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Background The performance requirements for hemoglobin (Hb) A1c analysis have been questioned as analytic methods have improved. We developed a statistical simulation that relates error to the clinical utility of an oft-used laboratory test, as a means of assessing test performance expectations. Methods Finite mixture modeling of the Centers for Disease Control and Prevention—National Health and Nutrition Examination Survey (NHANES) 2017–2020 Hb A1c data in conjunction with Monte Carlo sampling were used to model and simulate a population prior to the introduction of error into the results. The impact of error on clinical utility was assessed by categorizing the results using the American Diabetes Association (ADA) diagnostic criteria and assessing the sensitivity and specificity of Hb A1c under various degrees of error (bias and imprecision). Results With the current allowable total error threshold of 6% for Hb A1c measurement, the simulation estimated a worst case between 50% and 60% for both test sensitivity and specificity for the non-diabetic category. Similarly, sensitivity and specificity estimates for the pre-diabetic category were 30% to 40% and 60% to 70%, respectively. Finally, estimates for the diabetic category yielded values of 80% to 90% for sensitivity and >90% for specificity. Conclusions Bias and imprecision greatly affect the clinical utility of Hb A1c for all patient groups. The simulated error demonstrated in this modeling impacts 3 critical applications of the Hb A1c in diabetes management: the capacity to reliably screen, diagnostic accuracy, and utility in diabetes monitoring.

Xiaoshu Cao,1,2 Cristina de Oliveira Francisco,2 T Douglas Bradley,2– 4 Nasim Montazeri Ghahjaverestan,1,2 Susan M Tarlo,3,5,6 Matthew B Stanbrook,3,5 Kenneth R Chapman,3,5 Mark Inman,7 Azadeh Yadollahi1,2 1Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; 2KITE, Toronto Rehabilitation Institute - University Health Network, Toronto, ON, Canada; 3Department of Medicine, University of Toronto, Toronto, ON, Canada; 4Department of Medicine, University Health Network Toronto General Hospital, Toronto, ON, Canada; 5Department of Medicine, University Health Network Toronto Western Hospital, Toronto, ON, Canada; 6Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; 7Faculty of Medicine (Respirology), McMaster University, Hamilton, ON, CanadaCorrespondence: Azadeh Yadollahi, KITE, Toronto Rehabilitation Institute - University Health Network, Room 12-106, 550 University Avenue, Toronto, ON, M5G 2A2, Canada, Email azadeh.yadollahi@uhn.caRationale: Obstructive sleep apnea (OSA) is highly prevalent among patients with asthma, suggesting a pathophysiological link between the two, but a mechanism for this has not been identified.Hypothesis: Among patients with asthma, those with OSA will have greater overnight increases in thoracic fluid volume and small airways narrowing than those without OSA.Methods: We enrolled 19 participants with asthma: 9 with OSA (apnea-hypopnea index (AHI) ≥ 10) and 10 without OSA (AHI < 10). All participants underwent overnight polysomnography. Before and after sleep, thoracic fluid volume was measured by bioelectrical impedance and small airways narrowing was primarily assessed by respiratory system reactance at 5Hz using oscillometry.Results: Patients with asthma and OSA (OSA group) had a greater overnight increase in thoracic fluid volume by 120.5 mL than patients without OSA (non-OSA group) (164.4 ± 44.0 vs 43.9 ± 47.3 mL, p=0.006). Compared to the non-OSA group, the OSA group had greater overnight decrease in reactance at 5Hz (− 1.08 ± 0.75 vs 0.21 ± 0.27 cmH2O/L/s, p=0.02), and overnight increase in reactance area (14.81 ± 11.09 vs − 1.20 ± 2.46 cmH2O/L, p=0.04), frequency dependence of resistance (1.02 ± 0.68 vs 0.05 ± 0.18 cmH2O/L/s, p=0.04), and resonance frequency (2.80 ± 4.14 vs − 1.42 ± 2.13 cmH2O/L/s, p=0.04).Conclusion: Patients with asthma and co-existing OSA had greater overnight accumulation of fluid in the thorax in association with greater small airways narrowing than those without OSA. This suggests OSA could contribute to worsening of asthma at night by increasing fluid accumulation in the thorax.Keywords: asthma, obstructive sleep apnea, small airway narrowing, thoracic fluid volume

Background Primary hyperparathyroidism may present in a myriad of manners, varying from an incidental asymptomatic biochemical finding to gastrointestinal, psychiatric, renal, and bone manifestations. While hyperparathyroidism remains a rare diagnosis in the pediatric population, the initial approach to diagnosis and management of hypercalcemia in children is imperative for the general pediatrician. Herein, we describe an adolescent who presented with a lytic bone lesion and severe, symptomatic hypercalcemia due to primary hyperparathyroidism. Case presentation A 14-year-old male presented with vomiting, constipation, abdominal pain, and lethargy. He had an elevated total corrected calcium of 4.3 mmol/L. He was found to have a large pelvic lytic tumor consistent with a brown tumor due to primary hyperparathyroidism. He received pharmacologic therapy for stabilization of his hypercalcemia, including intravenous saline, intravenous bisphosphonates, and calcitonin. He subsequently received definitive therapy via parathyroidectomy and his post-operative course was complicated by hungry bone syndrome. Long-term follow-up has found full resolution of the lytic lesion and restored calcium homeostasis. Conclusions We present this case to highlight the possible presentations of hypercalcemia and hyperparathyroidism that are essential for a general pediatrician to recognize to ensure prompt diagnosis and management. Evaluation for hypercalcemia should be considered in patients with suggestive symptoms and physical exam findings. To our knowledge, this patient represents the first reported pediatric case of a pelvic brown tumor in an adolescent. While the multi-systemic complications of hyperparathyroidism may be quite severe, swift and appropriate management may mitigate these clinical outcomes.

Context.—Glycemic control requires accurate blood glucose testing. The extent of hematocrit interference is difficult to assess to assure quality patient care.Objective.—To predict the effect of patient hematocrit on the performance of a glucose meter and its corresponding impact on insulin-dosing error.Design.—Multilevel mixed regression was conducted to assess the extent that patient hematocrit influences Roche Accu-Chek Inform II glucose meters, using the Radiometer ABL 837 as a reference method collected during validation of 35 new meters. Regression coefficients of fixed effects for reference glucose, hematocrit, an interaction term, and random error were applied to 4 months of patient reference method results extracted from the laboratory information system. A hospital inpatient insulin dose algorithm was used to determine the frequency of insulin dose error between reference glucose and meter glucose results.Results.—Fixed effects regression for method and hematocrit predicted biases to glucose meter results that met the “95% within ±12%” for the US Food and Drug Administration goal, but combinations of fixed and random effects exceeded that target in emergency and hospital inpatient units. Insulin dose errors were predicted from the meter results. Twenty-eight percent of intensive care unit, 20.8% of hospital inpatient, and 17.7% of emergency department results were predicted to trigger a ±1 insulin dose error by fixed and random effects.Conclusions.—The current extent of hematocrit interference on glucose meter performance is anticipated to cause insulin error by 1-dose category, which is likely associated with low patient risk.

Objective To test the null hypothesis that there is no difference in patient cost savings between the telemedicine and traditional face-to-face approach. The second objective was to assess the financial impact on the peripheral healthcare system, as compared with staffing a conventional clinic with "on-site" otolaryngologist. Methods Twenty-one patients were enrolled. To assess "patient-benefit" cost savings, a model was formulated that would utilize a certified nurse practitioner (CNP) to conduct a general otolaryngology clinic at the peripheral site, as compared with having to travel to the tertiary referral center. A "peripheral site-benefit" cost analysis was performed to assess costs of initiating and operating a telemedicine clinic at the peripheral site, compared with having an on-site otolaryngologist. Results The total patient-benefit cost savings would be $182.09 per patient per encounter and $333.22 per patient annually. The fixed cost to the peripheral site to initiate the telemedicine system was $9,895. Two hundred sixty telemedicine encounters would be needed to offset the initial cost, and 537 encounters would be needed to surpass revenue of the conventional clinic. Conclusion A real-time telemedicine otolaryngology clinic provides significant cost savings for both patients and the peripheral healthcare system. This pilot study supports telemedicine as a cost-effective approach to providing general otolaryngology care to rural patients. Level of Evidence 4.

Background: Insulin-mediated pseudoacromegaly is a rarely described pediatric phenotype. We present two patients displaying excessive growth associated with marked acanthosis nigricans, hyperinsulinemia and metabolic dysregulation. Case presentation: Both patients, of First Nations descent, presented with excessive growth – patient one at 3.92 years (height z-score +3.75) and patient two at 9.0 years (height z-score 5.15). Insulin-like growth factor-1 (IGF-1) levels were normal with appropriate growth hormone suppression, yet marked hyperinsulinemia. Prepubescent growth velocities exceeded 9 cm/year, resulting in final adult height predictions exceeding 3 standard deviations (SDs) of predicted. Clinical courses were complicated by type 2 diabetes, marked acanthosis nigricans and long-standing psychosocial distress. Conclusions: Pediatric patients with insulin-mediated pseudoacromegaly are at risk of significant physical, metabolic and psychosocial comorbidities. Unlike adults, the implications in childhood prompt consideration for therapies to decelerate linear growth and avert progression to metabolic dysregulation. Increased recognition of this condition may improve pathophysiological understanding, diagnostic criteria and therapeutic options.

Objective To evaluate diagnostic concordance of a synchronous telemedicine otolaryngology clinic with use of currently available technology. Study design Prospective. Methods Patients in a rural otolaryngology clinic were enrolled in a pilot telemedicine clinic. To assess system fidelity, an on-site and remote (consulting) otolaryngologist conducted simultaneous patient evaluations using streaming telecommunication technology for all aspects of the clinical encounter, including high-definition examination and endoscopic images. Both physicians and patients were blinded and diagnoses recorded. Post-encounter physician surveys and an original patient-centered TeleENT Satisfaction Questionnaire (TESQ) were used to assess overall satisfaction. Results Twenty-one patients were enrolled consecutively. Visual technology was found acceptable in all cases, and audio technology was acceptable in 20 of 21 encounters. Patient satisfaction was 96%, and patients felt comfortable using a telemedicine system in the future. Encounters were not significantly longer than traditional encounters. Physician diagnostic agreement was found in 95% of cases, and the consulting physician indicated that all encounters provided sufficient history, examination, and high-quality images to generate an accurate diagnosis, order additional workup, and/or make an appropriate referral. Conclusion A synchronous otolaryngology telemedicine clinic is comparable to a standard clinic in terms of diagnostic concordance and patient satisfaction when using streaming technology and high-definition images. Using telemedical technology may be a viable way to increase otolaryngology access in remote or underserved areas. With system validity now established, future studies will assess the feasibility of using trained on-site physician extenders (nurse practitioners or physician assistants) to conduct in-person patient encounters with remote otolaryngologist support. Level of evidence 2c. Laryngoscope, 128:1068-1074, 2018.

We report a 17-year-old boy who met most of the major Prader−Willi syndrome (PWS) diagnostic criteria, including infantile hypotonia and poor feeding followed by hyperphagia, early-onset morbid obesity, delayed development, and characteristic facial features. However, unlike many children with PWS, he had spontaneous onset of puberty and reached a tall adult stature without growth hormone replacement therapy. A phenotype-driven genetic analysis using exome sequencing identified a heterozygous microdeletion of 71 kb in size at chr15:25,296,613-25,367,633, genome build hg 19. This deletion does not affect the SNURF-SNRPN locus, but results in the loss of several of the PWS-associated non-coding RNA species, including the SNORD116 cluster. We compared with six previous reports of patients with PWS who carried small atypical deletions encompassing the snoRNA SNORD116 cluster. These patients share similar core symptoms of PWS while displaying some atypical features, suggesting that other genes in the region may make lesser phenotypic contributions. Altogether, these rare cases provide convincing evidence that loss of the paternal copy of the SNORD116 snoRNA is sufficient to cause most of the major clinical features of PWS.

Background: The Canadian Pediatric Society (CPS) has endorsed an algorithm for the screening and immediate management of babies at risk of neonatal hypoglycemia that provides time-dependent glucose concentration action thresholds. The objective of this study was to evaluate the impact of glucose analytic error (bias and imprecision) on the misclassification of glucose meter results from a neonatal intensive care unit (NICU) using the CPS guidelines. Methods: A simulation dataset of true glucose values ( N = 100 000) was derived by finite mixture model analysis of NICU glucose data ( N = 23 749). Bias and imprecision were added to create measured glucose values. The percentages of measured glucose values that were misclassified at CPS action thresholds were determined by Monte Carlo simulation. Results: Measurement biases ranging from −20 to +20 mg/dL combined with coefficients of variation 0% to 20% were evaluated to predict misclassification rates at 32, 36, and 47 mg/dL. The models demonstrated low risk of false normoglycemia—at 5% CV and +10 mg/dL bias: 0.8% to 5% misclassification at the 32 and 47 mg/dL thresholds due to bias. The models demonstrated risk of false hypoglycemia—at 5% CV and −10 mg/dL bias: 3% to 12.5% misclassification at 32 and 47 mg/dL thresholds due to both bias and imprecision. Conclusion: Using CPS action thresholds, the simulation model predicted the proportion of neonates at risk of inappropriate clinical action—both of omission or “failure to treat” and commission or “overtreatment” in response to NICU glucose meter results at specific bias and imprecision values.

Background Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common cause of primary adrenal insufficiency in children. Current guidelines recommend the use of perioperative stress dose (supraphysiologic) glucocorticoids for children with CAH undergoing anesthesia, although a perceived difference in practice patterns among Canadian pediatric subspecialists prompted an assessment of perioperative glucocorticoid administration. Methods We performed a cross-sectional survey of Canadian Pediatric Anesthesia Society (CPAS) and Canadian Pediatric Endocrine Group (CPEG) members via membership email lists to assess reported practice patterns to select clinical scenarios. Results Responses were collected from 49 anesthesiologists and 37 pediatric endocrinologists. Less than half of anesthesiologists reported they would provide stress dose corticosteroids for patients undergoing cystoscopy while a significant majority of pediatric endocrinologists reported they would recommend stress dose corticosteroid administration (45% vs 92% respectively, p

Objectives Despite published clinical practice guidelines in pediatrics for the use of a standardized diabetic ketoacidosis (DKA) protocol, our centre lacked an accepted, evidence-informed protocol for pediatric DKA management. Our primary aim was to attain broad clinical uptake of a DKA order set. Secondary aims included improved standard-of-care DKA management principles regarding fluid, potassium and dextrose administration. Methods A pediatric multidisciplinary collaborative was created to examine evidence for the development and implementation of a DKA order set. A modified plan-do-study-act cycle guided by end-user feedback and early clinical outcomes allowed progressive order-set modifications and hospitalwide implementation. Results We achieved 83% uptake of the order set for patients presenting to our tertiary centre and 67% uptake for patients transferred from peripheral centres. Following the implementation of the DKA order set, we observed improvements in DKA management, which included more appropriate intravenous (IV) replacement fluid rates (30% vs. 55.1%; p=0.03); earlier administration of potassium to IV fluids (66% vs. 93.1%; p=0.006); more appropriate potassium chloride dosing to IV fluid (40% vs. 79.3%; p=0.0007) and earlier addition of IV dextrose (67.4% vs. 93.1%; p=0.009). Conclusions Implementation of a DKA order set in a tertiary hospital required identification of key stakeholders, formation of a multidisciplinary team and the development of an evaluation process. There was an observed increase in physician order-set uptake and DKA management practice improvements. Future goals involve expanding the implementation and evaluation process to provincial regional and remote centres and analyzing the impact on resource utilization.

To evaluate diagnostic concordance of a synchronous telemedicine otolaryngology clinic with use of currently available technology.Prospective.Patients in a rural otolaryngology clinic were enrolled in a pilot telemedicine clinic. To assess system fidelity, an on-site and remote (consulting) otolaryngologist conducted simultaneous patient evaluations using streaming telecommunication technology for all aspects of the clinical encounter, including high-definition examination and endoscopic images. Both physicians and patients were blinded and diagnoses recorded. Post-encounter physician surveys and an original patient-centered TeleENT Satisfaction Questionnaire (TESQ) were used to assess overall satisfaction.Twenty-one patients were enrolled consecutively. Visual technology was found acceptable in all cases, and audio technology was acceptable in 20 of 21 encounters. Patient satisfaction was 96%, and patients felt comfortable using a telemedicine system in the future. Encounters were not significantly longer than traditional encounters. Physician diagnostic agreement was found in 95% of cases, and the consulting physician indicated that all encounters provided sufficient history, examination, and high-quality images to generate an accurate diagnosis, order additional workup, and/or make an appropriate referral.A synchronous otolaryngology telemedicine clinic is comparable to a standard clinic in terms of diagnostic concordance and patient satisfaction when using streaming technology and high-definition images. Using telemedical technology may be a viable way to increase otolaryngology access in remote or underserved areas. With system validity now established, future studies will assess the feasibility of using trained on-site physician extenders (nurse practitioners or physician assistants) to conduct in-person patient encounters with remote otolaryngologist support.2c. Laryngoscope, 128:1068-1074, 2018.

Social determinants of health (SDH) impact clinical outcomes and are often poorly described in research trials. Using a validated tool, SDH dimensions were compared between adolescents enrolled and not enrolled into a large diabetes study. We observed that our study cohort reflected a SDH profile mirroring the eligible population.

BACKGROUND Diabetic ketoacidosis (DKA) is a common clinical presentation in new and previously diagnosed paediatric patients with type 1 diabetes. In contrast to other Canadian tertiary paediatric hospitals, our center lacked a physician-endorsed evidence-informed care pathway for management of DKA. In the absence of a standardized approach to DKA, variability in patient management and outcomes were observed. This project was a quality improvement initiative that sought to develop and pilot a paediatric DKA order set. OBJECTIVES Our primary aim was to attain broad clinical uptake of the order set at our tertiary care center over a 12-month period. Secondary aims included improved standard-of-care DKA management: appropriate fluid bolus volume and maintenance rates; initial potassium management; and timely dextrose supplementation. DESIGN/METHODS A paediatric multidisciplinary collaborative was created to examine evidence for the development and implementation of a DKA order set. Implementation of the order set involved department wide education, targeted end-user education, and quarterly end-user review. A modified plan-do-study-act (PDSA) cycle guided by end-user feedback and early clinical outcomes allowed progressive order set modifications. RESULTS A retrospective chart review of fifty paediatric patients presenting to our center between April 2014 and September 2016 (pre-implementation) was compared to thirty paediatric patients presenting in DKA during the post-implementation phase (September 2016 – September 2017). There were no statistically significant differences in demographic and clinical characteristics between the groups. We achieved 83% uptake of the order set for patients presenting to our tertiary center and 67% uptake for patients transferred from peripheral centers. Improvements in DKA management included: appropriate intravenous (IV) maintenance fluid rates (20% vs. 48.3%, p=0.008), earlier administration of potassium to IV fluids (66% vs. 93.1%, p=0.006); appropriate potassium chloride dosing (40 mmol/L) to IV fluid (40% vs. 79.3%, p=0.0007) and earlier addition of IV dextrose (67.4% vs. 93.1%, p=0.009). No differences in moderate to severe hypokalemia (< 3.0 mmol/L), hypoglycemia ( CONCLUSION Implementation of a DKA order set in a tertiary hospital required identification of key stakeholders, formation of a multidisciplinary team, and the development of an evaluation process. There was an observed increase in physician order set uptake and DKA management practice improvements. Future goals involve expanding the implementation and evaluation process to regional and remote centers and analyzing the impact on resource utilization.

To evaluate the relationship between social determinants of health (SDH) and cardiovascular disease (CVD) risk factors as well as a measure of arterial stiffness in adolescents with type 1 diabetes (T1D).SDH were measured with the validated Ontario Marginalization Index, derived from deidentified postal code data and stratified by quintile (first = least deprived; fifth = most deprived). SDH dimensions included material deprivation; ethnic concentration; and measures of dependency and residential instability. Metabolic control (hemoglobin A1c), cardiovascular risk metrics, and pulse wave velocity, as a measure of arterial stiffness, were related to SDH. Data were evaluated from a cohort of Canadian adolescents within the Adolescent Diabetes Cardiorenal Intervention Trial, a T1D clinical trialA total of 704 participants were evaluated, and significant differences in hemoglobin A1c were evident at the extremes of material deprivation (8.4% vs 9.1% for least vs most deprived, P .01). CVD risk factors were analyzed in 199 participants, with the most deprived reporting significantly less exercise (P = .004) and increased rates of smoking (P = .008). Increased material deprivation was associated with fewer metrics of "ideal" cardiovascular health attained. Arterial stiffness, as measured by pulse wave velocity, was associated positively with age, body mass index z score, and material deprivation.Increased material deprivation was associated with poorer glycemic control. Modifiable, lifestyle-related risk factors for CVD and early arterial wall change are associated with SDH and represent a target for clinical intervention to reduce future CVD burden in adolescents with T1D.

Examining radiation dose in the paediatric population is particularly important due to the vulnerability of paediatric patients (increased radiosensitive tissues and postexposure life-years) and risk for future radiogenic malignancy.To evaluate trends in paediatric computed tomography (CT) use and ionizing radiation exposure using population-based data from Nova Scotia.A retrospective, population-based cohort study of CT use in patients20 years of age, from January 1, 2004 to December 31, 2011, was performed in Nova Scotia. CT examination data were retrieved from a provincial imaging repository. Trends in CT use were described, and both annual and cumulative effective dose exposures were calculated.In total, 29,452 CT events, involving up to 22,867 individuals were retrieved. Overall annual paediatric CT examination rates remained static (range 17.4 to 18.8 per 1000 per year). However, use in children10 years of age decreased by50% (P0.001); this was counterbalanced by a steady increase among 15- to 19-year-olds (P0.0001). Overall, 15.4% of scanned patients underwent ≥2 examinations, of which 58 patients (1.6%) exceeded 50 mSv of exposure.Despite a static rate in CT imaging among the entire cohort, children15 years of age and, particularly, those10 years of age displayed marked reductions in CT use. This may reflect increased awareness of campaigns emphasizing judicious CT use, revised clinical practice guidelines and increased availability of alternative modalities. A small subgroup demonstrated high-dose exposure (50 mSv), and rates in individuals15 years of age steadily increased, suggesting further exposure reduction efforts are necessary.Il est particulièrement important d’examiner les doses de rayonnement dans la population pédiatrique en raison de sa vulnérabilité (augmentation des tissus radiosensibles et années de vie postexposition) et du risque de future tumeur radiogénique.Évaluer les tendances d’utilisation de la tomodensitométrie (TD) en pédiatrie et l’exposition ionisante au moyen de données en population provenant de la Nouvelle-Écosse.Les chercheurs ont réalisé une étude de cohorte rétrospective en population sur l’usage de la TD chez des patients de moins de 20 ans en Nouvelle-Écosse, entre le 1Les chercheurs ont extrait 29 452 TD effectuées auprès de 22 867 personnes. Dans l’ensemble, les taux annuels d’examens TD en pédiatrie sont demeurés inchangés (plage de 17,4 à 18,8 sur 1 000 enfants par année). Cependant, l’utilisation chez les enfants de moins de dix ans a diminué de plus de 50 % (P0,001), ce qui était compensé par une augmentation régulière chez les 15 à 19 ans (P0,0001). Au total, 15,4 % des patients ont subi au moins deux examens, et 58 d’entre eux (1,6 %) ont été exposés à plus de 50 mSv.Malgré un taux inchangé de TD dans l’ensemble de la cohorte, l’utilisation de la TD a beaucoup diminué chez les enfants de moins de 15 ans, et particulièrement ceux de moins de dix ans. Ce résultat reflète peut-être la sensibilisation accrue aux campagnes prônant une utilisation judicieuse de la TD, des guides de pratique clinique révisés et un meilleur accès à d’autres modalités. Un petit sous-groupe a présenté une exposition à de fortes doses (plus de 50 mSv), et les taux chez les personnes de plus de 15 ans augmentaient régulièrement, ce qui démontre la nécessité de poursuivre les efforts pour réduire l’exposition.