Comparison of Intranasal and Injectable Glucagon Administration Among Pediatric Population Responders.

Aims: Ease of use and acceptability of nasal versus injectable glucagon (IG) among pediatric responders have been little investigated. This study compared the performance of administering nasal and IG in parents of youth with type 1 diabetes (T1D) and in school workers. Enablers and barriers associated with each glucagon and preferred glucagon administration learning modality were also evaluated. Methods: Three months after watching short pedagogical videos, 30 parents and 30 school workers performed simulated scenarios where they administered both glucagon. Completion time and successful execution of critical steps were collected. Interviews assessed preferred learning modalities, barriers, and enablers associated with each glucagon. Results: Both groups administered nasal glucagon faster than IG (median [interquartile range]: parents 19 [12-29] vs. 97 [71-117] s, P < 0.001; school workers 24 [16-33] vs. 129 [105-165] s, P < 0.001). A lower proportion of participants successfully executed all critical steps for injectable versus nasal glucagon (significant difference for school workers [53% vs. 90%; P = 0.007] but not for parents [68% vs. 83%; P = 0.227]). Nasal glucagon was preferred for ease of use and acceptability. Preferred learning modalities were a combination of videos and workshops, but videos alone could suffice for nasal glucagon. Conclusions: Nasal glucagon is faster to use, more likely to be successfully administered, and more acceptable than IG for parents of children with T1D and school workers. Nasal glucagon training with videos could improve school workers' involvement in severe hypoglycemia management. Clinical Trial number, URL to the registration: NCT05395000, https://clinicaltrials.gov/ct2/show/NCT05395000.

Adrenal insufficiency among children treated with hormonal therapy for infantile spasms.

OBJECTIVE: Hormonal therapy is a standard treatment for children with infantile spasms. However, the high doses given and long treatment duration expose patients to the risk of adrenal insufficiency (AI). This study aims to quantify the cumulative incidence of AI among children with infantile spasms treated with high-dose corticosteroids and/or adrenocorticotropic hormone. METHODS: A retrospective chart review of patients treated for infantile spasms was performed between January 2009 and March 2020 in one pediatric specialized hospital. Variables collected include patient and treatment characteristics, risk factors of AI, and adrenal function testing. Analysis included descriptive statistics such as incidence and bivariate analysis. RESULTS: Thirty-one patients were included and received a total of 33 courses of treatment (17 corticosteroids [prednisone/prednisolone], 12 adrenocorticotropic hormone, and four combined). Physiologic hydrocortisone replacement therapy with stress supplementation was received after 32 of 33 (97%) courses of treatment. Adrenal function was assessed in 32 of 33 (97%) and AI occurred in 25 of 33 (76%, 95% confidence interval = 58-89). No predictive factor of AI was identified after hormonal treatment. No drug regimen was found to be safe. The two patients who developed an acute adrenal crisis presented to the emergency room within the days (between 2 and 7) following weaning off of hormonal treatment. They were the youngest children of the cohort, and both received prednisolone. SIGNIFICANCE: Adrenal insufficiency is frequent and can potentially lead to an adrenal crisis in this population. This study highlights the necessity of hydrocortisone replacement therapy until AI has been excluded in a patient who has received hormonal therapy to treat infantile spasms. As such, routine laboratory assessment of adrenal function should be done in all patients.

Risk of adrenal insufficiency following intra-articular or periarticular corticosteroid injections among children with chronic arthritis.

Objectives Intra-articular and/or periarticular corticosteroid injection (IACI) is a common procedure in pediatric rheumatology. Despite many adult studies demonstrating a significant risk of adrenal insufficiency (AI) following the procedure, very little evidence is available in the pediatric literature regarding this risk. The main goal of this study is to evaluate the prevalence of AI in children with chronic arthritis following IACI. Methods This is a retrospective study including children aged 0-18 years who had an IACI from June 2017 to July 2019. An 8:00 morning cortisol (8MC) sample was drawn around two weeks after the injection, and an ACTH 1mcg stimulation test was performed if morning cortisol level was low. AI was defined as an 8MC under 50 nmol/L or an abnormal ACTH stimulation test. Risks factors for AI and its duration were assessed. Results Sixty patients were included in this study. AI prevalence was 30% with 18 of 60 affected patients. The corticosteroid dose injected was statistically associated with the development of AI. Median duration of AI was 181 days for the nine patients who were followed up until resolution of AI. Four patients developed symptoms of AI, namely fatigue (2 of 4), nausea (2 of 4) and abdominal pain (3 of 4). None were hospitalized or died. Conclusions In this cohort of children with chronic arthritis who had an IACI, we found a high prevalence of AI. Monitoring and counseling of such complication is warranted until further evidence is available.

Somatic GPR101 Duplication Causing X-Linked Acrogigantism (XLAG)-Diagnosis and Management.

CONTEXT: Recent reports have proposed that sporadic or familial germline Xq26.3 microduplications involving the GPR101 gene are associated with early-onset X-linked acrogigantism (XLAG) with a female preponderance. CASE DESCRIPTION: A 4-year-old boy presented with rapid growth over the previous 2 years. He complained of sporadic headaches and had coarse facial features. His height Z-score was +4.89, and weight Z-score was +5.57. Laboratory testing revealed elevated serum prolactin (185 µg/L; normal, <18 µg/L), IGF-1 (745 µg/L; normal, 64-369 µg/L), and fasting GH > 35.0 µg/L. Magnetic resonance imaging demonstrated a homogenous bulky pituitary gland (18 × 15 × 13 mm) without obvious adenoma. A pituitary biopsy showed hyperplastic pituitary tissue with enlarged cords of GH and prolactin cells. Germline PRKAR1A, MEN1, AIP, DICER1, CDKN1B, and somatic GNAS mutations were negative. Medical management was challenging until institution of continuous sc infusion of short-acting octreotide combined with sc pegvisomant and oral cabergoline. The patient remains well controlled with minimal side effects 7 years after presentation. His phenotype suggested XLAG, but his peripheral leukocyte-, saliva-, and buccal cell-derived DNA tested negative for microduplication in Xq26.3 or GPR101. However, DNA isolated from the pituitary tissue and forearm skin showed duplicated dosage of GPR101, suggesting that he is mosaic for this genetic abnormality. CONCLUSIONS: Our patient is the first to be described with somatic microduplication leading to typical XLAG phenotype. This patient demonstrates that a negative test for Xq26.3 microduplication or GPR101 duplication on peripheral blood DNA does not exclude the diagnosis of XLAG because it can result from a mosaic mutation affecting the pituitary.

Programme to provide Quebec infants with free vitamin D supplements failed to encourage participation or adherence.

AIM: The aim of this study was to evaluate the uptake of a free vitamin D infant prescription programme and to determine the incidence of nutritional rickets. METHODS: This was a retrospective cohort study of infants from Quebec, Canada, involving term infants born between 1998 and 2008 and covered by the public insurance programme. Data were extracted from the Quebec Pregnancy Cohort. Predictors of programme participation were identified through logistic regression. RESULTS: A total of 123 018 infants were eligible, and the mean annual prevalence of supplemental vitamin D exposure was 17.9 ± 5.6%. The median age for obtaining the first bottle was 36 days and half only obtained one bottle of 50 doses. Mothers with higher socio-economic status, those who lived as a couple, older mothers or a prescription by a paediatrician significantly increased the odds of obtaining vitamin D. There was a decline in programme participation over time (OR 0.89/year, 95% CI = 0.88-0.90). The incidence of rickets was 23.9 cases per 100 000 live births, with an annual increase of 1.12 cases/year (95% CI = 1.01-1.24). CONCLUSION: Without educational measures, a free prescription programme for vitamin D failed to encourage participation or adherence. Moreover, participation decreased with time. New strategies, including educational support, need to be developed to increase vitamin D supplementation rates.

Glucose-responsive insulin and glucagon delivery (dual-hormone artificial pancreas) in adults with type 1 diabetes: a randomized crossover controlled trial.

BACKGROUND: Most patients with type 1 diabetes do not achieve their glycemic targets. We aimed to assess the efficacy of glucose-responsive insulin and glucagon closed-loop delivery for controlling glucose levels in adults with type 1 diabetes. METHODS: We conducted a randomized crossover trial involving 15 adults with type 1 diabetes, comparing standard insulin-pump therapy with dual-hormone, closed-loop delivery. Patients were admitted twice to a clinical research facility and received, in random order, both treatments. Each 15-hour visit (from 1600 to 0700) included an evening exercise session, followed by a medium-sized meal, a bedtime snack and an overnight stay. During visits that involved closed-loop delivery, basal insulin and glucagon miniboluses were delivered according to recommendations based on glucose sensor readings and a predictive dosing algorithm at 10-minute intervals. During visits involving standard insulin-pump therapy (control visits), patients used conventional treatment. RESULTS: Dual-hormone closed-loop delivery increased the percentage of time for which patients' plasma glucose levels were in the target range (median 70.7% [interquartile range (IQR) 46.1%-88.4%] for closed-loop delivery v. 57.3% [IQR 25.2%-71.8%] for control, p = 0.003) and decreased the percentage of time for which plasma glucose levels were in the low range (bottom of target range [< 4.0 mmol/L], 0.0% [IQR 0.0%-3.0%] for closed-loop delivery v. 10.2% [IQR 0.0%-13.0%] for control, p = 0.01; hypoglycemia threshold [< 3.3 mmol/L], 0.0% [IQR 0.0%-0.0%] for closed-loop delivery v. 2.8% [IQR 0.0%-5.9%] for control, p = 0.006). Eight participants (53%) had at least 1 hypoglycemic event (plasma glucose < 3.0 mmol/L) during standard treatment, compared with just 1 participant (7%) during closed-loop treatment (p = 0.02). INTERPRETATION: Dual-hormone, closed-loop delivery guided by advanced algorithms improved short-term glucose control and reduced the risk of hypoglycemia in a group of 15 adults with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01297946.