Pediatric Intersession: An Upfront Flipped-Classroom Curriculum to Promote Pediatric Clerkship Readiness.

OBJECTIVES: Best practices for content selection, mode of delivery, and timing of pediatric clerkship readiness curricula for medical students have, by and large, not been established. Capitalizing on changes in structure of the clinical clerkships during the COVID-19 pandemic, we created an upfront clerkship readiness curriculum, termed Pediatric Intersession (PI), to replace the existing weekly lecture-based clerkship didactics. METHODS: Our goal was to develop an interactive curriculum with innovative instructional design methodology intended to promote broad foundational pediatric knowledge and clerkship preparedness using case-based learning. We first conducted a needs assessment and crafted curriculum content using guiding principles from the 2019 Council on Medical Student Education in Pediatrics (COMSEP) curriculum. We then organized material into four daily modules prior to the start of the clerkship and employed flipped classroom (FC) methodology. RESULTS: Sixty-six percent of students completed course evaluations, and >90% of the 100 respondents reported that the PI enhanced their clinical learning. Pre-/post-testing demonstrated some knowledge gain following the small-group sessions and there was no change on the National Board of Medical Examiners (NBME) Subject Exam mean scores compared to prior cohorts of students. CONCLUSIONS: The global pandemic provided an opportunity to re-envision our pediatric clerkship didactics content, while also incorporating instructional design methodology preferred by students. Our curriculum promotes a small group-based, interactive approach to clerkship readiness that fosters learning in the clinical environment that can be adapted for various settings. Our evaluation suggests that the transition to a FC readiness curriculum can be done successfully while effectively preparing students for their pediatric clerkship.

Insulin Immunoassay Interference Due to Human Antimouse Antibodies in a Patient With Ketotic Hypoglycemia.

Misinterpretation of common endocrine hormonal immunoassays can distort the clinical picture and lead to unnecessary medical workups. Potential assay inference is important to recognize when the clinical presentation and laboratory evaluation are inconsistent. This is demonstrated by the case of an 18-month-old girl who initially presented with ketotic hypoglycemia and was found on diagnostic fasting evaluation to have the triad of hypoglycemia, inappropriately high insulin levels, and low C-peptide levels-point-of-care glucose 43 mg/dL (2.39 mmol/L) (confirmatory 52 mg/dL [2.89 mmol/L]), insulin 48.1 µIU/mL (334 pmol/L), and C-peptide 0.2 ng/mL (0.07 nmol/L) concerning for factitious insulin (insulin:C-peptide ratio 4.77). On repeat diagnostic fast, insulin assays measured by liquid chromatography-mass spectrometry were incongruent with prior testing by immunoassay, demonstrating a falsely elevated insulin level when measured by immunoassay, likely due to human antimouse antibody interference (HAMA 181 ng/mL). This case represents a diagnostic challenge in which is it imperative to recognize possible immunoassay interference. It is critical to establish the difference between insulin assay interference and factitious insulin through use of alternative laboratory methods as misdiagnosis could lead to the serious implication of Munchausen by proxy resulting in the removal of a child from their home and potentially parents being charged with a crime.

Early identification of a 12-bp tandem duplication in TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK): Clinical characterization and response to bisphosphonate therapy.

INTRODUCTION: Ultra-rare mendelian osteolytic disorders caused by different length in-frame activating duplications within exon 1 of TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK) comprise familial expansile osteolysis (FEO), expansile skeletal hyperphosphatasia (ESH), early-onset familial Paget's disease of bone (PDB2), juvenile Paget's disease 2 (JPD2), and panostotic expansile bone disease (PEBD). FEO typically presents with childhood-onset deafness followed by resorption of permanent dentition, and then appendicular bone pain, fractures, and deformities from progressive focal expansile osteolytic lesions emerging from a background of generalized high bone turnover. An 18-bp duplication in TNFRSF11A has been reported in all kindreds with FEO, whereas a 12-bp duplication was found in the young man with PEBD complicated by a massive jaw tumor. We report the clinical course and successful treatment with bisphosphonates of a girl with the 12-bp duplication yet a skeletal phenotype seemingly milder than PEBD. CASE PRESENTATION AND DISCUSSION: This 10-year-old girl presented for dental and orthodontic treatment and was found to have progressive external tooth root resorption. Speech delay was identified at age 18 months, and audiological evaluation showed both conductive and sensorineural hearing loss subsequently treated with a cochlear implant at age 3 years. Biochemical studies indicated increased bone turnover with elevated urinary N-telopeptide levels and serum alkaline phosphatase in the upper normal range. Low lumbar spine bone mineral density (BMD) was revealed by dual-energy X-ray absorptiometry, but whole-body Technetium-99 m bone scintigraphy was normal. Genetic testing identified the identical de novo 12-bp duplication within exon 1 of TNFRSF11A harbored by the young man with PEBD and massive jaw tumor. Bisphosphonate treatment, initiated with one dose of intravenous zoledronic acid that caused prolonged hypocalcemia, then comprised weekly oral alendronate that decreased bone turnover markers and normalized her BMD. CONCLUSION: Constitutive activation of RANK signaling should be considered a possible cause in any young person with rapid bone turnover, particularly in the context of early-onset deafness and/or root resorption of permanent teeth. Early diagnosis and anti-resorptive treatment, given judiciously to avoid sudden and prolonged hypocalcemia, may prevent further skeletal disease.

A Survey of Patient-Relevant Outcomes in Pediatric Craniopharyngioma: Focus on Hypothalamic Obesity.

Context: Individuals treated for pediatric craniopharyngioma, a rare, grade 1 brain tumor, frequently develop hypothalamic obesity, a complication often recalcitrant to intervention. Although hypothalamic obesity is known to adversely impact quality of life, less is known about how caregivers and patients experience this condition. Objective: Our goal was to examine the approaches that families take towards weight management and the impact on social function in individuals with craniopharyngioma and obesity. Individuals with craniopharyngioma without obesity were included as a comparison. Subjects and Methods: Adult caregivers of children <18y with craniopharyngioma completed a web-based survey posted by a patient advocacy organization between February and July 2020. Questions related to the child's diagnosis, medications, lifestyle modifications, and social function along with research priorities. Descriptive statistics were generated. Linear regression was used to assess the independent effects of obesity and other covariates on social function. Results: Of 106 respondents, 60 (57%) reported their child had obesity at the time of survey completion. In contrast, only 6 (5.7%) had obesity prior to craniopharyngioma diagnosis. A majority (92%) of those with obesity had tried limiting calories or carbohydrates; 31% and 69% found these helpful, respectively. Thirty-eight percent had tried weight loss medications (stimulants, metformin, GLP1R-agonists, and topiramate) and 48% found at least one helpful. Both stimulant and anti-depressant use were reported more frequently with obesity. An index (T-score) reflecting social function was lower in the cohort than a population reference, 41 (SD 11) vs. 50 (SD 10), p<0.001. In a linear model, both older age and obesity were independently associated with greater social impairment. Ninety-four percent of respondents caring for a child with obesity (and 79% of all respondents) identified "improving treatments and prevention for hypothalamic obesity" as a key research priority. Conclusions: Only a minority of individuals with hypothalamic obesity had trialed medication, even though many reported that lifestyle modification was inadequate. Furthermore, social function was significantly impaired overall in survivors compared to a reference cohort, and even more so in individuals with obesity. These findings highlight the opportunity to improve social functioning as an additional potential benefit of improved treatments for hypothalamic obesity.

Experience With Store-and-Forward Consultations in Providing Access to Pediatric Endocrine Consultations in Low- and Middle-Income Countries.

Pediatric specialists are often unavailable in low- and middle-income countries. As part of multiple professional associations' efforts to improve access to endocrine expertise globally, a pediatric endocrine teleconsultation network was established on a store-and-forward teleconsultation platform to facilitate focused, language-appropriate advice that can be kept for future reference while bypassing real-time video-conferencing, and obviating the need for a scheduled appointment. User information was recorded, and quality statistics on network performance and qualitative evaluation by referring physicians were analyzed. Over a 3-year period, 81 referrers (88% from Haiti) and 13 pediatric endocrinologists registered onto the network and discussed 47 pediatric endocrine cases, exchanging a total of 412 messages for a median of 7 messages (IQR 5, 11) per case. Diagnoses spanned the spectrum of pediatric endocrine disorders. According to referrers, an appropriate expert was consulted and an answer provided sufficiently quickly in 100% of cases. The answer was well-adapted to their environment in 86%, and referrers were able to follow the advice given in 72%. All but one referrer found the advice helpful, it clarified the diagnosis in 88%, assisted with management in 93%, improved patient's symptoms in 77%, improved function in 77%, and was considered cost-saving in 50%. Perceived benefits of the consultations were academic instruction, setting-adapted advice beyond the scope of guidelines or textbooks, and advancement in the diagnostic process. Pediatric endocrine remote store-and-forward consultations in low- and middle-income countries may provide a reasonable alternative to face-to-face visits, providing clinical and educational benefit, and a potential for cost-saving.

Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?

BACKGROUND: Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability. The recommended starting dose of levothyroxine (LT4) is between 10 and 15 µg/kg, an extremely wide range. We hypothesized that a sizable proportion of newborns treated for CH at the higher end of the dosage range become biochemically hyperthyroid at a follow-up visit. METHODS: This study is a retrospective chart review of infants with CH between 2002 and 2012. RESULTS: Of the 104 patients included in this analysis, the average age at diagnosis was 11 days and the average starting dose of LT4 was 12±2.5 µg/kg. At follow-up, 36.5% required a dose reduction because of iatrogenic hyperthyroxinemia, 51% required no dose adjustment and 12.5% required a dose increase due to an elevated thyroid stimulating hormone (TSH). The starting doses of LT4 for those requiring a dose reduction, those not requiring an adjustment and those requiring an increase in the dose were 13.2±2.4, 11.5±2.1 and 10.3±2.6 µg/kg/day, respectively (p≤0.0001). Of the 34% of infants treated with an initial dose of >12.5 µg/day, 57.1% required a dose reduction at follow-up, compared to 26.1% of those whose initial starting dose was ≤12.5 µg/kg/day (p=0.007). CONCLUSIONS: Following the guidelines for initiating therapy for CH, 36.5% of the infants required a dose reduction for iatrogenic hyperthyroxinemia. These infants received a higher dose of LT4 than the infants who either required no adjustment or required an increase in the dose. A narrower range for initial dosing in CH may be appropriate.