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[Purpose] The purposes of this study were to assess the fundamental motor skill (FMS) of children with Down syndrome (DS) and to compare their FMS proficiencies to those of chronological age-matched and gender-matched typically developing children (TDC). [Participants and Methods] This cross-sectional study involved a total of 60 participants (30 children with DS and 30 TDC). The FMS proficiency of participants was assessed by using the test of gross motor development, second edition (TGMD-2). The data were analyzed using independent samples t-tests to verify the differences between the two groups and gender. The effect size of Cohen's d was also determined for comparing the two groups. [Results] The results showed that there were significant differences between children with DS and the TDC on locomotor and object control standard scores, and the gross motor quotient (GMQ). However, there were no significant gender-based differences in the locomotor and object control standard scores and the GMQ in both groups. [Conclusion] Based on the current results, the FMS proficiency of children with DS is lower than the TDC. Therefore, a therapeutic intervention program is necessary for children with DS to improve their FMS proficiency., Competing Interests: No funding and conflict of interest., (2023©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system. Eligibility criteria for participation in the study included age between 14 and 17 years and a diagnosis of T1D before 8 years of age. Randomization to either a hybrid closed-loop or standard diabetes care group was performed after pre-qualification, consent, enrollment, and collection of medical background information. Of 46 participants assessed for eligibility, 44 met criteria and were randomized. Two randomized participants failed to complete baseline assessments and were excluded from final analyses. Participant data were collected across five academic medical centers in the United States. Research staff scoring the cognitive assessments as well as those processing imaging data were blinded to group status though participants and their families were not. Forty-two adolescents, 21 per group, underwent cognitive assessment and multi-modal brain imaging before and after the six month study duration. HbA1c and sensor glucose downloads were obtained quarterly. Primary outcomes included metrics of gray matter (total and regional volumes, cortical surface area and thickness), white matter volume, and fractional anisotropy. Estimated power to detect the predicted treatment effect was 0.83 with two-tailed, α = 0.05. Adolescents in the hybrid closed-loop group showed significantly greater improvement in several primary outcomes indicative of neurotypical development during adolescence compared to the standard care group including cortical surface area, regional gray volumes, and fractional anisotropy. The two groups were not significantly different on total gray and white matter volumes or cortical thickness. The hybrid closed loop group also showed higher Perceptual Reasoning Index IQ scores and functional brain activity more indicative of neurotypical development relative to the standard care group (both secondary outcomes). No adverse effects associated with study participation were observed. These results suggest that alterations to the developing brain in T1D might be preventable or reversible with rigorous glucose control. Long term research in this area is needed., (© 2022. The Author(s).)

Objective: To determine the relationship between level of supervision (LOS) ratings for the Common Pediatric Subspecialty Entrustable Professional Activities (EPAs) with their associated subcompetency milestones across subspecialties and by fellowship training year., Methods: Clinical Competency Committees (CCCs) in 14 pediatric subspecialties submitted LOS ratings for 6 Common Subspecialty EPAs and subcompetency milestone levels mapped to these EPAs. We examined associations between these subcompetency milestone levels and LOS ratings across subspecialty training year by fitting per-EPA linear mixed effects models, regressing LOS rating on milestone level and on training year., Results: CCCs from 211 pediatric fellowship programs provided data for 369 first, 336 second, and 331 third year fellows. Mean subcompetency milestone levels increased similarly among subspecialties for most EPAs compared with the reference, Adolescent Medicine. Mean subcompetency milestones mapped to each EPA and mean EPA LOS ratings generally increased by training year across all subspecialties., Conclusions: Subcompetency milestones levels mapped to each Common Subspecialty EPA and the EPA LOS ratings increase similarly across subspecialties and by training year, providing validity evidence for using EPA LOS to assess pediatric subspecialty trainee performance. This study supports the development of tools to facilitated the CCC evaluation process across all pediatric subspecialties., (Copyright © 2022. Published by Elsevier Inc.)

Although 37.5-51% of transgender adults state they would've considered freezing gametes before gender-affirming therapy if offered and 24-25.8% of transgender adolescents express interest in having biological children, less than 5% of transgender adolescents have opted for fertility preservation. We sought to assess fertility preservation utilization in our multidisciplinary adolescent gender clinic. We also aimed to identify fertility preservation utilization and interest among non-binary adolescents and young adults. A retrospective review was conducted of patients seen in the Stanford Pediatric & Adolescent Gender Clinic from October 2015 through March 2019 who were >10 years of age at initial visit. All individuals with documented discussion of fertility preservation were offered referral for formal fertility preservation consultation but only 24% of patients accepted. Only 6.8% of individuals subsequently underwent fertility preservation (n = 9). Transfeminine adolescents are more likely to pursue fertility preservation than transmasculine adolescents (p = 0.01). The rate of fertility preservation in non-binary adolescents did not significantly differ from those in transfeminine adolescents (p = 1.00) or transmasculine adolescents (p = 0.31). Although only one non-binary individual underwent fertility preservation, several more expressed interest with 36% accepting referral (n = 4) and 27% being seen in consultation (n = 3). Despite offering fertility preservation with designated members of a gender clinic team, utilization remains low in transgender adolescents. Additionally, non-binary adolescents and their families are interested in fertility preservation and referrals should be offered to these individuals. Further studies and advocacy are required to continue to address fertility needs of transgender adolescents., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: Entrustable Professional Activities (EPAs) were developed to assess pediatric fellows. We previously showed that fellowship program directors (FPDs) may graduate fellows who still require supervision. How this compares with their expectations for entrustment of practicing subspecialists is unknown., Methods: We surveyed US FPDs in 14 pediatric subspecialties through the Subspecialty Pediatrics Investigator Network between April and August 2017. For each of 7 common pediatric subspecialty EPAs, we compared the minimum level of supervision that FPDs required for graduation with the level they expected of subspecialists for safe and effective practice using the Friedman rank sum test and paired t test. We compared differences between subspecialties using linear regression., Results: We collected data from 660 FPDs (response rate 82%). For all EPAs, FPDs did not require fellows to reach the level of entrustment for graduation that they expected of subspecialists to practice ( P < .001). FPDs expected the least amount of supervision for the EPAs consultation and handovers. Mean differences between supervision levels for graduation and practice were smaller for clinical EPAs (consultation, handovers, lead a team) when compared with nonclinical EPAs (quality improvement, management, lead the profession and scholarship; P = .001) and were similar across nearly all subspecialties., Conclusions: Fellowship graduates may need continued development of clinical and nonclinical skills in their early practice period, underscoring a need for continued assessment and mentoring. Graduation readiness must be based on clear requirements, with alignment of FPD expectations and regulatory standards, to ensure quality care for patients., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Purpose: Entrustable professional activities (EPAs) are one approach to competency-based medical education (CBME), and 7 EPAs have been developed that address content relevant for all pediatric subspecialties. However, it is not known what level of supervision fellowship program directors (FPDs) deem necessary for graduation. The Subspecialty Pediatrics Investigator Network (SPIN) investigated FPD perceptions of the minimum level of supervision required for a trainee to successfully graduate., Method: In 2017, SPIN surveyed all FPDs of accredited fellowships for 14 subspecialties. For each EPA, the minimum supervision level for graduation (ranging from observation only to unsupervised practice) was set such that no more than 20% of FPDs would accept a lower level., Results: The survey response rate was 82% (660/802). The minimum supervision level for graduation varied across the 7 EPAs from 2 (direct) to 4 (indirect for complex cases), with significant differences between EPAs. The percentage of FPDs desiring a lower minimum supervision level ranged from 3% to 17%. Compared with the 4 nonclinical EPAs (quality improvement, management, lead within the profession, scholarship), the 3 clinical EPAs (consultation, handover, lead a team) had higher minimum supervision graduation levels (P < .001), with less likelihood that an FPD would graduate a learner below their minimum level (P < .001)., Conclusions: Consensus among FPDs across all pediatric subspecialties demonstrates the potential need for ongoing supervision for graduates in all 7 common pediatric subspecialty EPAs after fellowship. As CBME programs are implemented, processes and infrastructure to support new graduates are important considerations for leaders., Competing Interests: Other disclosures: The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2021 by the Association of American Medical Colleges.)

Objectives: To examine main factors that influence the decision to choose pediatric endocrinology as a career among pediatric endocrinologists and assess their work satisfaction or stress level and suggested strategies to increase interest in subspecialty training in pediatric endocrinology., Methods: A workforce survey was distributed among 1470 members of the Pediatric Endocrine Society., Results: The response rate was 37.4%, with 550 members responding. The most common reasons for the respondents choosing pediatric endocrinology were intellectual stimulation (79%), exposure to endocrinology during residency (57%) or medical school (43%), and ability to establish relationships with patients with chronic disorders (54%). Of the respondents, 97% considered intellectual stimulation as the most favorable aspect of the specialty, and 84% considered financial compensation as the most unfavorable aspect of pediatric endocrinology. Majority (77%) were satisfied or very satisfied with their work environment. The mean work-related stress score (0 [none] to 10 [worst]) was 5.7, standard deviation was 2.1, and median was 6 (Q1, Q3: 4, 7). Increased financial compensation for the services and loan payment or forgiveness option were the top strategies suggested to enhance interest among residents for training in the subspecialty. One third (37%) felt that reducing the duration of the fellowship to 2 years would increase interest in training in pediatric endocrinology., Conclusion: The pediatric endocrinologists reported overall excellent career satisfaction, indicating the potential to attract high-quality doctors to the specialty. Improving reimbursement and loan forgiveness were the top strategies suggested for increasing interest in subspecialty training in pediatric endocrinology., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)

Purpose: To capture and compare the perspectives of parents and their transgender and gender expansive (TGE) adolescents during pivotal moments of gender identity development and to report the level of adjustment during these parental experiences., Methods: We utilized a mixed-methods approach and interviewed 36 parents and 23 TGE adolescents at our Gender Clinic. Parents retrospectively identified "pivotal moments" in their child's gender identity development and rated their levels of support and adjustment. Adolescents independently rated their parent's level of support during these moments to allow for comparative analyses., Results: The supportive behavior most frequently identified by parents was connecting the adolescent to services, while adolescents considered their parents' use of the affirmed name or pronouns to be most supportive. We found a positive correlation between the parents' perceptions of support and those of TGE adolescents during pivotal moments (r = 0.4, p < 0.001). Adolescents rated the degree of parental support to be 3.73 points (95% confidence interval: [2.67,4.8], p < 0.001) higher on a Likert scale than corresponding ratings provided by parents in a generalized estimating equation model. Parents experienced moderate need for adjustment during these moments., Conclusions: Providers may use these findings to guide parents toward gender affirmative behaviors that may protect against negative mental health outcomes., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia., Research Design and Methods: One hundred forty-four children with type 1 diabetes and 72 age-matched control subjects without diabetes (mean ± SD age at baseline 7.0 ± 1.7 years, 46% female) had unsedated MRI and cognitive testing up to four times over 6.4 ± 0.4 (range 5.3-7.8) years; HbA 1c and continuous glucose monitoring were done quarterly. FreeSurfer-derived brain volumes and cognitive metrics assessed longitudinally were compared between groups using mixed-effects models at 6, 8, 10, and 12 years. Correlations with glycemia were performed., Results: Total brain, gray, and white matter volumes and full-scale and verbal intelligence quotients (IQs) were lower in the diabetes group at 6, 8, 10, and 12 years, with estimated group differences in full-scale IQ of -4.15, -3.81, -3.46, and -3.11, respectively ( P < 0.05), and total brain volume differences of -15,410, -21,159, -25,548, and -28,577 mm 3 at 6, 8, 10, and 12 years, respectively ( P < 0.05). Differences at baseline persisted or increased over time, and brain volumes and cognitive scores negatively correlated with a life-long HbA 1c index and higher sensor glucose in diabetes., Conclusions: Detectable changes in brain volumes and cognitive scores persist over time in children with early-onset type 1 diabetes followed longitudinally; these differences are associated with metrics of hyperglycemia. Whether these changes can be reversed with scrupulous diabetes control requires further study. These longitudinal data support the hypothesis that the brain is a target of diabetes complications in young children., (© 2021 by the American Diabetes Association.)

Objectives: Fellowship program directors (FPD) and Clinical Competency Committees (CCCs) both assess fellow performance. We examined the association of entrustment levels determined by the FPD with those of the CCC for 6 common pediatric subspecialty entrustable professional activities (EPAs), hypothesizing there would be strong correlation and minimal bias between these raters., Methods: The FPDs and CCCs separately assigned a level of supervision to each of their fellows for 6 common pediatric subspecialty EPAs. For each EPA, we determined the correlation between FPD and CCC assessments and calculated bias as CCC minus FPD values for when the FPD was or was not a member of the CCC. In addition, we examined the effect of program size, FPD understanding of EPAs, and subspecialty on the correlations. Data were obtained in fall 2014 and spring 2015., Results: A total of 1040 fellows were assessed in the fall and 1048 in the spring. In both periods and for each EPA, there was a strong correlation between FPD and CCC supervision levels ( P  < .001). The correlation was somewhat lower when the FPD was not a CCC member ( P  < .001). Overall bias in both periods was small., Conclusions: The correlation between FPD and CCC assignment of EPA supervision levels is strong. Although slightly weaker when the FPD is not a CCC member, bias is small, so this is likely unimportant in determining fellow entrustment level. The similar performance ratings of FPDs and CCCs support the validity argument for EPAs as competency-based assessment tools., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Glucose is a primary fuel source to the brain, yet the influence of dysglycemia on neurodevelopment in children with type 1 diabetes remains unclear. We examined brain activation using functional MRI in 80 children with type 1 diabetes (mean ± SD age 11.5 ± 1.8 years; 46% female) and 47 children without diabetes (control group) (age 11.8 ± 1.5 years; 51% female) as they performed a visuospatial working memory (N-back) task. Results indicated that in both groups, activation scaled positively with increasing working memory load across many areas, including the frontoparietal cortex, caudate, and cerebellum. Between groups, children with diabetes exhibited reduced performance on the N-back task relative to children in the control group, as well as greater modulation of activation (i.e., showed greater increase in activation with higher working memory load). Post hoc analyses indicated that greater modulation was associated in the diabetes group with better working memory function and with an earlier age of diagnosis. These findings suggest that increased modulation may occur as a compensatory mechanism, helping in part to preserve working memory ability, and further, that children with an earlier onset require additional compensation. Future studies that test whether these patterns change as a function of improved glycemic control are warranted., (© 2020 by the American Diabetes Association.)

Objective: Every year, 500,000 youths in the U.S. with chronic disease turn 18 years of age and eventually require transfer to adult subspecialty care. Evidence-based interventions on the organization of transfer of care are limited, although engagement and retention in adult clinic are considered appropriate outcomes. Sustained continuity of care improves patient satisfaction and reduces hospitalization. Methods: We conducted a prospective, nonrandomized cohort study of patients with pediatric endocrine conditions, age 16 to 26 years, enrolled upon referral to the adult endocrine clinic of a physician trained in both adult and pediatric endocrinology (Med+Peds endocrinologist). Patients differed based on whether their referral originated from another pediatric endocrinologist (traditional transfer) or if the Med+Peds endocrinologist previously saw the patient in his pediatric endocrine clinic (guided transfer). Rather than relying on arbitrary age criteria, guided transfer to adult clinic occurred when physician and patient considered it appropriate. The primary outcome was show rate at the first and second adult visits. Results: Of 36 patients, 21 were referred by another pediatric endocrinologist and 15 underwent guided transfer. For traditional transfer, show rate to the first and second visit was 38%, compared to 100% in the guided transfer group ( P = .0001). Subgroup analysis of 27 patients with diabetes revealed that both groups had similar initial hemoglobin A1c ( P = .38), and the guided transfer group maintained hemoglobin A1c. Conclusion: Most traditional transfers were unsuccessful. Guided transfer was significantly more effective, with every patient successfully transferring, and could be implemented with adult endocrinologists willing to see patients in the pediatric clinic. Abbreviations: DKA = diabetic ketoacidosis; HbA1c = hemoglobin A1c; Med+Peds = Internal Medicine and Pediatrics.

Cardiac syncope and epileptic seizure are two very similar presentations and difficult to differentiate without a proper history, physical examination and investigations. In a former study, 10 out of 22 episodes of induced ventricular tachycardia or fibrillation can result in stereotypical tonic-clonic movement with varied electroencephalography changes. We present a case which was diagnosed as ventricular tachycardia from seizure-like attack. It is to emphasise the importance of including ventricular tachycardia among other differential diagnoses of seizure-like activity in a patient with cardiovascular risks., (© Royal College of Physicians 2020. All rights reserved.)

When considered as a group, children with type 1 diabetes have subtle cognitive deficits relative to neurotypical controls. However, the neural correlates of these differences remain poorly understood. Using functional near-infrared spectroscopy (fNIRS), we investigated the brain functional activations of young adolescents (19 individuals with type 1 diabetes, 18 healthy controls, ages 8-16 years) during a Go/No-Go response inhibition task. Both cohorts had the same performance on the task, but the individuals with type 1 diabetes subjects had higher activations in a frontal-parietal network including the bilateral supramarginal gyri and bilateral rostrolateral prefrontal cortices. The activations in these regions were positively correlated with fewer parent-reported conduct problems (ie, lower Conduct Problem scores) on the Behavioral Assessment System for Children, Second Edition. Lower Conduct Problem scores are characteristic of less rule-breaking behavior suggesting a link between this brain network and better self-control. These findings are consistent with a large functional magnetic resonance imaging (fMRI) study of children with type 1 diabetes using completely different participants. Perhaps surprisingly, the between-group activation results from fNIRS were statistically stronger than the results using fMRI. This pilot study is the first fNIRS investigation of executive function for individuals with type 1 diabetes. The results suggest that fNIRS is a promising functional neuroimaging resource for detecting the brain correlates of behavior in the pediatric clinic., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims/hypothesis: Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status., Methods: Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1-49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study., Results: Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%., Conclusions/interpretation: Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress.

Purpose: Serum cortisol measurements after ACTH stimulation are currently used to evaluate for adrenal insufficiency in children. We aim to determine if salivary cortisol measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can confirm or replace serum cortisol during high dose ACTH stimulation test to improve test compliance and interpretation. We also aim to gain preliminary understanding of normal ranges of salivary cortisol in normal children at am, bedtime, and midnight., Methods: Children aged 6-17 years meeting study criteria and tested for adrenal insufficiency were recruited to concomitantly collect saliva and serum samples during high dose ACTH stimulation test. Normal children aged 3-18 years were recruited to collect morning, bedtime, and midnight saliva samples. Salivary cortisol was measured using LC-MS/MS while serum cortisol was determined by an immunoassay., Results: Salivary cortisol in normal children were higher at am and lower at bedtime and midnight (p value <0.0002 and <0.007, respectively). The midnight and bedtime levels were not sufficiently different (p value 0.36). Salivary cortisol during ACTH stimulation test positively and closely correlated with serum cortisol with 100% specificity and sensitivity when 18 µg/dL for serum and 500 ng/dL for salivary cortisol were used as cutoff values respectively for adrenal sufficiency., Conclusions: Measurement of salivary cortisol by LC-MS/MS is less invasive, more convenient and better time controlled in busy pediatric clinic, therefore is better suited for young children to be used during high dose ACTH stimulation test to evaluate for adrenal insufficiency and to assist interpretation of test results by serum cortisol.

Purpose: Body dissatisfaction in transgender youth (TY) may increase the risk for eating disorders. This is the first study using the Eating Disorders Examination Questionnaire (EDE-Q) to assess for eating disorder psychopathology in TY., Methods: Youth aged 13-22 years (n = 106) presenting to a gender clinic from January 2018 to January 2019 completed the EDE-Q and answered questions on weight manipulation for gender-affirming purposes., Results: Respondents identified as transmasculine (61%), transfeminine (28%), or nonbinary (11%). Mean age was 16.5 years (standard deviation = 2.0), mean weight was 119.9% median body mass index (standard deviation = 32.9), and 32% were on hormonal therapy. Of the participants, 15% had elevated EDE-Q scores. Most (63%) disclosed weight manipulation for gender-affirming purposes, with 11% of assigned females doing so for menstrual suppression. These behaviors had poor concordance with elevated EDE-Q scores (κ = .137 and .148)., Conclusions: Disordered eating behaviors are relatively common among TY. Further studies are needed to validate the EDE-Q in TY and establish meaningful cutoff score values., (Copyright © 2019 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Providers often encourage patients with type 1 diabetes (T1D) to contact them with blood glucose (BG) values between visits. However, patients and families find it cumbersome to share their BG values with clinical providers, creating a barrier to communication. Although many phone applications exist to help patients track BG values, most do not integrate with the electronic health record (EHR). Recent advances in technology can integrate the glucose meter (GM) data into the EHR. This pilot and feasibility study aimed to understand how an automated integration system of GM data into the EHR and remote monitoring by health care providers would impact patient-provider communication. Patients or parents of patients with T1D ( n  = 32, average hemoglobin A1c [HgbA1c]: 8.5%, SD: 1.7, average age: 13.9 years, SD: 3.8) who owned an Apple iPod ® or iPhone ® (5s or higher) participated, and their number of contacts through telephone calls or MyChart™ messages between clinic visits was recorded during each of the three phases: run-in, intervention, and learned. Twenty-eight families completed all phases, and despite guided review of BG trends and automated integration of BG values, the number of patient-initiated calls ( P  = 0.23) and HgbA1c values ( P  = 0.08) did not improve, nor was there a clinically significant change in the number of BG checks per day. Barriers to adoption and effectiveness of this technology exist, and patient motivation is still needed.

Objective: This study examined whether a history of diabetic ketoacidosis (DKA) is associated with changes in longitudinal cognitive and brain development in young children with type 1 diabetes., Research Design and Methods: Cognitive and brain imaging data were analyzed from 144 children with type 1 diabetes, ages 4 to <10 years, who participated in an observational study of the Diabetes Research in Children Network (DirecNet). Participants were grouped according to history of DKA severity (none/mild or moderate/severe). Each participant had unsedated MRI scans and cognitive testing at baseline and 18 months., Results: In 48 of 51 subjects, the DKA event occurred at the time of onset, at an average of 2.9 years before study entry. The moderate/severe DKA group gained more total and regional white and gray matter volume over the observed 18 months compared with the none/mild group. When matched by age at time of enrollment and average HbA 1c during the 18-month interval, participants who had a history of moderate/severe DKA compared with none/mild DKA were observed to have significantly lower Full Scale Intelligence Quotient scores and cognitive performance on the Detectability and Commission subtests of the Conners' Continuous Performance Test II and the Dot Locations subtest of the Children's Memory Scale., Conclusions: A single episode of moderate/severe DKA in young children at diagnosis is associated with lower cognitive scores and altered brain growth. Further studies are needed to assess whether earlier diagnosis of type 1 diabetes and prevention of DKA may reduce the long-term effect of ketoacidosis on the developing brain., (© 2018 by the American Diabetes Association.)

[Purpose] The purposes of this study were to assess and explore the gender-based differences in gross motor skill development of 5-year-old Japanese children. [Subjects and Methods] This cross-sectional study recruited 60 healthy 5-year-old (third-year kindergarten, i.e., nencho ) children (34 boys, 26 girls) from one local private kindergarten school in Otawara city, Tochigi Prefecture, Japan. Gross motor skills, including six locomotor and six object control skills, were assessed using the test of gross motor development, second edition (TGMD-2). All subjects performed two trials of each gross motor skill, and the performances were video-recorded and scored. Assessment procedures were performed according to the standardized guidelines of the TGMD-2. [Results] The majority of subjects had an average level of overall gross motor skills. Girls had significantly better locomotor skills. Boys had significantly better object control skills. [Conclusion] The gross motor skill development of 5-year-old Japanese children involves gender-based differences in locomotor and object control skills. This study provided valuable information that can be used to establish normative references for the gross motor skills of 5-year-old Japanese children.

The extant literature finds that children with type 1 diabetes mellitus (T1D) experience mild cognitive alterations compared to healthy age-matched controls. The neural basis of these cognitive differences is unclear but may relate in part to the effects of dysglycemia on the developing brain. We investigated longitudinal changes in hippocampus volume in young children with early-onset T1D. Structural magnetic resonance imaging data were acquired from 142 children with T1D and 65 age-matched control subjects (4-10 years of age at study entry) at 2 time points, 18 months apart. The effects of diabetes and glycemic exposure on hippocampal volume and growth were examined. Results indicated that although longitudinal hippocampus growth did not differ between children with T1D and healthy control children, slower growth of the hippocampus was associated with both increased exposure to hyperglycemia (interval HbA1c) and greater glycemic variability (MAGE) in T1D. These observations indicate that the current practice of tolerating some hyperglycemia to minimize the risk of hypoglycemia in young children with T1D may not be optimal for the developing brain. Efforts that continue to assess the factors influencing neural and cognitive development in children with T1D will be critical in minimizing the deleterious effects of diabetes., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: This new laser facilitated 'inside-out' technique was used for transvenous pacemaker insertion in a pacemaker-dependent patient with bilateral subclavian occlusion and a failed epicardial system who is not suitable for a transfemoral approach., Method and Results: Procedure was undertaken under general anaesthesia with venous access obtained from right femoral vein and left axillary vein. 7F multipurpose catheter was used to enter proximal edge of the occluded segment of subclavian vein via femoral approach, which then supported stiff angioplasty wires and microcatheters to tunnel into the body of occlusion. When encountered with impenetrable resistance, 1.4 mm Excimer laser helped delivery of a Pilot 200 wire, which then progressed towards the distal edge of occlusion. Serial balloon dilatations allowed wire tracked into subintimal plane, advanced towards left clavicle using knuckle wire technique, which was then externalized with blunt dissection from infraclavicular pocket area. It was later changed to Amplatz superstiff wire exiting from both ends to form a rail, which ultimately allowed passage of pacing leads after serial balloon dilatation from clavicular end., Conclusion: Our hybrid 'inside-out' technique permitted transvenous pacemaker insertion without complication and this is, to our knowledge, the first case using laser in this context., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

[Purpose] The purpose of this study was to investigate reliability of the test of gross motor development second edition (TGMD-2) for Kindergarten children in Myanmar. [Subjects and Methods] Fifty healthy Kindergarten children (23 males, 27 females) whose parents/guardians had given written consent were participated. The subjects were explained and demonstrated all 12 gross motor skills of TGMD-2 before the assessment. Each subject individually performed two trials for each gross motor skill and the performance was video recorded. Three raters separately watched the video recordings and rated for inter-rater reliability. The second assessment was done one month later with 25 out of 50 subjects for test-rest reliability. The video recordings of 12 subjects were randomly selected from the first 50 recordings for intra-rater reliability six weeks after the first assessment. The agreement on the locomotor and object control raw scores and the gross motor quotient (GMQ) were calculated. [Results] The findings of all the reliability coefficients for the locomotor and object control raw scores and the GMQ were interpreted as good and excellent reliability. [Conclusion] The results represented that TGMD-2 is a highly reliable and appropriate assessment tool for assessing gross motor skill development of Kindergarten children in Myanmar.

[Purpose] The purpose of this study was to examine the gross motor skill development of 5-year-old Kindergarten children in Myanmar. [Subjects and Methods] Total 472 healthy Kindergarten children (237 males, 235 females) of 2016-2017 academic year from four schools in urban area and four schools in rural area of Myanmar were recruited. The gross motor skill development of all subjects was assessed with the test of gross motor development second edition (TGMD-2). All subjects performed two trials for each gross motor skill and the performance was video recorded and scored. The assessment procedures were done according to the standardized guidelines of TGMD-2. [Results] The majority of subjects had average level of gross motor skill rank. The significant differences were found on the run and gallop of locomotor skills and the most of object control skills except the catch between males and females. The significant differences were also found between subjects from urban and rural areas. [Conclusion] Gross motor skill development of 5-year-old Kindergarten children in Myanmar had gender-based and region-based differences on both locomotor and object control skills. This study added a valuable information to the establishment of a normative reference of Kindergarten aged children for future studies.

[Purpose] The aim of this study was to compare immediate effects between new medical stretching (NMS) and conventional medical stretching (CMS) techniques on Hamstrings flexibility. [Subjects and Methods] Thirteen healthy adult males, with finger floor distance (FFD) less than zero centimeter, without known musculoskeletal and neurological impairment in spine or lower extremities, were included. The subjects were randomly allocated to two groups. The subjects were instructed to perform NMS and CMS (hold for 30 seconds once, twice for each side of lower extremity) for both sides (total two minutes, only one session for one day). The interval between the two techniques was one week. FFD was measured with digital standing trunk flexion meter at the pre-intervention and post-intervention of both techniques. [Results] The mean values of FFD improved at the post-interventions of both techniques. The tests of within subject effects indicated that the main effect of treatment was not significant but the main effect of time was significant and the interaction of treatment and time was also significant. [Conclusion] The results of this study indicated that both medical stretching techniques were effective on Hamstrings flexibility immediately after the intervention and NMS technique was more effective on improving flexibility.

Objective: To compare the frequency of elevated morning blood ketone levels according to age in 4-14 year olds with type 1 diabetes following overnight use of an automated low glucose insulin suspension system, or following control nights when the system was not used., Research Design and Methods: For 28 children ages 4-9 years and 54 youth ages 10-14 years, elevation of morning blood ketone levels was assessed using the Precision Xtra Ketone meter following 1155 and 2345 nights, respectively. Repeated measures logistic regression models were used to compare age groups for blood ketone level elevation following control nights (system not activated) and following intervention nights with and without insulin suspension., Results: Elevated morning blood ketones (≥0.6 mmol/L) were present following 10% of 580 control nights in the 4-9 year olds compared with 2% of 1162 control nights in 10-14 year olds (P < 0.001). Likewise, the frequency was greater following intervention nights in the younger age group (13% of 575 nights vs 2% of 1183 nights, P < 0.001). A longer duration of pump suspension resulted in a higher percentage of mornings with elevated blood ketones in the younger age group (P = 0.002), but not in the older age group (P = 0.63). The presence of elevated morning ketone levels did not progress to ketoacidosis in any subject., Conclusions: Elevated morning blood ketones are more common in younger children with type 1 diabetes with or without nocturnal insulin suspension. Care providers need to be aware of the differences in ketogenesis in younger age children relative to various clinical situations., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: National AIDS Programme in Myanmar has made significant progress in scaling up antiretroviral treatment (ART) services and recognizes the importance of differentiated care for people living with HIV. Indeed, long centred around the hospital and reliant on physicians, the country's HIV response is undergoing a process of successful decentralization with HIV care increasingly being integrated into other health services as part of a systematic effort to expand access to HIV treatment. This study describes implementation of differentiated care in Médecins Sans Frontières (MSF)-supported programmes and reports its outcomes., Methods: A descriptive cohort analysis of adult patients on antiretroviral treatment was performed. We assessed stability of patients as of 31 December 2014 and introduced an intervention of reduced frequency of physicians' consultations for stable patients, and fast tract ART refills. We measured a number of saved physician's visits as the result of this intervention. Main outcomes, remained under care, death, lost to follow up, treatment failure, were assessed on 31 December 2015 and reported as rates for different stable groups., Results: On 31 December 2014, our programme counted 16, 272 adult patients enrolled in HIV care, of whom 80.34% were stable. The model allowed for an increase in the average number of patients one medical team could care for - from 745 patients in 2011 to 1, 627 in 2014 - and, thus, a reduction in the number of teams needed. An assessment of stable patients enrolled on ART one year after the implementation of the new model revealed excellent outcomes, aggregated for stable patients as 98.7% remaining in care, 0.4% dead, 0.8% lost to follow-up, 0.8% clinical treatment failure and 5.8% with immunological treatment failure., Conclusions: Implementation of a differentiated model reduced the number of visits between stable clients and physicians, reduced the medical resources required for treatment and enabled integrated treatment of the main co-morbidities. We hope that these findings will encourage other stakeholders to implement innovative models of HIV care in Myanmar, further expediting the scale up of ART services, the decentralization of treatment and the integration of care for the main HIV co-morbidities in this context., Competing Interests: The authors have no competing interests to declare.

Background: We developed a system to suspend insulin pump delivery overnight when the glucose trend predicts hypoglycemia. This predictive low-glucose suspend (PLGS) system substantially reduces nocturnal hypoglycemia without an increase in morning ketosis. Evaluation of hypoglycemia risk factors that could potentially influence the efficacy of the system remains critical for understanding possible problems with the system and identifying patients that may have the greatest benefit when using the system., Methods: The at-home randomized trial consisted of 127 study participants with hemoglobin A1c (A1C) of ≤8.5% (mmol/mol) for patients aged 4-14 years and ≤8.0% for patient aged 15-45 years. Factors assessed included age, gender, A1C, diabetes duration, daily percentage basal insulin, total daily dose of insulin (units/kg-day), bedtime BG, bedtime snack, insulin on board, continuous glucose monitor (CGM) rate of change (ROC), day of the week, time system activated, daytime exercise intensity, and daytime CGM-measured hypoglycemia., Results: The PLGS system was effective in preventing hypoglycemia for each factor subgroup. There was no evidence that the PLGS system was more or less effective in preventing hypoglycemia in any one subgroup compared with the other subgroups based on that factor. In addition, the effect of the system on overnight hyperglycemia did not differ in subgroups., Conclusions: The PLGS system tested in this study effectively reduced hypoglycemia without a meaningful increase in hyperglycemia across a variety of factors., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Continuous glucose monitors and sensors were purchased at a bulk discount price from Medtronic MiniMed, Inc (Northridge, CA). Bayer HealthCare, LLC, Diabetes Care provided blood glucose meters, test strips, control solution, and lancets as product support through an investigator sponsored research grant. Home ketone meters and test strips were provided by Abbott Diabetes Care, Inc. The companies had no involvement in the design, conduct, or analysis of the trial or the manuscript preparation. PMC has no disclosures. BAB reports grants from NIDDK, during the conduct of the study; grants, personal fees, and nonfinancial support from Medtronic MiniMed, Inc, personal fees from Sanofi, personal fees from Tandem, personal fees from Novo-Nordisk, personal fees from Animas, outside the submitted work. In addition, BAB reports a Kalman filter based hypoglycemia prevention algorithm patent is pending. DMM reports grants from American Diabetes Association- Medtronic MiniMed, Inc. IH reports grants from JDRF-Federal Development funding during the conduct of the study, as well as grants, personal fees, and nonfinancial support from Abbott, from AstraZeneca/Bristol Myers Squibb; personal fees and nonfinancial support from Boehringer Ingelheim, grants, personal fees, and nonfinancial support from Eli Lilly, grants, personal fees, and nonfinancial support from Janssen-Ortho/Johnson & Johnson (JNJ), personal fees and nonfinancial support from Medtronic MiniMed, Inc, grants, personal fees, nonfinancial support, and other from Merck, grants, personal fees, and nonfinancial support from Novo Nordisk, grants from Pfizer, grants, personal fees, and nonfinancial support from Sanofi Aventis, outside the submitted work; DMW reports research supplies support from LifeScan, Inc and Medtronic MiniMed, Inc and a Kalman filter based hypoglycemia prevention algorithm patent pending. T. Aye has no disclosures. PC has no disclosures. HPC reports grants from Dexcom during the conduct of the study, as well as a Kalman filter based hypoglycemia prevention algorithm patent is pending. LM has no disclosures. RWB reports grants from NIH and from JDRF during the conduct of the study. CK reports consultant fees from Medtronic MiniMed, Inc. RWB reports grants from NIH and from JDRF during the conduct of the study. JWL has no disclosures., (© 2016 Diabetes Technology Society.)

Family medicine is an integral part of primary care within health systems. Globally, training programmes exhibit a great degree of variability in content and skill acquisition. While this may in part reflect the needs of a given setting, there exists standard criteria that all family medicine programmes should consider core activities. WONCA has provided an open-access list of standards that their expert community considers essential for family medicine (GP) post-graduate training. Evaluation of developing or existing training programmes using these standards can provide insight into the degree of variability, gaps within programmes and equally as important, gaps within recommendations. In collaboration with the host institution, two family medicine programmes in Nepal and Myanmar were evaluated based on WONCA global standards. The results of the evaluation demonstrated that such a process can allow for critical review of curriculum in various stages of development and evaluation. The implications of reviewing training programmes according to WONCA standards can lead to enhanced training world-wide and standardisation of training for post-graduate family medicine.

Geometric waveguides are being integrated into head-mounted display (HMD) systems, where having see-through capability in a compact, lightweight form factor is required. We developed methods for determining the field of view (FOV) of such waveguide HMD systems and have analytically derived the FOV for waveguides using planar and curved geometries. By using real ray-tracing methods, we are able to show how the geometry and index of refraction of the waveguide, as well as the properties of the coupling optics, impact the FOV. Use of this analysis allows one to determine the maximum theoretical FOV of a planar or curved waveguide-based system.

Objective: Prior studies examining beta-cell preservation in type 1 diabetes have predominantly assessed stimulated C-peptide concentrations approximately 10 wk after diagnosis. We examined whether earlier assessments might aid in prediction of beta cell function over time., Methods: Using data from a multi-center randomized trial assessing the effect of intensive diabetes management initiated within 1 wk of diagnosis, we assessed which clinical factors predicted 90-min mixed-meal tolerance test (MMTT) stimulated C-peptide values obtained 2 and 6 wk after diagnosis. We also studied associations of these factors with C-peptide values at 1- and 2-year post-diagnosis. Data from intervention and control groups were pooled., Results: Among 67 study participants (mean age 13.3 ± 5.7 yr, range 7.8-45.7 yr) in multivariable analyses, C-peptide increased from baseline to 2 wks and then 6 wk. C-peptide levels at these times were significantly correlated with 1- and 2-yr C-peptide concentrations (all p < 0.001), with the strongest observed associations between 6-wk C-peptide and the 1- and 2-yr values (r = 0.66 and r = 0.61, respectively). In multivariable analyses, greater baseline and 6-wk C-peptide, and older age independently predicted greater 1- and 2-yr C-peptide concentrations., Conclusions: C-peptide assessments close to diagnosis were predictive of subsequent C-peptide production. Our data demonstrate a clear increase in C-peptide over the initial 6 wk after diabetes diagnosis followed by a plateau. Our data do not suggest that MMTT assessments performed closer to diagnosis than 6 wk would improve prediction of subsequent residual beta cell function., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D., Methods: A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes., Results: Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function., Conclusions: The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned.

Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural MRI was performed on 141 children with diabetes (4-10 years of age at study entry) and 69 age-matched control subjects at two time points spaced 18 months apart. For the children with diabetes, the mean (±SD) HbA1c level was 7.9 ± 0.9% (63 ± 9.8 mmol/mol) at both time points. Relative to control subjects, children with diabetes had significantly less growth of cortical gray matter volume and cortical surface area and significantly less growth of white matter volume throughout the cortex and cerebellum. For the population with diabetes, the change in the blood glucose level at the time of scan across longitudinal time points was negatively correlated with the change in gray and white matter volumes, suggesting that fluctuating glucose levels in children with diabetes may be associated with corresponding fluctuations in brain volume. In addition, measures of hyperglycemia and glycemic variation were significantly negatively correlated with the development of surface curvature. These results demonstrate that early-onset type 1 diabetes has widespread effects on the growth of gray and white matter in children whose blood glucose levels are well within the current treatment guidelines for the management of diabetes., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

[Purpose] The purpose of this study was to determine whether strength training programs for hip extensors and knee extensors improve gross motor function of children with cerebral palsy in Myanmar. [Subjects and Methods] Forty children (25 boys and 15 girls, mean age: 6.07 ± 2.74 years) from National Rehabilitation Hospital, Yangon, Myanmar, who had been diagnosed with spastic diplegic cerebral palsy, Gross Motor Classification System I and II participated in a 6-week strength training program (45 minutes per day, 3 days per week) on hip and knee extensors. Assessment was made, before and after intervention, of the amount of training weight in pounds, as well as Gross Motor Function Measure (GMFM) dimensions D (standing) and E (walking, running, jumping). [Results] All scores had increased significantly after the strength-training program. [Conclusion] A simple method of strength-training program for hip and knee extensors might lead to improved muscle strength and gross motor function in children with spastic diplegic cerebral palsy.

Objective: Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system., Research Design and Methods: In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight., Results: Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis., Conclusions: In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: Hypoglycemia remains an impediment to good glycemic control, with nocturnal hypoglycemia being particularly dangerous. Information on major contributors to nocturnal hypoglycemia remains critical for understanding and mitigating risk., Materials and Methods: Continuous glucose monitoring (CGM) data for 855 nights were studied, generated by 45 subjects 15-45 years of age with hemoglobin A1c (HbA1c) levels of ≤8.0% who participated in a larger randomized study. Factors assessed for potential association with nocturnal hypoglycemia (CGM measurement of <60 mg/dL for ≥30 min) included bedtime blood glucose (BG), exercise intensity, bedtime snack, insulin on board, day of the week, previous daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal insulin, and daily insulin dose., Results: Hypoglycemia occurred during 221 of 885 (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend for lower bedtime BG levels to be associated with more frequent nocturnal hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend versus weekday, gender, and daily basal and bolus insulin were not associated with nocturnal hypoglycemia., Conclusions: Awareness that HbA1c level, exercise, bedtime BG level, and daytime hypoglycemia are all modifiable factors associated with nocturnal hypoglycemia may help patients and providers decrease the risk of hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear fashion across the range of variables, with no clear-cut thresholds to guide clinicians or patients for any particular night.

Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA1c performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Purpose: Recombinant activated factor VII (rFVIIa) is a pro-hemostatic drug that is approved for treatment of bleeding in hemophilia patients, but it is frequently used off-label in non-hemophiliacs. The purpose of this study was to determine if the off-label use of rFVIIa is expanding and whether this poses a net harm to patients., Methods: For this historical cohort study, data were collected on all non-hemophilia patients who received rFVIIa from 2007 to 2010 at 16 Canadian centres, and the pattern of use was examined. Logistic regression was used to determine the prognostic importance of severity of bleeding and the presence of an rFVIIa dose-effect relationship with major adverse events., Results: One thousand three hundred seventy-eight patients received rFVIIa off-label, and 987 (72%) of these patients underwent cardiac surgery. The median [interquartile range] dose was 57 [36-85] µg·kg(-1). Usage increased from 2007 to 2008 (n = 341 and 380, respectively) but decreased in 2009 and 2010 (n = 350 and 307, respectively). Dose of rFVIIa and bleeding severity were associated with measured adverse events (P < 0.05). After adjusting for bleeding severity, dose was not associated with any of the adverse events., Conclusions: The off-label use of rFVIIa in Canada remains stable. Since severity of bleeding is prognostically important, the benefits of rapidly gaining control of bleeding that is non-responsive to conventional therapies may at times warrant the use of potent hemostatic drugs with established risk profiles, such as rFVIIa.

Objective: Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels., Research Design and Methods: Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred., Results: Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm., Conclusions: Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis., (© 2014 by the American Diabetes Association.)

Objective: To investigate whether type 1 diabetes affects white matter (WM) structure in a large sample of young children., Research Design and Methods: Children (ages 4 to <10 years) with type 1 diabetes (n = 127) and age-matched nondiabetic control subjects (n = 67) had diffusion weighted magnetic resonance imaging scans in this multisite neuroimaging study. Participants with type 1 diabetes were assessed for HbA1c history and lifetime adverse events, and glucose levels were monitored using a continuous glucose monitor (CGM) device and standardized measures of cognition., Results: Between-group analysis showed that children with type 1 diabetes had significantly reduced axial diffusivity (AD) in widespread brain regions compared with control subjects. Within the type 1 diabetes group, earlier onset of diabetes was associated with increased radial diffusivity (RD) and longer duration was associated with reduced AD, reduced RD, and increased fractional anisotropy (FA). In addition, HbA1c values were significantly negatively associated with FA values and were positively associated with RD values in widespread brain regions. Significant associations of AD, RD, and FA were found for CGM measures of hyperglycemia and glucose variability but not for hypoglycemia. Finally, we observed a significant association between WM structure and cognitive ability in children with type 1 diabetes but not in control subjects., Conclusions: These results suggest vulnerability of the developing brain in young children to effects of type 1 diabetes associated with chronic hyperglycemia and glucose variability.

Background: The ability to lie still in an MRI scanner is essential for obtaining usable image data. To reduce motion, young children are often sedated, adding significant cost and risk., Objective: We assessed the feasibility of using a simple and affordable behavioral desensitization program to yield high-quality brain MRI scans in sedation-free children., Materials and Methods: 222 children (4-9.9 years), 147 with type 1 diabetes and 75 age-matched non-diabetic controls, participated in a multi-site study focused on effects of type 1 diabetes on the developing brain. T1-weighted and diffusion-weighted imaging (DWI) MRI scans were performed. All children underwent behavioral training and practice MRI sessions using either a commercial MRI simulator or an inexpensive mock scanner consisting of a toy tunnel, vibrating mat, and video player to simulate the sounds and feel of the MRI scanner., Results: 205 children (92.3%), mean age 7 ± 1.7 years had high-quality T1-W scans and 174 (78.4%) had high-quality diffusion-weighted scans after the first scan session. With a second scan session, success rates were 100% and 92.5% for T1-and diffusion-weighted scans, respectively. Success rates did not differ between children with type 1 diabetes and children without diabetes, or between centers using a commercial MRI scan simulator and those using the inexpensive mock scanner., Conclusion: Behavioral training can lead to a high success rate for obtaining high-quality T1-and diffusion-weighted brain images from a young population without sedation.

The aim of this study was to assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4-10 years across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data, and T1D glycemic history since diagnosis were collected. The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5 years and average onset age was 4 years. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < .001). Learning and memory (p = .46) and processing speed (p = .25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time.

Background: Children with type 1 diabetes (T1D) spend 4-7 h/day in school with very little supervision of their diabetes management. Therefore, families have become more dependent on technology, such as use of real-time continuous glucose monitoring (RT-CGM), to provide increased supervision of their diabetes management. We sought to assess the impact of RT-CGM use in the classroom/school environment., Subjects and Methods: Children with T1D using RT-CGM, their parents, and teachers completed a questionnaire about RT-CGM in the classroom/school environment., Results: The RT-CGM was tolerated well in the classroom/school environment. Seventy percent of parents, 75% of students, and 51% of teachers found RT-CGM useful in the classroom/school environment. The students found the device to be more disruptive than did their parents and teachers. However, all three groups agreed that RT-CGM increased their comfort with diabetes management at school., Conclusions: Our study suggests that RT-CGM is useful and not disruptive in the classroom/school environment. The development of education materials for teachers could further increase its acceptance in the classroom/school environment.

Objective: To detect clinical correlates of cognitive abilities and white matter (WM) microstructural changes using diffusion tensor imaging (DTI) in young children with type 1 diabetes., Research Design and Methods: Children, ages 3 to <10 years, with type 1 diabetes (n = 22) and age- and sex-matched healthy control subjects (n = 14) completed neurocognitive testing and DTI scans., Results: Compared with healthy controls, children with type 1 diabetes had lower axial diffusivity (AD) values (P = 0.046) in the temporal and parietal lobe regions. There were no significant differences between groups in fractional anisotropy and radial diffusivity (RD). Within the diabetes group, there was a significant, positive correlation between time-weighted HbA(1c) and RD (P = 0.028). A higher, time-weighted HbA(1c) value was significantly correlated with lower overall intellectual functioning measured by the full-scale intelligence quotient (P = 0.03)., Conclusions: Children with type 1 diabetes had significantly different WM structure (as measured by AD) when compared with controls. In addition, WM structural differences (as measured by RD) were significantly correlated with their HbA(1c) values. Additional studies are needed to determine if WM microstructural differences in young children with type 1 diabetes predict future neurocognitive outcome.