Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by intractable fatigue, postexertional malaise, and orthostatic intolerance, but its pathophysiology is poorly understood. Pharmacologic cholinergic stimulation was used to test the hypothesis that neurovascular dysregulation underlies exercise intolerance in ME/CFS.

Atrial fibrillation (AF) is a common complication of sepsis. It is unclear whether norepinephrine, an α- and β-agonist, and phenylephrine, an α-agonist, are associated with different heart rates among patients with sepsis and AF.

Mortality historically has been the primary outcome of choice for acute and critical care clinical trials. However, undue reliance on mortality can limit the scope of trials that can be performed. Large sample sizes are usually needed for trials powered for a mortality outcome, and focusing solely on mortality fails to recognize the importance that reducing morbidity can have on patients' lives. The COVID-19 pandemic has highlighted the need for rapid, efficient trials to rigorously evaluate new therapies for hospitalized patients with acute lung injury. Oxygen-free days (OFDs) is a novel outcome for clinical trials that is a composite of mortality and duration of new supplemental oxygen use. It is designed to characterize recovery from acute lung injury in populations with a high prevalence of new hypoxemia and supplemental oxygen use. In these populations, OFDs captures two patient-centered consequences of acute lung injury: mortality and hypoxemic lung dysfunction. Power to detect differences in OFDs typically is greater than that for other clinical trial outcomes, such as mortality and ventilator-free days. OFDs is the primary outcome for the Fourth Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) Host Tissue platform, which evaluates novel therapies targeting the host response to COVID-19 among adults hospitalized with COVID-19 and new hypoxemia. This article outlines the rationale for use of OFDs as an outcome for clinical trials, proposes a standardized method for defining and analyzing OFDs, and provides a framework for sample size calculations using the OFD outcome.

Accurate assessment of maximum respiratory pressure is vital when tracking disease progression and devising treatment strategies. Previous studies indicate a learning effect when undertaking maximum respiratory pressure measurements. The extent of this learning effect and methodologies undertaken to mitigate this learning effect have not been investigated systematically.

Chronic refractory cough significantly impairs the psychological and social aspects of quality of life. Loss of inhibitory control is suggested as a potential central neurobiological mechanism underlying chronic refractory cough.

The current approach to interpretation of lung function measurements assumes that differences in lung function between racial and ethnic groups represent inherent and biological differences. Observed differences in lung function between White and Black populations are often attributed to physiological differences in body proportions (eg, chest size, leg length); however, most studies investigating the observed differences have not considered the impact of socioeconomic status (SES).