Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Following Extubation on Liberation From Respiratory Support in Critically Ill Children

IMPORTANCE: The optimal first-line mode of noninvasive respiratory support following extubation of critically ill children is not known. OBJECTIVE: To evaluate the noninferiority of high-flow nasal cannula (HFNC) therapy as the first-line mode of noninvasive respiratory support following extubation, compared with continuous positive airway pressure (CPAP), on time to liberation from respiratory support. DESIGN, SETTING, AND PARTICIPANTS: This was a pragmatic, multicenter, randomized, noninferiority trial conducted at 22 pediatric intensive care units in the United Kingdom. Six hundred children aged 0 to 15 years clinically assessed to require noninvasive respiratory support within 72 hours of extubation were recruited between August 8, 2019, and May 18, 2020, with last follow-up completed on November 22, 2020. INTERVENTIONS: Patients were randomized 1:1 to start either HFNC at a flow rate based on patient weight (n = 299) or CPAP of 7 to 8 cm H2O (n = 301). MAIN OUTCOMES AND MEASURES: The primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which the child was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio (HR) of 0.75. There were 6 secondary outcomes, including mortality at day 180 and reintubation within 48 hours. RESULTS: Of the 600 children who were randomized, 553 children (HFNC, 281; CPAP, 272) were included in the primary analysis (median age, 3 months; 241 girls [44%]). HFNC failed to meet noninferiority, with a median time to liberation of 50.5 hours (95% CI, 43.0-67.9) vs 42.9 hours (95% CI, 30.5-48.2) for CPAP (adjusted HR, 0.83; 1-sided 97.5% CI, 0.70-∞). Similar results were seen across prespecified subgroups. Of the 6 prespecified secondary outcomes, 5 showed no significant difference, including the rate of reintubation within 48 hours (13.3% for HFNC vs 11.5 % for CPAP). Mortality at day 180 was significantly higher for HFNC (5.6% vs 2.4% for CPAP; adjusted odds ratio, 3.07 [95% CI, 1.1-8.8]). The most common adverse events were abdominal distension (HFNC: 8/281 [2.8%] vs CPAP: 7/272 [2.6%]) and nasal/facial trauma (HFNC: 14/281 [5.0%] vs CPAP: 15/272 [5.5%]). CONCLUSIONS AND RELEVANCE: Among critically ill children requiring noninvasive respiratory support following extubation, HFNC compared with CPAP following extubation failed to meet the criterion for noninferiority for time to liberation from respiratory support. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN60048867

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.AuthorOverflow(482

Genetic studies of body mass index yield new insights for obesity biology

Note: A full list of authors and affiliations appears at the end of the article. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p