Differences in sleep architecture according to body mass index in children with type 1 diabetes.

Slow wave sleep (SWS), or deep sleep, is thought to be the most restorative stage of sleep and may be of a particular interest in the pathophysiology of obesity. The aim of this study was to investigate differences in sleep architecture based on body mass index (BMI) among a pediatric population with type 1 diabetes mellitus (T1DM). We hypothesized that children with T1DM who are obese would have less SWS than those who are not obese. Of 105 children with T1DM (mean age 13.54 years, 49.5% females) in this study, 19% were obese, 22% were overweight, and 59% had a normal BMI (81% non-obese). The overall SWS% among the participants was 13.2%. In contrast to our hypothesis, there was no significant difference in SWS% between obese and non-obese participants. However, the percent of time spent in rapid eye movement (REM) sleep among obese participants was significantly lower than those who were not obese (P = .022), which remained after adjusting the result for multiple covariates. While we found no significant association between the SWS time and BMI, obese adolescents with T1DM spent less time in REM sleep than those who were not obese. This study adds to the growing body of evidence supporting the importance of addressing sleep in clinical care of youth with T1DM.

Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial.

BACKGROUND: Cannabis is one of the most widely used drugs worldwide. Cannabis use disorder is characterised by recurrent use of cannabis that causes significant clinical and functional impairment. There are no approved pharmacological treatments for cannabis use disorder. One approach is to potentiate endocannabinoid signalling by inhibiting fatty acid amide hydrolase (FAAH), the enzyme that degrades the endocannabinoid anandamide. We aimed to test the efficacy and safety of the FAAH-inhibitor PF-04457845 in reduction of cannabis withdrawal and cannabis use in men who were daily cannabis users. METHODS: We did a double-blind, placebo-controlled, parallel group phase 2a trial at one site in men aged 18-55 years with cannabis dependence according to DSM-IV criteria (equivalent to cannabis use disorder in DSM-5). After baseline assessments, participants were randomly assigned (2:1) to receive PF-04457845 (4 mg per day) or placebo using a fixed block size of six participants, stratified by severity of cannabis use and desire to quit. Participants were admitted to hospital for 5 days (maximum 8 days) to achieve abstinence and precipitate cannabis withdrawal, after which they were discharged to continue the remaining 3 weeks of treatment as outpatients. The primary endpoints were treatment-related differences in cannabis withdrawal symptoms during hospital admission, and week 4 (end of treatment) self-reported cannabis use and urine THC-COOH concentrations in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT01618656. FINDINGS: Between Sept 12, 2012, and Jan 18, 2016, 46 men were randomly assigned to PF-04457845 and 24 to placebo. Adherence to study medication was 88%, as confirmed by video-calling and pill count, and corroborated by corresponding drug and anandamide concentrations in blood. Relative to placebo, treatment with PF-04457845 was associated with reduced symptoms of cannabis withdrawal (first day of treatment mean symptom score 11·00 [95% CI 7·78-15·57] vs 6·04 [4·43-8·24]; difference 4·96 [0·71-9·21]; padj=0·048; second day of treatment 11·74 [8·28-16·66] vs 6·02 [4·28-8·47]; difference 5·73 [1·13-10·32]; padj=0·035) and related mood symptoms during the inpatient phase. Additionally, treatment with PF-04457845 was associated with lower self-reported cannabis use at 4 weeks (mean 1·27 joints per day [95% CI 0·82-1·97] vs 0·40 [0·25-0·62]; difference 0·88 [0·29-1·46]; p=0·0003) and lower urinary THC-COOH concentrations (mean 657·92 ng/mL [95% CI 381·60-1134·30] vs 265·55 [175·60-401·57]; difference 392·37 [17·55-767·18)]; p=0·009). Eight (17%) patients in the PF-04457845 group and four (17%) in the placebo group discontinued during the treatment period. During the 4-week treatment phase, 20 (43%) of 46 participants in the PF-04457845 group and 11 (46%) of 24 participants in the placebo group had an adverse event. There were no serious adverse events. INTERPRETATION: PF-04457845, a novel FAAH inhibitor, reduced cannabis withdrawal symptoms and cannabis use in men, and might represent an effective and safe approach for the treatment of cannabis use disorder. FUNDING: United States National Institute of Drug Abuse (NIDA).

The Development of a Clinically Relevant Sleep Modification Protocol for Youth with Type 1 Diabetes.

Findings from type 2 diabetes research indicate that sleep is both a predictor of onset and a correlate of disease progression. However, the role sleep plays in glucose regulation and daytime functioning in youth with type 1 diabetes mellitus (T1DM) has not been systematically investigated. Nonetheless, preliminary findings have supported that various sleep parameters are strongly correlated to health-related and neurobehavioral outcomes in youth with T1DM. This suggests that improving sleep might reduce morbidity. A critical step in developing evidence-based guidelines regarding sleep in diabetes management is to first determine that sleep modification in natural settings is possible (i.e., instructing youth to have a healthy sleep opportunity leads to more total sleep time) and that an increased sleep duration impacts disease and psychosocial outcomes in these youth. This article describes the background, design, and feasibility of an ongoing randomized clinical trial that aims to examine if increasing sleep relative to youth's own sleep routines affects glucose control and daytime functioning.

Feasibility and success of cell-phone assisted remote observation of medication adherence (CAROMA) in clinical trials.

OBJECTIVE: Medication nonadherence is a serious issue in clinical trials, especially in studies of substance abuse disorders. Measuring and confirming adherence is critical to ensuring that collected data is accurate and interpretable. This study evaluated the feasibility and success of a smartphone-based approach (Cellphone Assisted Remote Observation of Medication Adherence [CAROMA]) to visually confirm medication adherence in a clinical trial. METHOD: Medication adherence was confirmed visually via smartphones provided to participants in a double-blind, randomized, placebo-controlled trial for cannabis dependence. Every morning, subjects (n=20) were video-called by staff who observed consumption of study medication. Adherence was also assessed with weekly face-to-face visits, pill counts and plasma drug levels. Subjects were paid for completing daily CAROMA visits, and for returning the smartphone at study completion. RESULTS: CAROMA confirmed 96.04% adherence to medication. Concordance between expected and actual remaining study medication counted at weekly study visits was 87.69%. Subjects assigned to active study medication had detectable plasma drug levels, while those assigned to placebo did not. CAROMA was estimated to cost approximately $100 per subject per week - a total of $300.24 per subject for the 3-week outpatient portion of the trial. CONCLUSION: This pilot study demonstrates the feasibility, success and cost-effectiveness of CAROMA to facilitate and confirm medication adherence in a clinical trial. Preliminary findings support larger and longer studies, and possibly applying this approach to clinical care - especially in other populations with high rates of medication nonadherence.