The Proteogenomics of Prostate Cancer Radioresistance.

Unlabelled: Prostate cancer is frequently treated with radiotherapy. Unfortunately, aggressive radioresistant relapses can arise, and the molecular underpinnings of radioresistance are unknown. Modern clinical radiotherapy is evolving to deliver higher doses of radiation in fewer fractions (hypofractionation).

Addition of Contrast-enhanced Mammography to Tomosynthesis for Breast Cancer Detection in Women with a Personal History of Breast Cancer: Prospective TOCEM Trial Interim Analysis.

Background Digital breast tomosynthesis (DBT) is often inadequate for screening women with a personal history of breast cancer (PHBC). The ongoing prospective Tomosynthesis or Contrast-Enhanced Mammography, or TOCEM, trial includes three annual screenings with both DBT and contrast-enhanced mammography (CEM). Purpose To perform interim assessment of cancer yield, stage, and recall rate when CEM is added to DBT in women with PHBC.

Ten years of the manufacturing classification system: a review of literature applications and an extension of the framework to continuous manufacture.

The MCS initiative was first introduced in 2013. Since then, two MCS papers have been published: the first proposing a structured approach to consider the impact of drug substance physical properties on manufacturability and the second outlining real world examples of MCS principles. By 2023, both publications had been extensively cited by over 240 publications.

Intrathecal Gene Therapy for Giant Axonal Neuropathy.

Background: Giant axonal neuropathy is a rare, autosomal recessive, pediatric, polysymptomatic, neurodegenerative disorder caused by biallelic loss-of-function variants in , the gene encoding gigaxonin.

Methods: We conducted an intrathecal dose-escalation study of scAAV9/JeT-GAN (a self-complementary adeno-associated virus-based gene therapy containing the transgene) in children with giant axonal neuropathy. Safety was the primary end point.

Do pulmonary rehabilitation programmes improve outcomes in patients with COPD posthospital discharge for exacerbation: a systematic review and meta-analysis.

Introduction: Previous systematic reviews have provided heterogeneous and differing estimates for the efficacy of pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this review was to examine the efficacy of pulmonary rehabilitation programmes initiated within 3 weeks of hospital discharge following an exacerbation of COPD.

Methods: An update of a previous Cochrane review was undertaken using the Cochrane Airways Review Group Specialised Register.

Bayesian inference for prediction of survival probability in prime-boost vaccination regimes.

We focus on Bayesian inference for survival probabilities in a prime-boost vaccination regime in the development of an Ebola vaccine. We are interested in the heterologous prime-boost regimen (unmatched vaccine deliverys using the same antigen) due to its demonstrated durable immunity, well-tolerated safety profile, and suitability as a population vaccination strategy. Our research is motivated by the need to estimate the survival probability given the administered dosage.

Guidance on Mitigating the Risk of Transmitting Respiratory Infections During Nebulization by the COPD Foundation Nebulizer Consortium.

Background: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures.

Pulmonary Rehabilitation for Adults with Chronic Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Despite the known benefits of pulmonary rehabilitation (PR) for patients with chronic respiratory disease, this treatment is underused. Evidence-based guidelines should lead to greater knowledge of the proven benefits of PR, highlight the role of PR in evidence-based health care, and in turn foster referrals to and more effective delivery of PR for people with chronic respiratory disease. The multidisciplinary panel formulated six research questions addressing PR for specific patient groups (chronic obstructive pulmonary disease [COPD], interstitial lung disease, and pulmonary hypertension) and models for PR delivery (telerehabilitation, maintenance PR).

Exacerbations of COPD.

COPD exacerbations are associated with significant morbidity, mortality, and increased health care expenditures. The recently published Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations have further refined the definition of an exacerbation. A better understanding of the risk factors associated with the development of an exacerbation exists, and improvements are being made in earlier detection approaches.

Bayesian Complex Innovative Trial Designs (CIDs) and Their Use in Drug Development for Rare Disease.

As the temporal, financial, and ethical cost of randomized clinical trials (RCTs) continues to rise, researchers and regulators in drug discovery and development face increasing pressure to make better use of existing data sources. This pressure is especially high in rare disease, where traditionally designed RCTs are often infeasible due to the inability to recruit enough patients or the unwillingness of patients or trial leaders to randomly assign anyone to placebo. Bayesian statistical methods have recently been recommended in such settings for their ability to combine disparate data sources, increasing overall study power.

Lockdown under lockdown? Pandemic, the carceral and COVID-19 in British prisons.

The relationship between pandemic, or chronic infectious diseases, and the carceral, meaning set-apart spaces of enforced confinement for "wrong-doers," has a long, tangled history. It features in Foucault's inquiries into disciplinary power and its associated spatial formations, not least in the shape of the modern prison. Drawing lightly from Foucault's claims about disciplinary and biopolitical power, as well as on his anti-prison activism, this paper explores three possibilities for penal transformation arising during the early months of COVID-19 in UK prisons (circa March to August 2020).

A Delphi study of rescue and clinical subject matter experts on the extrication of patients following a motor vehicle collision.

Background: Approximately 1.3 million people die each year globally as a direct result of motor vehicle collisions (MVCs). Following an MVC some patients will remain trapped in their vehicle; these patients have worse outcomes and may require extrication.

Pulmonary comorbidities in cardiac rehabilitation.

Patients with cardiovascular disease (CVD) benefit greatly from participation in cardiac rehabilitation programs. Many patients with CVD have a concomitant pulmonary disease, yet the latter is often not diagnosed (and thus undertreated). Means to evaluate and manage patients with concomitant cardiovascular and pulmonary disease will be addressed in this article.

The telomere length landscape of prostate cancer.

Replicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance. Although the role of telomere length in cancer has been well studied, its association to genomic features is less well known. Here, we report the telomere lengths of 392 localized prostate cancer tumours and characterize their relationship to genomic, transcriptomic and proteomic features.

Hierarchical Bayesian modelling of disease progression to inform clinical trial design in centronuclear myopathy.

Background: Centronuclear myopathies are severe rare congenital diseases. The clinical variability and genetic heterogeneity of these myopathies result in major challenges in clinical trial design. Alternative strategies to large placebo-controlled trials that have been used in other rare diseases (e.

The Physiological Impact of Masking Is Insignificant and Should Not Preclude Routine Use During Daily Activities, Exercise, and Rehabilitation.

Purpose: Masking has been employed as a strategy for reducing transmission of a variety of communicable diseases. With the outbreak of SARS-CoV-2, many countries have implemented mandatory public masking. However, the perceived impact of mask use on pulmonary function has been a deterrent to public compliance with recommendations.

Home Oxygen Therapy for Adults with Chronic Lung Disease. An Official American Thoracic Society Clinical Practice Guideline.

Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations.

The Effect of Metabolic Syndrome Status on Lung Function and Patient-reported Outcomes in Patients with COPD Receiving Nebulized Glycopyrrolate.

Background: Concurrent chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) represent an important clinical phenotype with overlapping symptomology. The effect of MetS in COPD patients was assessed following treatment with nebulized glycopyrrolate (GLY; administered via eFlow® Closed System Nebulizer).

Methods: Posthoc analyses were performed on pooled lung function, patient-reported outcome (PRO) and safety data by MetS status from patients treated with placebo, GLY 25 and 50 mcg twice daily in two 12-week studies (GOLDEN 3 and 4; N=1293).

Pharmacokinetic/pharmacodynamic data extrapolation models for improved pediatric efficacy and toxicity estimation, with application to secondary hyperparathyroidism.

In most drug development settings, the regulatory approval process is accompanied by extensive studies performed to understand the drug's pharmacokinetic (PK) and pharmacodynamic (PD) properties. In this article, we attempt to utilize the rich PK/PD data to inform the borrowing of information from adults during pediatric drug development. In pediatric settings, it is especially crucial that we are parsimonious with the patients recruited for experimentation.

Medical Director Responsibilities for Outpatient Pulmonary Rehabilitation Programs in the United States: 2019: A STATEMENT FOR HEALTH CARE PROFESSIONALS FROM THE AMERICAN ASSOCIATION OF CARDIOVASCULAR AND PULMONARY REHABILITATION (AACVPR).

Clinical guidelines have been developed recognizing pulmonary rehabilitation (PR) as a key component in the management of patients with chronic lung disease. The medical director of a PR program is a key player in every program and is a requirement for operation of the program. The medical director must be a licensed physician who has experience in respiratory physiology management.