Severe hypoglycaemia in paediatric oncology: characterisation and risk factors.

OBJECTIVES: Primary objective was to describe the cumulative incidence of severe hypoglycaemia in paediatric patients with cancer. Secondary objectives were to determine risk factors for severe hypoglycaemia and to describe its clinical course and management. METHODS: In this single institution retrospective study, for the cumulative incidence cohort, we included cancer diagnosis and hypoglycaemia episodes between June 2018 and November 2021. For the chart review cohort, we included cancer diagnosis January 2009-November 2021 and hypoglycaemia episodes June 2018-November 2021. RESULTS: There were 1237 cancer diagnoses and 142 patients with severe hypoglycaemia in the cumulative incidence cohort. Cumulative incidence at 6 months after cancer diagnosis was 9.4% (95% CI 7.7% to 11.0%). Severe hypoglycaemia incidence significantly increased over time (r=0.77, p=0.004). Independent risk factors were age at diagnosis (HR 0.88, 95% CI 0.85 to 0.91); acute lymphoblastic leukaemia (HR 3.06, 95% CI 2.19 to 4.29) and relapse (HR 9.54, 95% CI 3.83 to 23.76). There were 4672 cancer diagnoses and 267 episodes of severe hypoglycaemia in the chart review cohort. CONCLUSIONS: The cumulative incidence of severe hypoglycaemia 6 months after cancer diagnosis was 9.4%. Severe hypoglycaemia increased over time. Younger patients, those with acute lymphoblastic leukaemia and those with a history of disease relapse, were at higher risk of severe hypoglycaemia.

An Approach to the Evaluation and Management of the Obese Child With Early Puberty.

With the declining age at onset of puberty and increasing prevalence of childhood obesity, early breast development in young obese girls has become a more frequent occurrence. Here, we examine available literature to answer a series of questions regarding how obesity impacts the evaluation and management of precocious puberty. We focus on girls as the literature is more robust, but include boys where literature permits. Suggestions include: (1) Age cutoffs for evaluation of precocious puberty should not differ substantially from those used for nonobese children. Obese girls with confirmed thelarche should be evaluated for gonadotropin-dependent, central precocious puberty (CPP) to determine if further investigation or treatment is warranted. (2) Basal luteinizing hormone (LH) levels remain a recommended first-line test. However, if stimulation testing is utilized, there is a theoretical possibility that the lower peak LH responses seen in obesity could lead to a false negative result. (3) Advanced bone age (BA) is common among obese girls even without early puberty; hence its diagnostic utility is limited. (4) Obesity does not eliminate the need for magnetic resonance imaging in girls with true CPP. Age and clinical features should determine who warrants neuroimaging. (5) BA can be used to predict adult height in obese girls with CPP to inform counseling around treatment. (6) Use of gonadotropin-releasing hormone analogues (GnRHa) leads to increased adult height in obese girls. (7) Obesity should not limit GnRHa use as these agents do not worsen weight status in obese girls with CPP.

Genetic Testing among Children in a Complex Care Program.

Little is known about the pattern of genetic testing and frequency of genetic diagnoses among children enrolled in structured complex care programs (CCPs). Such information may inform the suitability of emerging genome diagnostics for this population. The objectives were to describe the proportion of children with undiagnosed genetic conditions despite genetic testing and measure the testing period, types and costs of genetic tests used. A retrospective analysis of 420 children enrolled in Toronto's Hospital for Sick Children's CCP from January 2010 until June 2014 was conducted. Among those who underwent genetic testing (n = 319; 76%), a random sample of 20% (n = 63) was further analyzed. A genetic diagnosis was confirmed in 48% of those who underwent testing. Those with no genetic diagnosis underwent significantly more genetic tests than those with a confirmed genetic diagnosis [median interquartile range (IQR): six tests (4-9) vs. three tests (2-4), p = 0.002], more sequence-level tests and a longer, more expensive testing period than those with a genetic diagnosis [median (IQR): length of testing period: 4.12 years (1.73-8.42) vs. 0.35 years (0.12-3.04), p < 0.001; genetic testing costs C$8496 ($4399-$12,480) vs. C$2614 ($1605-$4080), p < 0.001]. A genetic diagnosis was not established for 52% of children. Integrating genome-wide sequencing into clinical care may improve diagnostic efficiency and yield in this population.