The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations.

The Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) study is an adaptive platform trial designed to investigate novel interventions to severe asthma. The study is conducted under a master protocol and utilizes a crossover design with each participant receiving up to five interventions and at least one placebo. Treatment assignments are based on the patients' biomarker profiles and precision health methods are incorporated into the interim and final analyses. We describe key elements of the PrecISE study including the multistage adaptive enrichment strategy, early stopping of an intervention for futility, power calculations, and the primary analysis strategy.

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course.

Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care.

Association of self-reported physical activity with obstructive sleep apnea: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

We examined associations of mild and moderate to severe obstructive sleep apnea (OSA; apnea-hypopnea index ≥5 and ≥15, respectively) with recommended amounts of moderate-vigorous physical activity (MVPA) or vigorous physical activity (VPA) and by type of activity (i.e., recreational, transportation, and work activity). The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter population-based study, enrolled individuals from 2008 to 2011 from four U.S. metropolitan areas (Bronx, New York; Chicago, Illinois; Miami, Florida; San Diego, California). Participants in this study included 14,087 self-identified Hispanic/Latino ages 18 to 74years from the HCHS/SOL. Survey logistic regression analysis was used to compute odds ratios [OR] and 95% confidence intervals [CI], adjusting for sociodemographics, smoking status, and body mass index (BMI). Relative to being inactive, performing some MVPA (>0 to <150min/week) or meeting the recommended MVPA (≥150min/week) were associated with lower odds of mild OSA (ORs and 95% CIs 0.70 [0.61-0.82] and 0.76 [0.63-0.91], respectively), as well as moderate to severe OSA (ORs and 95% CIs 0.76 [0.62-0.93] and 0.76 [0.59-0.98], respectively). Associations of VPA with OSA were not significant. Engaging in medium or high levels of transportation activity was associated with lower odds of mild OSA (OR: 0.84, 95% CI: 0.74-0.96; OR: 0.64, 95% CI: 0.43-0.95, respectively). Performing some recreational MVPA was associated with lower likelihood of mild and moderate to severe OSA (OR: 0.82, 95% CI: 0.71-0.93; OR: 0.79, 95% CI: 0.64-0.97, respectively). Health promotion and OSA prevention efforts should encourage individuals to engage in at least some MVPA.

Association of glucose homeostasis measures with heart rate variability among Hispanic/Latino adults without diabetes: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Reduced heart rate variability (HRV), a measure of cardiac autonomic function, is associated with an increased risk of cardiovascular disease (CVD) and mortality. Glucose homeostasis measures are associated with reduced cardiac autonomic function among those with diabetes, but inconsistent associations have been reported among those without diabetes. This study aimed to examine the association of glucose homeostasis measures with cardiac autonomic function among diverse Hispanic/Latino adults without diabetes. METHODS: The Hispanic community Health Study/Study of Latinos (HCHS/SOL; 2008-2011) used two-stage area probability sampling of households to enroll 16,415 self-identified Hispanics/Latinos aged 18-74 years from four USA communities. Resting, standard 12-lead electrocardiogram recordings were used to estimate the following ultrashort-term measures of HRV: RR interval (RR), standard deviation of all normal to normal RR (SDNN) and root mean square of successive differences in RR intervals (RMSSD). Multivariable regression analysis was used to estimate associations between glucose homeostasis measures with HRV using data from 11,994 adults without diabetes (mean age 39 years; 52 % women). RESULTS: Higher fasting glucose was associated with lower RR, SDNN, and RMSSD. Fasting insulin and the homeostasis model assessment of insulin resistance was negatively associated with RR, SDNN, and RMSSD, and the association was stronger among men compared with women. RMSSD was, on average, 26 % lower in men with higher fasting insulin and 29 % lower in men with lower insulin resistance; for women, the corresponding estimates were smaller at 4 and 9 %, respectively. Higher glycated hemoglobin was associated with lower RR, SDNN, and RMSSD in those with abdominal adiposity, defined by sex-specific cut-points for waist circumference, after adjusting for demographics and medication use. There were no associations between glycated hemoglobin and HRV measures among those without abdominal adiposity. CONCLUSIONS: Impairment in glucose homeostasis was associated with lower HRV in Hispanic/Latino adults without diabetes, most prominently in men and individuals with abdominal adiposity. These results suggest that reduced cardiac autonomic function is associated with metabolic impairments before onset of overt diabetes in certain subgroups, offering clues for the pathophysiologic processes involved as well as opportunity for identification of those at high risk before autonomic control is manifestly impaired.

Prevalence and Correlates of CKD in Hispanics/Latinos in the United States.

BACKGROUND AND OBJECTIVES: The prevalence of ESRD among Hispanics/Latinos is 2-fold higher than in non-Hispanic whites. However, little is known about the prevalence of earlier stages of CKD among Hispanics/Latinos. This study estimated the prevalence of CKD in US Hispanics/Latinos. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study of 15,161 US Hispanic/Latino adults of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American backgrounds enrolled in the multicenter, prospective, population-based Hispanic Community Health Study/Study of Latinos (HCHS/SOL). In addition, the prevalence of CKD in Hispanics/Latinos was compared with other racial/ethnic groups in the 2007-2010 National Health and Nutrition Examination Survey (NHANES). Prevalent CKD was defined as an eGFR <60 ml/min per 1.73 m(2) (estimated with the 2012 Chronic Kidney Disease Epidemiology Collaboration eGFR creatinine-cystatin C equation) or albuminuria based on sex-specific cut points determined at a single point in time. RESULTS: The overall prevalence of CKD among Hispanics/Latinos was 13.7%. Among women, the prevalence of CKD was 13.0%, and it was lowest in persons with South American background (7.4%) and highest (16.6%) in persons with Puerto Rican background. In men, the prevalence of CKD was 15.3%, and it was lowest (11.2%) in persons with South American background and highest in those who identified their Hispanic background as "other" (16.0%). The overall prevalence of CKD was similar in HCHS/SOL compared with non-Hispanic whites in NHANES. However, prevalence was higher in HCHS/SOL men and lower in HCHS/SOL women versus NHANES non-Hispanic whites. Low income, diabetes mellitus, hypertension, and cardiovascular disease were each significantly associated with higher risk of CKD. CONCLUSIONS: Among US Hispanic/Latino adults, there was significant variation in CKD prevalence among Hispanic/Latino background groups, and CKD was associated with established cardiovascular risk factors.