Decreasing severity of obesity from early to late adolescence and young adulthood associates with longitudinal metabolomic changes implicated in lower cardiometabolic disease risk.

BACKGROUND: Obesity in childhood is associated with metabolic dysfunction, adverse subclinical cardiovascular phenotypes and adult cardiovascular disease. Longitudinal studies of youth with obesity investigating changes in severity of obesity with metabolomic profiles are sparse. We investigated associations between (i) baseline body mass index (BMI) and follow-up metabolomic profiles; (ii) change in BMI with follow-up metabolomic profiles; and (iii) change in BMI with change in metabolomic profiles (mean interval 5.5 years). METHODS: Participants (n = 98, 52% males) were recruited from the Childhood Overweight Biorepository of Australia study. At baseline and follow-up, BMI and the % >95th BMI-centile (percentage above the age-, and sex-specific 95th BMI-centile) indicate severity of obesity, and nuclear magnetic resonance spectroscopy profiling of 72 metabolites/ratios, log-transformed and scaled to standard deviations (SD), was performed in fasting serum. Fully adjusted linear regression analyses were performed. RESULTS: Mean (SD) age and % >95th BMI-centile were 10.3 (SD 3.5) years and 134.6% (19.0) at baseline, 15.8 (3.7) years and 130.7% (26.2) at follow-up. Change in BMI over time, but not baseline BMI, was associated with metabolites at follow-up. Each unit (kg/m2) decrease in sex- and age-adjusted BMI was associated with change (SD; 95% CI; p value) in metabolites of: alanine (-0.07; -0.11 to -0.04; p < 0.001), phenylalanine (-0.07; -0.10 to -0.04; p < 0.001), tyrosine (-0.07; -0.10 to -0.04; p < 0.001), glycoprotein acetyls (-0.06; -0.09 to -0.04; p < 0.001), degree of fatty acid unsaturation (0.06; 0.02 to 0.10; p = 0.003), monounsaturated fatty acids (-0.04; -0.07 to -0.01; p = 0.004), ratio of ApoB/ApoA1 (-0.05; -0.07 to -0.02; p = 0.001), VLDL-cholesterol (-0.04; -0.06 to -0.01; p = 0.01), HDL cholesterol (0.05; 0.08 to 0.1; p = 0.01), pyruvate (-0.08; -0.11 to -0.04; p < 0.001), acetoacetate (0.07; 0.02 to 0.11; p = 0.005) and 3-hydroxybuturate (0.07; 0.02 to 0.11; p = 0.01). Results using the % >95th BMI-centile were largely consistent with age- and sex-adjusted BMI measures. CONCLUSIONS: In children and young adults with obesity, decreasing the severity of obesity was associated with changes in metabolomic profiles consistent with lower cardiovascular and metabolic disease risk in adults.

Growth hormone and targeted oncological agents: Are we stopping children with brain tumours from reaching their true height potential?

Children with low-grade gliomas have excellent long-term survival outcomes. The development of therapies targeted to the driver mutations along the Mitogen Activated Protein (MAP) kinase signalling pathway are providing long-term stability for many patients with these tumours. Given the frequency of these tumours residing within or near the suprasellar region, our patients commonly suffer from hormone deficiencies. In Australia, the Pharmaceutical Benefits Scheme currently restricts growth hormone therapy to patients who are not being actively treated for cancer, including those receiving targeted therapies. This viewpoint hopes to facilitate an important discussion amongst our colleagues as to whether this should be changed to allow growth hormone to become available to children on chronic tumour suppressive therapy.

Incidence Trends of Diabetic Ketoacidosis in Children and Adolescents with Type 1 Diabetes in British Columbia, Canada.

OBJECTIVES: To estimate the 11-year incidence trend of diabetic ketoacidosis (DKA) at and after the diagnosis of type 1 diabetes. STUDY DESIGN: A retrospective cohort study using a population-based administrative cohort diagnosed with type 1 diabetes at <20 years of age from 2002 to 2012 in British Columbia, Canada. DKA at (1 episode per individual) and DKA after (multiple episodes per individual) the diagnosis of diabetes were defined as DKA occurring ≤14 days or >14 days, respectively, from diagnosis, identified using International Classification of Diseases,9th and 10theditions codes. Incidence rate ratios were estimated using Poisson regression and DKA trends using Joinpoint regression analyses. RESULTS: There were 1519 individuals (mean age at first-DKA, 12.6 ± 5.9 years; 50% male) with ≥1 DKA episode identified. Of 2615 incident cases of type 1 diabetes, there were 847 (32.4%; mean age, 9.9 ± 4.8 years; 52% male) episodes of DKA at the diagnosis of diabetes. Among prevalent cases of type 1 diabetes (1790 cases in 2002 increasing to 2264 in 2012), there were 1886 episodes of DKA after the diagnosis of diabetes (mean age at first DKA, 15.7 ± 5.2 years). The rates per 100 person-years of DKA at diabetes diagnosis (ranging from 24.1 in 2008 to 37.3 in 2006) and DKA after diabetes diagnosis (ranging from 4.9 in 2002 to 7.7 in 2008) remained stable. Females showed a 67% higher rate of incidence of DKA after the diagnosis of diabetes compared with their male counterparts (incidence rate ratio, 1.67; 95% CI, 1.50-1.86; P < .001), adjusted for the temporal trend by fiscal year. Younger age at diagnosis (<5 years) was associated with a greater risk of DKA at the time of diabetes diagnosis and older children (≥10 years) had a greater risk of DKA after the diagnosis of diabetes. CONCLUSIONS: The risk of DKA at the time of diagnosis of diabetes was greater with younger age and the risk of DKA after the diagnosis of diabetes was higher in females and older children and youth.

Time spent watching television impacts on body mass index in youth with obesity, but only in those with shortest sleep duration.

AIM: To determine the interplay between sleep and sedentary behaviours on body mass index (BMI) in children with obesity. METHODS: Cross-sectional study of 343 children with obesity aged 4-17 years, from a tertiary care weight management clinic in Melbourne, Victoria, Australia. Multifaceted data relating to activity and sleep from child and parent questionnaires analysed with anthropometric data collected during routine clinical care. Associations between sleep duration and activity measures were examined via regression models with adjustment for potential confounders. RESULTS: Higher BMI was associated with more hours spent watching television (P = 0.04), as well as less reported enjoyment of physical activity (P = 0.005) and less time spent in organised sport activity (P = 0.005). Higher BMI was also associated with higher levels of obstructive sleep apnoea (P = 0.002). Less time in bed was associated with higher levels of BMI (P = 0.03) but analysis by sex revealed this association to only hold for males. In the whole group, a significant television and sleep interaction was seen, such that increasing television watching was associated with higher BMI, but only in those with shortest sleep duration. CONCLUSIONS: Both poor sleep and increasing screen time (including television viewing, smart-phone use, internet use or video-gaming) appear to impact BMI in children with obesity, with a particular detrimental effect of television viewing in those who sleep less. Efforts to improve sleep time and quality in children may minimise negative effects of screen time on increasing BMI and should be included in public health strategies to combat obesity in childhood.

Sex and puberty-related differences in metabolomic profiles associated with adiposity measures in youth with obesity.

BACKGROUND: Specific patterns of metabolomic profiles relating to cardiometabolic disease are associated with increased weight in adults. In youth with obesity, metabolomic data are sparse and associations with adiposity measures unknown. OBJECTIVES: Primary, to determine associations between adiposity measures and metabolomic profiles with increased cardiometabolic risks in youth with obesity. Secondary, to stratify associations by sex and puberty. METHODS: Participants were from COBRA (Childhood Overweight BioRepository of Australia; a paediatric cohort with obesity). Adiposity measures (BMI, BMI z-score, %truncal and %whole body fat, waist circumference and waist/height ratio), puberty staging and NMR metabolomic profiles from serum were assessed. Statistics included multivariate analysis (principal component analysis, PCA) and multiple linear regression models with false discovery rate adjustment. RESULTS: 214 participants had metabolomic profiles analyzed, mean age 11.9 years (SD ± 3.1), mean BMI z-score 2.49 (SD ± 0.24), 53% females. Unsupervised PCA identified no separable clusters of individuals. Positive associations included BMI z-score and phenylalanine, total body fat % and lipids in medium HDL, and waist circumference and tyrosine; negative associations included total body fat % and the ratio of docosahexaenoic acid/total fatty acids and histidine. Stratifying by sex and puberty, patterns of associations with BMI z-score in post-pubertal males included positive associations with lipid-, cholesterol- and triglyceride-content in VLDL lipoproteins; total fatty acids; total triglycerides; isoleucine, leucine and glycoprotein acetyls. CONCLUSION: In a paediatric cohort with obesity, increased adiposity measures, especially in post-pubertal males, were associated with distinct patterns in metabolomic profiles.

Psychosocial measures and weight change in a clinical paediatric population with obesity.

PURPOSE: Poor quality of life has been shown to occur in youth with obesity. This study aimed to assess associations between health-related quality of life, general mental health and general psychological distress measures, collectively termed psychosocial health questionnaires (PSH), with weight outcomes in a busy paediatric weight management service. METHODS: A cross-sectional longitudinal clinical cohort, 'Childhood Overweight BioRepository of Australia (COBRA)', was used (n = 250, median age 11, range 2-18 year, mean BMI z-score 2.5 ± 0.2). Clinical data were collected and HRQOL questionnaires; Pediatric Quality of Life 4.0 (PedsQL), 'Sizing Me/Them Up' (SMU/STU), and psychological well-being questionnaires; strengths and difficulties questionnaire (SDQ) and Kessler 10 (K10) were completed by the child and primary caregiver. PSH results were compared to age- and sex-adjusted BMI z-score at baseline and follow-up. Direct logistic regression modelling was performed to assess the impact of PSH factors on the likelihood of successful weight reduction over a period of ≥ 12 months. RESULTS: Mean self-report PSH scores were: 68.0 ± 15.28 (PedsQL, range 0-100), 64.8 ± 15.8, (SMU, range 0-100), 17.3 ± 4.4 (SDQ, range 0-40) and 20.0 ± 7.7 (K10, range 0-50). A significant negative correlation was observed between PSH scores and childhood obesity (baseline BMI z-scores (p < 0.01)). No correlations were observed between psychological well-being measures and BMI z-scores. Higher subscale scores of the PedsQL and SDQ, which measure impaired psychosocial health and more difficulties with hyperactivity and inattention, significantly predict weight loss in children with obesity after 12 months. CONCLUSION: PSH questionnaires may be useful in identifying individuals who require additional support to achieve weight loss goals in a tertiary weight management service.

Skeletal disproportion in glucocorticoid-treated boys with Duchenne muscular dystrophy.

We aimed to compare body segment and bone lengths in glucocorticoid-treated boys with Duchenne muscular dystrophy (DMD) with healthy controls using dual-energy absorptiometry (DXA) images. Total height (Ht), sitting height (SH), leg length (LL) and bone lengths (femur, tibia) in boys with DMD and age-matched control boys were measured using DXA. Thirty boys with DMD (median age 10.0 years (6.1, 16.8)) were compared with 30 controls. SH in DMD was 3.3 cm lower (95% CI - 6.1, - 0.66; p = 0.016). LL in DMD was 7.3 cm lower (95% CI - 11.2, - 3.4; p < 0.0001). SH:LL of boys with DMD was higher by 0.08 (95% CI 0.04, 0.12; p < 0.0001). Femur length in DMD was 2.4 cm lower (95% CI - 4.6, - 0.12; p = 0.04), whereas tibial length in DMD was 4.8 cm lower (95% CI - 6.7, - 2.9; p < 0.0001). SH:LL was not associated with duration of glucocorticoid use (SH:LL ß = 0.003, 95% CI - 0.01 to 0.002, p = 0.72).Conclusion: Glucocorticoid-treated boys with DMD exhibit skeletal disproportion with relatively shorter leg length and more marked reduction of distal long bones. As glucocorticoid excess is not associated with such disproportion, our findings raise the possibility of an intrinsic disorder of growth in DMD. What is Known • Severe growth impairment and short stature are commonly observed in boys with Duchenne muscular dystrophy (DMD), especially those treated with long-term glucocorticoids (GC). • In other groups of children with chronic conditions and/or disorders of puberty, skeletal disproportion with lower spinal length has been reported. What is New • Growth impairment in GC-treated boys with DMD was associated with skeletal disproportion in relation to age, with lower limbs and distal long bones affected to a greater degree.

Maternal inheritance of BDNF deletion, with phenotype of obesity and developmental delay in mother and child.

Childhood obesity is a significant world health problem. Understanding the genetic and environmental factors contributing to the development of obesity in childhood is important for the rational design of strategies for obesity prevention and treatment. Brain-derived neurotrophic factor (BDNF) plays an important role in the growth and development of the central nervous system, there is also an evidence that BDNF plays a role in regulation of appetite. Disruption of the expression of this gene in a child has been previously reported to result in a phenotype of severe obesity, hyperphagia, impaired cognitive function, and hyperactivity. We report a mother and child, both with micro-deletions encompassing the BDNF gene locus, who both have obesity and developmental delay, although without hyperactivity. This report highlights the maternal inheritance of a rare genetic cause of childhood obesity.

Type 2 diabetes mellitus in children and adolescents.

BACKGROUND: The incidence of type 2 diabetes mellitus (T2DM) in children and adolescents is increasing, mirroring the epidemic of paediatric obesity. Early-onset T2DM is associated with poor long-term outcomes. OBJECTIVE: In this article, we describe the growing problem of early-onset T2DM in Australia, explore the difference between early-onset and adult-onset T2DM, and review the management of T2DM in children and adolescents. DISCUSSION: T2DM is difficult to differentiate from the more common type 1 diabetes mellitus (T1DM) in the paediatric population. Risk factors for T2DM include obesity, ethnicity and family history, and adolescence is a predisposing time for the development of T2DM due to physiological insulin resistance. Early-onset T2DM is more associated with shorter duration to insulin requirement, development of diabetic complications and cardiovascular disease than adult-onset T2DM and T1DM. The main goals in management include normalising hyperglycaemia, facilitating lifestyle modifications and managing diabetes-related and obesity-related comorbidities.

Viewpoint article: Childhood obesity--looking back over 50 years to begin to look forward.

The last 50 years have seen the emergence of childhood obesity as a major public health concern and a condition now regularly encountered in routine general paediatric practice. Causes are extremely complex, bringing together multifactorial environmental factors and individual genetics, and we still do not have a clear understanding of why some children appear predisposed to exaggerated and sometimes extreme weight gain. Overweight and obese children of today face an uncertain future. They are likely to experience higher rates of type 2 diabetes and heart disease, as well as many other health problems. However, while the prevalence of childhood obesity has progressively increased over the last few decades, so has research into its underlying causes. This has led to large-scale trials aimed at improving prevention or treatment. As data have emerged from such studies, we have begun to accept that the heterogeneity of obesity means that broad 'common sense' strategies to address diet and activity will not lead to success on their own. Now is the time to begin to build on this information, dispelling myths and beliefs, in order to focus research efforts and take first steps towards more sophisticated strategies that go beyond the surface behaviours that simply potentiate obesity. Through carefully designed studies, aimed at tackling fundamental questions missed in the hasty development of 'common sense' approaches, will come answers that can lead to the development of more effective community- and health-care-orientated prevention and treatment programmes.

Low vitamin D is associated with hypertension in paediatric obesity.

AIM: The aim of this paper was to investigate the relationship between circulating 25-hydroxyvitamin D (25(OH)D) and cardio-metabolic risk factors in a large cohort of obese youth attending tertiary paediatric obesity services. METHODS: We conducted a retrospective cross-sectional study. Data were retrospectively collected from all new consultations of children and adolescents attending obesity outpatient clinics between 2008 and 2011 at the two major paediatric hospitals in Melbourne, Australia. Information collected included demographics, anthropometry, blood pressure, pubertal staging, body composition and fasting serum levels of 25(OH)D, glucose, insulin, cholesterol, triglyceride, high-density lipoprotein, liver function, calcium and phosphate. RESULTS: 25(OH)D data were available in 229 patients (age 3-18 years; 116 men; mean (standard deviation) body mass index ( BMI) Z-score 2.5 (0.5) ). One hundred four (45%) participants were 25(OH)D deficient (<50 nmol/L). Lower serum 25(OH)D levels were associated with higher BMI Z-score (P-trend = 0.001), total fat mass (P-trend = 0.009), systolic (P-trend = 0.03) and diastolic blood pressures(P-trend = 0.009). In multivariable-adjusted regression analysis, 25(OH)D was significantly lower in those with elevated blood pressure after adjustment for BMI(P-trend = 0.004) or total fat mass (P-trend = 0.01). CONCLUSION: Overweight and obese youth attending specialist obesity services have a high prevalence of vitamin D deficiency. In this population, lower levels of vitamin D were seen in those with greater adiposity, and independent of this, in those who had higher blood pressure.

Childhood insulinoma masquerading as seizure disorder.

A 9 year old girl presented with seizures, weight gain and early morning behavioural changes. She had been commenced on anticonvulsants and was subsequently diagnosed with hyperinsulinaemic hypoglycaemia. This case demonstrates the importance of blood glucose monitoring in children presenting with new-onset seizures and/or with early morning or fasting behavioural changes, the challenges in localizing the lesion, as well as the difficulties in achieving normoglycaemia prior to, and immediately following, surgery.

Clinical protocol using calcium and calcitriol after paediatric total thyroidectomy decreases postoperative hypocalcaemia and inpatient blood tests.

INTRODUCTION: Postoperative hypocalcaemia is common after thyroidectomy. This study aimed to evaluate whether a standardised post-thyroidectomy protocol using prophylactic calcium and calcitriol reduces hypocalcaemia incidence after total thyroidectomy in children and adolescents. METHODS: A cohort children and adolescents ≤18 years of age undergoing total thyroidectomy between January 2016 and October 2022 in one institution were retrospectively identified and divided into pre-protocol and post-protocol groups. The primary outcome measure was hypocalcaemia (total serum calcium of <2.0 mmol/L; ionised serum calcium of 0.9 mmol/L). Secondary outcome measures were the occurrence of hypercalcaemia (serum Calcium >2.7 mmol/L; ionised calcium >1.31 mmol/L), length of hospitalisation and number of postoperative blood tests. RESULTS: There were 22 patients in each group (mean age 11.8; SD 4.3 years, female 36 %). The rate of hypocalcaemia was significantly higher in the pre-protocol group than the post-protocol group (54 % vs 13.6 %, p = 0.010). Patients in the pre-protocol group had more inpatient blood tests (mean 5.4; SD 3.2) than the post-protocol group (mean 3.3; SD 1.8, p = 0.011), although the total postoperative blood test count was similar between the groups. Six (13.6 %) patients developed hypercalcaemia. The rate of hypercalcaemia was similar between groups (pre-protocol 2, 9.1 %; post-protocol 4, 18.1 %; p = 0.664). Length of hospitalisation was similar between groups. CONCLUSION: Our standardized protocol decreased hypocalcemia and inpatient blood tests after total thyroidectomy in children. Future research should explore if incorporating preoperative calcium and calcitriol treatment, along with intraoperative PTH levels for risk management, can further reduce hypocalcemia rates in paediatric patients.

Paediatric diabetes-related presentations to emergency departments in Victoria, Australia from 2008 to 2018.

OBJECTIVES: Despite significant treatment advances in paediatric diabetes management, ED presentations for potentially preventable (PP) complications such as diabetic ketoacidosis (DKA) remains a major issue. We aimed to examine the characteristics, rates and trends of diabetes-related ED presentations and subsequent admissions in youth aged 0-19 years from 2008 to 2018. METHODS: Data were obtained from the Victorian Emergency Minimum Dataset and the National Diabetes Register. A diabetes-related ED presentation is defined using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification diagnosis codes. 'Non-preventable' presentations were the number of youths with newly diagnosed diabetes, and the remaining are classified as PP diabetes-related presentations. Poisson regression model was used to examine the trends in incidence rate and prevalence. RESULTS: Four thousand eight hundred and seventy-two (59%) of 8220 presentations were PP, 4683 (57%) were for DKA whereas 6200 (82%) required hospital admission. Diabetes-related ED presentations decreased from 38.4 to 27.5 per 100 youth with diabetes per year between 2008 and 2018 (ß = -0.04; confidence interval [CI] -0.04 to -0.03; P < 0.001). Females, those aged 0-4 years and rural youth had higher rates of ED presentations than males, older age groups and metropolitan youth. DKA presentations decreased from 20.1 presentations per 100 youth with diabetes in 2008-2009 to 14.9 presentations per 100 youth with diabetes in 2017-2018. The rate of DKA presentations was 68% higher in rural areas compared to metropolitan areas (incidence rate ratio 1.68; CI 1.59-1.78; P < 0.001). CONCLUSIONS: Although the rates of diabetes-related ED presentations declined, PP diabetes-related presentations and subsequent hospitalisation remain high. Patient level research is required to understand the increased DKA presentations in rural youth.

Change in adiposity is associated with change in glycoprotein acetyls but not hsCRP in adolescents with severe obesity.

BACKGROUND: Obesity-associated chronic inflammation mediates the development of adverse cardiometabolic outcomes. There are sparse data on associations between severe obesity and inflammatory biomarkers in adolescence; most are cross-sectional and limited to acute phase reactants. Here, we investigate associations between adiposity measures and inflammatory biomarkers in children and adolescents with severe obesity both cross-sectionally and longitudinally. METHODS: From the Childhood Overweight Biorepository of Australia (COBRA) study, a total of n = 262 participants, mean age 11.5 years (SD 3.5) with obesity had measures of adiposity (body mass index, BMI; % above the 95th BMI-centile, %>95th BMI-centile; waist circumference, WC; waist/height ratio, WtH; % total body fat, %BF; % truncal body fat, %TF) and inflammation biomarkers (glycoprotein acetyls, GlycA; high-sensitivity C-Reactive Protein, hsCRP; white blood cell count, WBC; and neutrophil/lymphocyte ratio, NLR) assessed at baseline. Ninety-eight individuals at mean age of 15.9 years (3.7) participated in a follow-up study 5.6 (2.1) years later. Sixty-two individuals had longitudinal data. Linear regression models, adjusted for age and sex for cross-sectional analyses were applied. To estimate longitudinal associations between change in adiposity measures with inflammation biomarkers, models were adjusted for baseline measures of adiposity and inflammation. RESULTS: All adiposity measures were cross-sectionally associated with GlycA, hsCRP and WBC at both time points. Change in BMI, %>95th BMI-centile, WC, WtH and %TF were associated with concomitant change in GlycA and WBC, but not in hsCRP and NLR. CONCLUSION: GlycA and WBC but not hsCRP and NLR may be useful in assessing adiposity-related severity of chronic inflammation over time.

Mental healthcare for children with chronic conditions: a qualitative study.

OBJECTIVE: To explore parent perspectives on accessing mental healthcare for children with a chronic physical health condition. DESIGN: Qualitative research using semistructured interviews and Framework Analysis. Rankings were used to select attributes for a Discrete Choice Experiment (DCE). SETTING: Four specialty outpatient clinics (diabetes, epilepsy, bronchiectasis unrelated to cystic fibrosis and epidermolysis bullosa) at an Australian tertiary paediatric hospital. PARTICIPANTS: Eighteen parents of children with a chronical physical health condition. RESULTS: Most parents identified the child's general practitioner and/or hospital team as an initial pathway to seek help if they were worried about their child's mental health. Parents see mental healthcare as part of care for the whole child and want the outpatient clinics to proactively discuss child and family mental health, as well as refer to appropriate services as needed. The hospital being a familiar, child-friendly environment was identified as a key reason the hospital might be a desired place to access mental healthcare, as previous research has found. Six attributes of mental health services were identified as important and will be included in an upcoming DCE: travel time, cost, wait time, available hours, knowledge of physical health condition, and recommendation. CONCLUSIONS: This study highlights the opportunity presented in specialist outpatient clinics to address the often unmet mental healthcare needs of children with chronic physical health conditions. Parents identified practical ways for outpatient clinics to better facilitate access to mental healthcare. These will be further explored through a quantitative study of parent preferences.

Preferences of parents for mental health services to suit children with chronic medical conditions.

Objectives To identify features of mental health services that affect the uptake of services among parents of children with chronic medical conditions, to inform the design of pathways into mental health care. Methods A discrete choice experiment in which participants made choices between hypothetical mental health services described in terms of service features: cost, wait time, provider knowledge of chronic medical conditions, recommendations, opening hours, and travel time. Participants were parents of children attending The Royal Children's Hospital outpatient clinics for the management of a chronic medical condition who completed the online survey between August 2020 and January 2021. The uptake of mental health services with differing features was predicted based on regression models examining the relationship between choice and service features, and accounting for participant characteristics and unobserved heterogeneity. Results The sample comprised 112 parents, of whom 52% reported unmet needs. The most influential service features were wait times, cost, recommendation from medical specialists, and mental health provider knowledge of chronic medical conditions. Predicted uptake of a realistic service showed inequalities across income, parental education, and single parent status. A service comprising preferred features was predicted to eliminate these inequalities. Conclusions Reducing cost and wait time for mental health services could reduce unmet need among children with chronic medical conditions. Specific approaches to tackle the high levels of unmet needs in this group include equipping medical specialists to recommend mental health providers and training mental health providers on the impacts of chronic medical conditions on children. Offering preferred services could increase uptake and reduce inequalities in mental health care.

Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Long-term HbA1c in 7,961 Children and Young Adults in the Australasian Diabetes Data Network.

OBJECTIVE: The relationship between diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes and long-term glycemic control varies between studies. We aimed, firstly, to characterize the association of DKA and its severity with long-term HbA1c in a large contemporary cohort, and secondly, to identify other independent determinants of long-term HbA1c. RESEARCH DESIGN AND METHODS: Participants were 7,961 children and young adults diagnosed with type 1 diabetes by age 30 years from 2000 to 2019 and followed prospectively in the Australasian Diabetes Data Network (ADDN) until 31 December 2020. Linear mixed-effect models related variables to HbA1c. RESULTS: DKA at diagnosis was present in 2,647 participants (33.2%). Over a median 5.6 (interquartile range 3.2, 9.4) years of follow-up, participants with severe, but not moderate or mild, DKA at diagnosis had a higher mean HbA1c (+0.23%, 95% CI 0.11,0.28; [+2.5 mmol/mol, 95% CI 1.4,3.6]; P < 0.001) compared with those without DKA. Use of continuous subcutaneous insulin infusion (CSII) was independently associated with a lower HbA1c (-0.28%, 95% CI -0.31, -0.25; [-3.1 mmol/mol, 95% CI -3.4, -2.8]; P < 0.001) than multiple daily injections, and CSII use interacted with severe DKA to lower predicted HbA1c. Indigenous status was associated with higher HbA1c (+1.37%, 95% CI 1.15, 1.59; [+15.0 mmol/mol, 95% CI 12.6, 17.4]; P < 0.001), as was residing in postcodes of lower socioeconomic status (most vs. least disadvantaged quintile +0.43%, 95% CI 0.34, 0.52; [+4.7 mmol/mol, 95% CI 3.4, 5.6]; P < 0.001). CONCLUSIONS: Severe, but not mild or moderate, DKA at diagnosis was associated with a marginally higher HbA1c over time, an effect that was modified by use of CSII. Indigenous status and lower socioeconomic status were independently associated with higher long-term HbA1c.

Risk factors for the development of hypocalcemia in pediatric patients after total thyroidectomy - A systematic review.

OBJECTIVES: Post-thyroidectomy hypocalcemia is a common complication that causes increased morbidity. This review aims to identify the factors that predict occurrence of hypocalcemia after total thyroidectomy in children and adolescents. METHODS: Comprehensive searches of English language pediatric (≤18 years of age) articles were performed in Medline, CINAHL, EMBASE, Web of Science and the Cochrane Library. Studies published between January 1, 1970 to August 20, 2020 regarding risk factors and strategies to prevent hypocalcemia were included if the study: 1. included only pediatric patients who were ≤18 years of age, 2. included only patients who had total, subtotal or completion thyroidectomy, 3. defined hypocalcemia as serum total calcium of <2.0 mmol/L (8 mg/dL) or ionized calcium of <1.0 mmol/L. The quality of included papers was assessed using the Newcastle-Ottawa scale. Results of all included studies were summarised. Meta-analyses were performed if appropriate. RESULTS: Five studies with a total of 477 patients between 0 and 18 years, who had total/subtotal/completion thyroidectomy, were included. Overall rates of transient hypocalcemia were higher than permanent hypocalcemia (transient n = 104, 22%; permanent n = 48, 10%). Two studies found intraoperative parathyroid hormone (PTH) useful in predicting hypocalcemia. While two single institution cohort studies reported that neck dissection, male sex and a lower Parathyroid Gland Remaining In Situ score were associated with hypocalcemia, two other studies, including one population-based cohort study, reported that age at surgery, patient sex, hospital volume, type of thyroid disease, number of identified parathyroid glands, parathyroid auto-transplantation, operation time, thyroid specimen weight, and lymph node dissection were not risk factors for hypocalcemia. CONCLUSION: Intraoperative PTH may be useful in predicting hypocalcemia in children after total thyroidectomy. No consistent clinical risk factors or preventative methods were identified in the pediatric literature. High-quality pediatric research is urgently required to address this knowledge gap.

Modest decrease in severity of obesity in adolescence associates with low arterial stiffness.

BACKGROUND AND AIMS: Childhood obesity is associated with cardiovascular risk factors (CVRF), subclinical cardiovascular phenotypes (carotid intima-media thickness, cIMT; pulse-wave velocity, PWV; and carotid elasticity), and adult cardiovascular disease (CVD) mortality. In youth with obesity (body mass index, BMI ≥95th centile), we investigated associations between changes in adiposity and CVRF in early adolescence and subclinical cardiovascular phenotypes in late adolescence. METHODS: Participants had adiposity measures (the severity of obesity in percentage >95th BMI-centile (%>95th BMI-centile)), waist circumference (WC), percentage total body fat (%BF) and CVRF (systolic blood pressure, SBP; glycoprotein acetyls, GlycA; and low-density lipoprotein cholesterol) assessed in early (mean age 10.2 ± 3.5y) and late (15.7 ± 3.7y) adolescence. Subclinical cardiovascular phenotypes were assessed in late adolescence. Multivariable regression analysis was performed. RESULTS: Decreasing the %>95th BMI-centile was associated with carotid elasticity (0.945%/10 mmHg, p = 0.002) in females, and with PWV in males (-0.75 m/s, p < 0.001). Changes in all adiposity measures (per 1-unit increase) were associated with carotid elasticity (-0.020 to -0.063%/10 mmHg, p < 0.005), and PWV (0.011-0.045 m/s, p < 0.005). Changes in GlycA (per 50µmol-increase) were associated with elasticity (-0.162%/10 mmHg, p = 0.042), and changes in SBP (per 10 mmHg-increase) were associated with PWV (0.260 m/s, p < 0.001). Adjusted for change in BMI, the coefficient for GlycA was reduced by 46% and for SBP by 12%. Only male sex was associated with cIMT (+34 µm, p = 0.006). CONCLUSIONS: In youth with obesity, decreasing or maintaining the severity of obesity, and decreasing the levels of SBP and GlycA from early to late adolescence was associated with low arterial stiffness.