Association of Psychological Resilience, Cognitive Reserve, and Brain Reserve with Post-Concussive Symptoms in Children with Mild Traumatic Brain Injury and Orthopedic Injury: An A-CAP Study.

Protective factors, including psychological resilience, cognitive reserve, and brain reserve, may be positively associated with recovery after pediatric mild traumatic brain injury (mTBI) but have yet to be studied concurrently. We sought to examine these factors as moderators of post-concussive symptoms (PCS) in pediatric mTBI compared to mild orthopedic injury (OI). Participants included 967 children (633 mTBI, 334 OI) aged 8-16.99 years, recruited from 5 Canadian pediatric emergency departments as part of a prospective longitudinal cohort study. At 10 days post-injury, psychological resilience was measured using the Connor-Davidson Resilience Scale (CD-RISC) and brain reserve was measured using total brain volume (TBV) derived from structural magnetic resonance imaging . Cognitive reserve was measured at 3 months post-injury using IQ scores from the Wechsler Abbreviated Scale of Intelligence-Second Edition. Cognitive and somatic PCS were measured using child and parent ratings on the Health and Behavior Inventory, completed weekly for 3 months and bi-weekly to 6 months. Analyses involved generalized least squares regression models using restricted cubic splines. Covariates included age at injury, sex, racialized identity, material and social deprivation, pre-injury migraine and concussion history, and retrospective pre-injury PCS. Psychological resilience moderated group differences in parent-reported PCS. At 30 days post-injury, estimated group differences in parent-reported cognitive and somatic PCS (mTBI > OI) were larger at higher (75th percentile) resilience scores (Est = 2.25 [0.87, 3.64] and Est = 2.38 [1.76, 3.00], respectively) than at lower (25th percentile) resilience scores (Est = 1.44 [0.01, 2.86] and Est = 2.08 [1.45, 2.71], respectively). Resilience did not moderate group differences in child-reported PCS but was negatively associated with child-reported PCS in both groups (ps < .001). Brain reserve (i.e., TBV) also moderated group differences, but only for parent-reported somatic PCS (p = .018). Group difference (mTBI > OI) at 30 days were larger at smaller (25th percentile) TBV (Est = 2.78 [2.17, 3.38]) than at larger (75th percentile) TBV (Est = 1.95 [1.31, 2.59]). TBV was not associated with parent-reported cognitive PCS or child-reported PCS. IQ did not moderate PCS in either group but had a significant non-linear association in both groups with child-reported somatic PCS (p = .018) and parent-reported PCS (p < .001), with higher PCS scores at both lower and higher IQs. These findings suggest that higher resilience predicts fewer PCS, but less strongly after mTBI than OI; greater brain reserve may reduce the effect of mTBI on somatic PCS; and cognitive reserve has an unexpected curvilinear association with PCS across injury types. The results highlight the importance of protective factors as predictors of recovery and potential targets for intervention following pediatric mTBI.

Association of Fructosamine Levels With Glycemic Control in Children With Type 1 Diabetes as Determined by Continuous Glucose Monitoring: Results From the CGM TIME Trial.

OBJECTIVE: Our aim in this study was to determine the correlation between serum fructosamine and average blood glucose, as measured by continuous glucose monitoring (CGM) in children with type 1 diabetes. METHODS: Ninety-seven blood samples were collected from 70 participants in the Timing of Initiation of continuous glucose Monitoring in Established pediatric diabetes (CGM TIME) Trial. Each eligible participant had 3 weeks of CGM data with at least 60% CGM adherence before blood collection. Ordinary least-squares linear regression incorporating restricted cubic splines was used to determine the association between fructosamine levels and mean blood glucose. RESULTS: An association was found between fructosamine and mean blood glucose, with an F statistic of 9.543 (p<0.001). Data were used to create a formula and conversion chart for calculating mean blood glucose from fructosamine levels for clinical use. CONCLUSIONS: There is a complex relationship between average blood glucose, as determined by CGM and fructosamine. Fructosamine levels may be clinically useful for assessing short-term glycemic control when CGM is not available.

Postconcussive Symptoms After Early Childhood Concussion.

Importance: Research on postconcussive symptoms (PCS) following early childhood concussion has been hindered by a lack of measures suitable for this age group, resulting in a limited understanding of their evolution in young children. Objective: To document PCS in the first 3 months after early childhood concussion using a developmentally appropriate measure. Design, Setting, and Participants: This cohort study used data collected at 3 Canadian and 1 US urban pediatric emergency departments (EDs) and 8 Canadian daycares from December 2018 to December 2022 as part of the Kids' Outcomes and Long-Term Abilities (KOALA) project, a prospective, multicenter, longitudinal cohort study. Participants included children aged 6 to 72 months with early childhood concussion or orthopedic injury (OI) or uninjured children from the community to serve as controls. Data were analyzed from March 2023 to January 2024. Exposure: Concussion sustained between ages 6 and 72 months. Main Outcomes and Measures: Primary outcomes were cognitive, physical, behavioral and total PCS assessed prior to injury (retrospectively), acutely (within 48 hours), and at 10 days, 1 month, and 3 months after injury or recruitment through caregiver observations using the Report of Early Childhood Traumatic Injury Observations & Symptoms inventory. Group comparisons were analyzed using ordinal regression models. Results: The study included 303 children (mean [SD] age, 35.8 [20.2] months; 152 [50.2%] male). Of these, 174 children had a concussion (mean [SD] age, 33.3 [19.9] months), 60 children had an OI (mean [SD] age, 38.4 [19.8] months) and 69 children were uninjured controls (mean [SD] age, 39.7 [20.8] months). No meaningful differences were found between the concussion and comparison groups in retrospective preinjury PCS. Significant group differences were found for total PCS at the initial ED visit (concussion vs OI: odds ratio [OR], 4.33 [95% CI, 2.44-7.69]; concussion vs control: OR, 7.28 [95% CI, 3.80-13.93]), 10 days (concussion vs OI: OR, 4.44 [95% CI, 2.17-9.06]; concussion vs control: OR, 5.94 [95% CI, 3.22-10.94]), 1 month (concussion vs OI: OR, 2.70 [95% CI, 1.56-4.68]; concussion vs control: OR, 4.32 [95% CI, 2.36-7.92]), and 3 months (concussion vs OI: OR, 2.61 [95% CI, 1.30-5.25]; concussion vs control: OR, 2.40 [95% CI, 1.36-4.24]). Significant group differences were also found for domain-level scores (cognitive, physical, behavioral) at various time points. Conclusions and Relevance: In this early childhood cohort study, concussion was associated with more PCS than OIs or typical development up to 3 months after injury. Given the limited verbal and cognitive abilities typical of early childhood, using developmentally appropriate manifestations and behaviors is a valuable way of tracking PCS and could aid in concussion diagnosis in young children.

Do preinjury life events moderate the outcomes of mild traumatic brain injuries in children? An A-CAP Study.

OBJECTIVE: To examine preinjury life events as moderators of postconcussive symptoms (PCS) and quality of life (QoL) in children with pediatric mild traumatic brain injury (mTBI) versus orthopedic injury (OI). METHODS: Participants were 633 children with mTBI and 334 with OI, ages 8-16.99, recruited from 5 pediatric emergency departments and followed for 6 months postinjury as part of a prospective cohort study. Preinjury life events were measured retrospectively using the Child and Adolescent Survey of Experiences, PCS using the Health and Behavior Inventory (HBI) and Post-Concussion Symptom Interview (PCS-I), and QoL using the Pediatric Quality of Life Inventory (PedsQL). Analyses involved longitudinal regression using restricted cubic splines, with group, positive and negative life events, and time as primary predictors. Covariates included age, sex, race, socioeconomic status, preinjury history (i.e., headache, migraine, previous concussion), and parent-rated retrospective PCS-I, HBI, and PedsQL scores. RESULTS: PCS and QoL were worse after mTBI than OI, but group differences declined with time (all p < .001). Group differences in PCS were larger at higher levels of positive life events, which predicted lower PCS (p= .03 to p < .001) and higher QoL (p = .048) after OI but not after mTBI. Negative life events predicted worse PCS and QoL in both groups (p = .002 to p < .001). CONCLUSIONS: Preinjury positive life events moderate outcomes after pediatric injury, with a protective effect seen in OI but not in mTBI. Negative life events are consistently associated with worse outcomes regardless of injury type.

Laboratory stewardship perceptions and testing patterns at a pediatric tertiary care center.

BACKGROUND: Despite stewardship efforts, laboratory testing overuse persists across medicine. OBJECTIVES: To understand laboratory stewardship perceptions and testing patterns at a tertiary care pediatric hospital so that we could identify potential improvement opportunities. METHODS: An electronic survey exploring laboratory stewardship was sent to all pediatric medicine resident and staff physicians. Laboratory testing data were also assessed for patterns of testing and overuse. RESULTS: The survey response rate was 54% (43/80). The results indicated good familiarity with stewardship but poor familiarity with testing specifics (eg, cost). A mobile reference application was the most preferred quality improvement intervention, and online modules were the least desired. Overuse was apparent, with as many as 53% of laboratory tests being repeated within 7 days and only half of repeated tests subsequently yielding abnormal results. CONCLUSIONS: Altogether, the data we collated demonstrated poor understanding of laboratory stewardship and substantial repeat testing with few abnormal results. These study findings suggest that laboratory stewardship is lacking at our center, and that multiple improvement opportunities exist.

The association between symptom burden and processing speed and executive functioning at 4 and 12 weeks following pediatric concussion.

OBJECTIVES: Symptoms and cognition are both utilized as indicators of recovery following pediatric concussion, yet their interrelationship is not well understood. This study aimed to investigate: 1) the association of post-concussion symptom burden and cognitive outcomes (processing speed and executive functioning [EF]) at 4 and 12 weeks after pediatric concussion, and 2) the moderating effect of sex on this association. METHODS: This prospective, multicenter cohort study included participants aged 5.00-17.99 years with acute concussion presenting to four Emergency Departments of the Pediatric Emergency Research Canada network. Five processing speed and EF tasks and the Post-Concussion Symptom Inventory (PCSI; symptom burden, defined as the difference between post-injury and retrospective [pre-injury] scores) were administered at 4 and 12 weeks post-concussion. Generalized least squares models were conducted with task performances as dependent variables and PCSI and PCSI*sex interaction as the main predictors, with important pre-injury demographic and injury characteristics as covariates. RESULTS: 311 children (65.0% males; median age = 11.92 [IQR = 9.14-14.21 years]) were included in the analysis. After adjusting for covariates, higher symptom burden was associated with lower Backward Digit Span (χ2 = 9.85, p = .043) and Verbal Fluency scores (χ2 = 10.48, p = .033) across time points; these associations were not moderated by sex, ps ≥ .20. Symptom burden was not associated with performance on the Coding, Continuous Performance Test, and Color-Word Interference scores, ps ≥ .17. CONCLUSIONS: Higher symptom burden is associated with lower working memory and cognitive flexibility following pediatric concussion, yet these associations were not moderated by sex. Findings may inform concussion management by emphasizing the importance of multifaceted assessments of EF.

Autonomic Cardioregulatory Function Does Not Correlate With Symptom Improvement After Concussion in Children and Adolescents.

Although there is significant variability in the manifestations of persisting post-concussive symptoms (PPCS), autonomic dysfunction has been reported to contribute to PPCS and could serve as a biomarker of recovery. The objective of this study was to evaluate cardiac autonomic reflexes and autonomic function after concussion injury comparing those with prolonged concussion symptoms to those without. This is a case-control study where a non-referred population of concussed children or adolescent participants were enrolled from the Emergency Department (ED) of the Stollery Children's Hospital, a tertiary pediatric hospital in Edmonton, Alberta, Canada. Children and adolescents 8 through <18 years of age who presented with mild traumatic brain injury were diagnosed with concussion. Our study reported concussion symptoms and standardized clinical cardiac autonomic reflex testing at 4 and 12 weeks after injury. Our findings showed that 28 participants with concussion completed the 4-week follow-up questionnaires, and that 17 (61%) were diagnosed with PPCS. Difficulty concentrating, fatigue, noise sensitivity, light sensitivity, and headache were most commonly reported at baseline among those who were later diagnosed with PPCS. The mean change in heart rate (HR) with head-up tilt was 44.2 bpm (standard deviation [SD] 9.1) in the non-PPCS group and 46.6 bpm (SD 14.1) in the PPCS group at 4 weeks and was not significant in the unadjusted (p = 0.2) or adjusted analysis for age and female sex (p = 0.2). Overall, 70% (19/27) had significant orthostatic tachycardia >40 bpm, but PPCS and non-PPCS groups were similar. Similar results were observed among 23 participants at 12-week follow-up. The median maximum decrease in systolic blood pressure (SBP) with head-up tilt was -26.9 mm Hg (interquartile range [IQR] -32.6, -22.3) in the non-PPCS group and -25.1 mm Hg (IQR -32.2, -18.2) in the PPCS group, and was not significantly different in the unadjusted (p = 0.8) or adjusted (p = 0.8) analysis. Overall, 19 of 26 participants (73%) demonstrated orthostatic hypotension (SBP change >20 mm Hg) with no significant difference between the PPCS and non-PPCS groups. Similar results were observed at 12-week follow-up. In conclusion, cardiac autonomic reflex responses are abnormal in most children and adolescents with a concussion injury at 4- and 12-week follow-up and may reflect ongoing autonomic dysfunction. However, autonomic function did not differentiate PPCS, indicating that reported symptoms are not sensitive to autonomic abnormalities.

Health care impact of implementing a clinical pathway for acute care of pediatric concussion: a stepped wedge, cluster randomised trial.

OBJECTIVES: To test the effects of actively implementing a clinical pathway for acute care of pediatric concussion on health care utilization and costs. METHODS: Stepped wedge, cluster randomized trial of a clinical pathway, conducted in 5 emergency departments (ED) in Alberta, Canada from February 1 to November 30, 2019. The clinical pathway emphasized standardized assessment of risk for persistent symptoms, provision of consistent information to patients and families, and referral for outpatient follow-up. De-identified administrative data measured 6 outcomes: ED return visits; outpatient follow-up visits; length of ED stay, including total time, time from triage to physician initial assessment, and time from physician initial assessment to disposition; and total physician claims in an episode of care. RESULTS: A total of 2878 unique patients (1164 female, 1713 male) aged 5-17 years (median 11.00, IQR 8, 14) met case criteria. They completed 3009 visits to the 5 sites and 781 follow-up visits to outpatient care, constituting 2910 episodes of care. Implementation did not alter the likelihood of an ED return visit (OR 0.77, 95% CI 0.39, 1.52), but increased the likelihood of outpatient follow-up visits (OR 1.84, 95% CI 1.19, 2.85). Total length of ED stay was unchanged, but time from physician initial assessment to disposition decreased significantly (mean change - 23.76 min, 95% CI - 37.99, - 9.52). Total physician claims increased significantly at only 1 of 5 sites. CONCLUSIONS: Implementation of a clinical pathway in the ED increased outpatient follow-up and reduced the time from physician initial assessment to disposition, without increasing physician costs. Implementation of a clinical pathway can align acute care of pediatric concussion more closely with existing clinical practice guidelines while making care more efficient. TRIAL REGISTRATION: ClinicalTrials.gov NCT05095012.

ABSTRAIT: OBJECTIFS: Mettre à l'essai les effets de la mise en œuvre active d'une voie clinique pour le traitement aigu des commotions cérébrales chez les enfants sur l'utilisation et les coûts des soins de santé. MéTHODES: Essai randomisé en grappes d'une voie clinique, échelonné, mené dans cinq services d'urgence en Alberta, au Canada, du 1 février au 30 novembre 2019. Le cheminement clinique mettait l'accent sur l'évaluation normalisée du risque de symptômes persistants, la fourniture de renseignements uniformes aux patients et aux familles, et l'aiguillage vers un suivi externe. Les données administratives dépersonnalisées ont permis de mesurer six résultats : visites de retour à l'urgence; visites de suivi en clinique externe; durée du séjour à l'urgence, y compris le temps total. le temps entre le triage et l'évaluation initiale du médecin, et le temps entre l'évaluation initiale du médecin et la décision; et le nombre total de demandes de remboursement du médecin dans un épisode de soins. RéSULTATS: Un total de 2878 patients uniques (1164 femmes, 1713 hommes) âgés de 5 à 17 ans (médiane 11,00, IQR 8, 14) répondaient aux critères de cas. Ils ont effectué 3009 visites aux 5 sites et 781 visites de suivi aux soins ambulatoires, ce qui représente 2910 épisodes de soins. La mise en œuvre n'a pas modifié la probabilité d'une visite de retour à l'urgence (RC 0,77, IC à 95 %, 0,39, 1,52), mais a augmenté la probabilité de visites de suivi en clinique externe (RC 1,84, IC à 95 %, 1,19, 2,85). La durée totale du séjour à l'urgence est demeurée inchangée, mais le temps écoulé entre l'évaluation initiale du médecin et la décision a diminué considérablement (changement moyen : -23,76 minutes, IC à 95 %, -37,99, -9,52). Le nombre total de demandes de règlement de médecins a augmenté de façon significative à seulement 1 site sur 5. CONCLUSIONS: La mise en œuvre d'un cheminement clinique à l'urgence a augmenté le suivi des patients externes et réduit le temps entre l'évaluation initiale du médecin et son élimination, sans augmenter les coûts des médecins. La mise en œuvre d'un cheminement clinique peut harmoniser davantage les soins de courte durée en cas de commotion cérébrale pédiatrique avec les lignes directrices de pratique clinique existantes tout en rendant les soins plus efficaces. ENREGISTREMENT D'ESSAI: ClinicalTrials.gov NCT05095012.

Association of Posttraumatic Headache With Symptom Burden After Concussion in Children.

Importance: Headache is the most common symptom after pediatric concussion. Objectives: To examine whether posttraumatic headache phenotype is associated with symptom burden and quality of life 3 months after concussion. Design, Setting, and Participants: This was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study, conducted September 2016 to July 2019 at 5 Pediatric Emergency Research Canada (PERC) network emergency departments. Children aged 8.0-16.99 years presenting with acute (<48 hours) concussion or orthopedic injury (OI) were included. Data were analyzed from April to December 2022. Exposure: Posttraumatic headache was classified as migraine or nonmigraine headache, or no headache, using modified International Classification of Headache Disorders, 3rd edition, diagnostic criteria based on self-reported symptoms collected within 10 days of injury. Main Outcomes and Measures: Self-reported postconcussion symptoms and quality-of-life were measured at 3 months after concussion using the validated Health and Behavior Inventory (HBI) and Pediatric Quality of Life Inventory-Version 4.0 (PedsQL-4.0). An initial multiple imputation approach was used to minimize potential biases due to missing data. Multivariable linear regression evaluated the association between headache phenotype and outcomes compared with the Predicting and Preventing Postconcussive Problems in Pediatrics (5P) clinical risk score and other covariates and confounders. Reliable change analyses examined clinical significance of findings. Results: Of 967 enrolled children, 928 (median [IQR] age, 12.2 [10.5 to 14.3] years; 383 [41.3%] female) were included in analyses. HBI total score (adjusted) was significantly higher for children with migraine than children without headache (estimated mean difference [EMD], 3.36; 95% CI, 1.13 to 5.60) and children with OI (EMD, 3.10; 95% CI, 0.75 to 6.62), but not children with nonmigraine headache (EMD, 1.93; 95% CI, -0.33 to 4.19). Children with migraine were more likely to report reliable increases in total symptoms (odds ratio [OR], 2.13; 95% CI, 1.02 to 4.45) and somatic symptoms (OR, 2.70; 95% CI, 1.29 to 5.68) than those without headache. PedsQL-4.0 subscale scores were significantly lower for children with migraine than those without headache only for physical functioning (EMD, -4.67; 95% CI, -7.86 to -1.48). Conclusions and Relevance: In this cohort study of children with concussion or OI, those with posttraumatic migraine symptoms after concussion had higher symptom burden and lower quality of life 3 months after injury than those with nonmigraine headache. Children without posttraumatic headache reported the lowest symptom burden and highest quality of life, comparable with children with OI. Further research is warranted to determine effective treatment strategies that consider headache phenotype.

A Prospective Cohort Study of the Association Between Preinjury Psychosocial Function and Postconcussive Symptoms in Pediatric Mild Traumatic Brain Injury: An A-CAP Study.

OBJECTIVE: We evaluated the moderating effect of preinjury psychosocial function on postconcussion symptoms for children with mild traumatic brain injury (mTBI). DESIGN, SETTING, AND POPULATION: We conducted a prospective cohort study of children ages 8.0 to 16.9 years with mTBI ( n = 633) or orthopedic injury (OI; n = 334), recruited from 5 pediatric emergency departments from September 2016 to December 2018. MAIN MEASURES: Participants completed baseline assessments within 48 hours of injury, and postconcussion symptoms assessments at 7 to 10 days, weekly to 3 months, and biweekly to 6 months post-injury. Preinjury psychosocial function was measured using parent ratings on the Pediatric Quality of Life Inventory (PedsQL) and the Strengths and Difficulties Questionnaire (SDQ), retrospectively evaluating their child's status prior to the injury. Parent and child ratings on the Health and Behavior Inventory (HBI) (cognitive and somatic subscales) and the Post-Concussion Symptom Interview (PCS-I) were used as measures of postconcussion symptoms. We fitted 6 longitudinal regression models, which included 747 to 764 participants, to evaluate potential interactions between preinjury psychosocial function and injury group as predictors of child- and parent-reported postconcussion symptoms. RESULTS: Preinjury psychosocial function moderated group differences in postconcussion symptoms across the first 6 months post-injury. Higher emotional and conduct problems were significantly associated with more severe postconcussion symptoms among children with mTBI compared with OI. Wald's χ 2 for interaction terms (injury group × SDQ subscales) ranged from 6.3 to 10.6 ( P values <.001 to .043) across parent- and child-reported models. In contrast, larger group differences (mTBI > OI) in postconcussion symptoms were associated with milder hyperactivity (Wald's χ 2 : 15.3-43.0, all P < .001), milder peer problems (Wald's χ 2 : 11.51, P = .003), and higher social functioning (Wald's χ 2 : 12.435, P = .002). CONCLUSIONS: Preinjury psychosocial function moderates postconcussion symptoms in pediatric mTBI, highlighting the importance of assessing preinjury psychosocial function in children with mTBI.

Association Between Early Return to School Following Acute Concussion and Symptom Burden at 2 Weeks Postinjury.

Importance: Determining how the timing of return to school is related to later symptom burden is important for early postinjury management recommendations. Objective: To examine the typical time to return to school after a concussion and evaluate whether an earlier return to school is associated with symptom burden 14 days postinjury. Design, Setting, and Participants: Planned secondary analysis of a prospective, multicenter observational cohort study from August 2013 to September 2014. Participants aged 5 to 18 years with an acute (<48 hours) concussion were recruited from 9 Canadian pediatric emergency departments in the Pediatric Emergency Research Canada Network. Exposure: The independent variable was the number of days of school missed. Missing fewer than 3 days after concussion was defined as an early return to school. Main Outcomes and Measures: The primary outcome was symptom burden at 14 days, measured with the Post-Concussion Symptom Inventory (PCSI). Symptom burden was defined as symptoms status at 14 days minus preinjury symptoms. Propensity score analyses applying inverse probability of treatment weighting were performed to estimate the relationship between the timing of return to school and symptom burden. Results: This cohort study examined data for 1630 children (mean age [SD] 11.8 [3.4]; 624 [38%] female). Of these children, 875 (53.7%) were classified as having an early return to school. The mean (SD) number of days missed increased across age groups (5-7 years, 2.61 [5.2]; 8-12 years, 3.26 [4.9]; 13-18 years, 4.71 [6.1]). An early return to school was associated with a lower symptom burden 14 days postinjury in the 8 to 12-year and 13 to 18-year age groups, but not in the 5 to 7-year age group. The association between early return and lower symptom burden was stronger in individuals with a higher symptom burden at the time of injury, except those aged 5 to 7 years. Conclusions and Relevance: In this cohort study of youth aged 5 to 18 years, these results supported the growing belief that prolonged absences from school and other life activities after a concussion may be detrimental to recovery. An early return to school may be associated with a lower symptom burden and, ultimately, faster recovery.

Does age play a role in fever and neutropenia events and complications: A comparison of adolescents versus younger children with cancer at a tertiary care pediatric hospital, a pilot project.

BACKGROUND: Adolescents and young adults with cancer (AYA) are a complex group of patients. The development of fever and neutropenia (FN) is a potentially lethal complication of chemotherapy. Risk stratification of patients with FN has become increasingly valuable allowing for early intervention and to guide treatment type and duration appropriately. There are risk stratification guidelines that exist, but most are validated in young children with cancer (YCWC). AYA are frequently shown to have more numerous and severe side effects from chemotherapy. AIMS: This study aimed to identify whether age contributes to the incidence and severity of FN. METHODS AND RESULTS: Patients diagnosed with a malignancy in a 5-year period at our institution were included from ages 0-18 years. We reviewed details of their FN events, including duration of hospital admission, source (bacterial/fungal), PICU admission and duration, positive blood cultures and mortality. Adolescents with cancer (AWC) had a trend of being 1.56 times more likely to have FN events (CI 95% 0.936-2.622, p = 0.087). Assessment of the duration of PICU stay showed that AWC were 4.9 times more likely to have longer admissions (CI 95% 0.998-24.067, p = 0.050). There was no significant difference between the two groups in the rate of PICU admission, positive cultures, identification of a bacterial or fungal source, hospital admission duration or mortality from FN. CONCLUSION: This study demonstrated a trend towards AWC being more likely to develop FN events. When such events occur in this group, the severity of them may be heightened as evidenced by longer duration of PICU admission.

The association of age and adverse events of PEG-asparaginase in a pediatric tertiary care hospital; a retrospective review.

BACKGROUND: Pediatric patients have a better survival rate for lymphoid malignancies than adolescents and young adult patients (AYA) and current evidence suggests that asparaginase plays a role in improved response to treatment. This study aimed to evaluate if increasing age as a continuous variable demonstrated increasing toxicities to PEG-asparaginase (PEG-ASP) for those patients treated at a tertiary care pediatric hospital. METHODS: A retrospective chart review from 2007 to 2017 was conducted in the pediatric population at the Children's Hospital of Eastern Ontario (CHEO). Patients having received PEG-ASP were included. Event incidence and risk related to age at diagnosis were assessed through parameter estimates and Wald chi-square analysis. RESULTS: In total, 75 adverse events were observed: 34/186 (18.3%) experienced allergic reactions, 8/186 (4.3%) pancreatitis, 31/186 (16.7%) thrombosis, and 2/186 (1.1%) hemorrhage. One hundred and eighty two patients had complete information for inclusion in our model. A correlation between age at diagnosis and higher risk of allergic reaction (p < .001) and pancreatitis (p < .035) was observed. CONCLUSION: Allergic reaction and pancreatitis following administration of PEG-ASP have a higher risk of occurrence as age of diagnosis increases up to 18 years of age. This includes the lower limit of traditionally defined AYA population of 15-39 and warrants precaution as PEG-ASP is included in older populations treatment regimens at pediatric centers.

Factor structure and measurement invariance of post-concussion symptom ratings on the Health and Behaviour Inventory across time, raters, and groups: An A-CAP study.

OBJECTIVES: To validate the two-factor structure (i.e., cognitive and somatic) of the Health and Behaviour Inventory (HBI), a widely used post-concussive symptom (PCS) rating scale, through factor analyses using bifactor and correlated factor models and by examining measurement invariance (MI). METHODS: PCS ratings were obtained from children aged 8-16.99 years, who presented to the emergency department with concussion (n = 565) or orthopedic injury (OI) (n = 289), and their parents, at 10-days, 3-months, and 6-months post-injury. Item-level HBI ratings were analyzed separately for parents and children using exploratory and confirmatory factor analyses (CFAs). Bifactor and correlated models were compared using various fit indices and tested for MI across time post-injury, raters (parent vs. child), and groups (concussion vs. OI). RESULTS: CFAs showed good fit for both a three-factor bifactor model, consisting of a general factor with two subfactors (i.e., cognitive and somatic), and a correlated two-factor model with cognitive and somatic factors, at all time points for both raters. Some results suggested the possibility of a third factor involving fatigue. All models demonstrated strict invariance across raters and time. Group comparisons showed at least strong or strict invariance. CONCLUSIONS: The findings support the two symptom dimensions measured by the HBI. The three-factor bifactor model showed the best fit, suggesting that ratings on the HBI also can be captured by a general factor. Both correlated and bifactor models showed substantial MI. The results provide further validation of the HBI, supporting its use in childhood concussion research and clinical practice.

Reassessing the Need for Preoperative Transfusions in Sickle Cell Disease Patients With an Elevated Baseline Hemoglobin-A Retrospective Study.

BACKGROUND: Current guidelines recommend a preoperative hemoglobin of 10.0 g/dL in patients with sickle cell disease [SCD], however, this threshold continues to be an area of controversy. Previous studies demonstrating the benefits of preoperative transfusions have largely not captured patients with elevated baseline hemoglobin, in part due to low hydroxyurea uptake and exclusion of nonhemoglobin SS SCD. MATERIALS AND METHODS: We conducted a retrospective chart review of patients with SCD <18 years of age undergoing low and medium-risk procedures at 2 academic medical centers in Canada between 2007 and 2017. The primary objective was to study the association of preoperative transfusion on postoperative complications in patients with SCD with baseline hemoglobin between 9.0 and 10.0 g/dL. Multivariable logistic regression was used to estimate the adjusted effect of preoperative transfusion on the risk of developing postoperative complications. RESULTS: In all, 159 procedures in patients with hemoglobin <9.0 g/dL [Hb <9.0 ] and 173 procedures in patients with hemoglobin between 9.0 and 10.0 g/dL [Hb 9.0-10.0 ] were analyzed. In the absence of preoperative transfusion, Hb 9.0-10.0 patients had lower overall complications [23% vs. 34%] compared with Hb <9.0 patients [OR 0.29, 95% CI 0.12-0.72, P =0.008]. In total, 75% of Hb <9.0 and 21% of Hb 9.0-10.0 patients received a preoperative simple transfusion. Transfusion was associated with increased risk of postoperative complications in Hb 9.0-10.0 [OR 3.02, 95% CI 1.26-7.23, P =0.013], but not Hb <9.0 patients [OR 0.64, 95% CI 0.28-1.45, P =0.30]. CONCLUSIONS: Simple transfusion may not be warranted in Hb 9.0-10.0 patients undergoing low-risk procedures. Prospective studies validating these findings are needed.

Early Postinjury Screen Time and Concussion Recovery.

OBJECTIVES: To determine the association between early screen time (7-10 days postinjury) and postconcussion symptom severity in children and adolescents with concussion, as compared to those with orthopedic injury (OI). METHODS: This was a planned secondary analysis of a prospective longitudinal cohort study. Participants were 633 children and adolescents with acute concussion and 334 with OI aged 8 to 16, recruited from 5 Canadian pediatric emergency departments. Postconcussion symptoms were measured using the Health and Behavior Inventory at 7 to 10 days, weekly for 3 months, and biweekly from 3 to 6 months postinjury. Screen time was measured by using the Healthy Lifestyle Behavior Questionnaire. Generalized least squares models were fit for 4 Health and Behavior Inventory outcomes (self- and parent-reported cognitive and somatic symptoms), with predictors including screen time, covariates associated with concussion recovery, and 2 3-way interactions (self- and parent-reported screen time with group and time postinjury). RESULTS: Screen time was a significant but nonlinear moderator of group differences in postconcussion symptom severity for parent-reported somatic (P = .01) and self-reported cognitive symptoms (P = .03). Low and high screen time were both associated with relatively more severe symptoms in the concussion group compared to the OI group during the first 30 days postinjury but not after 30 days. Other risk factors and health behaviors had stronger associations with symptom severity than screen time. CONCLUSIONS: The association of early screen time with postconcussion symptoms is not linear. Recommending moderation in screen time may be the best approach to clinical management.

Early analgesic administration and headache presence 7 days post-concussion in children.

OBJECTIVE: This study investigates whether acute treatment with ibuprofen, acetaminophen, or both is associated with resolution of headache or reduction of headache pain at 7 days post-concussion in children and youth. METHODS: A secondary analysis of the Predicting and Preventing Post-concussive Problems in Pediatrics (5P) prospective cohort study was conducted. Individuals aged 5-18 years with acute concussion presenting to nine Canadian pediatric emergency departments (ED) were enrolled from August 2013 to June 2015. The primary outcome was the presence of headache at 7 days, measured using the Post-Concussion Symptom Inventory. The association between acute administration of ibuprofen, acetaminophen, or both and headache presence at 7 days was investigated with propensity scores and adjusted multivariate regression models. RESULTS: 2277 (74.3%) of 3063 participants had headache upon ED presentation. Of these participants, 1543 (67.8%) received an analgesic medication before or during their ED visit [ibuprofen 754 (33.1%), acetaminophen 445 (19.5%), both 344 (15.1%); or no medication 734 (32.2%)]. Multivariate analysis pertained to 1707 participants with propensity scores based on personal characteristics and symptoms; 877 (51.4%) reported headache at 7 days post-concussion. No association emerged between treatment and presence of headache at 7 days [ibuprofen vs. untreated: (relative risk (RR) = 1.12 (95% CI 0.99,1.26); acetaminophen vs untreated RR = 1.02 (95% CI 0.87,1.22); both vs untreated RR = 1.02 (95% CI 0.86,1.18)]. CONCLUSIONS: Exposure to ibuprofen, acetaminophen, or both in the acute phase does not decrease the risk of headache at 7 days post-concussion. Non-opioid analgesics like ibuprofen or acetaminophen may be prescribed for short-term headache relief but clinicians need to be cautious with long-term medication overuse in those whose headache symptoms persist.

RéSUMé: OBJECTIF: Cette étude vise à déterminer si un traitement aigu à l'ibuprofène, à l'acétaminophène ou aux deux est associé à la résolution des maux de tête ou à la réduction de la douleur des maux de tête 7 jours après la commotion cérébrale chez les enfants et les adolescents. MéTHODES: Une analyse secondaire de l'étude de cohorte prospective Predicting and Preventing Post-concussive Problems in Pediatrics (5P) a été réalisée. Des personnes âgées de 5 à 18 ans souffrant d'une commotion cérébrale aiguë se présentant dans neuf services d'urgence pédiatriques (SU) canadiens ont été inscrites d'août 2013 à juin 2015. Le résultat primaire était la présence de maux de tête à 7 jours, mesurée à l'aide du Post-Concussion Symptom Inventory. L'association entre l'administration aiguë d'ibuprofène, d'acétaminophène ou des deux et la présence de maux de tête à 7 jours a été étudiée à l'aide de scores de propension et de modèles de régression multivariés ajustés. RéSULTATS: 2277 (74,3%) des 3063 participants avaient des maux de tête lors de la présentation aux urgences. Parmi ces participants, 1 543 (67,8%) ont reçu un médicament analgésique avant ou pendant leur visite aux urgences [ibuprofène 754 (33,1%), acétaminophène 445 (19,5%), les deux 344 (15,1%); ou aucun médicament 734 (32,2%)]. L'analyse multivariée a porté sur 1707 participants avec des scores de propension basés sur les caractéristiques personnelles et les symptômes; 877 (51,4%) ont signalé des maux de tête 7 jours après la commotion cérébrale. Aucune association n'est apparue entre le traitement et la présence de céphalées à 7 jours [ibuprofène vs non traité: (risque relatif (RR) = 1,12 (95%CI:0,99,1,26); acétaminophène vs non traité RR = 1,02 (95% IC: 0,87,1,22); les deux vs non traité RR = 1,02 (95% IC: 0,86,1,18)]. CONCLUSIONS: L'exposition à l'ibuprofène, à l'acétaminophène ou aux deux dans la phase aiguë ne diminue pas le risque de céphalées 7 jours après la commotion. Les analgésiques non opioïdes comme l'ibuprofène ou l'acétaminophène peuvent être prescrits pour soulager les maux de tête à court terme, mais les cliniciens doivent faire attention à la surconsommation de médicaments à long terme chez les personnes dont les symptômes de maux de tête persistent.

Antibody Seronegativity in COVID-19 RT-PCR-Positive Children.

This substudy of a prospective case-ascertained household transmission study investigated severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction-positive individuals without antibody development and factors associated with nonseroconversion. Approximately 1 of 8 individuals with coronavirus disease 2019 did not seroconvert. Children, particularly the youngest, were approximately half as likely to seroconvert compared with adults. Apart from the absence of fever/chills, individual symptoms did not strongly predict nonseroconversion.

Longitudinal white matter microstructural changes in pediatric mild traumatic brain injury: An A-CAP study.

In the largest sample studied to date, white matter microstructural trajectories and their relation to persistent symptoms were examined after pediatric mild traumatic brain injury (mTBI). This prospective, longitudinal cohort study recruited children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) from five pediatric emergency departments. Children's pre-injury and 1-month post-injury symptom ratings were used to classify mTBI with or without persistent symptoms. Children completed diffusion-weighted imaging at post-acute (2-33 days post-injury) and chronic (3 or 6 months via random assignment) post-injury assessments. Mean diffusivity (MD) and fractional anisotropy (FA) were derived for 18 white matter tracts in 560 children (362 mTBI/198 OI), 407 with longitudinal data. Superior longitudinal fasciculus FA was higher in mTBI without persistent symptoms relative to OI, d (95% confidence interval) = 0.31 to 0.37 (0.02, 0.68), across time. In younger children, MD of the anterior thalamic radiations was higher in mTBI with persistent symptoms relative to both mTBI without persistent symptoms, 1.43 (0.59, 2.27), and OI, 1.94 (1.07, 2.81). MD of the arcuate fasciculus, -0.58 (-1.04, -0.11), and superior longitudinal fasciculus, -0.49 (-0.90, -0.09) was lower in mTBI without persistent symptoms relative to OI at 6 months post-injury. White matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6 months post injury in children with mTBI, especially in younger children with persistent symptoms, relative to OI. White matter microstructure appears more organized in children without persistent symptoms, consistent with their better clinical outcomes.

Household transmission of SARS-CoV-2 from unvaccinated asymptomatic and symptomatic household members with confirmed SARS-CoV-2 infection: an antibody-surveillance study.

BACKGROUND: Household transmission contributes to SARS-CoV-2 spread, but the role of children in transmission is unclear. We conducted a study that included symptomatic and asymptomatic children and adults exposed to SARS-CoV-2 in their households with the objective of determining how SARS-CoV-2 is transmitted within households. METHODS: In this case-ascertained antibody-surveillance study, we enrolled households in Ottawa, Ontario, in which at least 1 household member had tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction testing. The enrolment period was September 2020 to March 2021. Potentially eligible participants were identified if they had tested positive for SARS-CoV-2 at an academic emergency department or affiliated testing centre; people who learned about the study through the media could also self-identify for participation. At least 2 participants were required for a household to be eligible for study participation, and at least 1 enrolled participant per household had to be a child (age < 18 yr). Enzyme-linked immunosorbent assays were used to evaluate SARS-CoV-2-specific IgA, IgM and IgG against the spike-trimer and nucleocapsid protein. The primary outcome was household secondary attack rate, defined as the proportion of household contacts positive for SARS-CoV-2 antibody among the total number of household contacts participating in the study. We performed descriptive statistics at both the individual and household levels. To estimate and compare outcomes between patient subgroups, and to examine predictors of household transmission, we fitted a series of multivariable logistic regression with robust standard errors to account for clustering of individuals within households. RESULTS: We enrolled 695 participants from 180 households: 180 index participants (74 children, 106 adults) and 515 of their household contacts (266 children, 249 adults). A total of 487 household contacts (94.6%) (246 children, 241 adults) had SARS-CoV-2 antibody testing, of whom 239 had a positive result (secondary attack rate 49.1%, 95% confidence interval [CI] 42.9%-55.3%). Eighty-eight (36.8%, 95% CI 29.3%-43.2%) of the 239 were asymptomatic; asymptomatic rates were similar for children (51/130 [39.2%, 95% CI 30.7%-48.5%]) and adults (37/115 [32.2%, 95% CI 24.2%-41.4%]) (odds ratio [OR] 1.3, 95% CI 0.8-2.1). Adults were more likely than children to transmit SARS-CoV-2 (OR 2.2, 95% CI 1.3-3.6). The odds of transmission from asymptomatic (OR 0.6, 95% CI 0.2-1.4) versus symptomatic (OR 0.9, 95% CI 0.6-1.4) index participants to household contacts was uncertain. Predictors of household transmission included household density (number of people per bedroom), relationship to index participant and number of cases in the household. INTERPRETATION: The rate of SARS-CoV-2 transmission within households was nearly 50% during the study period, and children were an important source of spread. The findings suggest that children are an important driver of the COVID-19 pandemic; this should inform public health policy.