Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Can a Behavioral Weight-Loss Intervention Change Adolescents' Food Addiction Severity?

Objective: This study examines changes in the Yale Food Addiction Scale symptom count over a 24-week, weight-loss mobile Health (mHealth) intervention incorporating elements of addiction medicine. Methods: Adolescents (n = 117) with obesity (15.5 ± 1.3 years; 66% Hispanic) were randomized to the following: (1) mHealth intervention (AppAlone), (2) mHealth intervention+coaching (AppCoach), or (3) in-person intervention (Control). A multivariate mixed Poisson regression model was used to evaluate changes in symptom counts across intervention arms after adjusting for sex, age, depressive symptomatology, stress, and executive function. Results: After the intervention, 57% of adolescents showed a decrease in symptom count (median change: -0.3 [0 to -1.5]), with a significant change by intervention arm in the intention-to-treat analysis (p = 0.045). There was a positive linear relationship between change in symptom count and change in depressive symptomatology (p < 0.01) and stress (p < 0.01), with no association with change in weight (p = 0.3). Discussion: Both mHealth and in-person obesity interventions seemed to confer benefits in food addiction symptomatology associated with change in mood and stress. Clinical Trial Registration number: NCT035008353.

Spike in Diabetic Ketoacidosis Rates in Pediatric Type 2 Diabetes During the COVID-19 Pandemic.

OBJECTIVE: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) on the incidence of new-onset type 2 diabetes and diabetic ketoacidosis (DKA) is unclear. It is unknown whether the coincidence of DKA noted in adult patients with type 2 diabetes is an issue for youth during the coronavirus disease 2019 pandemic. RESEARCH DESIGN AND METHODS: A retrospective single-center medical record review was conducted in a large, urban children's hospital of pediatric subjects presenting with new-onset type 2 diabetes between March and August of 2018 to 2020. RESULTS: The proportion of subjects presenting with new-onset type 2 diabetes in DKA dramatically increased in 2020 (9% in 2018, 3% in 2019, and 20% in 2020, P = 0.029). CONCLUSIONS: In 2020, youth with new-onset type 2 diabetes had a greater incidence of DKA at presentation than previously observed. Future studies should examine the impact of SARS-CoV2 exposure on the presentation of type 2 diabetes in all age-groups to inform better patient care.

New onset diabetes with diabetic ketoacidosis in a child with multisystem inflammatory syndrome due to COVID-19.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a unique clinical complication of SARS-CoV-2 infection observed in pediatric patients. COVID-19 is emerging as a potential trigger for the development of diabetes in children. Here, we report a patient presenting with MIS-C and new onset diabetes, and discuss the implication and clinical management of these concomitant conditions. CASE PRESENTATION: An eight-year-old female presented with hyperglycemia, ketosis and metabolic acidosis consistent with diabetic ketoacidosis (DKA) in the setting of fever, rash, respiratory distress, hemodynamic instability, reduced systolic function with dilation of the left anterior descending artery, and positive SARS-CoV-2 antibodies suggestive of MIS-C.