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.

Human Factors and Ergonomics and the management of existential threats: A work domain analysis of a COVID-19 return from lockdown restrictions system.

Following strict "lockdown" restrictions designed to control the spread of the COVID-19 virus, many jurisdictions are now engaged in a process of easing restrictions in an attempt to stimulate economic and social activity while continuing to suppress virus transmission. This is challenging and complex, and in several regions, new outbreaks have emerged. We argue that systems Human Factors and Ergonomics methods can assist in understanding and optimizing the return from lockdown. To demonstrate, we used work domain analysis to develop an abstraction hierarchy model of a generic "return from lockdown restrictions" system. The model was assessed to identify (a) issues preventing a successful return from lockdown; and (b) leverage points that could be exploited to optimize future processes. The findings show that the aim of continuing to suppress virus transmission conflicts with the aims of returning to pre-virus economic and social activity levels. As a result, many functions act against each other, ensuring that the system cannot optimally achieve all three of its primary aims. Potential leverage points include modifying the goals and rules of the system and enhancing communications and feedback. Specifically, it is argued that moderating economic aims and modifying how social and community activities are undertaken will result in longer term suppression of the virus.

With Crisis Comes Opportunity: Redesigning Performance Departments of Elite Sports Clubs for Life After a Global Pandemic.

The suspension of major sporting competitions due to the global COVID-19 pandemic had a substantial negative impact on the sporting industry. As such, a successful and sustainable return to sport will require extensive modifications to the current operations of sporting organizations. In this article we argue that methods from the realm of sociotechnical systems (STS) theory are highly suited for this purpose. The aim of the study was to use such methods to develop a model of an Australian Football League (AFL) club's football department. The intention was to identify potential modifications to the club's operations to support a return to competition following the COVID-19 crisis. Subject Matter Experts from an AFL club participated in three online workshops to develop Work Domain Analysis and Social Organization and Cooperation Analysis models. The results demonstrated the inherent complexity of an AFL football department via numerous interacting values, functions and processes influencing the goals of the system. Conflicts within the system were captured via the modeling and included pursing goals that may not fully reflect the state of the system, a lack of formal assessment of core values, overlapping functions and objects, and an overemphasis on specialized roles. The current analysis has highlighted potential areas for modification in the football department, and sports performance departments in general.