Academic Achievement in School-Aged Children with Single Suture Craniosynostosis Over Time.

Introduction: Children with single suture craniosynostosis (SSC) are at risk for neurocognitive problems. The reported magnitude of differences between children with SSC and their normative peers on standardized tests of academic and intellectual ability are small. Evaluation of real-world academic outcomes of these children and its impact on educational resources have not been conducted. Methods: A retrospective cohort study of academic outcomes of children with SSC was conducted using the data from Ontario's Education Quality and Accountability Office (EQAO) standardized provincial reading, writing and mathematics tests. The need for special education was identified by documentation of the child's need for an Identification, Placement, and Review Committee (IPRC). Results: Of 296 eligible children, 42 participated in the study. Half of the children had sagittal synostosis, while the remaining were 10 (24%) unicoronal, 9 (21%) metopic, and 2 (5%) lambdoid synostosis. Thirty-six (86%) underwent operative management. The EQAO scores of operated children with SSC met the provincial academic standards on the Grade 3 and 6 EQAO scores across the 3 academic subjects. Converted grade-matched EQAO scores decreased in reading and writing over time, while math improved. Of the 21 patients with special education data, one child required an IPRC in Grade 3, while an additional four (24%) required an IPRC in Grade 6. Conclusions: Operated children with SSC had average academic performance, however, their needs appeared to change over time. Future studies are needed to evaluate academic difficulties and special education needs as these children progress through grade school.

Introduction: Les enfants ayant une craniosynostose simple (CSS) sont à risque de troubles neurocognitifs. Selon les tests standardisés des capacités scolaires et intellectuelles, les enfants ayant une CSS présentent des différences légères par rapport à leurs homologues en bonne santé. Les résultats scolaires concrets de ces enfants n'ont pas été évalués, ni leurs répercussions sur les ressources pédagogiques. Méthodologie: Les chercheurs ont effectué une étude de cohorte rétrospective des résultats des enfants ayant une CSS aux examens de lecture, d'écriture et de mathématique au moyen des données provinciales standardisées de l'Office de la qualité et de la responsabilité en éducation de l'Ontario (OQRÉO). Les besoins en éducation spécialisée étaient indiqués par un avis du comité d'identification, de placement et de révision (CIPR) au dossier de l'enfant. Résultats: Des 296 enfants admissibles, 42 ont participé à l'étude. La moitié des enfants présentaient une synostose sagittale (scaphocéphalie), tandis que dix (24 %) avaient une synostose unicoronale, neuf (21 %), une synostose métopique (trigonocéphalie), et deux (5 %), une synostose lambdoïde. Au total, 36 (86 %) ont été opérés. Les scores de l'OQRÉO des enfants opérés à cause d'une CSS respectaient les normes scolaires provinciales pour la 3e et la 6e années dans les trois matières scolaires. Les scores de l'OQRÉO convertis en fonction du degré ont diminué en lecture et en écriture au fil du temps, mais se sont améliorés en mathématiques. Des 21 patients sur qui les chercheurs possédaient des données en éducation spécialisée, un enfant a eu besoin d'un avis du CIPR en 3e année, et quatre (24 %), en 6e année. Conclusions: Les enfants opérés à cause d'une CSS avaient une performance scolaire moyenne, mais leurs besoins semblaient évoluer au fil du temps. D'autres études devront être réalisées pour évaluer les problèmes scolaires et les besoins d'éducation spécialisée des enfants au primaire.

Expression and Clinical Correlation of PD-1/PD-L1 and VE1(BRAFp.V600E) in Pediatric Langerhans Cell Histiocytosis.

Background And Objectives: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm with a wide spectrum of clinical presentations. Programmed Cell Death-1 (PD-1) receptor and its ligand (PD-L1) are overexpressed in LCH, but their clinical significance is unknown. We performed a clinical correlation study of PD-1/PD-L1 and VE1(BRAFp.V600E) expression in 131 children with LCH. Methods: A total of 111 samples were tested for PD-1/PD-L1 and 109 for VE1(BRAFp.V600E) mutant protein by immunohistochemistry. Results: PD-1, PD-L1 and VE1(BRAFp.V600E) positivity was observed in 40.5%, 31.53% and 55%, respectively. PD-1/ PD-L1 expression showed no significant effect on the rate of disease reactivations, early response to therapy or late sequelae. The 5-year EFS was not statistically different between patients with PD-1 positive compared to those with PD-1 negative tumours (47.7% vs.58.8%, p=0.17). Similar 5-year EFS rates were also seen in those who were PD-L1 positive compared to PD-L1 negative cases (50.5% vs.55.5%, p=0.61). VE1(BRAFp.V600E) positivity was associated with a significantly higher frequency of risk-organ involvement (p=0.0053), but no significant effect on early response to therapy or rates of reactivations or late sequelae. Conclusions: Our study showed no significant correlation between VE1(BRAFp.V600E) expression, PD-1 and PD-L1 and clinical outcome in pediatric LCH.

Surgical wait times and socioeconomic status in a public healthcare system: a retrospective analysis.

BACKGROUND: One aim of publicly-funded health care systems is to provide equitable access to care irrespective of ability to pay. At the same time, differences in socioeconomic status (SES) are associated with health outcomes and access to care, including waiting times for surgery. In public systems where both high- and low-SES patients use the same resources, low-SES patients may be adversely impacted in surgical waiting times. The purpose of this study was to determine whether a publicly-funded health system can provide equitable access to surgical care across socioeconomic status. METHODS: Patient-level records were obtained from a comprehensive provincially-administered surgical wait time database, encompassing years 2006-2015 and 98% of Ontario hospitals. Patient SES was determined by linking postal code with the Material and Social Deprivation Index. Surgical waiting times (time in days between decision to treat and surgery) accounted for patient-initiated delays in treatment, and regression analysis considered age, SES, rurality, sex, priority level for surgical urgency (assigned by surgeons), surgical subspecialty, number of visits, and procedure year. RESULTS: For the 4,253,305 surgical episodes, the mean wait time was 62.3 (SD 75.4) days. Repeated measures least squares regression analysis showed the least deprived SES quintile waited 3 days longer than the most deprived quintile. Wait times dropped in the initial study period but then increased. The proportion of procedures exceeding wait time access targets remained low at 11-13%. CONCLUSIONS: The least deprived SES quintile waited the longest, although the absolute difference was small. This study demonstrates that publicly-funded healthcare systems can provide equitable access to surgical care across SES.

International variation in evidence-based emergency department management of bronchiolitis: a retrospective cohort study.

OBJECTIVES: We aimed to evaluate the international variation in the use of evidence-based management (EBM) in bronchiolitis. We hypothesised that management consistent with full-EBM practices is associated with the research network of care, adjusted for patient-level characteristics. Secondary objectives were to determine the association between full-EBM and (1) hospitalisation and (2) emergency department (ED) revisits resulting in hospitalisation within 21 days. DESIGN: A secondary analysis of a retrospective cohort study. SETTING: 38 paediatric EDs belonging to the Paediatric Emergency Research Network in Canada, USA, Australia/New Zealand UK/Ireland and Spain/Portugal. PATIENTS: Otherwise healthy infants 2-11 months old diagnosed with bronchiolitis between 1 January 2013 and 31 December, 2013. OUTCOME MEASURES: Primary outcome was management consistent with full-EBM, that is, no bronchodilators/corticosteroids/antibiotics, no chest radiography or laboratory testing. Secondary outcomes included hospitalisations during the index and subsequent ED visits. RESULTS: 1137/2356 (48.3%) infants received full-EBM (ranging from 13.2% in Spain/Portugal to 72.3% in UK/Ireland). Compared with the UK/Ireland, the adjusted ORs (aOR) of full-EBM receipt were lower in Spain/Portugal (aOR 0.08, 95% CI 0.02 to 0.29), Canada (aOR 0.13 (95% CI 0.06 to 0.31) and USA (aOR 0.16 (95% CI 0.07 to 0.35). EBM was less likely in infants with dehydration (aOR 0.49 (95% CI 0.33 to 0.71)), chest retractions (aOR 0.69 (95% CI 0.52 to 0.91)) and nasal flaring (aOR 0.69 (95% CI 0.52 to 0.92)). EBM was associated with reduced odds of hospitalisation at the index visit (aOR 0.77 (95% CI 0.60 to 0.98)) but not at revisits (aOR 1.17 (95% CI 0.74 to 1.85)). CONCLUSIONS: Infants with bronchiolitis frequently do not receive full-EBM ED management, particularly those outside of the UK/Ireland. Furthermore, there is marked variation in full-EBM between paediatric emergency networks, and full-EBM delivery is associated with lower likelihood of hospitalisation. Given the global bronchiolitis burden, international ED-focused deimplementation of non-indicated interventions to enhance EBM is needed.

Significant reduction in hemarthrosis in boys with severe hemophilia A: The China hemophilia individualized low-dose secondary prophylaxis study.

INTRODUCTION: In countries with restricted access to clotting factor concentrates, early implementation of low-dose prophylaxis is recommended over episodic treatment. OBJECTIVE: The objective of this 1-year prospective secondary prophylaxis study was to evaluate the efficacy of a dose/frequency escalating protocol in young boys with hemophilia A in China. METHODS: Boys were started on a low-dose protocol (minimum 10-15 IU/kg of factor VIII [FVIII] twice weekly). Escalation was based on index joint bleeding, swelling/persistent joint swelling, and serial ultrasound (gray scale and color Doppler) examinations of index joints. RESULTS: Thirty-three boys, median age 4.8 years (interquartile range, 3.8-6.1) were enrolled in a 3-month observation period that preceded a 1-year prophylaxis phase. A significant reduction in total bleeding events (43.0%, P = .001), index joint bleeds (53.2%, P = .002), and target index joint bleeds (70.0%, P = 0.02) was observed during the prophylaxis phase. During the prophylaxis period, 40% of target joints resolved. The percentage of boys with zero index joint bleeds increased significantly (P = .004) from 51.5% during the observation phase to 81.8% in last quarter of the prophylaxis phase (months 10-12). There was no progression of arthropathy based on physical examination (Hemophilia Joint Health Score), X-ray, and ultrasound obtained at entry into the prophylaxis phase and at study exit. The median FVIII consumption over the prophylaxis phase was 1786 IU/kg/y. CONCLUSION: A low-dose, individualized prophylaxis protocol, guided by individual bleeding profiles and serial assessment of joint status, enables escalation of treatment intensity in boys with severe hemophilia A, leading to a significant reduction in bleeding events and reduction in target joint bleeding.

Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma: Secondary Analysis of a Randomized Clinical Trial.

Importance: Despite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has remained stable, and IV magnesium therapy is independently associated with hospitalization. Objective: To examine the association between IV magnesium therapy administered in the emergency department (ED) and subsequent hospitalization among pediatric patients with refractory acute asthma after adjustment for patient-level variables. Design, Setting, and Participants: This post hoc secondary analysis of a double-blind randomized clinical trial of children with acute asthma treated from September 26, 2011, to November 19, 2019, at 7 Canadian tertiary care pediatric EDs was conducted between September and November 2020. In the randomized clinical trial, 816 otherwise healthy children aged 2 to 17 years with Pediatric Respiratory Assessment Measure (PRAM) scores of 5 points or higher after initial therapy with systemic corticosteroids and inhaled albuterol with ipratropium bromide were randomly assigned to 3 nebulized treatments of albuterol plus either magnesium sulfate or 5.5% saline placebo. Exposures: Intravenous magnesium sulfate therapy (40-75 mg/kg). Main Outcomes and Measures: The association between IV magnesium therapy in the ED and subsequent hospitalization for asthma was assessed using multivariable logistic regression analysis. Analyses were adjusted for year epoch at enrollment, receipt of IV magnesium, PRAM score after initial therapy and at ED disposition, age, sex, duration of respiratory distress, previous intensive care unit admission for asthma, hospitalizations for asthma within the past year, atopy, and receipt of oral corticosteroids within 48 hours before arrival in the ED, nebulized magnesium, and additional albuterol after inhaled magnesium or placebo, with site as a random effect. Results: Among the 816 participants, the median age was 5 years (interquartile range, 3-7 years), 517 (63.4%) were boys, and 364 (44.6%) were hospitalized. A total of 215 children (26.3%) received IV magnesium, and 190 (88.4%) of these children were hospitalized compared with 174 of 601 children (29.0%) who did not receive IV magnesium. Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 (odds ratio [OR], 22.67; 95% CI, 6.26-82.06; P < .001) and from 2017 to 2019 (OR, 4.19; 95% CI, 1.99-8.86; P < .001), use of additional albuterol (OR, 5.94; 95% CI, 3.52-10.01; P < .001), and increase in PRAM score at disposition (per 1-U increase: OR, 2.24; 95% CI, 1.89-2.65; P < .001). In children with a disposition PRAM score of 3 or lower, receipt of IV magnesium therapy was associated with hospitalization (OR, 8.52; 95% CI, 2.96-24.41; P < .001). Conclusions and Relevance: After adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization. This association also existed among children with mild asthma at ED disposition. Evidence of a benefit of IV magnesium regarding hospitalization may clarify its use in the treatment of refractory pediatric asthma. Trial registration: ClinicalTrials.gov: NCT01429415.

Feasibility of implementation of CARD™ for school-based immunizations in Calgary, Alberta: a cluster trial.

BACKGROUND: Negative experiences with school-based immunizations can contribute to vaccine hesitancy in youth and adulthood. We developed an evidence-based, multifaceted and customizable intervention to improve the immunization experience at school called the CARD™ (C-Comfort, A-Ask, R-Relax, D-Distract) system. We evaluated the feasibility of CARD™ implementation for school-based immunizations in Calgary, Canada. METHODS: In a mixed methods study, two Community Health Centres providing immunization services, including 5 schools each with grade 9 students (aged approximately 14 years), were randomized to CARD™ or control (usual care). In the CARD™ group, public health staff and students were educated about coping strategies prior to immunization clinics. Clinics were organized to reduce fear and to support student's choices for coping strategies. Public health staff in the CARD™ group participated in a focus group discussion afterwards. We sought a recruitment rate of 80% for eligible schools, an external stakeholder focus group (e.g., school staff) with 6 or more individuals, 85% of individual injection-related data acquisition (student and immunizer surveys), and 80% absolute agreement between raters for a subset of data that were double-coded. Across focus groups, we examined perceptions of acceptability, appropriateness, feasibility and fidelity of CARD™. RESULTS: Nine (90%) of eligible schools participated. Of 219 students immunized, injection-related student and immunizer data forms were acquired for 195 (89.0%) and 196 (89.5%), respectively. Reliability of data collection was high. Fifteen public health and 5 school staff participated in separate focus groups. Overall, attitudes towards CARD™ were positive and compliance with individual components of CARD™ was high. Public health staff expressed skepticism regarding the value of student participation in the CARD™ system. Suggestions were made regarding processes to refine implementation. CONCLUSION: While most outcome criteria were satisfied and overall perceptions of implementation outcomes were positive, some important challenges and opportunities were identified. Feedback is being used to inform a large cluster trial that will evaluate the impact of CARD™ during school-based immunizations. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov ( NCT03948633 ); Submitted April 24, 2019.

A Practical, One-Clinic Visit Protocol for Pharmacokinetic Profile Generation with the ADVATE myPKFiT Dosing Tool in Severe Hemophilia A Subjects.

Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72-hour washout and 5 to 11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout, 6-sampling time point PPK protocol with a no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol in persons with severe hemophilia A (SHA) receiving ADVATE. A total of 39 inhibitor-negative males with SHA (factor VIII activity [FVIII:C] < 2%) were enrolled in a prospective sequential design PK study. Participants completed a washout, 6-sampling time point PPK protocol as well as a no-washout, reverse 2-sampling time point protocol, with samples taken during a single 3-hour clinic visit 24 hours post home infusion of FVIII and then 3 hours post infusion in clinic. FVIII:C levels were analyzed by one-stage and chromogenic assays; blood group and von Willebrand factor antigen (VWF:Ag) were determined; and PK parameters were analyzed using the ADVATE myPKFiT dosing tool. There was moderate to almost perfect agreement for the PK parameters obtained with the 2- and the 6- point PPK protocols using a one-stage FVIII:C assay and a substantial to almost perfect agreement using a chromogenic FVIII:C assay. Significant associations between specific PK parameters and blood group and VWF:Ag were observed. The no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol can be used in the routine clinical setting since it demonstrates sufficient accuracy compared with the more demanding and less practical washout, 6-sampling time point PPK protocol in persons with SHA receiving ADVATE.

Long-Term Visual Outcomes and Clinical Course of Patients With Peters Anomaly.

PURPOSE: To present long-term clinical and visual outcomes of patients with Peters anomaly. METHODS: The charts of all patients diagnosed with Peters anomaly from January 2000 to December 2012 were reviewed retrospectively. Peters anomaly was classified as type I (with no lens involvement) or type II (presence of keratolenticular adhesions or cataract), with further severity grading to mild, moderate, and severe disease depending on corneal opacity location and size. Mild cases were observed. Moderate cases were managed with pupillary dilation either pharmacologically or surgically. Penetrating keratoplasty (PKP) was reserved for more severe opacity. The main outcome measures were final best spectacle-corrected visual acuity (BSCVA), incidence of glaucoma, graft survival, and nystagmus rates. RESULTS: Sixty eyes of 40 patients were included in the study. The median age of patients at presentation was 0.5 ± 20.7 months (range, 0.0-111.0 months), with a mean follow-up time of 75.8 ± 52.9 months (range, 12.1-225.3 months). Overall, final best spectacle-corrected visual acuity ranged from 0.1 logMAR to no light perception with 33 eyes (55.9%) achieving vision of 1.0 logMAR or better. Clear grafts at the last follow-up were obtained in 67.6% (25/37) of transplanted eyes, 76.0% (19/25) in Peters type I, and 50.0% (6/12) in Peters type II (P = 0.11). The probability of a clear graft at 10 years was 74.2% and 38.9% for type I and type II, respectively. Glaucoma was diagnosed in 33.3% eyes, 90.0% of which occurred after PKP. Nystagmus was highly associated with PKP intervention, occurring in 81.1% (30/37) of eyes undergoing PKP compared with 34.8% (8/23) of eyes with no PKP (P = 0.0003). CONCLUSIONS: Visual rehabilitation in Peters anomaly remains a challenge, but outcomes can be optimized using a comprehensive clinical management algorithm according to disease severity.

Désinfection à la chaleur humide des respirateurs N95, inactivation du SRAS-CoV-2 et effets sur les propriétés des respirateurs.

CONTEXTE: La demande sans précédent de respirateurs N95 durant la pandémie de maladie à coronavirus 2019 (COVID-19) a entraîné une pénurie mondiale. Nous avons validé un protocole de décontamination rapide et économique répondant aux normes réglementaires afin de permettre la réutilisation sûre de ce type de masque. MÉTHODES: Nous avons contaminé 4 modèles courants de respirateurs N95 avec le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) et avons évalué l'inactivation virale après une désinfection de 60 minutes à 70 °C et à une humidité relative de 0 %. De même, nous avons étudié l'efficacité de la désinfection thermique, à une humidité relative allant de 0 % à 70 %, de masques contaminés à Escherichia coli. Enfin, nous avons examiné des masques soumis à de multiples cycles de désinfection thermique: nous avons évalué leur intégrité structurelle à l'aide d'un microscope à balayage, et leurs propriétés protectrices au moyen des normes du National Institute for Occupational Safety and Health des États-Unis relatives à la filtration particulaire, à la résistance respiratoire et à l'ajustement. RÉSULTATS: Une seule désinfection thermique a suffi pour que le SRAS-CoV-2 ne soit plus décelable sur les masques étudiés. En ce qui concerne les masques contaminés à E. coli, une culture de 24 heures a révélé que la bactérie n'était pratiquement plus décelable sur les masques désinfectés à 70 °C et à une humidité relative de 50 %, contrairement aux masques non désinfectés (densité optique à une longueur d'onde de 600 nm : 0,02 ± 0,02 contre 2,77 ± 0,09; p < 0,001), mais qu'elle persistait sur les masques traités à une humidité relative moindre. Les masques ayant subi 10 cycles de désinfection avaient toujours des fibres de diamètre semblable à celui des fibres des masques non traités, et ils répondaient encore aux normes d'ajustement, de filtration et de résistance respiratoire. INTERPRÉTATION: La désinfection thermique a réussi à décontaminer les respirateurs N95 sans compromettre leur intégrité structurelle ni modifier leurs propriétés. Elle pourrait se faire dans les hôpitaux et les établissements de soins de longue durée avec de l'équipement facilement accessible, ce qui réduirait la pénurie de N95.

Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency Department: A Randomized Clinical Trial.

Importance: While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown. Objective: To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy. Design, Setting, and Participants: A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed. Interventions: Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408). Main Outcomes and Measures: The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes. Results: Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, -4.2%; absolute risk difference 95% [exact] CI, -11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, -0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, -1.32 to 1.67]; P = .82); oxygen saturation (-0.04% [95% CI, -0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, -1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%). Conclusions and Relevance: Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT01429415.

Causes of death in pediatric neuro-oncology: the sickkids experience from 2000 to 2017.

PURPOSE: Primary benign and malignant central nervous system (CNS) tumors are the most frequent solid tumors in the pediatric age and represent the leading cause of death by cancer in children in high income countries. However, information regarding specific causes of death in this population is still limited. The objective of this work was to investigate mortality in a large cohort of children diagnosed at our institution. METHODS: We identified patients consecutively diagnosed with CNS tumor and treated at a Tertiary Care Canadian Children's Hospital between January 2000 and December 2017. Patient charts were reviewed and different variables such as tumor diagnosis, location, gender, age at diagnosis, age at death and cause of death collected. RESULTS: Of 1274 patients, 306 (24%) succumbed to their disease. Mortality rate varied significantly according to tumor subtype, ranging from 3.1% in low grade glioma (LGG) to 97.8% in diffuse intrinsic pontine glioma (DIPG). While high grade gliomas (HGG) and DIPG represented only 6.3 and 7.1% of total diagnoses respectively, together they accounted for 49.3% of total deaths (n = 151). Median time from diagnosis to death was 15 months (4 days to 15 years) and shortest for DIPG (11 months). Two hundred and ninety patients (94.8%) died as a result of the primary disease, 4 of treatment-related toxicity, two patients' deaths were unrelated to the primary disease (idiopathic encephalopathy and domestic fire) whereas 10 patients succumbed to a secondary malignancy. Of note, four of these ten patients had a confirmed underlying cancer predisposition syndrome. CONCLUSION: Disease progression is the main cause of death in children with brain tumor, while treatment related mortality is low in this series. Research should continue to focus on improving treatment strategies for patients whose prognosis remains dismal.

Effect of moist heat reprocessing of N95 respirators on SARS-CoV-2 inactivation and respirator function.

BACKGROUND: Unprecedented demand for N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic has led to a global shortage of these masks. We validated a rapidly applicable, low-cost decontamination protocol in compliance with regulatory standards to enable the safe reuse of N95 respirators. METHODS: We inoculated 4 common models of N95 respirators with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and evaluated viral inactivation after disinfection for 60 minutes at 70°C and 0% relative humidity. Similarly, we evaluated thermal disinfection at 0% to 70% relative humidity for masks inoculated with Escherichia coli. We assessed masks subjected to multiple cycles of thermal disinfection for structural integrity using scanning electron microscopy and for protective functions using standards of the United States National Institute for Occupational Safety and Health for particle filtration efficiency, breathing resistance and respirator fit. RESULTS: A single heat treatment rendered SARS-CoV-2 undetectable in all mask samples. Compared with untreated inoculated control masks, E. coli cultures at 24 hours were virtually undetectable from masks treated at 70°C and 50% relative humidity (optical density at 600 nm wavelength, 0.02 ± 0.02 v. 2.77 ± 0.09, p < 0.001), but contamination persisted for masks treated at lower relative humidity. After 10 disinfection cycles, masks maintained fibre diameters similar to untreated masks and continued to meet standards for fit, filtration efficiency and breathing resistance. INTERPRETATION: Thermal disinfection successfully decontaminated N95 respirators without impairing structural integrity or function. This process could be used in hospitals and long-term care facilities with commonly available equipment to mitigate the depletion of N95 masks.

International Practice Patterns of Antibiotic Therapy and Laboratory Testing in Bronchiolitis.

BACKGROUND AND OBJECTIVES: International patterns of antibiotic use and laboratory testing in bronchiolitis in emergency departments are unknown. Our objective is to evaluate variation in the use of antibiotics and nonindicated tests in infants with bronchiolitis in 38 emergency departments in Pediatric Emergency Research Networks in Canada, the United States, Australia and New Zealand, the United Kingdom and Ireland, and Spain and Portugal. We hypothesized there would be significant variation, adjusted for patient characteristics. METHODS: We analyzed a retrospective cohort study of previously healthy infants aged 2 to 12 months with bronchiolitis. Variables examined included network, poor feeding, dehydration, nasal flaring, chest retractions, apnea, saturation, respiratory rate, fever, and suspected bacterial infection. Outcomes included systemic antibiotic administration and urine, blood, or viral testing or chest radiography (CXR). RESULTS: In total, 180 of 2359 (7.6%) infants received antibiotics, ranging from 3.5% in the United Kingdom and Ireland to 11.1% in the United States. CXR (adjusted odds ratio [aOR] 2.3; 95% confidence interval 1.6-3.2), apnea (aOR 2.2; 1.1-3.5), and fever (aOR 2.4; 1.7-3.4) were associated with antibiotic use, which did not vary across networks (P = .15). In total, 768 of 2359 infants (32.6%) had ≥1 nonindicated test, ranging from 12.7% in the United Kingdom and Ireland to 50% in Spain and Portugal. Compared to the United Kingdom and Ireland, the aOR (confidence interval) results for testing were Canada 5.75 (2.24-14.76), United States 4.14 (1.70-10.10), Australia and New Zealand 2.25 (0.86-5.74), and Spain and Portugal 3.96 (0.96-16.36). Testing varied across networks (P < .0001) and was associated with suspected bacterial infections (aOR 2.12; 1.30-2.39) and most respiratory distress parameters. Viral testing (591 of 768 [77%]) and CXR (507 of 768 [66%]) were obtained most frequently. CONCLUSIONS: The rate of antibiotic use in bronchiolitis was low across networks and was associated with CXR, fever, and apnea. Nonindicated testing was common outside of the United Kingdom and Ireland and varied across networks irrespective of patient characteristics.

IVMP+IVIG raises platelet counts faster than IVIG alone: results of a randomized, blinded trial in childhood ITP.

Children with immune thrombocytopenia (ITP) rarely suffer from life-threatening bleeds (eg, intracranial hemorrhage). In such settings, the combination of IV methylprednisolone (IVMP) with IV immune globulin (IVIG) is used to rapidly increase platelet counts (PCs). However, there are no controlled data to support using combination therapy over IVIG alone. We conducted a randomized, double-blind, placebo-controlled study to evaluate the rapidity of the PC increment and associated adverse events (AEs) between 2 regimens: A (IV placebo) and B (IVMP 30 mg/kg), both given over 1 hour, followed in both cases by IVIG (Gamunex 10%) 1 g/kg over 2-3 hours in children 1-17 years old with primary ITP and PCs <20 × 109/L in whom physicians had decided to treat with IVIG. Thirty-two children (ages: median, 8 years; range, 1.2-17.5 years) with a mean baseline PC of 9.2 × 109/L participated. Eighteen were randomized to regimen A and 14 to regimen B. By 8 hours after initiating therapy, 55% of all children had a PC ≥20 × 109/L (no group difference). By 24 hours, mean PCs were 76.9 × 109/L (B) vs 55 × 109/L (A) (P = .06; P = .035 when adjusted for intergroup differences in patient ages). No patient experienced severe bleeding/unexpected severe AEs. There were statistically fewer IVIG-related headaches in the group receiving combination therapy (P = .046). Our findings show a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations. This trial was registered at www.clinicaltrials.gov as #NCT00376077.

Evaluating Curricular Modules in the Care of Children With Medical Complexity: A Mixed-Methods Randomized Controlled Trial.

OBJECTIVE: Children with medical complexity (CMC) are a growing population, yet training in complex care varies across pediatric residency programs. The purpose of this study was 1) to evaluate the effectiveness of a curriculum for pediatric residents in improving performance in a simulated clinical scenario, and 2) to explore residents' perceived self-efficacy in caring for CMC. METHODS: A randomized controlled trial was conducted supplemented by qualitative inquiry. Pediatric residents from 2 residency programs were randomly assigned to participate in interactive modules on: 1) clinical assessment, care planning, and technological dependency or 2) noncomplex care topics. The primary outcome was mean score on an Observed Structured Clinical Examination (OSCE) of tracheostomy care. Semistructured interviews were conducted postintervention and analyzed using qualitative content analysis. RESULTS: Ninety-four eligible residents were randomized. Residents who attended all modules and the OSCE and consented to participate (intervention [n = 20] and control [n=24]) were included in the final analysis. At baseline, few (9%) reported being comfortable caring for CMC. There was no significant difference in mean OSCE score between intervention and control groups (39.0 ± 1.1 vs 38.0 ± 1.0, P = .48). Qualitative analysis revealed 3 emerging themes related to resident self-efficacy: building a system of care, navigating uncertainty, and professional identity formation. CONCLUSIONS: A standardized complex care curriculum delivered in a classroom setting did not lead to improved performance in an OSCE station despite increased resident-reported self-efficacy in approaching care for CMC. These findings highlight the need for multidimensional educational interventions and assessments in complex care.

An eHealth decision-support tool to prioritize referral practices for genetic evaluation of patients with Wilms tumor.

Over 10% of children with Wilms tumor (WT) have an underlying cancer predisposition syndrome (CPS). Cognizant of increasing demand for genetic evaluation and limited resources across health care settings, there is an urgent need to rationalize genetic referrals for this population. The McGill Interactive Pediatric OncoGenetic Guidelines study, a Canadian multi-institutional initiative, aims to develop an eHealth tool to assist physicians in identifying children at elevated risk of having a CPS. As part of this project, a decisional algorithm specific to WT consisting of five tumor-specific criteria (age <2 years, bilaterality/multifocality, stromal-predominant histology, nephrogenic rests, and overgrowth features) and universal criteria including features of family history suspicious for CPS and congenital anomalies, was developed. Application of the algorithm generates a binary recommendation-for or against genetic referral for CPS evaluation. To evaluate the algorithm's sensitivity for CPS identification, we retrospectively applied the tool in consecutive pediatric patients (n = 180) with WT, diagnosed and/or treated at The Hospital for Sick Children (1997-2016). Odds ratios were calculated to evaluate the strengths of associations between each criterion and specific CPS subtypes. Application of the algorithm identified 100% of children with WT and a confirmed CPS (n = 27). Age <2 years, bilaterality/multifocality, and congenital anomalies were strongly associated with pathogenic variants in WT1. Presence of >1 overgrowth feature was strongly associated with Beckwith-Wiedemann syndrome. Stromal-predominant histology did not contribute to CPS identification. We recommend the incorporation of the WT algorithm in the routine assessment of children with WT to facilitate prioritization of genetic referrals in a sustainable manner.

Utility of Soft Tissue Lateral Neck Radiographs in the Emergency Department: The 5-Year Experience of a Large Tertiary Care Pediatric Hospital.

INTRODUCTION: Although retropharyngeal infection (RPI) may present with voice change, drooling, fever, and a toxic appearance, diagnosis based on symptoms alone is unreliable. As incidence is increasing in children and drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus are becoming more common, we decided to assess the clinical utility of lateral neck radiography. OBJECTIVE: The aim of this study was to review the experience of a large tertiary care pediatric emergency department (ED) in using lateral soft tissue neck radiographs in the diagnosis of suspected RPI. METHODS: A retrospective analysis of all lateral soft tissue neck radiograph reports from 2011 to 2015 in conjunction with a review of patients' charts to describe clinical and laboratory findings, disposition, and final diagnosis was performed. Patients aged 31 days to 18 years who presented to the ED with suspicion of RPI were included. RESULTS: Review of 366 radiographic reports revealed that 46 were positive for RPI, 286 were negative, and 34 indeterminate. A final discharge diagnosis of RPI was made in 38 patients. Lateral neck radiographs had a sensitivity of 84.3% and a specificity of 93.7% for diagnosing RPI. In triage, most patients had no fever (264, 72.1%), stridor (356, 97%), drooling (348, 95%), or voice change (342, 93%). Surgical intervention occurred in 15 patients (39.5%) with a final diagnosis of RPI. CONCLUSIONS: Lateral neck radiography is useful for diagnosis of RPI in the ED with good sensitivity and specificity. Additional imaging is to be considered at the behest of physician's clinical judgment.

Posttransplant Lymphoproliferative Disorder in Pediatric Patients: Characteristics of Disease in EBV-seropositive Recipients.

BACKGROUND: Patients at greatest risk of posttransplant lymphoproliferative disorder (PTLD) are those who acquire primary Epstein-Barr virus (EBV) infection after solid organ transplantation. The incidence of PTLD among patients who are EBV-seropositive before transplant is lower, and little is known about the differences in presentation and outcome of this population. We describe the characteristics of EBV-seropositive transplant recipients (R+) who developed PTLD and compare survival outcomes with EBV-seronegative recipients (R-). METHODS: A hospital-based registry was used to identify all patients with biopsy-proven PTLD for the period 2000-2014. Characteristics and outcomes were compared between R+ and R- patients with PTLD. RESULTS: Sixty-nine patients were included, among which 20 (29.0%) were R+ and 49 (71.0%) were R-. Multiorgan transplant patients accounted for 25% of PTLD cases in R+ patients, while accounting for only 2.1% of all transplants during the study period. There was no difference in PTLD site between R+ and R- patients. PTLD among R+ individuals occurred during the second year after transplant (median: 1.92; range: 0.35-3.09 y) compared with during the first year for R- individuals (median: 0.95; range: 0.48-2.92 y; P = 0.380). There was a trend for a higher overall mortality among R+ individuals (log rank: 0.09). PTLD-related mortality did not differ between R+ and R- individuals (log rank: 0.17). CONCLUSIONS: PTLD among R+ individuals was more likely to occur among multiorgan recipients, and there was a tendency for poorer outcomes at 1 and 5 years after the diagnosis of PTLD.