Evaluating the Impact of Applying Personal Glucose Targets in a Closed-Loop System for People With Type 1 Diabetes.

BACKGROUND: CamAPS FX is a hybrid closed-loop smartphone app used to manage type one diabetes. The closed-loop algorithm has a default target glucose of 5.8 mmol/L (104.5 mg/dL), but users can select personal glucose targets (adjustable between 4.4 mmol/L and 11.0 mmol/L [79 mg/dL and 198 mg/dL, respectively]). METHOD: In this post-hoc analysis, we evaluated the impact of personal glucose targets on glycemic control using data from participants in five randomized controlled trials. RESULTS: Personal glucose targets were widely used, with 20.3% of all days in the data set having a target outside the default target bin (5.5-6.0 mmol/L [99-108 mg/dL]). Personal glucose targets >6.5 mmol/L (117 mg/dL) were associated with significantly less time in target range (3.9-10.0 mmol/L [70-180 mg/dL]; 6.5-7.0 mmol/L [117-126 mg/dL]: mean difference = -3.2 percentage points [95% CI: -5.3 to -1.2; P < .001]; 7.0-7.5 mmol/L [126-135 mg/dL]: -10.8 percentage points [95% CI: -14.1 to -7.6; P < .001]). Personal targets >6.5 mmol/L (117 mg/dL) were associated with significantly lower time (<3.9 mmol/L [<70 mg/dL]; 6.5-7.0 mmol/L [117-126 mg/dL]: -1.85 percentage points [95% CI: -2.37 to -1.34; P < .001]; 7.0-7.5 mmol/L [126-135 mg/dL]: -2.68 percentage points [95% CI: -3.49 to -1.86; P < .001]). CONCLUSIONS: Discrete study populations showed differences in glucose control when applying similar personal targets.

Upper arm length model suggests transient bilateral asymmetry is associated with right thoracic adolescent idiopathic scoliosis (RT-AIS) with implications for pathogenesis and estimation of linear skeletal overgrowth.

INTRODUCTION: In girls with adolescent idiopathic scoliosis (AIS) the finding of abnormal extra-spinal bilateral skeletal length asymmetries in upper limbs, periapical ribs, and ilia begs the question whether these bilateral asymmetries are connected in some way with pathogenesis. MATERIAL AND METHODS: We investigated upper arm length (UAL) asymmetries in two groups of right-handed girls aged 11-18 years with right thoracic adolescent idiopathic scoliosis (RT-AIS, n=95) from preoperative and screening referrals (mean Cobb angle 46°) and healthy controls (n=240). Right and left UAL were measured with a Harpenden anthropometer of the Holtain equipment, Asymmetry was calculated as UAL difference, right minus left, in mm. Repeatability of the measurements was assessed as technical error of the measurement and coefficient of reliability. RESULTS: In girls with RT-AIS, UAL asymmetry was greater than in healthy girls, regressed negatively with age and correlated significantly with Cobb angle and apical vertebral rotation. In healthy girls, UAL asymmetry was unrelated to age. Plotted against years after estimated menarcheal age, UAL asymmetry decreased significantly for girls with RT-AIS but not for healthy girls. DISCUSSION AND CONCLUSIONS: The apparent transience of the abnormal UAL asymmetry suggests it is not secondary to spinal deformity but pathogenetically associated with it. We suggest two hypotheses to account for these changes: (1) a transient asymmetry process with growth velocity; and (2) in the light of subsequent research, early skeletal overgrowth with catch-down growth affecting right but not left upper arm. The relation of the upper arm length asymmetry to the increased length of periapical left ribs reported for RT-AIS is unknown. Right upper arm length may provide a more simple model than arm span, for estimating linear skeletal overgrowth of girls with RT-AIS.

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy.

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans.

Safety of the newer inhaled corticosteroids in childhood asthma.

Inhaled corticosteroids (ICS) remain a vital part of the management of persistent asthma, but concerns have been raised about their potential adverse effects in children. This review examines the safety data on three new ICS - fluticasone propionate, mometasone, and extrafine beclomethasone in hydrofluoroalkane (HFA-134a) propellant (QVAR The use of tradenames is for product identification purposes only and does not imply endorsement. formulation) in relation to the older corticosteroids. Topical adverse effects such as thrush and dysphonia are rare, but dental erosion is a possibility with powder forms of ICS because of their low pH. Thus, it is important to stress mouth rinsing after administration and maintaining good dental hygiene to minimize this risk. Biochemical adrenal suppression can be readily demonstrated, particularly with high doses of all ICS. The clinical relevance of this was uncertain in the past, but there have now been >50 reported cases of acute adrenal crises in children receiving ICS, most of whom were on fluticasone propionate. In order to minimize the risk of symptomatic adrenal suppression, it is important to back-titrate the ICS dose and alert families of children receiving high-dose ICS of this potential adverse effect. A pediatric endocrine opinion should be sought if adrenal suppression is suspected. The older ICS cause temporary slowing of growth velocity, but the limited data available do not show any significant compromise of final adult height. The effect on growth of fluticasone propionate may not be as great as with the older ICS, but the studies have been short term and only used low doses of fluticasone propionate. There have been case reports of growth suppression in children receiving high doses of fluticasone propionate. The limited studies performed on the effect of ICS on bone mineral density in children did not show any adverse effects, but there may be an increased risk of fractures. Hydrofluoroalkane beclomethasone (QVAR) is essentially the same drug as chlorofluorocarbon beclomethasone, but with double the lung deposition owing to the smaller particle size. Thus, it could be expected that any adverse effects seen with chlorofluorocarbon beclomethasone would be the same with hydrofluoroalkane beclomethasone. However, some of the published data, particularly in adults, suggest that hydrofluoroalkane beclomethasone may be less systemically active than chlorofluorocarbon beclomethasone, even at equipotent doses. As yet, there are no long-term data on mometasone, but initial studies in adults suggest there may be less suppression of the hypothalamic-pituitary-adrenal axis, although further studies are required, particularly in children.ICS will remain a cornerstone in the management of persistent pediatric asthma, provided that the diagnosis of asthma is secure. It is very important to use ICS appropriately and to ensure the lowest possible doses are used to achieve symptom control, thus minimizing the risk of serious adverse effects.

Adrenal crises in children treated with high-dose inhaled corticosteroids for asthma.

Three children presented with adrenal crises, manifested by vomiting and hypoglycaemia, after protracted courses of high-dose inhaled corticosteroids for asthma. Significant dose reduction was possible in all three without loss of asthma control, emphasising the importance of back-titration to minimise dose. Parents of children taking high doses of inhaled corticosteroids should be alerted to the clinical features of adrenal insufficiency. If suspected, prompt medical assessment should be arranged, including serum glucose and cortisol measurement.