Precocious Puberty and GnRH analogs: Current treatment practices and perspectives amongst US pediatric endocrinologists.

INTRODUCTION: GnRHas are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. METHODS: The Drugs & Therapeutics subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the United States. The survey consisted of four main subsections: 1. Description of clinical practice; 2. Self-assessment of knowledge base of pediatric and adult GnRHa formulations; 3. Current practice for treating CPP; and 4. Utilization of healthcare resources. RESULTS: There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the three-month preparation, and the histrelin implant (Supprelin®) (61.9%, 71.7%, and 34.5%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) and 22.9% and six-month subcutaneous leuprolide (Fensolvi®). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44.4%), but in practice, respondents reported a higher percentage of patients were treated with 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (65.5%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. CONCLUSIONS: The survey indicated there is more familiarity with older, shorter-acting GnRHas, which are prescribed in greater numbers than newer, longer-acting formulations. There is lack of consensus on the need for CNS imaging in girls presenting with CPP between 6-8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers, while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.

Social Determinants of Health Screening in Type 1 Diabetes Management.

Type 1 diabetes management is intricately influenced by social determinants of health. Economic status impacts access to vital resources like insulin and diabetes technology. Racism, social injustice, and implicit biases affect equitable delivery of care. Education levels affect understanding of self-care, leading to disparities in glycemic outcomes. Geographic location can limit access to health care facilities. Stressors from discrimination or financial strain can disrupt disease management. Addressing these social factors is crucial for equitable diabetes care, emphasizing the need for comprehensive strategies that go beyond medical interventions to ensure optimal health outcomes for all individuals with type 1 diabetes.

Insulin Pump Utilization in 2017-2021 for More Than 22,000 Children and Adults With Type 1 Diabetes: A Multicenter Observational Study.

This large type 1 diabetes cohort study showed that insulin pump utilization has increased over time and that use differs by sex, insurance type, and race/ethnicity. Insulin pump use was associated with more optimal A1C, increased use of continuous glucose monitoring (CGM), and lower rates of diabetic ketoacidosis and severe hypoglycemia. People who used an insulin pump with CGM had lower rates of acute events than their counterparts who used an insulin pump without CGM. These findings highlight the need to improve access of diabetes technology through provider engagement, multidisciplinary approaches, and efforts to address health inequities.

Longitudinal Trends in Glycemic Outcomes and Technology Use for Over 48,000 People with Type 1 Diabetes (2016-2022) from the T1D Exchange Quality Improvement Collaborative.

Objective: Previous studies revealed that hemoglobin A1c (HbA1c) increased overall in the United States in the past decade. In addition, health inequities in type 1 diabetes (T1D) outcomes by race/ethnicity and insurance type persist. This study examines the trends in HbA1c from 2016 to 2022 stratified by race/ethnicity and insurance in a large multicenter national database. Research Design and Methods: We analyzed glycemic outcomes and diabetes device use trends for >48,000 people living with type 1 diabetes (PwT1D) from 3 adult and 12 pediatric centers in the T1D Exchange Quality Improvement Collaborative (T1DX-QI), comparing data from 2016 to 2017 with data from 2021 to 2022. Results: The mean HbA1c in 2021-2022 was lower at 8.4% compared with the mean HbA1c in 2016-2017 of 8.7% (0.3% improvement; P < 0.01). Over the same period, the percentage of PwT1D using a continuous glucose monitor (CGM), insulin pump, or hybrid closed-loop system increased (45%, 12%, and 33%, respectively). However, these improvements were not equitably demonstrated across racial/ethnic groups or insurance types. Racial/ethnic and insurance-based inequities persisted over all 7 years across all outcomes; comparing non-Hispanic White and non-Hispanic Black PwT1D, disparate gaps in HbA1c (1.2%-1.6%), CGM (30%), pump (25%-35%), and hybrid-closed loop system (up to 20%) are illuminated. Conclusion: Population-level data on outcomes, including HbA1c, can provide trends and insights into strategies to improve health for PwT1D. The T1DX-QI cohort showed a significant improvement in HbA1c from 2016 to 2022. Improvements in diabetes device use are also demonstrated. However, these increases were inconsistent across all racial/ethnic groups or insurance types, an important focus for future T1D population health improvement work.

Role of Psychologists in Pediatric Endocrinology.

The care of youth managed within pediatric endocrine clinics is complex and requires a multi- or interdisciplinary approach. Psychosocial aspects of chronic health conditions are well-documented. Clinical practice guidelines outline the importance of routine psychosocial screening and support for youth with diabetes and obesity. This article outlines the diverse role of psychologists in pediatric endocrinology, including screening, in-clinic intervention, outpatient psychological services, and inpatient consultation. Although research exists documenting the effectiveness of behavioral interventions to improve adherence and health-related quality of life, cost analysis research is emerging.

Glycemic control, depression, diabetes distress among adolescents with type 2 diabetes: effects of sex, race, insurance, and obesity.

AIMS: To determine (1) differences in depression and distress scores between adolescents with type 1 (T1D) and type 2 diabetes (T2D), (2) how socioeconomic factors, obesity, race, and treatment regimen affect depression and diabetes distress in adolescent T2D, (3) the relationships between depression and diabetes distress scores in adolescents with T2D, and (4) how depression and diabetes distress scores relate to current and future glycemic control in adolescents with T2D. BACKGROUND: Diabetes distress is a negative emotional reaction to diabetes complications, self-management demands, unresponsive providers, poor interpersonal relationships, and to diabetes itself. It is frequently mistaken for depression and the two are interrelated. Increases in both predict poor glycemic control in adolescents with T1D. METHOD: Depression (PHQ-9) and diabetes distress (PAID-T) scores from self-administered tests were studied in 364 patients with diabetes between the ages of 13-17. Kruskal-Wallis test was used to assess differences between types of diabetes, sexes, races, and insurance status. Spearman correlations, and robust rank order multivariable regression analysis were used to assess relationships. Medical records were reviewed for follow-up hemoglobin A1c (HbA1c) levels over 3 years. RESULTS: HbA1c was significantly lower in females with T2D than with T1D (p = 0.019) but not in males. It, also, did not differ between females and males with T2D. Median PHQ-9 score in females with T2D was significantly greater than in females with T1D (p = 0.007) but did not differ between females and males with T2D. PHQ-9 scores did not differ between males with T2D and T1D. PAID-T scores, however, were higher in males with T2D than in males with T1D but did not differ between females. PHQ-9 scores and PAID-T scores were significantly related in T2D (rs = 0.65, p < 0.001). Neither was related to HbA1c in T2D. CONCLUSIONS: As in adolescents with T1D, depression and diabetes distress screening scores are closely related in adolescent T2D. However, unlike T1D, they are not related to glycemic control in T2D. Depression and diabetes distress may be more closely related to weight and lifestyle concerns.

Increase in newly diagnosed type 1 diabetes in youth during the COVID-19 pandemic in the United States: A multi-center analysis.

BACKGROUND: An increase in newly diagnosed type 1 diabetes (T1D) has been posited during the COVID-19 pandemic, but data are conflicting. We aimed to determine trends in newly diagnosed T1D and severity of presentation at diagnosis for pediatric and adolescent patients during COVID-19 (2020) as compared to the previous year (2019) in a multi-center analysis across the United States. METHODS: This retrospective study from seven centers in the T1D Exchange Quality Improvement Collaborative (T1DX-QI) included data on new onset T1D diagnosis and proportion in DKA at diagnosis from January 1 to December 31, 2020, compared to the prior year. Chi-square tests were used to compare differences in patient characteristics during the pandemic period compared to the prior year. RESULTS: Across seven sites, there were 1399 newly diagnosed T1D patients in 2020, compared to 1277 in 2019 (p = 0.007). A greater proportion of newly diagnosed patients presented in DKA in 2020 compared to 2019 (599/1399(42.8%) vs. 493/1277(38.6%), p = 0.02), with a higher proportion presenting with severe DKA (p = 0.01) as characterized by a pH <7.1 and/or bicarbonate of <5 mmol/L. Monthly data trends demonstrated a higher number of new T1D diagnoses over the spring and summer months (March to September) of 2020 compared to 2019 (p < 0.001). CONCLUSIONS: We found an increase in newly diagnosed T1D and a greater proportion presenting in DKA at diagnosis during the COVID-19 pandemic compared to the prior year. Future longitudinal studies are needed to confirm these findings with population level data and determine the long-term impact of COVID-19 on diabetes trends.

Factors Associated With Achieving Target A1C in Children and Adolescents With Type 1 Diabetes: Findings From the T1D Exchange Quality Improvement Collaborative.

The optimal care of type 1 diabetes involves consistent glycemic management to avoid short- and long-term complications. However, despite advancements in diabetes technology and standards, achieving adequate glycemic levels in children and adolescents remains a challenge. This study aimed to identify factors associated with achieving the recommended A1C target of <7% from the United States-based multicenter T1D Exchange Quality Improvement Collaborative cohort, including 25,383 children and adolescents living with type 1 diabetes.

A Quality Improvement Project to Implement Choking Prevention and First Aid Education in Prader-Willi Syndrome Caregivers.

Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder characterized by hypotonia and hyperphagia. Consequently, individuals with PWS are at high risk of choking, and choking is a leading cause of morbidity and mortality. The aim of this quality improvement (QI) project is to provide choking prevention and first aid education from 0% to 80% of PWS caregivers seen in a multidisciplinary PWS clinic, and to assess the effectiveness of this education program. A QI initiative was developed to standardize and implement choking prevention and first aid education for PWS caregivers. Using a Likert scale, pre- and post-education assessments were conducted to measure caregiver (1) awareness of the PWS choking risk, (2) self-reported knowledge of choking prevention strategies, and (3) comfort in providing choking first aid. The American Heart Association Family and Friends® CPR (Dallas, TX, USA) curriculum was utilized. Education was provided during a regularly scheduled PWS clinic appointment. At project conclusion, 45/52 (87%) of PWS caregivers received education. A post-education assessment revealed an improvement in PWS caregivers' awareness of choking risk, self-reported knowledge of choking prevention strategies, and comfort in providing choking first aid. This QI project supports a practice change to implement choking prevention and first aid education as standard process within our PWS clinic.

Case Studies in Pediatric Lipid Disorders and Their Management.

CONTEXT: Identification of modifiable risk factors, including genetic and acquired disorders of lipid and lipoprotein metabolism, is increasingly recognized as an opportunity to prevent premature cardiovascular disease (CVD) in at-risk youth. Pediatric endocrinologists are at the forefront of this emerging public health concern and can be instrumental in beginning early interventions to prevent premature CVD-related events during adulthood. AIM: In this article, we use informative case presentations to provide practical approaches to the management of pediatric dyslipidemia. CASES: We present 3 scenarios that are commonly encountered in clinical practice: isolated elevation of low-density lipoprotein cholesterol (LDL-C), combined dyslipidemia, and severe hypertriglyceridemia. Treatment with statin is indicated when the LDL-C is ≥190 mg/dL (4.9 mmol/L) in children ≥10 years of age. For LDL-C levels between 130 and 189 mg/dL (3.4-4.89 mmol/L) despite dietary and lifestyle changes, the presence of additional risk factors and comorbid conditions would favor statin therapy. In the case of combined dyslipidemia, the primary treatment target is LDL-C ≤130 mg/dL (3.4 mmol/L) and the secondary target non-high-density lipoprotein cholesterol <145 mg/dL (3.7 mmol/L). If the triglyceride is ≥400 mg/dL (4.5 mmol/L), prescription omega-3 fatty acids and fibrates are considered. In the case of triglyceride >1000 mg/dL (11.3 mmol/L), dietary fat restriction remains the cornerstone of therapy, even though the landscape of medications is changing. CONCLUSION: Gene variants, acquired conditions, or both are responsible for dyslipidemia during childhood. Extreme elevations of triglycerides can lead to pancreatitis. Early identification and management of dyslipidemia and cardiovascular risk factors is extremely important.

Increasing Insulin Pump Use Among 12- to 26-Year-Olds With Type 1 Diabetes: Results From the T1D Exchange Quality Improvement Collaborative.

Insulin pump therapy in pediatric type 1 diabetes has been associated with better glycemic control than multiple daily injections. However, insulin pump use remains limited. This article describes an initiative from the T1D Exchange Quality Improvement Collaborative aimed at increasing insulin pump use in patients aged 12-26 years with type 1 diabetes from a baseline of 45% in May 2018 to >50% by February 2020. Interventions developed by participating centers included increasing in-person and telehealth education about insulin pump technology, creating and distributing tools to assist in informed decision-making, facilitating insulin pump insurance approval and onboarding processes, and improving clinic staff knowledge about insulin pumps. These efforts yielded a 13% improvement in pump use among the five participating centers, from 45 to 58% over 22 months.

An endocrine perspective on menstrual suppression for adolescents: achieving good suppression while optimizing bone health.

Suppression of menstruation and/or ovarian function in adolescent girls may be desired for a variety of reasons. Numerous medical options exist. The choice of the appropriate modality for an individual patient depends on several factors based on differences in the efficacy of achieving menstrual suppression as well as in their side effect profiles. Adolescence is also a period of bone mass accrual in girls, and several of these modalities may negatively influence peak bone mass. This review focuses on the efficacy of achieving menstrual suppression and the effect on bone health of the various options through an overview of the current literature and also highlights areas in need of further research.

SARS-CoV-2 infection and paediatric endocrine disorders: Risks and management considerations.

Background: Coronavirus-19 (COVID-19) is a disease caused by the SARS-CoV-2 virus, the seventh coronavirus identified as causing disease in humans. The SARS-CoV-2 virus has multiple potential pathophysiologic interconnections with endocrine systems, potentially causing disturbances in glucose metabolism, hypothalamic and pituitary function, adrenal function and mineral metabolism. A growing body of data is revealing both the effects of underlying endocrine disorders on COVID-19 disease outcome and the effects of the SARS-CoV-2 virus on endocrine systems. However, comprehensive assessment of the relationship to endocrine disorders in children has been lacking. Content: In this review, we present the effects of SARS-CoV-2 infection on endocrine systems and review the current literature on complications of COVID-19 disease in underlying paediatric endocrine disorders. We provide recommendations on management of endocrinopathies related to SARS-CoV-2 infection in this population. Summary and outlook: With the surge in COVID-19 cases worldwide, it is important for paediatric endocrinologists to be aware of the interaction of SARS-CoV-2 with the endocrine system and management considerations for patients with underlying disorders who develop COVID-19 disease. While children and adults share some risk factors that influence risk of complications in SARS-CoV-2 infection, it is becoming clear that responses in the paediatric population are distinct and outcomes from adult studies cannot be extrapolated. Evidence emerging from paediatric studies provides some guidance but highlights the need for more research in this area.

Glycemic control, depression, diabetes distress among adolescents with type 1 diabetes: effects of sex, race, insurance, and obesity.

AIMS: To determine whether diabetes distress or depression screening better predict increased hemoglobin A1c (HbA1c) and to assess interactions with age, sex, race, obesity, and insurance status. BACKGROUND: Diabetes distress is a negative emotional reaction to diabetes, diabetes complications, self-management demands, unresponsive providers, and/or poor interpersonal relationships. Guidelines recommend annual depression screening, however diabetes distress may be mistaken for depression. METHOD: Depression (PHQ-9) and diabetes distress (PAID-T) scores from self-administered tests were studied in 313 patients with type 1 diabetes (T1D) between the ages of 13-17. Spearman correlations and robust rank order multivariable regression analysis were used to assess relationships to age, duration, HbA1c. Kruskal-Wallis test was used to assess differences between sexes, races, and insurance status. Receiver operator curves (ROC) were constructed to see whether PAID-T or PHQ-9 scores more closely predicted HbA1c greater than 9%. RESULTS: HbA1c was more strongly correlated with PAID-T (rs = 0.37, p < 0.01), than PHQ-9 (rs = 0.27, p < 0.01) scores. Area under ROC curve for poor HbA1c was 0.75 for PAID and 0.64 for PHQ-9. PAID-T and PHQ-9 scores were increased in females and subjects with public insurance and both were significantly related to HbA1c even when accounting for age, sex, race obesity, and insurance status. PHQ-9 and PAID-T scores correlated with BMI-Z scores in Blacks, but not Whites. CONCLUSIONS: Both depression and diabetes distress are associated with increased HbA1c in adolescents with T1D, though distress is more so. Diabetes distress and depression should be routinely assessed in T1D adolescents, particularly those with public insurance.

Vitamin D has no impact on outcomes after HSCT in children-A retrospective study.

Vitamin D not only plays an important role in bone metabolism but is also involved in multiple immune-mediated processes in the body which may be adversely affected in those with low levels. Most pediatric studies evaluating the association of vitamin D in patients undergoing allogeneic HSCT are single-center studies. We present the results of retrospective study at 5 centers across the United States in pediatric patients undergoing allogeneic HSCT. (VDD) and (VDI) were defined by vitamin D levels of <20 ng/ml and 21-30 ng/ml, respectively. The mean vitamin D levels pre-HSCT, day +30, and +100 were suggestive of VDI, but normalized thereafter. We compared the transplant characteristics and outcomes in 233 patients with VDD and VDI and those with normal levels and found no statistical difference in neutrophil or platelet engraftment, infections (viral, bacterial, or fungal) post-HSCT, length of hospital stay during HSCT, graft failure, acute or chronic GvHD, survival at day +100 and 1 year, or relapse of primary malignancy. We conclude that VDI or deficiency does not affect any of the common transplant variables after allogeneic HSCT in children. There is a need of a large multicenter prospective study to evaluate its role further.

Inequities in Diabetic Ketoacidosis Among Patients With Type 1 Diabetes and COVID-19: Data From 52 US Clinical Centers.

OBJECTIVE: We examined whether diabetic ketoacidosis (DKA), a serious complication of type 1 diabetes (T1D) was more prevalent among Non-Hispanic (NH) Black and Hispanic patients with T1D and laboratory-confirmed coronavirus disease 2019 (COVID-19) compared with NH Whites. METHOD: This is a cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 52 clinical sites in the United States, data were collected from April to August 2020. We examined the distribution of patient factors and DKA events across NH White, NH Black, and Hispanic race/ethnicity groups. Multivariable logistic regression analysis was performed to examine the odds of DKA among NH Black and Hispanic patients with T1D as compared with NH White patients, adjusting for potential confounders, such as age, sex, insurance, and last glycated hemoglobin A1c (HbA1c) level. RESULTS: We included 180 patients with T1D and laboratory-confirmed COVID-19 in the analysis. Forty-four percent (n = 79) were NH White, 31% (n = 55) NH Black, 26% (n = 46) Hispanic. NH Blacks and Hispanics had higher median HbA1c than Whites (%-points [IQR]: 11.7 [4.7], P < 0.001, and 9.7 [3.1] vs 8.3 [2.4], P = 0.01, respectively). We found that more NH Black and Hispanic presented with DKA compared to Whites (55% and 33% vs 13%, P < 0.001 and P = 0.008, respectively). After adjusting for potential confounders, NH Black patients continued to have greater odds of presenting with DKA compared with NH Whites (OR [95% CI]: 3.7 [1.4, 10.6]). CONCLUSION: We found that among T1D patients with COVID-19 infection, NH Black patients were more likely to present in DKA compared with NH White patients. Our findings demonstrate additional risk among NH Black patients with T1D and COVID-19.

The Diagnostic Error Index: A Quality Improvement Initiative to Identify and Measure Diagnostic Errors.

OBJECTIVE: To develop a diagnostic error index (DEI) aimed at providing a practical method to identify and measure serious diagnostic errors. STUDY DESIGN: A quality improvement (QI) study at a quaternary pediatric medical center. Five well-defined domains identified cases of potential diagnostic errors. Identified cases underwent an adjudication process by a multidisciplinary QI team to determine if a diagnostic error occurred. Confirmed diagnostic errors were then aggregated on the DEI. The primary outcome measure was the number of monthly diagnostic errors. RESULTS: From January 2017 through June 2019, 105 cases of diagnostic error were identified. Morbidity and mortality conferences, institutional root cause analyses, and an abdominal pain trigger tool were the most frequent domains for detecting diagnostic errors. Appendicitis, fractures, and nonaccidental trauma were the 3 most common diagnoses that were missed or had delayed identification. CONCLUSIONS: A QI initiative successfully created a pragmatic approach to identify and measure diagnostic errors by utilizing a DEI. The DEI established a framework to help guide future initiatives to reduce diagnostic errors.

The Type 1 Diabetes Composite Score: An Innovative Metric for Measuring Patient Care Outcomes Beyond Hemoglobin A1c.

INTRODUCTION: Patient outcomes resulting from optimal type 1 diabetes (T1D) care have historically focused on driving a single metric, hemoglobin A1c. Our objectives were to design, build, and launch an aggregate clinical indicator that comprehensively reflects patient management status beyond hemoglobin A1c alone. This project aimed to show proof of principle that an aggregate score comprised of T1D outcome metrics could be built to track quality performance. METHODS: We established an electronic medical record-based diabetes registry and utilized its population health modules to design and build this diabetes care metric. Elements representing optimal diabetes management, as defined by current guidelines and expert opinion, were identified. Nine elements fall into categories of management tools, care assessments, and complications risk. The Type 1 Diabetes Composite Score (T1DCS) aggregates these outcome measures to reflect the overall diabetes care status for each patient. Higher scores suggest better management and overall improved patient health. RESULTS: We launched this metric build in November 2018 and applied the scoring to our T1D population (≈1,900 patients). The T1DCS quickly provides a summary of current diabetes management status. T1DCS viewed over the registry cohort demonstrates a normal distribution, and scores improved from March to September 2019, reflecting better care and outcomes, and illustrating the potential to track program effectiveness. CONCLUSIONS: The T1DCS is a useful metric to evaluate the clinical status of T1D patients, assess the capability of a clinical program to achieve optimal diabetes outcomes, identify patient diversity opportunities, and document outcome improvement as a novel comprehensive quality measure.

Management and Appropriate Use of Diazoxide in Infants and Children with Hyperinsulinism.

BACKGROUND: The diagnosis of hypoglycemia and the use of diazoxide have risen in the last decade. Diazoxide is the only Food and Drug Agency-approved pharmacologic treatment for neonatal hypoglycemia caused by hyperinsulinism (HI). Recent publications have highlighted that diazoxide has serious adverse effects (AEs) such as pulmonary hypertension (2-3%) and neutropenia (15%). Despite its increasing use, there is little information regarding dosing of diazoxide and/or monitoring for AEs. METHODS: We convened a working group of pediatric endocrinologists who were members of the Drug and Therapeutics Committee of the Pediatric Endocrine Society (PES) to review the available literature. Our committee sent a survey to its PES members regarding the use of diazoxide in their endocrine practices. Our review of the results concluded that there was substantial heterogeneity in usage and monitoring for AEs for diazoxide among pediatric endocrinologists. CONCLUSIONS: Based on our extensive literature review and on the lack of consensus regarding use of diazoxide noted in our PES survey, our group graded the evidence using the framework of the Grading of Recommendations, Assessment, Development and Evaluation Working Group, and has proposed expert consensus practice guidelines for the appropriate use of diazoxide in infants and children with HI. We summarized the information on AEs reported to date and have provided practical ideas for dosing and monitoring for AEs in infants treated with diazoxide.