Sleep, Internalizing Symptoms, Executive Functioning, and Diabetes Outcomes in Adolescents with Type 1 Diabetes Mellitus

Insufficient sleep is a nearly universal problem during adolescence and is likely associated with various biopsychosocial and contextual factors present with this developmental period. Youth with type 1 diabetes mellitus (T1DM) may experience greater sleep difficulties, poorer sleep quality, and greater daytime sleepiness/fatigue compared to healthy youth. Also, sleep difficulties are associated with poorer diabetes outcomes (e.g., treatment adherence). Understanding how sleep may impact illness management during adolescence is critical given increasing rates of non-adherence during this developmental period. Although research suggests poor sleep is associated with decreased neurocognitive functioning and increased internalizing behavior among healthy youth, limited research has examined these relationships in adolescents with T1DM. Further, adolescents with T1DM are at increased risk for difficulties with executive functioning and internalizing behaviors compared to healthy peers, and these difficulties have been implicated in T1DM-related outcomes. As such, the present study examined relationships among adolescent-reported sleep quality, quantity, and diabetes-related outcomes and the indirect effects of sleep quality on T1DM-related outcomes through internalizing symptoms and executive functioning. Eighty-one adolescents diagnosed with T1DM (ages 12-17) and their caregivers completed the study. Caregivers and adolescents completed questionnaires assessing adolescents’ executive functioning and adherence to diabetes management tasks. Adolescents completed additional questionnaires assessing sleep quality, daytime sleepiness, and internalizing symptoms. Adolescents’ medical records were reviewed to collect most recent hemoglobin A1c (HbA1c) values, which represent metabolic control. Results partially supported hypotheses in that poorer sleep quality, greater daytime sleepiness, and longer sleep duration on the weekend were associated with poorer treatment adherence, but not metabolic control. As predicted, sleep quality was associated with adherence through anxiety, depression, and executive functioning. Daytime sleepiness was associated with adherence through anxiety and had a direct effect on adherence independent of anxiety, depression, and executive functioning. Overall, results underscore the importance of assessing sleep quality and quantity in adolescents’ with T1DM. Targeting sleep as a point of intervention may help to improve adherence behaviors through internalizing symptoms and executive functioning

Parent-Adolescent Communication about Health Risk Behaviors Among Adolescents with type 1 diabetes mellitus

Health risk behaviors, like drinking alcohol or using tobacco, are a common problem among adolescents in the United States. For healthy adolescents, health risk behaviors may be hazardous to their health; for adolescents with chronic illnesses, the risks associated with these types of behavior are compounded and may further impact their health status. This is particularly true for adolescents with type 1 diabetes mellitus (T1DM), whose blood sugar may be directly impacted by consumption of alcohol or use of tobacco. Parent-child communication has been found to act as a protective factor against adolescent engagement in health risk behaviors; however, this relationship has not been explored within the context families raising an adolescent with T1DM. As such, the present study will examine the relationships among health risk behavior of adolescents with T1DM, aspects of maternal caregiver-female adolescent communication, diabetes management, and metabolic control. Fifty-four female caregivers and fifty-two female adolescents (ages 14-19) diagnosed with T1DM completed the study. Parents and adolescents completed questionnaires assessing adolescent lifetime and previous 12 month use of alcohol and cigarettes or tobacco, various aspects of communication, and adherence to diabetes management tasks. Additionally, adolescents\u27 medical records were reviewed to collect most recent hemoglobin A1C (HbA1C values), which represent metabolic control during the past 2-3 months. In general, adolescents reported low rates of engagement in health risk behaviors. Results generally supported our hypotheses in that adolescents who reported lifetime or previous 12 month engagement in health risk behaviors had poorer parent- and self- reported treatment adherence; however, health risk behavior engagement was not associated with metabolic control. Additionally, parent- and adolescent-reported open and problem communication and parent-reported comfort with discussing risk behaviors were associated with and predicted adolescent-reported lifetime use of alcohol and cigarettes and previous 12 month use of alcohol. Together, aspects of parent- and adolescent-reported communication and adolescent health risk behavior engagement predicted parent- and adolescent-reported adherence to diabetes management tasks. Overall, present findings suggest that diabetes health care providers should discuss the potential impact of health risk behavior engagement on diabetes management and how the quality of parent-adolescent communication may influence adolescent health risk behaviors

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee