School Attendance Among Pediatric Oncology Patients During the COVID-19 Pandemic in Ontario, Canada.

Supporting schooling for current and past pediatric oncology patients is vital to their quality of life and psychosocial recovery. However, no study has examined the perspectives toward in-person schooling among pediatric oncology families during the COVID-19 pandemic. In this online survey study, we determined the rate of and attitudes toward in-person school attendance among current and past pediatric oncology patients living in Ontario, Canada during the 2020-2021 school year. Of our 31-family cohort, 23 children (74%) did attend and 8 (26%) did not attend any in-person school during this time. Fewer children within 2 years of treatment completion attended in-person school (5/8; 62%) than those more than 2 years from treatment completion (13/15; 87%). Notably, 22 of 29 parents (76%) felt that speaking to their care team had the greatest impact compared to other potential information sources when deciding about school participation, yet 13 (45%) were unaware of their physician's specific recommendation regarding whether their child should attend. This study highlights the range in parental comfort regarding permitting in-person schooling during the COVID-19 pandemic. Pediatric oncologists should continue to address parental concerns around in-person school during times of high transmission of COVID-19 and potentially other communicable diseases in the future.

A Pediatric Investigators Collaborative Network on Infections in Children (PICNIC) multi-centre Canadian descriptive analysis of Haemophilus influenzae bacteremia in children: Emerging serotypes.

Background: There has been dramatic reduction in Haemophilus influenzae serotype b (Hib) since introduction of Hib vaccines, but children still experience serious invasive Haemophilus influenzae (Hi) disease caused by various serotype and non-typeable bacteria. The object of this study was to describe the serotype distribution and clinical spectrum of Hi bacteremia in children admitted to Canadian hospitals. Methods: All children with Hi bacteremia admitted 2013 through 2017 to 10 centres across Canada were included. Demographic, clinical, treatment and outcome data were collected. Results: Haemophilus influenzae bacteremia occurred in 118 children of median age 12 months (inter-quartile range: 7-48 months). Forty-three (36%) isolates were non-typeable (NTHi) and 8 were not typed. Of the 67 typeable (THi), Hia (H. influenzae serotype a) (n=36, 54%), Hif (serotype f) (n=19, 26%) and Hib (serotype b) (n=9, 13%) dominated. The THi was more likely than NTHi bacteremia to present as meningitis (p<0.001), particularly serotype a (p=0.04) and less likely to present as pneumonia (p<0.001). Complicated disease (defined as intensive care unit admission, need for surgery, long-term sequelae or death) occurred in 31 (26%) cases and were more likely to have meningitis (p<0.001) than were those with uncomplicated disease. Conclusion: In the era of efficacious conjugate Hib vaccines, NTHi, Hia and Hif have emerged as the leading causes of invasive Hi in Canadian children, with Hia being most likely to result in meningitis and complicated disease. A vaccine for all NTHi and THi would be ideal, but knowledge of the current disease burden from circulating strains will inform prioritization of vaccine targets.

Lessons learned and new strategies for success: Evaluating the Implementation of Competency-Based Medical Education in Queen's Pediatrics.

Objectives: In 2017, Queen's University launched Competency-Based Medical Education (CBME) across 29 programs simultaneously. Two years post-implementation, we asked key stakeholders (faculty, residents, and program leaders) within the Pediatrics program for their perspectives on and experiences with CBME so far. Methods: Program leadership explicitly described the intended outcomes of implementing CBME. Focus groups and interviews were conducted with all stakeholders to describe the enacted implementation. The intended versus enacted implementations were compared to provide insight into needed adaptations for program improvement. Results: Overall, stakeholders saw value in the concept of CBME. Residents felt they received more specific feedback and monthly Competence Committee (CC) meetings and Academic Advisors were helpful. Conversely, all stakeholders noted the increased expectations had led to a feeling of assessment fatigue. Faculty noted that direct observation and not knowing a resident's previous performance information was challenging. Residents wanted to see faculty initiate assessments and improved transparency around progress and promotion decisions. Discussion: The results provided insight into how well the intended outcomes had been achieved as well as areas for improvement. Proposed adaptations included a need for increased direct observation and exploration of faculty accessing residents' previous performance information. Education was provided on the performance expectations of residents and how progress and promotion decisions are made. As well, "flex blocks" were created to help residents customize their training experience to meet their learning needs. The results of this study can be used to inform and guide implementation and adaptations in other programs and institutions.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children.

OBJECTIVE: To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. DESIGN: Multicentre retrospective cohort study. SETTING: 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. PATIENTS: Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). MAIN OUTCOME MEASURE: Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. RESULTS: We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45-9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. CONCLUSION: We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

INTRODUCTION: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited. METHODS: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes. RESULTS: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage. CONCLUSION: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.

Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study.

BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time. METHODS: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement. RESULTS: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 µg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%). INTERPRETATION: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.

Infants hospitalized for acute COVID-19: disease severity in a multicenter cohort study.

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)).    Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: • A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. • For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: • One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. • Infants had half the odds of older children of having severe or critical disease.

Dedicated Assessors: description of an innovative education intervention to facilitate direct observation in the clinical setting.

BACKGROUND: The Department of Pediatrics at Queen's University undertook a pilot project in July 2017 to increase the frequency of direct observations (DO) its residents received without affecting the patient flow in a busy hospital-based pediatric ambulatory care clinic. Facilitating DO for authentic workplace-based assessments is essential for assessing resident's core competencies. The purpose of this study was to pilot an innovative education intervention to address the challenge of implementing DO in the clinical setting. METHODS: The project allowed for staff physicians to act as "dedicated assessors" (DA), a faculty member who was scheduled to conduct direct observations of trainees' clinical skills, while not acting as the attending physician on duty. At the end of the project, focus group interviews were conducted with faculty and residents, and thematic analysis was completed. RESULTS: Participants reported an increase in the overall quality of feedback received during the observations performed by a DA, with more specific feedback and a broader focus of assessment. There seemed to be little disruption to patient care. Some residents described the observations as anxiety-provoking. CONCLUSIONS: Overall, this project provides insight into an educational approach that medical residency programs can apply to increase the frequency of workplace-based DO and boost the quality of feedback residents receive while maintaining the flow of already busy ambulatory care clinics.

CONTEXTE: En juillet 2017, le département de pédiatrie de l'Université Queen's a lancé un projet pilote visant à augmenter la fréquence des observations directes (OD) dont faisaient l'objet ses résidents sans affecter le flux de patients dans une clinique achalandée de soins pédiatriques ambulatoires. Il est essentiel de faciliter l'OD, permettant une évaluation authentique en milieu de travail, afin d'évaluer les compétences fondamentales des résidents. L'objectif de cette étude était de piloter une intervention éducative novatrice pour relever le défi de la mise en place de l'OD dans le cadre clinique. MÉTHODES: Le projet permettait aux médecins d'agir en tant qu'« évaluateurs attitrés ¼ (ÉA) : c'est-à-dire un membre du corps professoral chargé de l'observation directe des compétences cliniques des apprenants alors qu'il n'était pas le médecin traitant de service. Une analyse thématique a été réalisée sur la base d'entrevues de groupe menées avec le corps professoral et les résidents à la fin du projet. RÉSULTATS: Les participants ont signalé une augmentation de la qualité générale de la rétroaction reçue au cours des observations effectuées par un ÉA, notamment des commentaires plus précis et une évaluation plus complète. Il semble y avoir eu peu de perturbations dans les soins aux patients. Certains résidents ont décrit les observations comme étant anxiogènes. CONCLUSIONS: Dans l'ensemble, ce projet donne un aperçu d'une approche éducative qui peut être appliquée dans le cadre des programmes de résidence en médecine dans le but d'augmenter la fréquence des OD en milieu de travail et d'améliorer la qualité de la rétroaction reçue par les résidents sans perturber le flux de patients dans les cliniques de soins ambulatoires déjà très achalandées.

Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of the current landscape of invasive meningococcal disease in children.

BACKGROUND: Immunizations have led to a decrease in the incidence of invasive meningococcal disease (IMD) in Canada, but this infection still leads to significant morbidity and mortality. OBJECTIVES: The purpose of this study was to determine the burden of illness and management of IMD in paediatric hospitals. METHODS: Data were collected on all cases of IMD in eight paediatric hospitals from 2013 to 2017. RESULTS: There were 17 cases of IMD. Three of eight hospitals had no cases. Just over half of the cases were serogroup B (n=9); a quarter (n=4) were serogroup W; less than a quarter (n=3) were serogroup Y; and one was unknown. Two infected children were not started on antibiotics until day one and day five after the initial blood culture was collected, but had uneventful recoveries. Six cases required admission to intensive care units; two died. Six cases had probable or proven meningitis. Thrombocytopenia was documented in seven cases. All cases had elevated C-reactive protein levels. Seven children received more than seven days of antibiotics; of these seven, only two had complications that justified prolonged therapy (subdural empyema and septic knee). Six cases had a central line placed. CONCLUSION: IMD is now rare in Canadian children, but about one-third of the cases in our study required treatment in the intensive care unit and two died. Clinicians appear to not always be aware that a five to seven-day course is adequate for uncomplicated cases of bacteremia or meningitis.

Just the Facts: Methicillin-resistant Staphylococcus aureus and soft tissue abscess in the emergency department.

Soft tissue abscess used to be an easy emergency department (ED) presentation: perform an incision and drainage (I + D) and discharge your patient. Times have changed. Methicillin-resistant Staphylococcus aureus (MRSA) is now a major cause of soft tissue abscess in ED patients. MRSA is, by definition, resistant to cloxacillin and cephalosporins. Almost all Canadian strains are susceptible to vancomycin and linezolid. MRSA strains are variably susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), tetra/doxycycline, and clindamycin, with pooled Canadian clindamycin resistance just over 40%.

Pediatric Investigators Collaborative Network on Infections in Canada Study of Respiratory Syncytial Virus-associated Deaths in Pediatric Patients in Canada, 2003-2013.

Background: Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in children. Mortality rates in previously healthy children hospitalized with RSV are <0.5%, but up to 37% in patients with underlying medical conditions. The objective of this study was to characterize factors associated with deaths among children hospitalized with RSV infection in Canadian pediatric centers. Methods: A retrospective case series of children aged ≤18 years with RSV-associated deaths at centers affiliated with the Pediatric Investigators Collaborative Network on Infections in Canada from 2003­2013, inclusive, was performed [corrected]. Cases were identified using RSV-specific International Classification of Diseases codes to capture deaths where a diagnosis of RSV infection was present. Results: Eleven centers reported 79 RSV-associated deaths. RSV was regarded as primarily responsible for death in 32 cases (40.5%). Median age at death was 11 months (range, <1 month to 16 years). Thirty-nine patients (49.4%) were male. Fourteen patients (17.7%) had no known risk factors for severe RSV infection. Healthcare-associated RSV infections (HAIs) accounted for 29 deaths (36.7%), with RSV judged to be the primary cause of death in 9 of these cases. Conclusions: RSV-associated deaths were predominantly associated with chronic medical conditions and immunocompromised states among infants; however, 1 in 5 deaths occurred among patients with no known risk factors for severe RSV. Mortality associated with HAI accounted for over a third of cases. These findings highlight patient groups that should be targeted for RSV prevention strategies such as infection control practices, immunoprophylaxis, and future vaccination programs.

Disseminated Neonatal Herpes Simplex Virus Type 1 After a Water Birth.

Neonatal herpes simplex virus (NHSV) infections are associated with significant morbidity and mortality. Numerous factors influence the transmission of HSV infection to newborns; however, immersion in water during labor has received very little attention as a possible risk factor despite the increasing popularity of water births. We report a case of disseminated NHSV type 1 infection, possibly acquired during a water birth. The purpose of this report is to alert healthcare providers to this potential route of transmission and to highlight the importance of screening guidelines for HSV before a water birth. Furthermore, it is essential to consider NHSV infection in any febrile infant who is not responding to standard empirical antibiotic management, even in the absence of herpetic lesions.

Clinical characteristics of pediatric patients hospitalized with methicillin-resistant Staphylococcus aureus in Canadian hospitals from 2008 to 2010.

Methicillin-resistant Staphylococcus aureus (MRSA) infections were uncommon in children in Canada until the 1990s. Using a standardized case report form, treating physicians reported children hospitalized due to MRSA infections in Canadian hospitals through the Canadian Pediatric Surveillance Program in a 24-month period (2008 to 2010). Of 155 cases reported, 70% were ≤4 years of age and approximately one-third had an underlying medical condition. The most common clinical infections involved skin and soft tissue (69%), the lower respiratory tract (12%), and bone and joint (10%). Almost one-third had had contact with the health care environment in the previous year and 18% had a known household member with MRSA. Initial therapy with a beta-lactam alone occurred in 65%, while 22% included vancomycin. No child in this cohort died but 14% required admission to the intensive care unit. Of 143 reports of individual isolates, 93% were reported susceptible to trimethoprim-sulfamethoxazole, 63% to clindamycin and 50% to mupirocin. The present study involved only children hospitalized with MRSA infections. It may not be representative of the children treated as outpatients nor children in selected areas of Canada where MRSA infections may be more endemic. Further targeted surveillance to identify risks and treatment practices in these populations may be important.

Jusque dans les années 1990, l'infection par le staphylocoque doré méthicillinorésistant (SARM) était peu courante chez les enfants du Canada. Au moyen d'un formulaire de déclaration de cas standardisé, des médecins traitants ont signalé les enfants hospitalisés à cause d'une infection par le SARM dans les hôpitaux canadiens par l'entremise du Programme canadien de surveillance pédiatrique au cours d'une période de 24 mois (2008 à 2010). Des 155 cas déclarés, 70 % avaient quatre ans ou moins, et environ le tiers présentait un problème de santé sous-jacent. Les infections cliniques les plus courantes touchaient la peau et les tissus mous (69 %), les voies respiratoires inférieures (12 %) ainsi que les os et les articulations (10 %). Près du tiers avait eu des contacts avec le milieu de la santé au cours de l'année précédente, et dans 18 % des cas, un membre de la famille était atteint d'une SARM connue. Chez 65 % des patients, le traitement initial se limitait à une bêta-lactamine, tandis que dans 22 % des cas, il incluait la vancomycine. Aucun enfant de cette cohorte n'est décédé, mais 14 % ont dû être hospitalisés aux soins intensifs. Des 143 déclarations d'isolats individuels, on a signalé que 93 % étaient susceptibles au triméthoprim-sulfaméthoxazole, 63 % à la clin-damycine et 50 % à la mupirocine.La présente étude portait seulement sur les enfants hospitalisés à cause d'une infection par le SARM. Elle n'est peut-être pas représentative des enfants traités en consultations externes ou des enfants de certaines régions du Canada où les infections par le SARM sont peut-être plus endémiques. Il serait peut-être important de poursuivre une surveillance ciblée pour déterminer les risques et les pratiques thérapeutiques au sein de ces populations.

Heterologous expression of cyan and yellow fluorescent proteins from the Kluyveromyces lactis KlMAL21-KlMAL22 bi-directional promoter.

We have identified the Kluyveromyces lactis maltase (KlMAL22) and maltose permease (KlMAL21) intergenic region as a candidate bi-directional promoter for heterologous gene expression. The expressions of cyan and yellow fluorescent proteins from, respectively, the KlMAL22 and KlMAL21 orientations of the promoter, were compared between two promoter variants during growth in media containing glucose, galactose or glycerol. Expression from both orientations of the native promoter was repressed during growth in glucose and galactose and was induced during growth in glycerol. Disruption of a putative Mig1p binding site caused some de-repression of the maltase orientation of the promoter by 48 h of growth in glucose. The KlMAL21-KlMAL22 bi-directional promoter can be used to carry out regulated expression of heterologous gene products.

Genomic and proteomic expression analysis of Leishmania promastigote and amastigote life stages: the Leishmania genome is constitutively expressed.

Leishmania are protozoan parasites that cause a wide spectrum of clinical diseases in humans and are a major public health risk in several countries. Leishmania life cycle consists of an extracellular flagellated promastigote stage within the midgut of a sandfly vector, and a morphological distinct intracellular amastigote stage within macrophages of a mammalian host. This study reports the use of DNA oligonucleotide genome microarrays representing 8160 genes to analyze the mRNA expression profiles of L. major promastigotes and lesion derived amastigotes. Over 94% of the genes were expressed in both life stages. Advanced statistical analysis identified a surprisingly low degree of differential mRNA expression: 1.4% of the total genes in amastigotes and 1.5% in promastigotes. These microarray results demonstrate that the L. major genome is essentially constitutively expressed in both life stages and suggest that Leishmania is constitutively adapted for survival and replication in either the sandfly vector or macrophage host utilizing an appropriate set of genes for each vastly different environment. Quantitative proteomics, using the isotope coded affinity tag (ICAT) technology and mass spectrometry, was used to identify L. infantum promastigote and axenic amastigote differentially expressed proteins. Of the 91 distinct proteins identified, 8% were differentially expressed in the amastigote stage, 20% were differentially expressed in the promastigote stage, and the remaining 72% were considered constitutively expressed. The differential expression was validated by the identification of previously reported stage specific proteins and identified several amastigote and promastigote novel stage specific proteins.