Defining a Childhood Type 1 Diabetes Cohort, Clinical Practice Measures, and Outcomes Within Administrative Data in British Columbia.

OBJECTIVE: We used administrative data to 1) establish a cohort of individuals with childhood-onset type 1 diabetes (T1D) in British Columbia (BC), and 2) define T1D-related clinical practice measures. METHODS: We applied a validated diabetes case-finding definition and differentiating algorithm to linked administrative data (1992-1993 to 2019-2020). Cases were removed when they did not meet inclusion criteria for childhood-onset T1D. Clinical practice measures were defined based on clinical practice guidelines. RESULTS: We developed an administrative cohort that included 5,901 individuals with childhood-diagnosed T1D between April 1, 1996, and March 31, 2020. The mean age was 22.31 (standard deviation 8.21) years. Clinical practice measures derived included diabetes outpatient visits (N=4,935) and glycated hemoglobin tests (N=4,935), and screening for thyroid function (N=4,457), retinopathy (N=1,602), and nephropathy (N=2,369). CONCLUSIONS: We established an administrative cohort of ∼6,000 individuals with childhood-onset T1D with 20+ years of follow-up data that can be used to describe the association between clinical practice measures and clinical outcomes.

Vitamin D Toxicity from an Unusual and Unexpected Source: A Report of 2 Cases.

INTRODUCTION: Hypervitaminosis D is a relatively uncommon etiology of hypercalcemia. Toxicity is usually caused by very high doses, mostly secondary to erroneous prescription or administration of vitamin D, and less commonly, contaminated foods or manufacturing errors of vitamin D-containing supplements. CASE PRESENTATION: A 16-year-old male, previously healthy, presented with 2-week history of nonspecific symptoms (fatigue, gastrointestinal complaints). Investigations showed acute kidney injury and hypercalcemia (total calcium 3.81 mmol/L). Further diagnostic workup revealed markedly elevated 25-hydroxyvitamin D levels (1,910 nmol/L). He denied taking any vitamin D supplements; however, he reported consumption of creatine and protein supplements. Mass spectrometry analysis of the creatine supplement estimated a vitamin D content of 425,000 IU per serving (100 times the upper tolerable daily dose). A few months later, another previously healthy adolescent presented with severe hypercalcemia and acute kidney injury secondary to hypervitaminosis D. He was also using a creatine supplement, from the same manufacturer brand and lot. Both patients were treated with intravenous hydration, calcitonin, and pamidronate. They maintained normocalcemia after their initial presentation but required low-calcium diets and laboratory testing for months after this exposure. DISCUSSION/CONCLUSION: We present 2 cases of hypervitaminosis D caused by a manufacturing error of a natural health product which did not claim to contain vitamin D. The use of dietary supplements is highly prevalent; this should be incorporated while taking medical history, and considered a potential source of toxicity when an alternative source cannot be found, regardless of the product label.

An Analysis of Self-Reported Barriers to Type 1 Diabetes Care in a Pediatric Population in British Columbia, Canada.

OBJECTIVES: Our aim in this study was to identify patient-level barriers to attending pediatric type 1 diabetes mellitus (T1DM) clinic and to better understand the demographic and clinical characteristics of these reporting barriers. METHODS: Patients were recruited from pediatric T1DM clinics throughout British Columbia. Barriers to attending clinic were identified through a survey. Demographic and clinical characteristics of patients who reported difficulty attending clinic appointments were compared with those who did not. RESULTS: Of the 197 study participants, 31% reported difficulty attending appointments. Commonly reported barriers were distance to clinic and missing work. Younger child age and residing in northern regions increased the odds of reporting a barrier, whereas residing on Vancouver Island decreased odds of reporting a barrier. There were no differences in glycated hemoglobin levels between the 2 groups. CONCLUSIONS: Approximately 1 in 3 patients identified challenges in attending T1DM appointments in British Columbia. Further research is needed to determine whether similar challenges exist in other provinces.

Family conflict in type 1 diabetes: Who is at risk?

BACKGROUND/OBJECTIVE: Diabetes-related conflict between caregiver and child has been associated with lower quality of life, reduced treatment adherence, and higher hemoglobin A1C. The objective of this project was to identify patient and family characteristics associated with higher levels of diabetes-specific family conflict. METHODS: This was a cross-sectional study. Caregivers of children aged 4- to 18-years-old with type 1 diabetes were recruited from diabetes clinics across British Columbia. Data were collected through chart reviews and patient surveys, including the Diabetes Family Conflict Scale and the Adherence in Diabetes Questionnaire. All caregivers and children ≥8-years-old were invited to complete the survey. Potential predictors were explored using univariate and multivariable linear regression models. RESULTS: In the unadjusted analysis, higher caregiver report of conflict (n = 196) was associated with: low family income, non-Caucasian ethnicity, missed school, older age at diagnosis, and insulin regimen (2-3 injections/day rather than multiple daily injections or pump). When all variables were adjusted for simultaneously, income, insulin regimen, one or more stay at home parent and recent hospitalization were significant. For the child report (n = 111), higher maternal education was associated with lower conflict in the unadjusted analysis and non-Caucasian ethnicity was associated with higher conflict in the adjusted analysis. CONCLUSIONS: This exploratory study identified possible novel associations between patient and family characteristics and diabetes-related family conflict.

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.

Clinical Impact and Cost Efficacy of Newborn Screening for Congenital Adrenal Hyperplasia.

OBJECTIVES: To evaluate the clinical impact of a congenital adrenal hyperplasia (CAH) newborn screening program and incremental costs relative to benefits in screened vs unscreened infants. We hypothesized that screening would lead to clinical benefits and would be cost effective. STUDY DESIGN: This was an ambispective cohort study at British Columbia Children's Hospital, including infants diagnosed with CAH from 1988-2008 and 2010-2018. Data were collected retrospectively (unscreened cohort) and prospectively (screened cohort). Outcome measures included hospitalization, medical transport, and resuscitation requirements. The economic analysis was performed using a public payer perspective. RESULTS: Forty unscreened and 17 screened infants were diagnosed with CAH (47% vs 53% male). Median days to positive screen was 6 and age at diagnosis was 5 days (range, 0-30 days) and 6 days (range, 0-13 days) in unscreened and screened populations, respectively. In unscreened newborns, 55% required transport to a tertiary care hospital, 85% required hospitalization, and 35% required a fluid bolus compared with 29%, 29%, and 12% in screened infants, respectively. The cost of care was $33 770 per case in unscreened vs $17 726 in screened newborns. In the screened cohort, the incremental cost-effectiveness ratio was $290 in the best case analysis and $4786 in the base case analysis, per hospital day avoided. CONCLUSIONS: Compared with unscreened newborns, those screened for CAH were less likely to require medical transport and had shorter hospital stays. Screening led to a decrease in hospitalization costs. Although screening did not result in cost savings, it was assessed to be cost effective considering the clinical benefits and incremental cost-effectiveness ratio.

Non-invasive assessment of aortic stiffness and blood pressure in young Turner syndrome patients.

Background Females with Turner syndrome (TS) carry an elevated risk of aortic dissection. The objective of the study was to assess the biophysical properties of the aorta and ambulatory blood pressure (BP) in females with TS and compare these findings to those in healthy female age-matched controls. Methods This was a prospective cohort study including subjects aged 8-25 years. Utilizing two-dimensional (2D) echocardiography and Doppler, proximal aortic dimensions were measured and biophysical properties of the aorta were calculated including pulse wave velocity (PWV), arterial pressure-strain elastic modulus and stiffness index. Resting BP was measured and ambulatory blood pressure monitoring (ABPM) was performed. Results Of 23 TS patients and 46 controls (median age 16.3 years), aortic annulus, sinus of Valsalva and sinotubular (ST) junction diameters, as well as left ventricular (LV) mass, were significantly greater in TS patients compared with controls when scaled for height2.7, but not for body surface area (BSA), although ascending aorta diameter was greater when scaled for both. Median PWV was faster in TS patients compared to controls (451 vs. 360 cm/s) while arterial pressure-strain elastic modulus and stiffness index were similar. Resting BP was abnormal in seven out of 22 patients and ABPM was abnormal in 16 out of 21 patients. Conclusions Young patients with TS had dilated proximal aortas when scaled for height2.7 and stiffer aortas when compared with healthy female age-matched controls. Moreover, resting BP underdiagnosed pre-hypertension and hypertension compared to ABPM. These findings are consistent with the presence of a primary aortopathy in TS.

Type 1 diabetes outcomes: Does distance to clinic matter?

BACKGROUND AND OBJECTIVES: To access care, pediatric type 1 diabetes (T1D) patients living in British Columbia (BC), Canada, travel to the sole tertiary pediatric hospital (BC Children's Hospital; BCCH), or they receive community care from pediatric endocrinologists and/or pediatricians. We sought to determine whether hemoglobin A1C (HbA1C ) and patient-reported outcomes were associated with (1) distance to clinic and (2) tertiary vs community care. METHODS: Patients were recruited from T1D clinics across BC. Clinical chart review and patient surveys were completed, including the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Clinic type was categorized as tertiary (BCCH) or community, and the travel time to BCCH was categorized as <1 hour, 1 to 2 hours, or >2 hours. RESULTS: There were 189 participants. Age and duration of T1D were similar across groups. Mean number of visits/year for BCCH groups were 2.23, 2.24, and 2.05 for the <1-hour, 1- to 2-hour, and >2-hour groups, respectively, vs 3.26 for the community group. Adjusted mean difference in HbA1C was +0.65% (95% confidence interval [CI]: 0.15, 1.15) and +0.52% (95% CI: 0.02, 1.02) for the BCCH >2-hour group compared to the BCCH <1-hour group and community groups, respectively. Child DTSQ scores were significantly lower in the BCCH >2-hour group compared to the BCCH <1-hour and community groups. CONCLUSIONS: Children traveling >2 hours to T1D clinic at BCCH had significantly higher HbA1C values and lower satisfaction with care vs those traveling <1 hour to BCCH and those receiving community care. Access to care closer to home may benefit glycemic control in children with T1D and improve treatment satisfaction. Future research should determine whether these findings can be replicated in other regions.

Type 1 diabetes incidence and prevalence trends in a cohort of Canadian children and youth.

BACKGROUND AND OBJECTIVE: Incidence rates of type 1 diabetes have long been on the rise across the globe, however, there is emerging evidence that the rate of rise may be slowing. The objective of this study was to describe trends in the incidence and prevalence of type 1 diabetes in a sample of Canadian children and youth. METHODS: Cases were extracted using linked administrative datasets and a validated diabetes case-finding definition. Incidence and prevalence trends were analyzed using the JoinPoint regression analysis program. RESULTS: A small increase in the incidence of type 1 diabetes was observed over the 11-year period from 2002-2003 to 2012-2013. Total incident cases per year ranged from 201 (2005-2006) to 250 (2007-2008). Total prevalent cases per year ranged from 1790 (2002-2003) to 2264 (2012-2013). Incidence was highest among children aged 5 to 14 years, and lowest in the youngest (1-4 years) and oldest (15-19 years) age brackets. The most significant increase in incidence was in children aged 10 to 14 years. Age-standardized prevalence increased significantly throughout the study period. CONCLUSION: These results are similar to data from the United States but differ from European data with respect to the annual percent change for incidence as well as age-specific incidence trends. In keeping with the low mortality rates associated with type 1 diabetes, the prevalence continues to rise.

Hyperthyroidism hidden by congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy with severe central hypoventilation. CCHS results from a mutation in the paired-like homeobox 2B gene (PHOX2B). In addition to hypoventilation, patients with CCHS display a wide array of autonomic nervous system abnormalities, including decreased heart rate variability and abrupt sinus pauses, esophageal dysmotility, abnormal pupillary light response, and temperature dysregulation, to name a few. To date, there has been no documentation of a child with both CCHS and hyperthyroidism. We report the case of a young child with CCHS who presented with tachycardia, which was later found to be due to Grave's disease, after many months of investigation.

Kabuki syndrome and Crohn disease in a child with familial hypocalciuric hypercalcemia.

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) results from a mutation of the calcium sensing receptor (CASR) gene and typically presents as asymptomatic hypercalcemia with inappropriately low urinary calcium excretion and normal or mildly elevated levels of parathyroid hormone. OBJECTIVE: To describe a case of FHH associated with Kabuki syndrome and Crohn disease. METHOD: Genomic DNA was screened for CASR mutations and a retrospective chart review was performed. RESULTS: Heterozygosity was observed in exon 3, which encodes a portion of the extra-cellular domain. Sequencing revealed a n.476T>G nucleotide transversion, predicting a non-conservative substitution of arginine for leucine at codon 159 (p.L159R). CONCLUSION: An association between Kabuki syndrome and autoimmune disease has been described in the literature, which may explain the connection between Kabuki syndrome and Crohn disease. However, it remains unclear if there is a link between FHH, Kabuki syndrome and Crohn disease in this case.