Maximum expiratory flow rate at 30 percent of vital capacity above residual volume served as an index of airway obstruction in comparing the effects of leukotriene C and histamine administered by aerosol to five normal persons. Leukotriene C was 600 to 9500 times more potent than histamine on a molar basis in producing an equivalent decrement in the residual volume. The leukotriene C response was slow in onset and prolonged, reminiscent of the effects of aerosol allergen challenge in asthmatic allergic subjects.

Spondyloocular syndrome is an autosomal-recessive disorder with spinal compression fractures, osteoporosis, and cataract. Mutations in XYLT2, encoding isoform of xylosyltransferase, were recently identified as the cause of the syndrome. We report on 4 patients, 2 unrelated patients and 2 siblings, with spondyloocular syndrome and novel mutations in XYLT2. Exome sequencing revealed a homozygous nonsense mutation, NM_022167.3(XYLT2): c.2188C>T, resulting in a premature stop codon (p.Arg730 Ã ) in a female patient. The patient presents visual impairment, generalized osteoporosis, short stature with short trunk, spinal compression fractures, and increased intervertebral disc space and hearing loss. We extended our XYLT2 analysis to a cohort of 22 patients with generalized osteoporosis, mostly from consanguineous families. In this cohort, we found by Sanger sequencing 2 siblings and 1 single patient who were homozygous for missense mutations in the XYLT2 gene (p.Arg563Gly and p.Leu605Pro). The patients had osteoporosis, compression fractures, cataracts, and hearing loss. Bisphosphonate treatment in 1 patient resulted in almost complete normalization of vertebral structures by adolescence, whereas treatment response in the others was variable. This report together with a previous study shows that mutations in the XYLT2 gene result in a variable phenotype dominated by spinal osteoporosis, cataract, and hearing loss.

OBJECTIVE <p>This study aims to examine insulin delivery methods, glucose monitoring modalities and related outcomes in a large, international, diverse cohort of children and adolescents with type 1 diabetes from the SWEET-Registry</p> <p> </p> <p>RESEARCH DESIGN AND METHODS</p> <p>Participants with type 1 diabetes of <u>></u>1 year of duration, aged ≤18y and documented pump/sensor usage during the period August 2017-July 2019 were stratified into four categories: injections-no sensor (reference); injections+sensor; pump-no sensor; pump+sensor. HbA_1c and proportion of patients with DKA or SH were analyzed; linear and logistic regression models adjusted for demographics, region and gross-domestic-product (GDP)-per capita were applied.</p> <p> </p> <p>RESULTS</p> <p>Data of 25,654 subjects were analyzed. Injections-no sensor: 37.44% [adjusted-HbA_1c 8.72 (95%CI 8.68-8.75)]; injections+sensor: 14.98% [adjusted-HbA_1c 8.30 (8.25-8.35)]; pump-no sensor: 17.22% [adjusted-HbA_1c 8.07 (8.03-8.12)]; pump+sensor: 30.35% [adjusted-HbA_1c 7.81 (7.77-7.84)]. HbA_1c was lower in all categories of subjects using pump and/or sensor compared to injections-no sensor treatment method (p<0.001, respectively). Proportion of DKA episodes was lower in subjects with pump+sensor [1.98 (1.64-2.48); p<0.001] and pump-no sensor [2.02 (1.64-2.48); p<0.05)] when compared to injections-no sensor [2.91 (2.59-3.31)]. Proportion of SH was lower in pump-no sensor [1.10 (0.85-1.43); p<0.001] but higher in the injections+sensor [4.25 (3.65-4.95); p<0.001] compared to injections-no sensor [2.35 (2.04-2.71)].</p> <p> </p> <p>CONCLUSIONS</p> Lower HbA_1c and fewer DKA episodes were observed in subjects using either a pump, CGM or both. Pump use was associated with lower rate of SH. Across SWEET centers, use of pumps and CGM is increasing. The concomitant use of pump and CGM was found to be associated with an additive benefit.

OBJECTIVE Insulin delivery methods, glucose-monitoring modalities, and related outcomes were examined in a large, international, diverse cohort of children and adolescents with type 1 diabetes from the Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) -Registry. RESEARCH DESIGN AND METHODS Participants with type 1 diabetes of ≥1 year, aged ≤18 years, and who had documented pump or sensor usage during the period August 2017–July 2019 were stratified into four categories: injections–no sensor (referent); injections + sensor; pump–no sensor; and pump + sensor. HbA1c and proportion of patients with diabetic ketoacidosis (DKA) or severe hypoglycemia (SH) were analyzed; linear and logistic regression models adjusted for demographics, region, and gross domestic product per capita were applied. RESULTS Data of 25,654 participants were analyzed. The proportions of participants (adjusted HbA1c data) by study group were as follows: injections–no sensor group, 37.44% (8.72; 95% CI 8.68–8.75); injections + sensor group, 14.98% (8.30; 95% CI 8.25–8.35); pump–no sensor group, 17.22% (8.07; 95% CI 8.03–8.12); and pump + sensor group, 30.35% (7.81; 95% CI 7.77–7.84). HbA1c was lower in all categories of participants who used a pump and/or sensor compared with the injections–no sensor treatment method (P &lt; 0.001). The proportion of DKA episodes was lower in participants in the pump + sensor (1.98%; 95% CI 1.64–2.48; P &lt; 0.001) and the pump–no sensor (2.02%; 95% CI 1.64–2.48; P &lt; 0.05) groups when compared with those in the injections–no sensor group (2.91%; 95% CI 2.59–3.31). The proportion of participants experiencing SH was lower in pump–no sensor group (1.10%; 95% CI 0.85–1.43; P &lt; 0.001) but higher in the injections + sensor group (4.25%; 95% CI 3.65–4.95; P &lt; 0.001) compared with the injections–no sensor group (2.35%; 95% CI 2.04–2.71). CONCLUSIONS Lower HbA1c and fewer DKA episodes were observed in participants using either a pump or continuous glucose monitoring (CGM) or both. Pump use was associated with a lower rate of SH. Across SWEET centers, use of pumps and CGM is increasing. The concomitant use of pump and CGM was associated with an additive benefit.

Severe obesity in childhood is increasing in prevalence and is associated with considerable morbidity. Studies into pediatric obesity have focused largely on interventions that do not necessarily target the unique biologic or psychological underpinnings for the weight gain in the individual child or adolescent. Outcomes show modest improvement and are of questionable benefit for patients with severe obesity. Although weight is a commonly used outcome, other psychological and metabolic parameters including normalization of physical activity and eating behaviors should be primary outcome goals. The durability of weight loss is often limited by physiologic systems that are evolutionarily designed to promote weight gain. Drug therapies for children are limited, as is their effect on weight and metabolism. Existing drugs that are incidentally found to cause weight loss through off-target effects are being actively investigated for obesity indications. Bariatric surgery results in the most significant weight reduction, but it is associated with potential morbidity and long term data are not available for adolescents undergoing this procedure. As understanding of the biologic and psychosocial contributors to eating behaviors and body weight regulation increases, multifaceted and targeted behavioral, pharmacological, and surgical treatment algorithms should be developed and applied to target the underlying pathways involved for the individual child or adolescent with severe obesity.

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Introduction Implementation of telemedicine has been shown to improve health outcomes, such as body mass index (BMI). However, it is unclear whether telemedicine is useful alongside traditional weight-management programmes for adolescents with complex obesity. The objective was to evaluate implementation of the Ontario Telemedicine Network (OTN), a videoconferencing programme, as an adjunctive tool to face-to-face counselling within the setting of an established interdisciplinary obesity treatment programme. Methods Our observational cohort included two groups of adolescents enrolled in a clinical obesity-management programme over a two year period. Adolescents ( n = 50) in group 1 attended both in-person and virtual visits (OTN group), and adolescents ( n = 50) in group 2 received only in-person visits (comparison group). Within the OTN group, satisfaction survey responses were compared between patients and healthcare professionals. Change in BMI per month, paediatric quality of life scores, session attendance and demographic variables were compared between groups. Results OTN subjects averaged 4.9 telehealth visits per adolescent over the two year programme. Both OTN and comparison groups had similar changes in BMI ( p = 0.757), with increases over time ( p = 0.042). Paediatric quality of life scores in both groups improved over time compared to baseline ( p < 0.001), with higher scores for children compared to parental-reported child scores ( p = 0.008). Both adolescents and healthcare professionals using the OTN were similarly satisfied with their experience. Conclusion Adjunctive use of the OTN within the setting of a weight-management programme is feasible, well accepted by families and healthcare providers, and led to similar outcomes compared to usual care.

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