Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.

Background: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment.

Methods: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity.

Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.

Background: Weight reduction is a standard recommendation for obstructive sleep apnea (OSA) treatment in people with obesity or overweight; however, weight loss can be challenging to achieve and maintain without bariatric surgery. Currently, no approved anti-obesity medication has demonstrated effectiveness in OSA management. This study is evaluating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA in people with obesity.

Win ratio approach for analyzing composite time-to-event endpoint with opposite treatment effects in its components.

There is an increasing interest in the use of win ratio with composite time-to-event due to its flexibility in combining component endpoints. Exploring this flexibility further, one interesting question is in assessing the impact when there is a difference in treatment effect in the component endpoints. For example, the active treatment may prolong the time to occurrence of the negative event such as death or ventilation; meanwhile, the treatment effect may also shorten the time to achieving positive events, such as recovery or improvement.

Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial.

Background: The oral, selective Janus kinase 1/2 inhibitor baricitinib has shown efficacy in studies of hospitalised adults with COVID-19. COV-BARRIER (NCT04421027) was a multinational, phase 3, randomised, double-blind, placebo-controlled trial of baricitinib in patients with confirmed SARS-CoV-2 infection. We aimed to evaluate the efficacy and safety of baricitinib plus standard of care in critically ill hospitalised adults with COVID-19 requiring invasive mechanical ventilation or extracorporeal membrane oxygenation.

Estimands, Handling of Missing Data and Impact on Assumed Effect Size and Power in Pivotal COVID-19 Treatment Trials.

Estimands play an important role for aligning study objectives, study design and analyses through a precise definition of the quantity of interest. For COVID-19 studies, apart from intercurrent events, high volume of missing data has been observed. We explore their impact on several estimands through a synthetic COVID-19 data generated from a discrete-time multi-state model.

Baricitinib and primary biliary cholangitis.

Background And Aims: There is an unmet need for alternative treatments for patients with primary biliary cholangitis (PBC) who do not respond to treatment with ursodeoxycholic acid (UDCA). A proof-of-concept study of baricitinib, an orally administered Janus kinase 1 and 2 inhibitor, was initiated to evaluate its use in PBC patients.

Approach And Results: Patients with PBC showing inadequate response or intolerance to UDCA were eligible.

Inverse probability weighted estimators of vaccine effects accommodating partial interference and censoring.

Estimating population-level effects of a vaccine is challenging because there may be interference, that is, the outcome of one individual may depend on the vaccination status of another individual. Partial interference occurs when individuals can be partitioned into groups such that interference occurs only within groups. In the absence of interference, inverse probability weighted (IPW) estimators are commonly used to draw inference about causal effects of an exposure or treatment.

Author Correction: Transitions from Ideal to Intermediate Cholesterol Levels may vary by Cholesterol Metric.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Transitions from Ideal to Intermediate Cholesterol Levels may vary by Cholesterol Metric.

To examine the ability of total cholesterol (TC), a low-density lipoprotein cholesterol (LDL-C) proxy widely used in public health initiatives, to capture important population-level shifts away from ideal and intermediate LDL-C throughout adulthood. We estimated age (≥20 years)-, race/ethnic (Caucasian, African American, and Hispanic/Latino)-, and sex- specific net transition probabilities between ideal, intermediate, and poor TC and LDL-C using National Health and Nutrition Examination Survey (2007-2014; N = 13,584) and Hispanic Community Health Study/Study of Latinos (2008-2011; N = 15,612) data in 2016 and validated and calibrated novel Markov-type models designed for cross-sectional data. At age 20, >80% of participants had ideal TC, whereas the race/ethnic- and sex-specific prevalence of ideal LDL-C ranged from 39.

Heterogeneity in Blood Pressure Transitions Over the Life Course: Age-Specific Emergence of Racial/Ethnic and Sex Disparities in the United States.

Importance: Many studies have assessed racial/ethnic and sex disparities in the prevalence of elevated blood pressure (BP) from childhood to adulthood, yet few have examined differences in age-specific transitions between categories of BP over the life course in contemporary, multiracial/multiethnic populations.

Objective: To estimate age, racial/ethnic, and sex-specific annual net transition probabilities between categories of BP using Markov modeling of cross-sectional data from the National Health and Nutrition Examination Survey.

Design, Setting, And Participants: National probability sample (National Health and Nutrition Examination Survey in 2007-2008, 2009-2010, and 2011-2012) of 17 747 African American, white American, and Mexican American participants aged 8 to 80 years.

Targeting physical activity interventions for adults: When should intervention occur?

Understanding demographic differences in transitions across physical activity (PA) levels is important for informing PA-promoting interventions, yet few studies have examined these transitions in contemporary multi-ethnic adult populations. We estimated age-, race/ethnicity-, and sex-specific 1-year net transition probabilities (NTPs) for National Health and Nutrition Examination Survey (2007-2012, n=11,556) and Hispanic Community Health Study/Study of Latinos (2008-2011, n=15,585) adult participants using novel Markov-type state transition models developed for cross-sectional data. Among populations with ideal PA (≥150min/week; ranging from 56% (non-Hispanic black females) to 88% (non-Hispanic white males) at age 20), NTPs to intermediate PA (>0-<149min/week) generally increased with age, particularly for non-Hispanic black females for whom a net 0.

Disparities in Early Transitions to Obesity in Contemporary Multi-Ethnic U.S. Populations.

Background: Few studies have examined weight transitions in contemporary multi-ethnic populations spanning early childhood through adulthood despite the ability of such research to inform obesity prevention, control, and disparities reduction.

Methods And Results: We characterized the ages at which African American, Caucasian, and Mexican American populations transitioned to overweight and obesity using contemporary and nationally representative cross-sectional National Health and Nutrition Examination Survey data (n = 21,220; aged 2-80 years). Age-, sex-, and race/ethnic-specific one-year net transition probabilities between body mass index-classified normal weight, overweight, and obesity were estimated using calibrated and validated Markov-type models that accommodated complex sampling.

Reducing the Blood Pressure-Related Burden of Cardiovascular Disease: Impact of Achievable Improvements in Blood Pressure Prevention and Control.

Background: US blood pressure reduction policies are largely restricted to hypertensive populations and associated benefits are often estimated based on unrealistic interventions.

Methods And Results: We used multivariable linear regression to estimate incidence rate differences contrasting the impact of 2 pragmatic hypothetical interventions to reduce coronary heart disease, stroke, and heart failure (HF) incidence: (1) a population-wide intervention that reduced systolic blood pressure by 1 mm Hg and (2) targeted interventions that reduced the prevalence of unaware, untreated, or uncontrolled blood pressure above goal (per Eighth Joint National Committee treatment thresholds) by 10%. In the Atherosclerosis Risk in Communities Study (n=15 744; 45 to 64 years at baseline, 1987-1989), incident coronary heart disease and stroke were adjudicated by physician panels.

A quantile-based method for association mapping of quantitative phenotypes: an application to rheumatoid arthritis phenotypes.

Genetic association of population-based quantitative trait data has traditionally been analyzed using analysis of variance (ANOVA). However, violations of certain statistical assumptions may lead to false-positive association results. In this study, we have explored model-free alternatives to ANOVA using correlations between allele frequencies in the different quantile intervals of the quantitative trait and the quantile values.