An Automated Risk Index for Diabetic Ketoacidosis in Pediatric Patients With Type 1 Diabetes: The RI-DKA.

Identifying patients at high risk for diabetic ketoacidosis (DKA) is crucial for informing efforts at preventive intervention. This study sought to develop and validate an electronic medical record (EMR)-based tool for predicting DKA risk in pediatric patients with type 1 diabetes. Based on analysis of data from 1,864 patients with type 1 diabetes, three factors emerged as significant predictors of DKA: most recent A1C, type of health insurance (public vs. private), and prior DKA. A prediction model was developed based on these factors and tested to identify and categorize patients at low, moderate, and high risk for experiencing DKA within the next year. This work demonstrates that risk for DKA can be predicted using a simple model that can be automatically derived from variables in the EMR.

A Comprehensive System for Identifying Patients With Type 1 Diabetes at Increased Risk for Diabetic Ketoacidosis at Texas Children's Hospital.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a project at Texas Children's Hospital aimed at improving identification of patients with type 1 diabetes at high risk for diabetic ketoacidosis.

Comparison of hypothyroidism, growth hormone deficiency, and adrenal insufficiency following proton and photon radiotherapy in children with medulloblastoma.

BACKGROUND: Endocrine deficiencies are common following Craniospinal irradiation (CSI) in children with brain tumors, but empirical data comparing outcomes following proton (PRT) and photon radiation therapy (XRT) are limited. METHODS: This retrospective chart review compared the incidence of hypothyroidism, Growth hormone deficiency (GHD), and Adrenal insufficiency (AI) in patients with medulloblastoma treated with XRT and PRT between 1997 and 2016. All patients received CSI and had routine endocrine screening labs to evaluate for thyroid dysfunction, GHD, and AI. We used proportional hazards regression to calculate hazard ratios (HR) and 95% confidence intervals (CI) comparing the development of hypothyroidism, AI, and GHD between radiation modalities, adjusting for age at diagnosis, sex, race/ethnicity, and CSI dose. RESULTS: We identified 118 patients with medulloblastoma who were followed for a median of 5.6 years from the end of radiotherapy. Thirty-five (31%) patients developed hypothyroidism, 71 (66%) GHD, and 20 (18%) AI. Compared to PRT, XRT was associated with a higher incidence of primary hypothyroidism (28% vs. 6%; HR = 4.61, 95% CI 1.2-17.7, p = 0.03). Central hypothyroidism, GHD, and AI incidence rates were similar between the groups. CONCLUSIONS: Primary hypothyroidism occurs less often after PRT CSI, compared to XRT CSI. This suggests that the thyroid and pituitary glands receive less radiation after spine and posterior fossa boost RT, respectively, using PRT.

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.

Methylphenidate improves weight control in childhood brain tumor survivors with hypothalamic obesity.

BACKGROUND: Hypothalamic obesity causes unrelenting weight gain for childhood brain tumor survivors. No single therapy has proven effective for treatment. We aimed to evaluate effectiveness of long-term methylphenidate therapy on body mass index (BMI) change in children with hypothalamic obesity. METHODS: A retrospective analysis included children with a history of brain tumor and hypothalamic obesity receiving methylphenidate (10-60 mg/day) for hypothalamic obesity. Subjects were evaluated for BMI trajectory before and after methylphenidate start. Given that z-scores can be skewed in severely obese children, we calculated BMI as a percent of the BMI at the 95th percentile for the child's age and gender (BMI% 95th). RESULTS: Twelve patients with hypothalamic obesity completed methylphenidate therapy for at least 6 months (median 3.1 years, range 1.0-5.8 years). All subjects had a suprasellar tumor (nine [75%] with craniopharyngioma) and pituitary dysfunction. Pretreatment median BMI percent of the 95th percentile was 125.6% (interquartile range [IQR] 25-75: 115.3-138.3%) with BMI z-score of 2.4 (IQR 25-75: 2.1-2.6). Following methylphenidate treatment, there was a 69.9% reduction in the median slope of BMI change. Eleven of 12 patients (92%) had a reduction in the slope of their BMI change on methylphenidate treatment. Postmethylphenidate median BMI percent of the 95th percentile decrease to 115.2% (IQR 25-75: 103.6-121.2%) with median BMI z-score of 2.1 (IQR 25-75: 1.8-2.2). Mild side effects were noted in six patients. CONCLUSIONS: Methylphenidate use reduced and sustained BMI change in children with hypothalamic obesity. Stimulant therapy is an effective first-line agent for treatment of hypothalamic obesity.

Establishment of the T1D Exchange Quality Improvement Collaborative (T1DX-QI).

The T1D Exchange established a learning platform by evaluating the current state of care and engaging 10 diabetes clinics in collaborative quality improvement (QI) activities. Participating clinics are sharing data and best practices to improve care delivery for people with type 1 diabetes. This article describes the design and initial implementation of this platform, known as the T1D Exchange Quality Improvement Collaborative. This effort has laid a foundation for learning from variation in type 1 diabetes care delivery via QI methodology and has demonstrated success in improving processes through iterative testing cycles and transparent sharing of data.

Erratum. Establishment of the T1D Exchange Quality Improvement Collaborative (T1DX-QI). Clinical Diabetes 2020;38:141-151 (DOI: 10.2337/cd19-0032).

[This corrects the article on p. 141 in vol. 38, PMID: 32327886.].

Hypothyroidism after craniospinal irradiation with proton or photon therapy in patients with medulloblastoma.

BACKGROUND: Craniospinal irradiation (CSI) often results in endocrine deficiencies in children with medulloblastoma due to irradiation of the hypothalamic-pituitary axis (HPA) or the thyroid gland. CSI with Proton radiation therapy (PRT) has the potential to decrease the risk of hypothyroidism by reduction in radiation dose to these organs. This study compares the risk for hypothyroidism in patients with medulloblastoma treated with Photon radiation therapy (XRT) or PRT. METHODS: The records of patients with medulloblastoma diagnosed at a single institution between 1997 and 2014 who received CSI were, retrospectively, reviewed. Ninety-five patients (54 XRT and 41 PRT) who had baseline and yearly follow-up thyroid studies were included. We used interval censored Cox regression to calculate hazard ratios of developing any, primary, and central hypothyroidism. RESULTS: With a median time to last thyroid studies post radiation of 3.8 years in PRT and 9.6 years in XRT, 33/95 (34.7%) patients developed hypothyroidism (median time to hypothyroidism: 2.6 years). Hypothyroidism developed in 25/54 (46.3%) who received XRT vs. 8/41 (19%) in the PRT group (HR =1.85, p = .14). Primary hypothyroidism developed in 15/95 (15.8%) patients: 12/54 (22.2%) after XRT and 3/41 (7.3%) after PRT (HR =2.1, p = .27). Central hypothyroidism developed in 17/95 (18.0%) patients: 13/54 (24.0%) after XRT and 4/41 (9.8%) after PRT (HR =2.16, p = .18). CONCLUSIONS: The use of PRT in patients with medulloblastoma was associated with numerically lower but not significantly lower risk of hypothyroidism. Further studies including larger numbers and longer follow up must be performed to assess whether lower radiation doses achieved with PRT show statistically significant differences.

An Observational Crossover Study of People Using Real-Time Continuous Glucose Monitors Versus Self-Monitoring of Blood Glucose: Real-World Evidence Using EMR Data From More Than 12,000 People With Type 1 Diabetes.

BACKGROUND: We used real-world electronic health record (EHR) data to examine HbA1c levels among children and adults with type 1 diabetes (T1D) who are classified as continuous glucose monitor (CGM) users after T1D diagnosis and switch to self-monitoring of blood glucose (SMBG) during follow-up, versus people who opt for SMBG after T1D diagnosis and switch to CGM during follow-up visits. METHODS: We conducted an observational, case-crossover study using electronic medical record (EMR) data from the T1D Exchange Quality Improvement Collaborative. The primary outcome in this study was HbA1c. Baseline HbA1c levels were taken at the index date, corresponding to initial device classification, and compared with HbA1c value recorded at the clinic visit following device switch. RESULTS: Of all patients classified in the SMBG group, 7,706 switched to CGM use within the 5-year study time frame, and 5,123 of all initial CGM users switched to SMBG within the study time frame and were included in this analysis. At baseline, median (interquartile range [IQR]) HbA1c for SMBG use was 8.1 (2.4), whereas postcrossover to CGM use, there was a decline in median (IQR) levels to 7.7 (1.9) (P < .001). For baseline CGM users, median (IQR) HbA1c levels were 7.9 (2.0), and postcrossover to SMBG, median (IQR) HbA1c levels increased to 8.0 (2.9) (P < .001). CONCLUSION: We found that people who switched to CGM use had significantly improved HbA1c levels compared to those who switched to glucose monitoring with SMBG.

Hyperglycemia during induction therapy is associated with poorer survival in children with acute lymphocytic leukemia.

OBJECTIVES: To investigate whether children with acute lymphocytic leukemia (ALL) who have development of hyperglycemia during induction may have worse relapse-free (RFS) and overall survival (OS) rates. STUDY DESIGN: A review of 167 children diagnosed with ALL between 1999 to 2002 at Texas Children's Hospital was performed. Blood glucose concentrations during induction therapy were reviewed; patients were assigned to 3 groups: euglycemia (blood glucose < 140 mg/dL), mild hyperglycemia (blood glucose between 140-200 mg/dL), and overt hyperglycemia (blood glucose > 200 mg/dL). RFS and OS among groups were compared by use of Kaplan-Meier and Cox-proportional hazard analyses, adjusting for potential confounding variables. RESULTS: The median follow-up in survivors was 6 years; there were 18 deaths and 36 relapses. Overt hyperglycemia was seen in 56 (34%) patients. Patients with overt hyperglycemia had poorer RFS (68% +/- [SE] 6.7 vs 85% +/- 3.6, P = .025) and OS (74% +/- 6.1 vs 96% +/- 1.9, P < .0001) at 5 years than their counterparts. Patients with overt hyperglycemia had 6.2 times (95% CI 1.6-24.7, P = .01) greater risk for death, independent of risk group and type of steroid. CONCLUSIONS: Overt hyperglycemia may be an independent predictor of survival in children with ALL.

Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia.

BACKGROUND: Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hyperglycemic during induction chemotherapy have an increased risk for infection during their first year of treatment. PROCEDURE: We conducted a retrospective chart review of 135 patients diagnosed with ALL during 1999-2001 at Texas Children's Hospital. Infectious outcomes during the first year of therapy were compared in three groups patients based on blood glucose concentrations during induction therapy: euglycemic (<140 mg/dl), mild hyperglycemic (MH) (140-199 mg/dl) and overt hyperglycemic (OH) (blood glucose >200 mg/dl). RESULTS: Seventy-five (56%) patients met criteria for either MH (21%) or OH (35%). Hyperglycemia was more prevalent in older children (P < 0.001) and those at risk for being overweight (BMI% >85%) at diagnosis (P < 0.01). Patients with MH and OH were 2.5 times (95% CI 1.0-6.2) and 2.1 times (95% CI 1.0-4.6) more likely to have documented infections, respectively. Patients with OH were 4.2 times (95% CI 1.5-12) more likely to have bacteremia/fungemia, 3.8 times (95% CI 1.2-11.6) more likely to have cellulitis, and 4.0 times (95% CI 1.7-9.3) more likely to be admitted for fever and neutropenia than the euglycemia group. CONCLUSION: Hyperglycemia, especially when overt, may be a previously unrecognized risk factor of infectious complications in children with ALL during the first year of treatment.

Comparison of height and weight after 12 vs. 18 Gy cranial radiation therapy in pediatric acute lymphoblastic leukemia (ALL) patients.

PURPOSE: To compare the effect of 12 versus 18 Gy cranial radiation therapy (RT) on height and weight indices among pediatric patients with acute lymphoblastic leukemia (ALL). METHODS AND MATERIALS: Records of children with ALL who were 2 to 14 years old at the time of RT and were treated at a single institution between 2000 and 2011 were reviewed. Patients' height, weight, and body mass index were converted into z-scores using the Centers for Disease Control growth charts to normalize the values to number of standard deviations from the mean. These values were measured at the pre-RT clinic visit and subsequent yearly intervals. The z-scores of the growth indices were fitted into a generalizing estimating equations model and analyzed by various clinical factors. RESULTS: A total of 48 patients met the study criteria, including 32 boys and 16 girls. The median age at the time of RT was 7 years (range, 2-14 years). Patients were separated into 2 dose groups: 12 Gy (n = 30) and 18 Gy (n = 18). Median follow-up was 4.9 years (range, 3.0-11.8 years) and 6.0 years (range, 3.1-10.5 years) and the median pre-RT height z-scores were -0.55 (range, -2.2 to 1.4) and -0.85 (range, -3.1 to 0.8) for the 2 groups, respectively (P = .65). Patients who received 18 Gy had a significant difference in change in height compared with those who received 12 Gy, who were able to maintain normal growth during the first 3 years of follow-up. This did not appear to be sex-specific, and there was no difference in change in weight or body mass index. CONCLUSIONS: Compared with 18 Gy, patients with ALL who received 12 Gy of cranial RT had less height impairment in the first 3 years post-RT, but further prospective studies are needed.

Staphylococcus aureus infections in pediatric patients with diabetes mellitus.

OBJECTIVES: To describe Staphylococcus aureus infections in children with diabetes mellitus (DM). METHODS: Children with DM (cases) and S. aureus infections (2/02-6/10) were identified from a surveillance database. Patient charts were reviewed, and S. aureus isolates were characterized by molecular methods. Cases were compared to age-matched controls without DM but with CA-S. aureus skin and soft tissue infections (SSTI) using conditional logistic regression. RESULTS: Forty-seven cases were identified; 41 were matched with 123 controls. Four cases had osteomyelitis and 43 had SSTI. Mean age was 14.2 years and 63% of cases had hemoglobin (Hb) A1c levels above 10%. Cases and controls differed by gender (85% vs. 45% female, P < 0.001), BMI% (median 87% vs. 72%, P = 0.04), methicillin-resistant S. aureus (MRSA) infection (49% vs. 68%, P = 0.04), and recurrent infections (22% vs. 4%, P = 0.001). Among cases, 88% of recurrences were caused by MRSA. CONCLUSIONS: The majority of cases had poor glycemic control, more recurrences, fewer primary MRSA infections and were more likely to be female compared to a control group. Improved glycemic control may reduce the risk for infection, and decrease hospitalizations due to S. aureus infections.