Extending sleep to improve glycemia: The Family Routines Enhancing Adolescent Diabetes by Optimizing Management (FREADOM) randomized clinical trial protocol.

Sleep deficiencies amongst individuals with type 1 diabetes mellitus (T1DM) have been linked with dysregulated glycemic control and greater morbidities. Sleep extension (EXT) has been identified as a viable intervention target to improve adolescent outcomes. The intervention aims to emphasize collaborative work with families to engage in behaviors that increase the likelihood of the youth increasing their sleep duration consistently. This study will randomize up to 175 youth with T1DM and at least one caregiver to either an EXT intervention or a family routines support (FRS) consultation. It is hypothesized that the EXT condition will lead to improvements in sleep, which in turn, will contribute to improved glycemic control. The primary endpoint is improved glycemic control assessed via a continuous glucose monitor (CGM) to ascertain average glucose levels across a week, glycemic variability, and percent time in the target range at one month and HbA1c at three months. Analyses will control for co-morbid conditions, including sleep-disordered breathing and obesity. This study will provide the needed data to support addressing sleep as part of the standards of care in youth with T1DM.

A Prolonged QTc Interval Leads to the Diagnosis of Hyperthyroidism in an Adolescent Boy.

BACKGROUND: Syncope is a common cause of pediatric emergency department visits and carries a broad differential diagnosis, which includes a few rare but critical cardiac conditions. CASE REPORT: We review the case of an adolescent boy who presented to the emergency department after a syncopal event. He was found to have a prolonged QTc interval on electrocardiogram (ECG), without personal or family history or known risk factors. He was screened for thyroid dysfunction on a second ED visit for presyncope and was subsequently diagnosed with hyperthyroidism. The patient was treated with methimazole for 2 weeks and a repeat ECG showed normalization of the QTc interval with a QTc reduction of more than 100 ms; routine thyroid studies showed correction of thyroid stimulating hormone and free thyroxine levels shortly thereafter. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case and review of the medical literature should raise awareness for the emergency physician to consider evaluation of thyroid function in pediatric patients with QT interval prolongation and vice versa, potentially averting dangerous dysrhythmias.

Increased length of stay and hospital charges in adolescents with type 1 diabetes and psychiatric illness.

OBJECTIVES: Type I diabetes mellitus (T1DM) is one of the most common chronic diseases of childhood. Diabetic ketoacidosis (DKA) in this population contributes to significant healthcare utilization, including emergency room visits, hospitalizations, and ICU care. Comorbid psychiatric illnesses (CPI) are additional risks for increased healthcare utilization. While CPI increased risk for DKA hospitalization and readmission, there are no data evaluating the relationship between CPI and hospital outcomes. We hypothesized that adolescents with T1DM and CPI admitted for DKA have increased length of stay (LOS) and higher charges compared to those without CPI. METHODS: Retrospective review of 2000-2012 Healthcare Cost and Utilization Project's (HCUP) Kids' Inpatient Databases (KID). Patients 10-21 years old admitted with ICD-9 codes for DKA or severe diabetes (250.1-250.33) with and without ICD-9 codes for depression (296-296.99, 311) and anxiety (300-300.9). Comparisons of LOS, mortality, and charges between groups (No CPI, Depression and Anxiety) were made with one way ANOVA with Bonferroni correction, independent samples Kruskal-Wallis test with Bonferroni correction and χ2. RESULTS: There were 79,673 admissions during the study period: 68,573 (86%) No CPI, 8,590 (10.7%) Depression and 12,510 (15.7%) Anxiety. Female patients comprised 58.2% (n=46,343) of total admissions, 66% of the Depression group, and 71% of the Anxiety group. Patients with depression or anxiety were older and had longer LOS and higher mean charges (p<0.001 for both). CONCLUSION: Comorbid depression or anxiety are associated with significantly longer LOS and higher charges in adolescents with T1DM hospitalized for DKA. This study adds to the prior findings of worse outcomes for patients with both T1DM and CPI, emphasizing the importance of identifying and treating these comorbid conditions.

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.

Acetylation of prostaglandin H2 synthases by aspirin is inhibited by redox cycling of the peroxidase.

Aspirin exerts its unique pharmacological effects by irreversibly acetylating a serine residue in the cyclooxygenase site of prostaglandin-H2-synthases (PGHSs). Despite the irreversibility of the inhibition, the potency of aspirin varies remarkably between cell types, suggesting that molecular determinants could contribute to cellular selectivity. Using purified enzymes, we found no evidence that aspirin is selective for either of the two PGHS isoforms, and we showed that hydroperoxide substrates of the PGHS peroxidase inhibited the rate of acetylation of PGHS-1 by 68%. Using PGHS-1 reconstituted with cobalt protoporphyrin, a heme devoid of peroxidase activity, we demonstrated that reversal by hydroperoxides of the aspirin-mediated acetylation depends upon the catalytic activity of the PGHS peroxidase. We demonstrated that inhibition of PGHS-2 by aspirin in cells in culture is reversed by 12-hydroperoxyeicosatetraenoic acid dose-dependently (ED50=0.58+/-0.15 microM) and that in cells with high levels of hydroperoxy-fatty acids (RAW264.7) the efficacy of aspirin is markedly decreased as compared to cells with low levels of hydroperoxides (A549; IC50s=256+/-22 microM and 11.0+/-0.9 microM, respectively). Together, these findings indicate that acetylation of the PGHSs by aspirin is regulated by the catalytic activity of the peroxidase, which yields a higher oxidative state of the enzyme.