Ruxolitinib in addition to standard of care for the treatment of patients admitted to hospital with COVID-19 (RUXCOVID): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: COVID-19 is associated with acute respiratory distress and cytokine release syndrome. The Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib reduces inflammatory cytokine concentrations in disorders characterised by cytokine dysregulation, including graft-versus-host disease, myelofibrosis, and secondary hemophagocytic lymphohistiocytosis. We assessed whether treatment with the JAK1/JAK2 inhibitor ruxolitinib would be beneficial in patients with COVID-19 admitted to hospital. Methods: RUXCOVID was an international, randomised, double-blind, phase 3 trial of ruxolitinib plus standard of care versus placebo plus standard of care in patients with COVID-19. Patients who were hospitalised but not on mechanical ventilation or in the intensive care unit [ICU] were randomly assigned (2:1) to oral ruxolitinib 5 mg twice per day or placebo for 14 days (14 additional days were allowed if no improvement). The primary endpoint was a composite of death, respiratory failure (invasive ventilation), or ICU care by day 29, analysed by logistic regression including region, treatment, baseline clinical status, age, and sex as covariates. This trial is registered with ClinicalTrials.gov, NCT04362137. Findings: Between May 4 and Sept 19, 2020, 432 patients were randomly assigned to ruxolitinib (n=287) or placebo (n=145) plus standard of care; the mean age was 56·5 years (SD 13·3), 197 (46%) were female, and 235 (54%) were male. The primary objective was not met: the composite endpoint occurred in 34 (12%) of 284 ruxolitinib-treated patients versus 17 (12%) of 144 placebo-treated patients (odds ratio 0·91, 95% CI 0·48-1·73; p=0·77). By day 29, nine (3%) of 286 ruxolitinib-treated patients had died compared with three (2%) of 145 placebo-treated patients; 22 (8%) of 286 ruxolitinib-treated patients had received invasive ventilation compared with ten (7%) of 145 placebo-treated patients; and 30 (11%) of 284 ruxolitinib-treated patients had received ICU care compared with 17 (12%) of 144 placebo-treated patients. In an exploratory analysis, median time to recovery was 1 day faster with ruxolitinib versus placebo (8 days vs 9 days; hazard ratio 1·10, 95% CI 0·89-1·36). Adverse events included headache (23 [8%] of 281 on ruxolitinib vs 11 [8%] of 143 on placebo) and diarrhoea (21 [7%] vs 12 [8%]). Interpretation: Ruxolitinib 5 mg twice per day showed no benefit in the overall study population. A larger sample is required to determine the clinical importance of trends for increased efficacy in patient subgroups. Funding: Novartis and Incyte.

Efficacy and safety of inhaled once-daily low-dose indacaterol acetate/mometasone furoate in patients with inadequately controlled asthma: Phase III randomised QUARTZ study findings.

BACKGROUND: Global initiative for asthma (GINA) 2019 recommends adding a long-acting ß2-agonist (LABA) to an inhaled corticosteroid (ICS) as a maintenance controller therapy in patients with inadequately controlled asthma. Indacaterol acetate (IND, a LABA) in combination with mometasone furoate (MF, an ICS) is under development for the treatment of these patients. OBJECTIVE: This phase III QUARTZ was a multicentre, randomised, double-blind, double-dummy and parallel-group study to assess the efficacy and safety of low-dose IND/MF 150/80 µg once daily (o.d.) versus MF 200 µg o.d. in adult and adolescent patients with inadequately controlled asthma. METHODS: Eligible patients (n = 802) were randomised (1:1) to receive either low-dose IND/MF 150/80 µg o.d. via Breezhaler® or MF 200 µg o.d. via Twisthaler® for 12 weeks. Primary endpoint was trough forced expiratory volume in 1 s (FEV1) and key secondary endpoint was Asthma Control Questionnaire (ACQ-7) treatment difference after 12-week treatment. Other secondary endpoints included ACQ-7 responder analysis, morning and evening peak expiratory flow, Asthma Quality of Life Questionnaire total score, rescue medication use, daily symptom score, nighttime awakenings and rate of exacerbations, evaluated over 12-week treatment. Safety was also assessed including serious asthma outcomes. RESULTS: Low-dose IND/MF significantly improved trough FEV1 (least squares mean treatment difference [LSMTD]: 0.182 L; p < 0.001) and ACQ-7 (LSMTD: -0.218; p < 0.001) versus MF at Week 12. Improvements in all other secondary endpoints favoured low-dose IND/MF. Safety was comparable. CONCLUSION: These results support the use of low-dose IND/MF 150/80 µg o.d. as a potential therapy for adult and adolescent patients with inadequately controlled asthma.

Food, Health, & Choices: Curriculum and Wellness Interventions to Decrease Childhood Obesity in Fifth-Graders.

OBJECTIVE: To evaluate Food, Health, & Choices, two 10-month interventions. DESIGN: Cluster-randomized, controlled study with 4 groups: curriculum, wellness, curriculum plus wellness, and control. SETTING: Twenty elementary schools (5/group) in New York City. PARTICIPANTS: Fifth-grade students (n = 1,159). At baseline, 44.6% were at the ≥85th body mass index (BMI) percentile for age and 86% qualified for free or reduced-price lunch. INTERVENTION: Curriculum was 23 science lessons based on social cognitive and self-determination theories, replacing 2 mandated units. Wellness was classroom food policy and physical activity bouts of Dance Breaks. MAIN OUTCOME MEASURES: For obesity, age- and sex-specific BMI percentiles were used (anthropometric measures). The researchers also employed 6 energy balance-related behaviors and 8 theory-based determinants of behavior change (by questionnaire). ANALYSIS: Pairwise adjusted odds in hierarchical logistic regression models were determined for >85th BMI percentile. Behaviors and theory-based determinants were examined in a 2-level hierarchical linear model with a 2 × 2 design for intervention effects and interactions. RESULTS: Obesity showed no change. For behaviors, there was a negative curriculum intervention change in physical activity (P = .04). The wellness intervention resulted in positive changes for sweetened beverages frequency (P = .05) and size (P = .006); processed packaged snacks size (P = .01); candy frequency (P = .04); baked good frequency (P = .05); and fast food frequency (P = .003), size (P = .01), and combo meals (P = .002). Theory-based determinants demonstrated no change. CONCLUSIONS AND IMPLICATIONS: The findings of the lack of a decrease in obesity, behavior changes only for the wellness intervention, and no changes in theory-based determinants warrant further research.

Impact of NFL PLAY 60 Programming on Elementary School Children's Body Mass Index and Aerobic Capacity: The NFL PLAY 60 FitnessGram Partnership Project.

BACKGROUND: We examined the impact of the Fuel Up to Play 60 (FUTP60) program on children's body mass index (BMI) and aerobic capacity (AC). METHODS: Participation in the FUTP60 and both BMI and AC profiles were collected through the NFL PLAY 60 FitnessGram Partnership Project involving over 100 schools from 22 US states. We specifically examined the distributions of BMI and AC among participating versus nonparticipating schools in the 2012-2013 school year. Hierarchical linear models tested the impact of participation and availability of additional funding for program implementation on the proportions of youth meeting FitnessGram health-related fitness standards (ie, Needs Improvement-Health Risk [NIHR] and Healthy Fitness Zone [HFZ] categories). RESULTS: After 1 year implementing the program, participating schools had lower proportions of boys (-4.1 ± 2.0%, p = .04) and girls (-4.5 ± 2.0%, p = .03) in the NIHR for BMI, and lower proportion of girls (-9.7 ± 4.0%, p = .02) in the NIHR for AC. There were no differences in the distributions for the HFZ and the availability of additional funding did not alter the relationships (p > .05). CONCLUSIONS: This study provides preliminary evidence that participation in the FUTP60 is associated with improved profiles of health-related fitness.

Associations among measures of energy balance related behaviors and psychosocial determinants in urban upper elementary school children.

BACKGROUND: Childhood obesity prevention is a pressing issue. Understanding the relationships among eating and physical activity behaviors and potential psychosocial determinants of behavior will help us design more effective interventions. This study aimed to examine such relationships in a large sample of urban elementary school children. METHODS: Fifth grade students in 20 recruited New York City public schools completed a validated questionnaire on six "do more" (fruits and vegetables and physical activity) and "do less" (sweetened beverages, processed packaged snacks, fast food and sedentary behavior) energy balance related behaviors (EBRBs) and psychosocial determinants of behavior from social cognitive and self-determination theories. Correlations among behaviors and hierarchical linear model analyses of the relationship between psychosocial determinants and behaviors were conducted for those with complete data (n = 952). RESULTS: The "do more" and the "do less" behaviors were significantly correlated within categories (p < 0.01). "Do more" food-related behaviors were correlated with physical activity but so were sports drinks, while the "do less" food-related behaviors tended to be correlated to sedentary behavior (p < 0.01). "Do more" behaviors were associated with self-efficacy and habit strength, and "do less" behaviors with outcome expectations, self-efficacy, habit strength, and behavioral intention. CONCLUSIONS: Interventions can address the healthy and less healthy clusters of behaviors together, focusing on strategies to enhance their self-efficacy and habit strength for the "do more" behaviors and outcome expectations to motivate intention to choose fewer "do less" behaviors, along with enhancing self-efficacy and habit. Research can examine these determinants as potential mediators of change in intervention.

Validity and Reliability of Behavior and Theory-Based Psychosocial Determinants Measures, Using Audience Response System Technology in Urban Upper-Elementary Schoolchildren.

OBJECTIVE: To examine the validity and reliability of a questionnaire administered with an audience response system (ARS). DESIGN: Cross-sectional study. SETTING: Two New York City public elementary schools. PARTICIPANTS: Fourth- and fifth-grade students. MAIN OUTCOME MEASURES: A Food, Health, and Choices questionnaire (FHC-Q) assessed energy balance-related behaviors (EBRBs) including intake of fruits and vegetables, sugar-sweetened beverages, processed packaged snacks, and fast food; physical activity; recreational screen time; and associated psychosocial determinants (≥ 3 questions/outcome scale). Previously validated reference instruments were used for relative validation. The ARS format was compared with a paper-and-pencil format. All measures were administered in a classroom setting. ANALYSIS: Pearson correlation coefficients between the reference instruments and the FHC-Q were calculated. Internal consistency reliabilities were evaluated with Cronbach α. Spearman rank correlation, intra-class correlation, and percent agreement were used for test-retest reliability between paper-and-pencil and ARS, and between 2 ARS FHC-Q administrations. RESULTS: Correlations for EBRBs with reference instruments ranged from 0.38 to 0.61 (P < .01). Cronbach α ranged from .77 to .92 for EBRBs and .74 to .90 for psychosocial determinants. Test-retest reliability correlations ranged from 0.36 to 0.87 (P < .001). Agreement for knowledge questions ranged from 69.8% to 84.8%. CONCLUSIONS AND IMPLICATIONS: The ARS FHC-Q has acceptable validity and reliability for collecting data on EBRBs and associated psychosocial determinants for upper-elementary students.