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Competing Interests: Declaration of competing interests There are no competing interests to disclose.

The introduction of emicizumab into the treatment regime of persons with hemophilia A has dramatically reduced frequency of bleeding in patients with and without inhibitors. However, in children with Hemophilia A (CwHA) who require surgical or other invasive procedures, additional treatment with factor replacement or other hemostatic agents may still be needed to prevent intraoperative or postoperative bleeding. This review will look at the reported outcomes in CwHA on emicizumab who have had surgery and propose recommendations for the best perioperative management of major and minor procedures., Competing Interests: MBe: Advisory Board attendee with Roche Canada, Sanofi Canada, Bayer Canada, Octapharma Canada; invited speaker for Roche Canada, Octapharma Canada. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Belletrutti, Bhatt and Samji.)

Objectives: The COVID-19 pandemic has impacted mental health at a population level. Families of children with health vulnerabilities have been disproportionately affected by pandemic-related policies and service disruptions as they substantially rely on the health and social care system. We elicited the impact of the COVID-19 pandemic on children with health and disability-related vulnerabilities, their families, and their health care providers (HCPs)., Methods: Children with diverse health vulnerabilities (cardiac transplantation, respiratory conditions, sickle cell disease, autism spectrum disorder, mental health issues, and nearing the end of life due to a range of underlying causes), as well as their parents and HCPs, participated in semi-structured interviews. Data were analyzed using qualitative content analysis in determining themes related to impact and recommendations for practice improvement., Results: A total of 262 participants (30 children, 76 parents, 156 HCPs) were interviewed. Children described loneliness and isolation; parents described feeling burnt out; and HCPs described strain and a sense of moral distress. Themes reflected mental health impacts on children, families, and HCPs, with insufficient resources to support mental health; organizational and policy influences that shaped service delivery; and recommendations to enhance service delivery., Conclusion: Children with health vulnerabilities, their families and HCPs incurred profound mental health impacts due to pandemic-imposed public health restrictions and care shifts. Recommendations include the development and application of targeted pandemic information and mental health supports. These findings amplify the need for capacity building, including proactive strategies and mitigative planning in the event of a future pandemic., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: This study aimed to assess the impact of hemophilia on families, in the context of current and emerging hemostatic therapies, and explore the need for a hemophilia-specific tool targeted at parents of boys aged <4 years. A secondary aim was to develop and validate the new tool., Methods: Focus groups were conducted with parents of boys with hemophilia and hemophilia health care providers at Canadian hemophilia treatment centers (HTCs) to review the relevance of the Pediatric Quality of Life Family Impact Module (PedsQL-FIM); a novel questionnaire was developed by identifying core themes expressed. This questionnaire, the Hemophilia Family Impact Tool (H-FIT) was validated in a sample of parents of boys with hemophilia relative to the PedsQL-FIM., Results: Seven focus groups were conducted at four HTCs, generating themes specific to hemophilia not covered by the PedsQL-FIM, suggesting that a new tool be developed (the H-FIT). In the validation phase, 54 parents completed the H-FIT and PedsQL-FIM. The H-FIT had a strong correlation with the PedsQL-FIM across all ages (r = 0.79; P  < .0001) and a moderate correlation for parents of boys aged <7 years (r = 0.64; P  = .0007). There was a significant difference between the mean H-FIT scores for parents of boys using extended half-life factor (68.1; standard deviation [SD]=14.2) compared to standard half-life factor (54.7; SD=18.4; P  = .04)., Conclusion: A novel, disease-specific tool, the H-FIT, has been developed to measure the impact of hemophilia on families. The H-FIT has good preliminary measurement properties and may be responsive to changes in therapy associated with a decreased burden of administration., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Introduction: The purpose of this study was to review and update the content of the Canadian Hemophilia Outcomes-Kids' Life Assessment Tool version 2.0 (CHO-KLAT), in the context of extended half-life (EHL) factor concentrates (FCs) and to establish the validity and reliability of the updated CHO-KLAT., Methods: Focus groups were conducted with boys with hemophilia, their parents, and health care providers across Canada to review the CHO-KLAT v2.0 and determine if any modifications were required. The validity of the revised CHO-KLAT (version 3.0) was then determined in a sample of boys with hemophilia and their parents by calculating its correlation with the Pediatric Quality of Life Core Module (PedsQL-Core). Test-retest reliability was assessed using an intraclass correlation coefficient (ICC)., Results: Thirteen focus groups at 5 pediatric hemophilia treatment centers (HTCs) (n = 71) resulted in 19 changes to the CHO-KLAT v2.0, generating a revised 40-item CHO-KLAT, the CHO-KLAT v3.0. Thirty-five boys with hemophilia (median age, 14; range, 7-17 years) and 47 parents participated in the validation of the CHO-KLAT v3.0. There was a moderate correlation between the CHO-KLAT v3.0 child self-report and PedsQL-Core ( r  = 0.56, P  = .01), and a strong correlation between the CHO-KLAT v3.0 parent-proxy and PedsQL-Core ( r  = .79, P  = .0007). The test-retest reliability ICC was 0.90 for the child self-report CHO-KLAT v3.0 and 0.68 for the parent-proxy CHO-KLAT v3.0., Conclusion: The CHO-KLAT v3.0 is a reliable and valid child-centric tool that effectively measures health-related quality of life in boys with hemophilia who are receiving standard half-life or EHL FCs., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Like other recipients of health care services, pediatric patients and their families/caregivers have been profoundly impacted by health care shifts and broader societal restrictions associated with the COVID-19 pandemic. An online roundtable discussion was facilitated with 7 pediatric clinicians and investigators of a current study examining the impacts of COVID-19 on pediatric care at multiple Canadian sites. Discussants represented a range of pediatric specialities: developmental disability, mental health, cardiac transplantation, respiratory medicine, hematology, and palliative care. We offer the transcript of the roundtable in which discussants reflected on clinical and programmatic experiences of the pandemic, including perceived impacts on children receiving care and their families, potential opportunities for improved health care delivery, impacts on health care providers, and recommendations as we move toward easing restrictions and pandemic recovery. Discussants convey a range of considerations that may have varying relevance for pediatric specialities in terms of practice and program planning., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Introduction: Air travel may expose patients with sickle cell disease (SCD) to an increased risk of disease-related complications. Several factors are felt to contribute including prolonged hypoxia, dehydration, temperature changes, and stress. The Canadian Paediatric Society (CPS) position statement, published in 2007, recommends that SCD patients use supplemental oxygen on flights. While the National Heart, Lung and Blood Institute (NHLBI) recommend that SCD patients dress warmly, stay hydrated, and move about the cabin. Other guidelines do not make specific recommendations., Methods: A cross-sectional online survey was circulated through the Canadian Hemoglobinopathy Association (CanHaem) and American Society of Pediatric Hematology and Oncology (ASPHO) listservs to North American health care practitioners (HCPs). Participants were asked to share their air travel recommendations for patients with SCD. Similarly, a patient survey regarding experiences with air travel was circulated through the Sickle Cell Disease Association of Canada (SCDAC) and the Sickle Cell Foundation of Alberta (SCFOA) listservs and discussion boards., Results: Although air travel is perceived to be a risk factor for sickling complications, only 18% of HCPs recommend supplemental oxygen. Most HCPs advise patients to increase hydration, carry analgesics, and wear warm clothes to prevent sickling complications. The patient survey was limited by a low response rate., Conclusion: The majority of HCPs are not routinely recommending prophylactic oxygen to patients with SCD during air travel., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Fathers are under-represented in pediatric palliative care research despite frequently playing a key role in the lives of their children. The purpose of this study was to identify factors that affected paternal study invitation and participation. A secondary mixed-methods evaluation design guided examination of interview and focus group data as well as field notes from a qualitative study that examined the experiences and support needs of fathers of children with a life-limiting illness. Facilitators of paternal participation in the study consisted of: fathers' desire to gain from study participation either for themselves or others, perception of the study's importance, sense of appreciation for the study's focus on fathers and an established relationship with recruiting health care providers. Barriers to study participation included: recruiting health care providers' appraisal of fathers' lack of well-being, bereaved fathers' self-reported poor coping and the inability to locate and contact fathers, particularly after a child's death. Strategies for improving the engagement of fathers into research entailed: educating recruitment personnel, designing "father-focused" studies, communicating the value of the research to recruitment personnel and potential participants, and ensuring that child health records are accurate and include fathers' contact information.

Background: Genetic and environmental factors affect the occurrence of vaso-occlusive crises (VOCs) in patients with sickle cell disease (SCD). Research provides inconsistent evidence on how environmental temperature affects SCD. Edmonton, Alberta, has an increasing SCD population and is the northern-most city in North America with a population of over a million., Objective: The objective of this study was to identify whether pediatric patients with SCD experience increased morbidity in cold external temperatures., Materials and Methods: This study was a retrospective case series. Emergency visits, phone calls, and admission data for VOC in children were recorded from July 2011 to June 2016. Temperatures were recorded and statistically analyzed using descriptive statistics, to determine the relation to VOC., Results: A total of 118 patients with 257 VOC events were reviewed. When analyzing the mean, minimum, and change in temperatures at presentation, the largest percentage of VOC events occurred at mild to moderate temperatures. Temperature data at 24 and 48 hours before the presentation had similar results. When accounting for the relative frequency of extreme weather days, there are increased VOC events with temperature fluctuations >20°C., Conclusions: There was no correlation between mean and minimum temperature change. Fluctuation in temperature of >20°C was associated with increased relative VOC frequency, suggesting that large temperature variability should be avoided in SCD, but a prospective study is required to determine causality.

Introduction: Nuwiq ® (Human-cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq ® in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq ® in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study., Methods: The study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5 years maximum. The primary objective is to assess the immunogenicity of Nuwiq ® (inhibitor activity ≥0.6 BU) using the Nijmegen-modified Bethesda assay at a central laboratory., Results: Data for 66 PUPs with ≥20 EDs from a preplanned interim analysis were analysed. High-titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6-24). Five patients developed low-titre inhibitors (4 transient). The cumulative incidence (95% confidence interval) was 12.8% (4.5%, 21.2%) for HT inhibitors and 20.8% (10.7%, 31.0%) for all inhibitors. During inhibitor-free periods, median annualized bleeding rates during prophylaxis were 0 for spontaneous bleeds and 2.40 for all bleeds. Efficacy was rated as "excellent" or "good" in treating 91.8% of bleeds. Efficacy of surgical prophylaxis was "excellent" or "good" for 8 (89%) procedures and "moderate" for 1 (11%). No tolerability concerns were evident., Conclusion: These interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq ® ., (© 2017 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

We report the case of a 10-year-old boy, 8 years post-M7 acute myeloid leukemia with a history of significant thrombocytopenia and bleeding, requiring treatment, after 2 surgical procedures performed under general anesthesia. In both instances, the thrombocytopenia and bleeding responded to intravenous immunoglobulin treatment. Between surgeries, the platelet counts were normal. Before a third surgical procedure, he was successfully pretreated with dexamethasone and experienced no bleeding or thrombocytopenia after the operation. This case highlights the potential utility of corticosteroid pretreatment in patients with a history of immune thrombocytopenia before surgical procedures under general anesthesia.

Venous thromboembolism (VTE) incidence is increasing among children owing to many factors, including improved diagnosis of VTE. There is a need for alternative treatment options. Our objective was to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran etexilate in adolescents with VTE. Adolescents aged 12 to <18 years (n = 9) who successfully completed planned treatment for primary VTE were administered dabigatran etexilate twice daily for three days; initially 1.71 (± 10 %) mg/kg (80 % of a 150 mg/70 kg twice daily adult dose), followed by 2.14 (± 10 %) mg/kg (target adult dose adjusted for patient's weight), if there were no safety concerns. No bleeding events, deaths or drug-related serious adverse events (AEs) were reported; three treatment-emergent AEs, all gastrointestinal-related, occurred in two patients. In these adolescent patients with normal renal function, presumed steady-state trough plasma concentrations of dabigatran were low (geometric mean dose-normalised total dabigatran plasma concentration: 0.493 ng/ml/mg at 72 hours). Total dabigatran concentrations were well predicted by the RE-LY® population PK model (94 % of trough concentrations were within the 80 % prediction interval). The relationship between total dabigatran plasma concentration, diluted thrombin time and ecarin clotting time (ECT) was linear; the relationship with activated partial thromboplastin time (aPTT) was non-linear. Adult population PK/PD models predicted the adolescent concentration-ECT and -aPTT relationships well. In conclusion, dabigatran etexilate was generally well tolerated, except for occurrence of dyspepsia in two patients, over the three-day treatment period. The dabigatran PK/PD relationship observed in adolescent patients was similar to that in adult patients.

Families who have a child diagnosed with a life-limiting illness (LLI) face substantial challenges resulting from the complexity and devastating impact of the condition and potential closeness of death. The experiences of fathers of a child with LLI have been understudied; therefore, this study explored the stresses, experiences, and strategies of these fathers, including their perceptions about support needs. Based on grounded theory, in-depth semi-structured interviews were conducted with 18 fathers of children with LLI. Six fathers had experienced the death of their child. The overarching themes were stresses, means of coping, and perceived needs for support. Generally, fathers in this study struggled relative to discursive and internalized notions of fathers as providers and protectors for their children, combined with an inability to ease their child's vulnerability to LLI. Participants were engaged in the care of their child with LLI, but several felt marginalized by health care providers in care planning and staff/family communication. Some fathers recognized and valued their support network while others had few supports. Some described personal growth and desired to help other fathers. Practice implications and recommendations include renewed application of family-centered care, overcoming presumptions about fathers' roles, and recognizing the impact of LLI beyond physical health.

Background: Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or radiotherapy changes outcomes in these patients., Methods: Ten pediatric institutions across North America and Europe contributed data of their patients with LCH and single-bone CNS-risk lesions. Clinical information on age, sex, specific craniofacial site involvement, and intracranial extension at diagnosis, therapy, and disease course was collected for all eligible patients., Results: The final analysis included 93 eligible children who were either treated with systemic therapy (chemotherapy, chemo-radiotherapy, or radiotherapy) or local therapy (biopsy, curettage, and/or intralesional steroids). Fifty-nine patients had systemic and 34 had local therapy. The 5-year event-free survival (EFS) and overall survival (OS) were 80 ± 5% and 98 ± 2% in the systemic therapy group versus 85 ± 6% and 95 ± 5% in the local therapy group. There was no statistically significant difference between either group with regard to EFS (P = 0.26) and OS (P = 0.78). On multivariable analysis, there was no significant difference among the two treatment groups after adjusting for site and intracranial soft tissue extension, nor any trend favoring systemic therapy (HR = 2.26, 95% CI = 0.77-6.70; P = 0.14)., Conclusion: Systemic therapy may not reduce the risk of recurrence or late sequelae in children with LCH and single-bone CNS-risk lesions as compared to local treatment., (© 2015 Wiley Periodicals, Inc.)

Background: Phenotypic overlap among the inherited bone marrow failure syndromes (IBMFSs) frequently limits the ability to establish a diagnosis based solely on clinical features. >70 IBMFS genes have been identified, which often renders genetic testing prolonged and costly. Since correct diagnosis, treatment and cancer surveillance often depend on identifying the mutated gene, strategies that enable timely genotyping are essential., Methods: To overcome these challenges, we developed a next-generation sequencing assay to analyse a panel of 72 known IBMFS genes. Cases fulfilling the clinical diagnostic criteria of an IBMFS but without identified causal genotypes were included., Results: The assay was validated by detecting 52 variants previously found by Sanger sequencing. A total of 158 patients with unknown mutations were studied. Of 75 patients with known IBMFS categories (eg, Fanconi anaemia), 59% had causal mutations. Among 83 patients with unclassified IBMFSs, we found causal mutations and established the diagnosis in 18% of the patients. The assay detected mutant genes that had not previously been reported to be associated with the patient phenotypes. In other cases, the assay led to amendments of diagnoses. In 20% of genotype cases, the results indicated a cancer surveillance programme., Conclusions: The novel assay is efficient, accurate and has a major impact on patient care., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: 1) To investigate the presence of hemoglobin Constant Spring (HbCS) in a patientwith severe microcytic anemia who had previously been diagnosed with alpha thalassemia minor. 2) To assess the stability of HbCS post blood collection by high performance liquid chromatography (HPLC)., Design and Methods: Hemoglobin fractionation was performed by HPLC immediately after specimen collection using the β-thalassemia Short Program on the BioRad Variant II. To assess HbCS stability, the patient's specimen was re-analyzed over a 17 day period., Results: HPLC analysis showed a low abundance peak with chromatographic properties consistent with HbCS. Presence of this hemoglobin variant was confirmed by electrophoresis and gene sequencing. HbCS remained detectable by HPLC for 17 days after specimen collection, with minimal degradation., Conclusions: Our results suggest that HbCS is stable many days after blood collection. Consequently, it is not necessary to analyze specimens immediately after collection when assessing the potential presence of this hemoglobin variant., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

In a case-control study, medical records of all children (below 18 y of age) who were diagnosed with any malignancy between January 1988 and December 2008 were reviewed. Children who developed typhlitis during the course of their malignancy were identified. Age and sex-matched controls who were diagnosed with malignancy during the same time period but did not develop typhlitis were identified (1:4 ratio). The variables that were examined included underlying malignancy, chemotherapy, and final outcome. A total of 410 children (226 males, mean age of 87.29 ± 56.8 mo) with malignancy were recruited. Nine children (0.22%) (4 boys, mean age of 87.56 ± 60.48 mo) developed typhlitis during the course of their disease. In the control group, 36 age and sex-matched children were included (mean age of 87.67 ± 57.91 mo). Children who had Clostridium difficile infection within 8 weeks before developing typhlitis were more likely to develop typhlitis compared with controls (odds ratio 7.99, 95% confidence interval 1.46-43.7, P=0.01). One patient died from typhlitis. Clostridium difficile infection is a risk factor for developing typhlitis in children with cancer. Larger multicenter trials are needed to confirm our conclusions.

Unlabelled: Enoxaparin is a low molecular weight heparin (LMWH) commonly used for thromboprophylaxis children. Enoxaparin dosing is based on patients' weight and results in decimal dosing. Due to the high concentration of enoxaparin the resultant decimal dose makes precise measurement difficult. Dilution is necessary and often results in ten-fold medication administration errors [Ghaleb MA, Barber N, Franklin BD, Yeung VWS, Khaki ZF, Wong ICK. Systematic review of medication errors in pediatric patients. Ann Pharmacother Oct 2006;40(10):1766-76, Raju TN, Kecskes S, Thornton JP, Perry M, Feldman S. Medication errors in neonatal and paediatric intensive-care units. Lancet Aug 12 1989;2(8659):374-6]. Enoxaparin may be administered in whole milligram doses via insulin syringe, where one milligram of enoxaparin equals one unit on the 100 unit graduated insulin syringe., Study Design: A retrospective chart review of 514 children. Data was collected on underlying diagnosis, reason for anticoagulation, anti-Xa levels, hemorrhagic events, and medication errors identified., Outcome: to determine the occurrence rate of supra-therapeutic anticoagulation as indicated by anti-Xa levels >1.0 u/ml, when enoxaparin doses are rounded up to the whole milligram, and are administered using insulin syringes. The secondary objectives were to determine if the supra-therapeutic anti-Xa levels were associated with hemorrhagic events. To determine if children achieved and maintained therapeutic anti-Xa range using whole milligram dosing and to evaluate the impact of utilizing insulin syringes for administration on reducing dose measurement errors., Results: All 514 patients were prescribed whole milligram enoxaparin dosing, and achieved therapeutic anti-Xa within a mean time of 2 days. No infant or child required decimal doses to achieve therapeutic levels. Five children achieved an initial supra-therapeutic anti-Xa level (1.04 -1.36 U/ml), requiring a single whole milligram dose decrease. There were no associated hemorrhagic events., Conclusion: Whole milligram enoxaparin dosing administered via an insulin syringe safely and effectively, achieved therapeutic levels in infants and children. The reduced incidence of enoxaparin dosing errors suggests that whole milligram enoxaparin dosing via an insulin syringe is a method that should be considered for standard of care.

Background: Immune thrombocytopenic purpura (ITP) in children is a common pediatric bleeding disorder with heterogeneous manifestations and a natural history that is not fully understood. To better understand the natural history of chronic ITP and detect response trends and outcomes of therapy, we conducted a 10-year retrospective survey of children from age 1 to 18 years with a diagnosis of chronic ITP., Results: Data on 198 patients from 8 Canadian Pediatric Hematology/Oncology centers were analyzed. The majority of patients were female (58%), and were previously diagnosed with acute (primary) ITP (85%). The age at diagnosis of chronic ITP ranged from 1.1 to 17.2 years with a mean of 8.2+/-4.4 years. Ninety percent of patients received some form of treatment. Untreated patients had a higher mean platelet count at diagnosis of chronic ITP (P=0.009) despite similarities in mean age at first presentation and mean duration of follow-up. Thirty-four (17%) patients underwent splenectomy. Splenectomized patients tended to be significantly older, had a lower mean platelet count at diagnosis of chronic ITP, and had a longer duration of follow-up., Conclusions: The results from this study are consistent with published reports.