Impact of SARS-CoV-2 pandemic on the mental and physical health of children enrolled in a paediatric weight management clinic.

Background: Obesity is a global public health concern. Given the widespread disruption caused by the SARS-CoV-2 pandemic, it is important to evaluate its impact on children with chronic health conditions. This study examines the health of paediatric patients with obesity enrolled in a tertiary hospital weight management program, before and 1 year into the COVID-19 pandemic. Methods: This is a retrospective chart review of patients aged 2 to 17 years enrolled in a paediatric weight management clinic. Mental health outcomes (i.e., new referrals to psychologist, social work, eating disorder program, incidence of dysregulated eating, suicidal ideation, and/or self-harm) and physical health (anthropometric measures) were compared before and 1 year into the pandemic. Results: Among the 334 children seen in either period, there was an increase in referrals to psychologist (12.4% versus 26.5%; P=0.002) and the composite mental health outcome (17.2% versus 30.2%; P=0.005) during the pandemic compared with pre-pandemic. In a subset of children (n=30) with anthropometric measures in both periods, there was a lower rate of decline in BMIz score (-1.5 [2.00] versus -0.3 [0.73]/year; P=0.002) and an increase in adiposity (-0.8 [4.64] versus 2.7 [5.54]%/year; P=0.043) during the pandemic. Discussion: The pandemic has impacted the mental and physical health of children with obesity engaged in a weight management clinic. While our study provides evidence of a negative impact on mental health outcomes and less improvement in anthropometric measures, future research when patients return to in-person care will enable further examination of our findings with additional objective measures.

Bariatric interventions in obesity treatment and prevention in pediatric acute lymphoblastic leukemia: a systematic review and meta-analysis.

Most children are surviving acute lymphoblastic leukemia (ALL) today. Yet, the emergence of cardiometabolic comorbidities in this population may impact long-term outcomes including the quality of life and lifespan. Obesity is a major driver of cardiometabolic disorders in the general population, and in ALL patients it is associated with increased risk of hypertension, dysglycemia, and febrile neutropenia when compared with lean ALL patients undergoing therapy. This systematic review aims to assess the current evidence for bariatric interventions to manage obesity in children with ALL. The primary outcome for this systematic review was the change in BMI z-score with implementation of the interventions studied. Literature searches were conducted in several databases. Ten publications addressing the study question were included in this review, and five studies were used in the meta-analysis to assess the impact of the bariatric interventions on obesity. The BMI z-score did not change significantly with the interventions. However, the quality of evidence was low, which precluded the recommendation of their use. In conclusion, prospective, rigorous, adequately powered, and high-quality longitudinal studies are urgently needed to deliver effective lifestyle interventions to children with ALL to treat and prevent obesity. These interventions, if successful, may improves cardiometabolic health outcomes and enhance the quality of life and life expectancy in children with ALL.

Vomiting and Cardiac Arrest in a 10-Year-Old Girl.

ABSTRACT: Primary adrenal insufficiency is a potentially life-threatening condition that provides a diagnostic challenge because many patients have months to years of insidious symptomatology. Adrenal crisis is the extreme acute manifestation of primary adrenal insufficiency, presenting with any, or all, of severe weakness, altered mental status, hypotension, and rarely cardiorespiratory arrest. Primary adrenal insufficiency should be considered in patients with clinical features of glucocorticoid and/or mineralocorticoid deficiency. These features however, such as hyperpigmentation, may be subtle, and so a degree of suspicion is needed to make the diagnosis. In extremis, children may present with fluid and catecholamine refractory shock. The management of an adrenal crisis includes prompt delivery of stress-dose corticosteroids together with aggressive organ support and correction of metabolic and electrolyte disturbances. We report the case of a previously healthy 10-year-old child that presented to a community emergency department in pulseless arrest, in whom adrenal crisis was suspected as well as treated early, and was subsequently successfully resuscitated.

Safety Audits in the Emergency Department: Applying the Threat and Error Model to the Management of Pediatric Diabetic Ketoacidosis.

OBJECTIVES: This study aims to better understand factors that impact management of patients with diabetic ketoacidosis (DKA) in the pediatric emergency department (ED) by novel application of the threat-and-error model, commonly used in the aviation industry. METHODS: This study was a retrospective chart review of all patients diagnosed with DKA and managed in our pediatric ED during a 1-year period. A "flight plan" was created for each patient's ED visit, from triage to final disposition. Each flight was analyzed with the goal of identifying threats and errors that may impact patients' clinical status or management. Particular focus was placed on physicians' adherence to hospital and provincial DKA protocols. Unintended patient states or outcomes were also noted. RESULTS: A total of 46 patient flights were outlined and analyzed. A total of 146 threats were identified, affecting 43 (93%) patient flights. No flight was error-free. Errors in communication and lack of adherence to protocol were the most common types of errors. Unintended patient states occurred in 30 cases (65%), some of which were preceded by at least 1 error. There were no cases of cerebral edema or death. CONCLUSIONS: It is important to identify and appropriately mitigate threats and errors that commonly occur during initial management of DKA in the ED to prevent unintended states and patient morbidity. This study demonstrates the threat-and-error model as a potentially useful tool for focusing quality improvement initiatives in the pediatric ED setting.

Salvage Therapy for Childhood Medulloblastoma: A Single Center Experience.

INTRODUCTION: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. METHODS: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. RESULTS: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. CONCLUSION: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.

Traitement de sauvetage dans le cas du médulloblastome chez l'enfant : une expérience menée au sein d'un établissement hospitalier. Introduction: Les enfants chez qui l'on a diagnostiqué un médulloblastome réfractaire à un traitement initial ou qui sont victimes d'une récidive présentent d'habitude des pronostics de guérison vraiment défavorables. Bien qu'il existe des traitements basés sur des essais cliniques de phases I et II, ces traitements ont tendance à produire des taux notables de morbidité et de mortalité. Méthodes: Nous avons ainsi mené à l'Université McMaster une analyse rétrospective des dossiers d'enfants chez qui l'on avait diagnostiqué entre 2002 et 2015 une récidive de médulloblastome. Résultats: La réapparition de cette maladie chez 10 patients a provoqué un phénomène de diffusion leptoméningée, trois d'entre eux étant victimes d'une récidive locale. Sur ces 10 jeunes patients, la maladie a progressé de façon importante : ces enfants ont alors été transférés aux soins palliatifs. Quant aux autres 10 enfants, ils ont subi un certain type de traitement de sauvetage (des résections chirurgicales, de la radiothérapie, de la chimiothérapie), que ce soit de façon exclusive ou en variant les combinaisons possibles. Sur les 13 enfants réfractaires à un traitement initial ou victimes d'une récidive, 4 sont toujours en vie, leur suivi médian ayant été de 38,5 mois (75,5 mois). Sur les 8 patients pour qui on a pu obtenir des données moléculaires, aucun de ceux qui étaient atteints d'un médulloblastome du sous-type Wnt n'a connu de récidive. Conclusion: Les médulloblastomes qui réapparaissent après une période de guérison complète présentent un pronostic de guérison défavorable. Leur taux de survie globale est en effet de 18,2 % au cours d'une période de 5 ans, et ce, même après avoir bénéficié d'un traitement de sauvetage. Ajoutons aussi que le type de traitement initial reçu, la disponibilité des traitements ainsi que la tolérance à l'égard des traitements de sauvetage proposés a entraîné une grande hétérogénéité dans le traitement de ces jeunes patients victimes d'une récidive.

Analysis of surgical and MRI factors associated with cerebellar mutism.

The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. Therefore, we aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with individuals who did not acquire CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). A total of 22 patients (11 with and 11 without CM) were included. Medulloblastoma was the most common pathology among CM patients (91%); the remaining 9% were diagnosed with a pilocytic astrocytoma. Tumor attachment to the floor of the fourth ventricle (OR 6; 95% CI 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR 5; 95% CI 0.5-236.5) were found to have the highest measures of association with CM. Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia have a relatively higher prevalence in patients with CM. Collectively, our work calls for a larger multi-institutional cohort study of CM patients to encourage further investigation of the determinants and management of CM in order to potentially minimize its development and predict onset.

The impact of age and race on longevity in pediatric astrocytic tumors: A population-based study.

OBJECTIVE: Despite improvements in pediatric brain tumor outcomes, the survivors of childhood brain tumor are burdened by multiple comorbidities. This work reports on the relative survival ratios and excess mortality rate in children with astrocytic tumors over the past four decades. METHODS: Survival analysis was conducted using flexible parametric model to estimate relative survival and excess mortality rate for non-white and white children (0-19 years old) using the Surveillance, Epidemiology & End Results (SEER) database. We incorporated age group and year of diagnosis into the model to estimate these indices for the period of 1973-2010. RESULTS: Progressive decline in relative survival ratios was noted over time. Non-white children had lower survival rates than white children, and these survival patterns persisted over the four-decade span of the study. Fifty percent of non-white survivors were deceased 30 years post diagnosis, compared to 35 years in white survivors. CONCLUSIONS: Survivors of childhood brain tumors have progressively lower survival rates as they get older, and this is higher in non-white when compared to white children. Future research efforts need to focus on understanding the factors mediating the effect of the tumor or its treatment on survival in these patients, and the ethnic variations that derive these survival trends.

AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice.

AIMS/HYPOTHESIS: Obesity is characterised by lipid accumulation in skeletal muscle, which increases the risk of developing insulin resistance and type 2 diabetes. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status and is activated in skeletal muscle by exercise, hormones (leptin, adiponectin, IL-6) and pharmacological agents (5-amino-4-imidazolecarboxamide ribonucleoside [AICAR] and metformin). Phosphorylation of acetyl-CoA carboxylase 2 (ACC2) at S221 (S212 in mice) by AMPK reduces ACC activity and malonyl-CoA content but the importance of the AMPK-ACC2-malonyl-CoA pathway in controlling fatty acid metabolism and insulin sensitivity is not understood; therefore, we characterised Acc2 S212A knock-in (ACC2 KI) mice. METHODS: Whole-body and skeletal muscle fatty acid oxidation and insulin sensitivity were assessed in ACC2 KI mice and wild-type littermates. RESULTS: ACC2 KI mice were resistant to increases in skeletal muscle fatty acid oxidation elicited by AICAR. These mice had normal adiposity and liver lipids but elevated contents of triacylglycerol and ceramide in skeletal muscle, which were associated with hyperinsulinaemia, glucose intolerance and skeletal muscle insulin resistance. CONCLUSIONS/INTERPRETATION: These findings indicate that the phosphorylation of ACC2 S212 is required for the maintenance of skeletal muscle lipid and glucose homeostasis.

Chemokine (C-C motif) Ligand 2 is a potential biomarker of inflammation & physical fitness in obese children: a cross-sectional study.

BACKGROUND: Obesity is a global epidemic that is impacting children around the world. Obesity is a chronic inflammatory state with enhanced production of multiple cytokines and chemokines. Chemokine (C-C motif) Ligand 2 (CCL2) is produced by immune and metabolic cells and attracts immune cells into liver, muscle and adipose tissue, resulting in initiation and propagation of the inflammatory response in obesity. How obesity and fitness affect the production of this chemokine in children is unknown.This study tested the hypotheses that CCL2 levels are higher in obese children when compared to lean controls, and that fitness modulates CCL2 levels allowing its use as a biomarker of fitness. METHODS: This was a cross sectional case-control study conducted in a Pediatric Tertiary care center in Hamilton, Ontario, Canada. Controls were recruited from the community. This study recruited overweight/obese children (BMI ≥ 85th percentile, n = 18, 9 female, mean age 14.0 ± 2.6 years) and lean controls (BMI < 85th percentile, n = 18, 8 female, mean age 14.0 ± 2.6 years) matched for age, sex and biological maturation.Aerobic fitness test was done using a cycle ergometer performing the McMaster All-Out Progressive Continuous Cycling test to exhaustion to determine peak oxygen uptake. Fasting CCL2 samples were taken prior to test. Categorical variables including subject categorization into different aerobic fitness levels in overweight/obese and lean children was reported based on the median split in each group. RESULTS: Obese participants had significantly higher CCL2 levels when compared to lean group (150.4 ± 61.85 pg/ml versus 112.7 ± 38 pg/ml, p-value 0.034).To establish if CCL2 is a biomarker of fitness, we divided the groups based on their fitness levels. There was a main effect for group (F (3,32) = 3.2, p = 0.036). Obese high fitness group were similar to lean unfit and fit participants. Post-hoc analysis revealed that the overweight/obese low fitness group had significantly higher level of CCL2 compared to the lean low fitness group when adjusted to age, sex and maturity offset (F (3,29) = 3.1, p = 0.04). CONCLUSIONS: CCL2 serves a dual role as a potential biomarker of inflammation and fitness in obese children.

Insulin Infusion Dosing in Pediatric Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

In children with diabetic ketoacidosis (DKA), insulin infusions are the mainstay of treatment; however, optimal dosing remains unclear. Our objective was to compare the efficacy and safety of different insulin infusion doses for the treatment of pediatric DKA. DATA SOURCES: We searched MEDLINE, EMBASE, PubMed, and Cochrane from inception to April 1, 2022. STUDY SELECTION: We included randomized controlled trials (RCTs) of children with DKA comparing intravenous insulin infusion administered at 0.05 units/kg/hr (low dose) versus 0.1 units/kg/hr (standard dose). DATA EXTRACTION: We extracted data independently and in duplicate and pooled using a random effects model. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: We included four RCTs (n = 190 participants). In children with DKA, low-dose compared with standard-dose insulin infusion probably has no effect on time to resolution of hyperglycemia (mean difference [MD], 0.22 hr fewer; 95% CI, 1.19 hr fewer to 0.75 hr more; moderate certainty), or time to resolution of acidosis (MD, 0.61 hr more; 95% CI, 1.81 hr fewer to 3.02 hr more; moderate certainty). Low-dose insulin infusion probably decreases the incidence of hypokalemia (relative risk [RR], 0.65; 95% CI, 0.47-0.89; moderate certainty) and hypoglycemia (RR, 0.37; 95% CI, 0.15-0.80; moderate certainty), but may have no effect on rate of change of blood glucose (MD, 0.42 mmol/L/hr slower; 95% CI, 1 mmol/L/hr slower to 0.18 mmol/L/hr faster; low certainty). CONCLUSIONS: In children with DKA, the use of low-dose insulin infusion is probably as efficacious as standard-dose insulin, and probably reduces treatment-related adverse events. Imprecision limited the certainty in the outcomes of interest, and the generalizability of the results is limited by all studies being performed in a single country.

Global Prevalence of Diabetic Retinopathy in Pediatric Type 2 Diabetes: A Systematic Review and Meta-analysis.

Importance: Type 2 diabetes (T2D) is increasing globally. Diabetic retinopathy (DR) is a leading cause of blindness in adults with T2D; however, the global burden of DR in pediatric T2D is unknown. This knowledge can inform retinopathy screening and treatments to preserve vision in this population. Objective: To estimate the global prevalence of DR in pediatric T2D. Data Sources: MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, the Web of Science, and the gray literature (ie, literature containing information that is not available through traditional publishing and distribution channels) were searched for relevant records from the date of database inception to April 4, 2021, with updated searches conducted on May 17, 2022. Searches were limited to human studies. No language restrictions were applied. Search terms included diabetic retinopathy; diabetes mellitus, type 2; prevalence studies; and child, adolescent, teenage, youth, and pediatric. Study Selection: Three teams, each with 2 reviewers, independently screened for observational studies with 10 or more participants that reported the prevalence of DR. Among 1989 screened articles, 27 studies met the inclusion criteria for the pooled analysis. Data Extraction and Synthesis: This systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines for systematic reviews and meta-analyses. Two independent reviewers performed the risk of bias and level of evidence analyses. The results were pooled using a random-effects model, and heterogeneity was reported using χ2 and I2 statistics. Main Outcomes and Measures: The main outcome was the estimated pooled global prevalence of DR in pediatric T2D. Other outcomes included DR severity and current DR assessment methods. The association of diabetes duration, sex, race, age, and obesity with DR prevalence was also assessed. Results: Among the 27 studies included in the pooled analysis (5924 unique patients; age range at T2D diagnosis, 6.5-21.0 years), the global prevalence of DR in pediatric T2D was 6.99% (95% CI, 3.75%-11.00%; I2 = 95%; 615 patients). Fundoscopy was less sensitive than 7-field stereoscopic fundus photography in detecting retinopathy (0.47% [95% CI, 0%-3.30%; I2 = 0%] vs 13.55% [95% CI, 5.43%-24.29%; I2 = 92%]). The prevalence of DR increased over time and was 1.11% (95% CI, 0.04%-3.06%; I2 = 5%) at less than 2.5 years after T2D diagnosis, 9.04% (95% CI, 2.24%-19.55%; I2 = 88%) at 2.5 to 5.0 years after T2D diagnosis, and 28.14% (95% CI, 12.84%-46.45%; I2 = 96%) at more than 5 years after T2D diagnosis. The prevalence of DR increased with age, and no differences were noted based on sex, race, or obesity. Heterogeneity was high among studies. Conclusions and Relevance: In this study, DR prevalence in pediatric T2D increased significantly at more than 5 years after diagnosis. These findings suggest that retinal microvasculature is an early target of T2D in children and adolescents, and annual screening with fundus photography beginning at diagnosis offers the best assessment method for early detection of DR in pediatric patients.

The Effectiveness of Indigenous Knowledge-Based Lifestyle Interventions in Preventing Obesity and Type 2 Diabetes Mellitus in Indigenous Children in Canada: A Systematic Review.

Background: Indigenous children in Canada have high rates of obesity and type 2 diabetes mellitus (T2DM). Culturally appropriate interventions, guided by an Indigenous knowledge-based view of health, are crucial to target these conditions. The objective of this systematic review was to assess the impact of indigenous Knowledge-based lifestyle interventions on the prevention of obesity and T2DM in Indigenous children in Canada. Methods: Database searches were conducted from inception until February 22, 2022. The main outcomes were changes in Body Mass Index (BMI) z-score and the development of T2DM. The other outcomes included adiposity, metabolic, and lifestyle determinants of health. The GRADE approach was used to assess confidence in the evidence. Results: Four non-randomized controlled trials (non-RCTs) and six uncontrolled studies were identified. Peer-led interventions led to a reduction in BMI z-score and waist circumference. GRADE assessment revealed very low quality of evidence due to a lack of randomization and small sample sizes. There were no diabetes-specific reported programs. Conclusion: Limited evidence from non-randomized studies suggest that peer-led indigenous Knowledge-based lifestyle interventions improve BMI z-score and central adiposity. There is a need for community-owned and adequately powered randomized studies for interventions that aim to treat and prevent obesity and T2DM in Indigenous children in Canada. Systematic Review Registration: PROSPERO CRD42017072781.

24-h ambulatory blood pressure readings and associations with albuminuria in youth with type 2 diabetes: A cross sectional analysis from the iCARE cohort.

AIMS: To evaluate associations between 24-h ambulatory blood pressure monitor (ABPM) data vs. single casual blood pressure (BP) and albuminuria in youth with type 2 diabetes. METHODS: A cross-sectional analysis of youth with type 2 diabetes 10-<18 yrs. from the iCARE cohort. MAIN EXPOSURES: daytime HTN (+/- nocturnal), isolated nocturnal HTN and single casual BP. MAIN OUTCOME: non-orthostatic urine albumin: creatinine ratio (ACR) ≥ 3 mg/mmol and log-transformed urine ACR. Regressions evaluated associations between 1. HTN status based on ABPM and log-transformed urine ACR (continuous) and 2. ABPM-derived BP z-scores and casual BPcentiles and albuminuria status (categorical). RESULTS: Of 281 youth included, 19.6 % had daytime HTN (+/- nocturnal), and 28.5 % isolated nocturnal HTN on 24-h ABPM. In multivariate linear regression, HTN (ABPM) (ß = 0.553; p = 0.001), duration of diabetes (ß = 0.857; p = 0.02), HbA1c (ß = 1.172; p ≤0.0001) and ACEI/ARB use (ß = 3.94; p < 0.0001) were positively associated with log-transformed ACR; (R2 = 0.184). In logistic regression analysis, all ABPM LMS z-scores were positively associated with albuminuria; casual BPcentile was not significant. CONCLUSIONS: Youth with type 2 diabetes have high rates of HTN based on 24-ABPM data. ABPM-derived measures of BP are associated with albuminuria. These data support the routine use of ABPM devices to diagnose hypertension in youth with type 2 diabetes.

Metformin therapy in pediatric type 2 diabetes mellitus and its comorbidities: A review.

Type 2 diabetes (T2D) rates in children and adolescents are rising globally. T2D is a complex and aggressive disease in children with several comorbidities, high treatment failure rates, and insulin needs within a few years from diagnosis. While myriads of pharmacotherapies are licensed to treat adults with T2D, treatments accessible to children and adolescents have been limited until recently. Metformin is an old drug with multiple beneficial metabolic health effects beyond glycemic control. This review discusses Metformin's origins, its mechanisms of action, and evidence for its use in the pediatric population to treat and prevent T2D. We also explore the evidence for its use as an obesity therapy, which is the primary driver of T2D, and T2D-driven comorbidities. While emerging therapies create new horizons for managing pediatric T2D, Metformin remains an inexpensive and safe part of the treatment plans of many T2D children globally for its beneficial metabolic effects.

Impact of virtual care on health-related quality of life in children with diabetes mellitus: a systematic review protocol.

INTRODUCTION: Diabetes mellitus is the most common endocrine disorder in children, and the prevalence of paediatric type 1 and type 2 diabetes continue to rise globally. Diabetes clinical care programs pivoted to virtual care with the COVID-19 pandemic-driven social distancing measures. Yet, the impact of virtual care on health-related quality of life in children living with diabetes remains unclear. This protocol reports on the methods that will be implemented to conduct a systematic review to assess the health-related quality of life and metabolic health impacts of virtual diabetes care. METHODS AND ANALYSIS: We will search MEDLINE, Embase, EMCare, PsycInfo, Web of Science, and the grey literature for eligible studies. We will screen title, abstract, and full-text papers for potential inclusion and assess the risk of bias and the overall confidence in the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. A meta-analysis will be conducted if two studies report similar populations, study designs, methods, and outcomes.This systematic review will summarise the health-related quality of life outcomes for virtual diabetes care delivery models. ETHICS AND DISSEMINATION: No ethics approval is required for this systematic review protocol as it does not include patient data. The systematic review will be published in a peer-reviewed journal and presented at international conferences. PROSPERO REGISTRATION NUMBER: CRD42021235646.

The triponderal mass index as a measure of adiposity in pediatric survivors of acute lymphoblastic leukemia: a cross-sectional study.

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Treatments of ALL predispose survivors to obesity, which increases the risk of cardiovascular disease and diabetes. The hallmark of obesity is excess fat mass, and adiposity is a superior predictor of cardiometabolic risk when compared to Body Mass Index (BMI), yet clinical measures of adiposity in children are lacking. The Tri-Ponderal Mass Index (TMI) (kg/m3) is a more accurate adiposity measure compared to BMI z-score in the general pediatric population. This cross-sectional study aimed to validate TMI as an adiposity measure against DEXA scan-derived adiposity, and to compare it to BMI z-score, in pediatric ALL survivors. This study was a retrospective chart review of pediatric ALL survivors diagnosed between 2004 and 2015 at McMaster Children's Hospital, a tertiary pediatric center in Ontario, Canada. One hundred and thirteen patients (Female n = 55, 48.70%) were included, and adiposity was measured using DEXA scans. Exploratory partial correlations and linear regression analyses were adjusted for age, sex, ethnicity, and ALL risk status. Both TMI and BMI z-score correlated with the DEXA-measured fat mass percentage (FM%) (partial correlation TMI versus FM% r = 0.56; p value < 0.0001; BMI z-score versus FM% r = 0.55; p value < 0.0001). In regression analyses, the association of TMI was not inferior to BMI z-score in assessing adiposity (TMI versus FM% estimated unstandardized B 0.80, 95% CI 0.56, 1.02; p value < 0.0001; BMI z-score versus FM% (unstandardized B 0.37, 95% CI 0.26, 0.49; p value < 0.0001). The TMI is a useful clinical adiposity-specific measure in survivors of pediatric ALL.

Pharmacotherapy in paediatric type 2 diabetes mellitus: a protocol for a systematic review and network meta-analysis of randomised trials.

INTRODUCTION: The rates of type 2 diabetes mellitus (T2DM) in children and adolescents have risen globally over the past few years. While a few diabetes pharmacotherapies have been used in this population, their comparative benefits and harms are unclear. Thus, we will conduct a systematic review and network meta-analysis (NMA) of randomised controlled trials (RCTs) to compare the efficacy and safety of pharmacotherapies for managing paediatric T2DM. METHODS AND ANALYSIS: We will include RCTs that enrolled T2DM patients ≤18 years of age and who were randomised to monotherapy or combination pharmacotherapies with or without lifestyle interventions. Comparator groups will include placebo or non-pharmacological treatments including lifestyle interventions.Treatment outcomes will include change from baseline in glycated haemoglobin A1c, body mass index z-score, weight, systolic/diastolic blood pressure, fasting plasma glucose, fasting insulin and lipid profiles, T2DM-related complications, as well as the incidence of treatment-related adverse events.Literature searches will be conducted in Medline, Embase, CINAHL, CENTRAL and Web of Science. We will also search the grey literature and the reference list of included trials and relevant reviews. Two reviewers will assess the eligibility of articles identified through our searches and will extract data from eligible studies independently. We will use a modified Cochrane instrument to evaluate the risk of bias. Disagreements will be resolved through consensus or arbitration by a third reviewer.A frequentist random-effects model will be used for conducting NMA. The quality of evidence will be assessed using the Confidence in Network Meta-Analysis platform. We will assess the effect modification through network meta-regression and subgroup analyses for sex, age at study inclusion, duration of T2DM, follow-up duration and risk of bias ratings. ETHICS AND DISSEMINATION: This study will not require ethics approval. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022310100.

An exploratory analysis of the impact of the COVID-19 pandemic on pediatric type 1 diabetes mellitus patient outcomes: A single-center study.

Background: The COVID-19 pandemic led to substantial shifts in pediatric diabetes care delivery to virtual and hybrid models. It is unclear if these changes in care delivery impacted short-term patient outcomes. Objectives: We aimed to explore glycemic control and other diabetes-related outcomes in children living with Type 1 Diabetes Mellitus (T1DM) during the first year of the COVID-19 pandemic at a tertiary pediatric academic center in Canada. Subjects: Patients <18 years of age with a confirmed diagnosis of T1DM for at least one year were included. Methods: This was a retrospective chart review. We compared data from two years pre-pandemic (March 15, 2018-March 14, 2020) to the first year of the pandemic (March 15, 2020-March 14, 2021). The data assessed included glycemic control [Hemoglobin A1c (HbA1c)], diabetic ketoacidosis (DKA), hospital attendance and hospitalizations, hypoglycemia, and hyperglycemia. The generalized estimating equation (GEE) analysis was used to model potential factors affecting the HbA1c and diabetes-related morbidities. Multiple imputations were conducted as a sensitivity analysis. Results: There were 346 eligible patients included in the study. The HbA1c remained stable during the pandemic compared to the pre-pandemic phase (MD-0.14, 95% CI, -0.28, 0.01; p = 0.058). The pandemic saw an increase in the number of newly diagnosed patients (X2 = 16.52, p < 0.001) and a higher number of newly diagnosed patients presenting in DKA (X2 = 12.94, p < 0.001). In patients with established diabetes, there was an increase in hyperglycemia (OR1.38, 95% CI, 1.12,1.71; p = 0.003) and reduced DKA (OR 0.30, 95% CI, 0.12,0.73; p = 0.009) during the pandemic compared to the pre-pandemic phase. Stable rates of hospitalization (OR0.57, 95% CI, 0.31,1.04, p = 0.068) and hypoglycemia (OR1.11, 95% CI, 0.83,1.49; p = 0.484) were noted. These results were retained in the sensitivity analysis. Conclusions: Glycemic control in children with T1DM remained stable during the first year of the pandemic. There were more newly diagnosed patients during the pandemic compared to the pre-pandemic phase, and more of these new patients presented in DKA. The latter presentation was reduced in those with established diabetes during the same period.Further studies are needed to assess the ongoing impact of the COVID-19 pandemic on T1DM care pathways and outcomes to allow children, families, and diabetes teams to personalize choices of care models.

Prevalence of Polycystic Ovary Syndrome in Patients With Pediatric Type 2 Diabetes: A Systematic Review and Meta-analysis.

Importance: The prevalence of pediatric type 2 diabetes (T2D) is increasing globally. Girls with T2D are at risk of developing polycystic ovary syndrome (PCOS), but the prevalence of PCOS among girls with T2D is unknown. Objective: To determine the prevalence of PCOS in girls with T2D and to assess the association of obesity and race with this prevalence. Data Sources: In this systematic review and meta-analysis, MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science: Conference Proceedings Citation Index-Science, and the gray literature were searched from inception to April 4, 2021. Study Selection: Two reviewers independently screened for studies with observational study design that recruited 10 or more participants and reported the prevalence of PCOS in girls with T2D. Data Extraction and Synthesis: Risk of bias was evaluated using a validated tool, and level of evidence was assessed using the Oxford Centre for Evidence-Based Medicine criteria. A random-effects meta-analysis was performed. This study follows the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Main Outcomes and Measures: The main outcome of this systematic review was the prevalence of PCOS in girls with T2D. Secondary outcomes included assessing the associations of obesity and race with PCOS prevalence. Results: Of 722 screened studies, 6 studies involving 470 girls with T2D (mean age at diagnosis, 12.9-16.1 years) met the inclusion criteria. The prevalence (weighted percentage) of PCOS was 19.58% (95% CI, 12.02%-27.14%; I2 = 74%; P = .002). Heterogeneity was moderate to high; however, it was significantly reduced after excluding studies that did not report PCOS diagnostic criteria, leading to a calculated prevalence (weighted percentage) of 24.04% (95% CI, 15.07%-33.01%; I2 = 0%; P = .92). Associations with obesity and race could not be determined because of data paucity. Conclusions and Relevance: In this meta-analysis, approximately 1 in 5 girls with T2D had PCOS, but the results of this meta-analysis should be considered with caution because studies including the larger numbers of girls did not report the criteria used to diagnose PCOS, which is a challenge during adolescence. The associations of obesity and race with PCOS prevalence among girls with T2D need further evaluation to help define at-risk subgroups and implement early assessment and treatment strategies to improve management of this T2D-related comorbidity.

The Prevalence of Obesity Among Children With Type 2 Diabetes: A Systematic Review and Meta-analysis.

Importance: The childhood obesity epidemic is presumed to drive pediatric type 2 diabetes (T2D); however, the global scale of obesity in children with T2D is unknown. Objectives: To evaluate the global prevalence of obesity in pediatric T2D, examine the association of sex and race with obesity risk, and assess the association of obesity with glycemic control and dyslipidemia. Data Sources: MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science were searched from database inception to June 16, 2022. Study Selection: Observational studies with at least 10 participants reporting the prevalence of obesity in patients with pediatric T2D were included. Data Extraction and Synthesis: Following the Meta-analysis of Observational Studies in Epidemiology reporting guideline, 2 independent reviewers in teams performed data extraction and risk of bias and level of evidence analyses. The meta-analysis was conducted using a random-effects model. Main Outcomes and Measures: The primary outcomes included the pooled prevalence rates of obesity in children with T2D. The secondary outcomes assessed pooled prevalence rates by sex and race and associations between obesity and glycemic control and dyslipidemia. Results: Of 57 articles included in the systematic review, 53 articles, with 8942 participants, were included in the meta-analysis. The overall prevalence of obesity among pediatric patients with T2D was 75.27% (95% CI, 70.47%-79.78%), and the prevalence of obesity at diabetes diagnosis among 4688 participants was 77.24% (95% CI, 70.55%-83.34%). While male participants had higher odds of obesity than female participants (odds ratio, 2.10; 95% CI, 1.33-3.31), Asian participants had the lowest prevalence of obesity (64.50%; 95% CI, 53.28%-74.99%), and White participants had the highest prevalence of obesity (89.86%; 95% CI, 71.50%-99.74%) compared with other racial groups. High heterogeneity across studies and varying degrees of glycemic control and dyslipidemia were noted. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that obesity is not a universal phenotype in children with T2D. Further studies are needed to consider the role of obesity and other mechanisms in diabetes genesis in this population.