

Prero MY, Birnkrant DJ, Carter JC. Albeit ever more technological, there’s no place like home. .

Sustained virological response rates with direct-acting antivirals in black subjects with HCV genotype 1 infection: systematic analysis of clinical trials.

Objectives: Under representation of black subjects in trials of hepatitis C virus (HCV) direct-acting antivirals (DAAs) complicates assessment of differential outcomes for black individuals non-black individuals. HCV trials submitted to the Food and Drug Administration (2013-2017) to support approval or to expand an indication of 12-week interferon-free DAA regimens with or without ribavirin to treat HCV genotype 1 (GT1) infection were pooled to explore efficacy comparisons by ethnicity.

Methods: Twenty-six trials were pooled and included 2869 individuals with HCV GT1 alone and 742 individuals with both HCV GT1 and HIV.

Pediatric Pulmonology Year in Review 2018: Rare lung disease, neuromuscular disease, and diagnostic testing.

Pediatric Pulmonology publishes original research, case reports, and review articles on topics related to a wide range of children's respiratory disorders. In this article, we highlight the past year's publications in the topic areas of rare lung diseases, respiratory complications of neuromuscular disorders, and diagnostic testing, as well as selected literature in these areas from other journals.

Cardiopulmonary phenotypic discordance is common in Duchenne muscular dystrophy.

Objective: To determine the prevalence of discordant cardiopulmonary function among patients with Duchenne muscular dystrophy (DMD) in our clinic.

Methods: Retrospective chart review from 1999 to 2017.

Inclusion Criteria: DMD patients age ≥ 18 years, alive, with discordant cardiopulmonary function.

Primary Care and Emergency Department Management of the Patient With Duchenne Muscular Dystrophy.

Primary care providers (PCPs) are usually the first point of contact with the health care system for patients with Duchenne muscular dystrophy (DMD), and patients often present to emergency departments in which providers have little experience in dealing with this condition. With this article, we give primary care and emergency medicine providers a background in the common issues that affect people with DMD. By acquiring some specialized knowledge about the multisystem medical complications of DMD and by applying general principles of primary care, such as timely immunization, anticipatory safety counseling, behavioral screening, and routine nutritional and developmental assessments, the PCP can be a valued and effective medical provider to patients with DMD.

Orthopedic and Surgical Management of the Patient With Duchenne Muscular Dystrophy.

Orthopedic care is an important aspect of the overall management of patients with Duchenne muscular dystrophy (DMD). In addition to progressive muscle weakness and loss of function, patients may develop joint contractures, scoliosis, and osteoporosis, causing fractures; all of these necessitate intervention by a multidisciplinary team including an orthopedic surgeon as well as rehabilitation specialists such as physio- and occupational therapists. The causes of these musculoskeletal complications are multifactorial and are related to primary effects on the muscles from the disease itself, secondary effects from weak muscles, and the related side effects of treatments, such as glucocorticoid use that affect bone strength.

Respiratory Management of the Patient With Duchenne Muscular Dystrophy.

In 2010, Care Considerations for Duchenne Muscular Dystrophy, sponsored by the Centers for Disease Control and Prevention, was published in , and in 2018, these guidelines were updated. Since the publication of the first set of guidelines, survival of individuals with Duchenne muscular dystrophy has increased. With contemporary medical management, survival often extends into the fourth decade of life and beyond.

Pediatric pulmonology year in review 2017: Part 1.

Pediatric Pulmonology publishes original research, case reports and review articles on topics related to a wide range of children's respiratory disorders. In this article (Part 1 of a series), we summarize the past year's publications in our major topic areas, as well as selected literature in these areas from other journals. In Part 1, we review selected articles on diagnostic testing/endoscopy, respiratory complications of neuromuscular disorders, and rare lung diseases.