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Resume Contexte: Les facteurs de risque de complications graves de l’infection par le SRAS-CoV-2 n’ont pas ete bien etablis chez les enfants. Nous avons voulu decrire les hospitalisations pediatriques associees au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave. Methodes: Nous avons procede a une etude prospective nationale en utilisant l’infrastructure du Programme canadien de surveillance pediatrique (PCSP). Les hospitalisations d’enfants ayant contracte une infection par le SRAS-CoV-2 confirmee en laboratoire de microbiologie ont ete rapportees du 8 avril au 31 decembre 2020 au moyen de questionnaires hebdomadaires en ligne distribues au reseau du PCSP, qui compte plus de 2800 pediatres. Nous avons categorise les hospitalisations comme suit : liees a la COVID-19, infections decouvertes fortuitement, ou hospitalisations pour des raisons sociales ou de controle des infections, et degage les facteurs de risque associes a la gravite de la maladie chez les patients hospitalises. Resultats: Sur les 264 hospitalisations d’enfants ayant contracte le SRAS-CoV-2 au cours de la periode de l’etude de 9 mois, 150 (56,8 %) ont ete associees a la COVID-19 et 100 (37,9 %) etaient des cas decouverts fortuitement (admission pour d’autres raisons et decouverte fortuite du SRAS-CoV-2 par depistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) representaient la majorite des cas. Parmi les hospitalisations liees a la COVID-19, 52 patients (34,7 %) etaient atteints d’une forme grave de la maladie, dont 42 (28,0 % des cas lies a la COVID-19) ont eu besoin d’une forme d’assistance respiratoire ou hemodynamique, et 59 (39,3 %) presentaient au moins 1 comorbidite sous-jacente. Les enfants atteints d’obesite, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, a l’exclusion de l’asthme, etaient plus susceptibles de presenter une forme grave ou critique de la COVID-19. Interpretation: Parmi les enfants hospitalises au Canada chez lesquels on a diagnostique une infection par le SRAS-CoV-2 au debut de la pandemie de COVID-19, la decouverte fortuite du SRAS-CoV-2 a ete frequente. Chez les enfants hospitalises pour une COVID-19 aigue, l’obesite et les comorbidites neurologiques et respiratoires ont ete associees a une gravite accrue.

Long before the classification of vascular anomalies from the International Society for the Study of Vascular Anomalies (ISSVA) provided a framework to differentiate vascular anomalies, otherwise known as vascular birthmarks, it was recognized that patients with such lesions can present with acute life-threatening hemostatic and/or thrombotic complications, as well as chronic long-standing bleeding or thrombotic issues. Scenarios such as a rapidly growing vascular lesion with severe acute thrombocytopenia, a visceral hemorrhagic lesion, a lesion associated with repetitive and painful superficial thrombosis, and cases of unprovoked or post-procedural fatal pulmonary embolism highlight the wide spectrum of manifestations of abnormal coagulation in patients with vascular anomalies. The separation of vascular anomalies into two distinct groups, vascular tumors and vascular malformations, was followed by the characterization that their respective coagulopathies were due to either a derangement of platelets or to a disequilibrium of the patient's coagulation/fibrinolytic process. This configuration of coagulopathies will be the foundation for this two-chapter review series. In the initial review, coagulopathies where thrombocytopenia is the main feature will be characterized, whereas the second review will focus on vascular malformations that have a coagulation disorder secondary to some degree of coagulation consumption and/or fibrinolytic pathway derangement.

BackgroundPaediatric inflammatory multisystem syndrome (PIMS) is a rare but serious condition temporally associated with SARS-CoV-2 infection. Using the Canadian Paediatric Surveillance Program (CPSP), a national surveillance system, we aimed to 1) study the impact of SARS-CoV-2 linkage on clinical and laboratory characteristics, and outcomes in hospitalized children with PIMS across Canada 2) identify risk factors for ICU admission, and 3) establish the minimum national incidence of hospitalizations due to PIMS and compare it to acute COVID-19.MethodsWeekly online case reporting was distributed to the CPSP network of more than 2800 pediatricians, from March 2020 to May 2021. Comparisons were made between cases with respect to SARS-CoV-2 linkage. Multivariable modified Poisson regression was used to identify risk factors for ICU admission and Minimum incidence proportions were calculated.FindingsIn total, 406 PIMS cases were analyzed, of whom 202 (49· 8%) had a positive SARS-CoV-2 linkage, 106 (26· 1%) had a negative linkage, and 98 (24· 1%) had an unknown linkage. The median age was 5· 4 years (IQR 2· 5–9· 8), 60% were male, and 83% had no identified comorbidities. Compared to cases with a negative SARS-CoV-2 linkage, children with a positive SARS-CoV-2 linkage were older (8· 1 years [IQR 4· 2–11· 9] vs. 4· 1 years [IQR 1· 7–7· 7]; pInterpretationWhile PIMS is rare, almost 1 in 3 hospitalized children required ICU admission and respiratory/hemodynamic support, particularly those ≥ 6 years and with a positive SARS-CoV-2 linkage.FundingFinancial support for the CPSP was received from the Public Health Agency of Canada.

Background/Objectives Heavy menstrual bleeding (HMB) affects 34% to 37% of adolescent girls. The Menstrual Bleeding Questionnaire (MBQ) is a validated measure of menstrual bleeding–specific health‐related quality of life (HRQoL) for women aged ≥18 years. No similar measure existed for adolescents with HMB. Patients/Methods HMB was defined by the Pictorial Bleeding Assessment Chart (PBAC) score ≥100. In Phase 1, a focus group of adolescents with HMB adapted the MBQ, to generate the Adolescent MBQ (aMBQ). In phase 2, participants with and without HMB were recruited from clinics and self‐referral. Each participant completed 3 questionnaires (aMBQ, Pediatric Quality of Life module [PedsQL]©, PBAC) at two time points. Validity of the aMBQ was assessed by Pearson’s correlation with the PedsQL©. Reliability was calculated using intra‐class correlation (ICC) in those without HMB. The receiver operating characteristic curve assessed the aMBQ’s ability to identify those with HMB. Results Phase 1 included five girls with a mean age of 17.1 (13‐18) years. The aMBQ was adapted from the MBQ by substituting four words/phrases that altered 8 of the 20 questions and by adding 1 new question. The 21‐item aMBQ has a score range of 0 to 77 (77 = worst HRQoL). Phase 2 included 52 participants: 20 with and 32 without HMB, with a mean age of 14.8 (11‐17) years. The validity of the aMBQ was confirmed by a moderate correlation with PedsQL© (r = −0.63; P 30 identified those with HMB with excellent discrimination (area under the curve = 0.82; sensitivity, 70.0%; specificity, 84.4%). Conclusions The aMBQ is a valid and reliable tool to assess HRQoL in adolescents with HMB.

INTRODUCTION In many countries, there is a shift from standard half-life (SHL) to extended half-life (EHL) clotting factor concentrates (CFCs). AIM To describe the experience of switching from SHL to an EHL FVIII CFC and the impact of this on frequency of infusions, factor consumption, bleeding rates and HRQoL using the Canadian Hemophilia Kids' Life Assessment Tool (CHO-KLAT). METHODS A retrospective chart review was conducted at a single haemophilia treatment centre in 2018 that included boys (ages: 4-18 years) with moderate/severe haemophilia A, without inhibitors, who switched from a SHL to an EHL FVIII CFC in the previous 2 years and for whom HRQoL data were available. RESULTS The study cohort comprised 38 boys [mean (SD) age: 11.0 (3.4) years] with moderate (n = 5)/severe (n = 33) haemophilia A. The switch was associated with a 33% reduction in the number of weekly infusions from a median of 3.5 to 2.3 (P

Background Menstrual poverty is defined as the inability of people who menstruate to obtain menstrual products due to financial burden. The impact of menstrual poverty on adolescents is unknown. Objectives This study aimed to estimate the impact of menstrual poverty on adolescents who reside in Nova Scotia (NS), Canada. Design/Methods The authors developed a web-based, 25-item questionnaire, the adolescent Menstrual Poverty Questionnaire (aMPQ), and distributed it via social media. Adolescents who were less than 18 years of age, English-speaking, and living in NS were eligible to complete the survey. Data were analyzed using descriptive analysis. 420 adolescents completed the survey, with a mean age of 16.1 years (14.4 – 17.9 years). Results Results revealed that 65% of respondents do not always have enough money to buy menstrual products. This led to unsafe menstrual hygiene practices including using alternatives for menstrual products (e.g., rags), washing disposable menstrual products, and/or wearing products for longer than intended. 40% of respondents reported a lack of affordability of menstrual products as a cause for school absenteeism and lack of participation in sport/social activities. 70% of respondents feel embarrassed to ask for products even when they are provided for free, and almost all supported the idea of having freely available menstrual products in public washrooms. Conclusion This study determined that menstrual poverty impacts adolescents in Nova Scotia. To address menstrual poverty, menstrual products should be freely available in all public washrooms, as this will provide unrestricted access to menstruators and promote their full participation in society.

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

BACKGROUND: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease. METHODS: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital. RESULTS: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19. INTERPRETATION: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.

Background: Recently, the randomized EINSTEIN-Jr study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for treatment of pediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling. Methods: Rivaroxaban treatment with tablets or the newly developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily, or thrice-daily for children with bodyweights of ≥30, ≥12 to (0-24)ss] and trough [C trough,ss] and maximum [C max,ss] steady-state plasma concentrations were derived using population PK modeling. Exposure-response graphs were generated to evaluate the potential relationship of individual PK parameters with recurrent VTE, repeat imaging outcomes, and bleeding or adverse events. A taste-and-texture questionnaire was collected for suspension-recipients. Results: Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable. Discussion: Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE.

Background There is no uniform guideline for postchemotherapy vaccination of children with acute lymphoblastic leukemia (ALL). We evaluated waning immunity to 14 pneumococcal serotypes, pertussis toxin (PT), tetanus toxoid (TT) and varicella, and immunogenicity of postchemotherapy diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) and pneumococcal vaccination among previously vaccinated children treated for ALL. Methods This was a multicenter trial of children with ALL enrolled 4–12 months postchemotherapy completion. Exclusion criteria included: infant ALL, relapsed ALL, and stem cell transplant recipients. Immunocompetent children were recruited as controls. Postchemotherapy participants received DTaP-IPV-Hib and 13-valent pneumococcal conjugate vaccine (PCV13) concurrently, followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later. Serology was measured at baseline, 2 and 12 months postvaccination. Adverse events were captured via surveys. Results At enrollment, postchemotherapy participants (n = 74) were less likely than controls (n = 78) to be age-appropriately immunized with DTaP (41% vs 89%, P, In this multicenter trial, previously vaccinated children treated for acute lymphoblastic leukemia had lower antibody levels than controls to Streptococcus pneumoniae, tetanus toxoid, pertussis toxin, and varicella. Booster vaccination was immunogenic and well tolerated, suggesting benefit of systematic revaccination postchemotherapy.

Background: Recently, the randomised EINSTEIN-Jr. study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for acute and continued treatment of paediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling. Methods: Rivaroxaban treatment with tablets or the newly-developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily or thrice-daily for children with bodyweights of ≥30, ≥12

Background: Klippel–Trenaunay syndrome (KTS) is an overgrowth syndrome defined by capillary/venous/lymphatic malformations (CVLM) with soft tissue and/or bone hypertrophy. Whether KTS pred...

There are no Canadian immunization guidelines for children treated for malignancy. Guidelines do exist for patients who underwent hematopoietic stem cell transplant (HSCT), but they provide broad timeframes for initiating vaccination; there is no standard schedule. The optimal approach to immunization in these populations is unclear. We sought to describe immunization practices at Canadian Pediatric Hematology/Oncology centers. A 43-item online questionnaire was distributed to the 16 programs in the C(17) research network of pediatric hematology/oncology centers to capture information on timing and criteria for immunization of patients with acute lymphocytic leukemia (ALL) and those who have undergone HSCT. At each center, 1-2 physicians or pharmacists completed the survey to reflect center-wide immunization practices. Responses were received from 11/16 (69%) programs; 11 respondents reported on practices for patients with ALL and 9 reported on practices for patients who are post-HSCT. In 5/11 ALL programs (45%) re-immunization is recommended routinely after chemotherapy, starting 3-6 months post-chemotherapy. In HSCT programs, timing of pneumococcal conjugate vaccination (PCV) varied from 3 months post-HSCT (4 programs) to 12 months post-HSCT (4 programs). Live vaccines were administered 24 months post-HSCT in 8/9 programs. All HSCT programs considered graft-versus-host-disease and 7 considered discontinuation of immunosuppression in immunization decisions. Pediatric hematology/oncology programs were divided in regards to re-immunization of patients with ALL post-chemotherapy. After HSCT, timing of PCV administration varied, with 4 programs initiating immunization later than Canadian guidelines recommend (3-9 months post-HSCT). These findings suggest a need to standardize immunization practices in these populations.

Background Venous thromboembolism (VTE) is a relatively rare condition in childhood with treatment mainly based on extrapolation from studies in adults. Therefore, clinical trials of anticoagulation in children require novel approaches to deal with numerous challenges. The EINSTEIN-Jr program identified pediatric rivaroxaban regimens commencing with in vitro dose finding studies followed by evaluation of children of different ages through phase I and II studies using extensive modeling to determine bodyweight-related doses. Use of this approach resulted in drug exposure similar to that observed in young adults treated with rivaroxaban 20 mg once-daily. Methods EINSTEIN-Jr phase III is a randomized, open-label, study comparing the efficacy and safety of rivaroxaban 20 mg-equivalent dose regimens with those of standard anticoagulation for the treatment of any types of acute VTE in children aged 0–18 years. A total of approximately 500 children are expected to be included during the 4-year study window. Flexibility of treatment duration is allowed with study treatment to be given for 3 months with the option to continue treatment in 3-month increments, up to a total of 12 months. However, based on most common current practice, children younger than 2 years with catheter-related thrombosis will have a main treatment period of 1 month with the option to prolong treatment in 1-month increments, up to a total of 3 months. Conclusions EINSTEIN-Jr will compare previously established 20 mg-equivalent rivaroxaban dosing regimens with standard anticoagulation for the treatment of VTE in children. Demonstration of similarity of disease, as well as equivalent rivaroxaban exposure and exposure-response will enable extrapolation of efficacy from adult trials, which is critical given the challenges of enrollment in pediatric anticoagulation trials. Trial registration Clinicaltrials.gov NCT02234843, registered on 9 September 2014.

Newborns with hemophilia are at risk of intracranial hemorrhage, extracranial hemorrhage, and other bleeding complications. The safe delivery of a healthy newborn with hemophilia is a complex process that can begin even before conception, and continues throughout pregnancy, birth, and the newborn period. This process involves the expectant parents and a wide variety of health-care professionals: genetic counselors, obstetricians, neonatologists, pediatricians, radiologists, adult and pediatric hematologists, and nurses with expertise in hemophilia. Because of this multidisciplinary complexity, the relative rarity of births of newborns with hemophilia, and the lack of high-quality evidence to inform decisions, there is considerable variation in practice in this area. We present a comprehensive multidisciplinary approach, from preconception counseling to discharge planning after birth, and describe available options for management decisions. We highlight a number of areas of important uncertainty and controversy, including the preferred mode of delivery, the appropriate use and timing of neuroimaging tests, and the appropriate use of clotting factor concentrates in the newborn period. While the approach presented here will aid clinicians in planning and providing care, further research is required to optimize the care of newborns with hemophilia.

BACKGROUND Fever in the setting of neutropenia is a potentially life-threatening complication of cancer treatment. A time of less than 60 minutes from presentation to antibiotic administration is therefore recommended. OBJECTIVE To use Lean Six Sigma methodology, a quality improvement initiative, to improve time to antibiotics (TTA) for children with chemotherapy-induced febrile neutropenia presenting to the emergency department. METHODS Lean Six Sigma is a quality improvement method that engages all impacted stakeholders and focuses on streamlining the process by removing process wastes. Stakeholders identified multiple process wastes in an in-depth study of 49 fever episodes in patients attending a tertiary care pediatric hospital, including patients waiting to be registered, waiting for laboratory technicians, delay in accessing central venous access device, waiting for absolute neutrophil count, and delayed antibiotics orders. We implemented multiple solutions: engaging patients in the process through predischarge tours of the emergency department, home application of topical anesthetic, nurse-initiated pathway, early access of central venous access device for all blood work, and planned antibiotic administration no later than 45 minutes after triage. We prospectively determined the impact of these interventions on TTA. RESULTS The TTA significantly improved to a median of 59 minutes (interquartile range, 38.5-77.5 minutes) compared with the baseline of 99 minutes (interquartile range, 72.0-132.0 minutes; P < 0.0001). CONCLUSIONS Lean methodology effectively identifies barriers and provides solutions to remove barriers and improve administration of antibiotics in febrile oncology patients. These can be widely applied, including in smaller institutions with minimal increased utilization of resources.

Introduction and objectives Although economic evaluations of haemophilia-related care have highlighted both the health care payer and societal perspectives, the costs to families with children with haemophilia have not been examined. This study determined the costs incurred by families of children with haemophilia, attending a haemophilia treatment centre (HTC), servicing a large geographical area in Eastern Canada. Methods Families recorded all direct and indirect costs associated with haemophilia-related care for a year. Costs incurred to receive care at the HTC and local health care centres were compared. The relationship between distance to the HTC and costs was modelled using linear regression. Results Participants included 31/45 children (68%) from 27 families attending the HTC. Median age was 12 years (range: 0.5–17 years); 24/31 (77%) had severe haemophilia. The median distance to the HTC and local health care facility was 230 km (range: 7–600 km) and 33.5 km (range: 2–400 km) respectively. Due to this difference in distance, 23/31 (74%) children do not attend the HTC for management of acute haemorrhage. The median annual total cost per family to attend the HTC is $775.93 (range: $200.00–$5741.00). The total cost to attend the HTC increases by $2.16 (95% CI 1.24–3.9) per kilometer from the HTC. The median total annual cost of haemophilia-related care per family is $1222.50 (range: $396.00–$8037.00). Conclusion Families incur high costs related to haemophilia care. The distance to the HTC is a barrier to care. Improving access to HTCs is paramount in improving haemophilia-related outcomes.

1. Nathalie Schindler, MD* 2. Victoria Price, MD† 1. *Division of Pediatric Emergency Medicine, Department of Pediatrics, McMaster Children’s Hospital, McMaster University, Hamilton, Ontario, Canada. 2. †Division of Paediatric Hematology/Oncology, Department of Paediatrics, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada. A 4½-year-old girl presents to the emergency department with a 2-day history of right cheek erythema, pain, and fever. Her past medical history includes trigonocephaly, bilateral optic nerve atrophy with vision loss, possible very mild hearing loss, pituitary hypoplasia with normal endocrine function, left nasolacrimal duct obstruction, spontaneously closed ventricular septal defect, chronic anemia, and symmetric growth restriction. On physical examination, she appears well. Her oral temperature is 102.6°F (39.2°C), heart rate is 120 beats per minute, respiratory rate is 24 breaths per minute, blood pressure is 100/50 mm Hg, and oxygen saturation is 100% in room air. Her weight is 13 kg (

Summary Background Severe haemophilia A has high morbidity, and treatment, while effective, is very expensive. We report the 16-year follow-up of the Canadian Hemophilia Prophylaxis Study, which examined the effectiveness of tailored frequency-escalated primary prophylaxis with a focus on health outcomes within the domains of body structures and functions, and activities and participation (according to the WHO International Classification of Functioning, Disability and Health [WHO-ICF] framework) and a view to reducing consumption of costly clotting factor, which accounts for more than 90% of the cost of care of severe haemophilia. Methods In this longitudinal study, boys with severe haemophilia A from 12 Canadian centres were enrolled at age 1·0–2·5 years. They were treated with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once-weekly prophylaxis with 50 IU/kg and escalating in frequency (with accompanying dose adjustments) in response to breakthrough bleeding as determined by the protocol. The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores (CCPES) at study end. All analyses were done by intention to treat. The trial is complete, and is registered with ClinicalTrials.gov, number NCT01085344. Findings Between June 26, 1997, and Jan 30, 2007, 56 boys were enrolled. They were followed for a median of 10·2 years (to a maximum of 16·1 years). Median rFVIII usage was about 3600 IU/kg per year. The median end-of-study CCPES physical examination score was 1 (IQR 1–3; range 0–12) for the left ankle and 1 (1–2; 0–12) for the right ankle, with all other joints having a median score of 0. No treatment-related safety events occurred over the duration of the study, including central venous catheter infections. The median annualised index joint bleeding rate was 0·95 per year (IQR 0·44–1·35; range 0·00–13·43), but 17 (30%) patients had protocol-defined unacceptable breakthrough bleeding at some point during the study. Interpretation Tailored frequency-escalated prophylaxis leads to very little arthropathy and very good health outcomes within the WHO-ICF domains, and only uses a moderate amount of expensive clotting factor as compared with standard prophylaxis protocols. Some sequelae of bleeding were observed in our cohort, and future studies should consider a more stringent protocol of escalation. Funding This study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and the Bayer/Canadian Blood Services/Hema-Quebec Partnership Fund. Subsequent renewals were funded by Bayer.

Background: The evaluation of health related quality of life (HRQOL) is essential for a full assessment of the influence of an illness on patients’ lives. The aim of this paper is to critically appraise and compare the measurement properties of HRQOL questionnaires studied in haemophilia. Methods: Bibliographic databases (Embase, Medline, Cinahl and PsycInfo) were searched for articles evaluating measurement properties of HRQOL questionnaires in haemophilia. Articles were excluded that did not report HRQOL measurement properties, or when

Les enfants peuvent avoir une fonction splenique absente ou defaillante en raison de l’absence anatomique congenitale de la rate, de son ablation chirurgicale ou de problemes medicaux qui rendent la fonction splenique deficiente ou inexistante. Au Canada, l’anemie falciforme est une cause courante de cette affection. L’absence de rate et une fonction splenique defaillante s’associent a un risque eleve de sepsis bacterien fulminant, particulierement en presence de bacteries encapsulees. Les enfants splenectomises de moins de 15 ans et les nourrissons presentant une asplenie congenitale sont plus a risque de sepsis fulgurant que les adultes apres une splenectomie.(1) Les personnes atteintes de troubles sanguins sous-jacents, telles les hemoglobinopathies (p. ex., anemie falciforme, thalassemie majeure) ou la spherocytose hereditaire, sont plus vulnerables que ceux qui ont subi une splenectomie apres un traumatisme.(1,2) Les patients presentant une asplenie sont vulnerables a un sepsis fulgurant tout au long de leur vie, la frequence la plus elevee s’observant dans les trois ans suivant la splenectomie ou pendant les trois premieres annees suivant la naissance lorsque l’asplenie est congenitale.(3) Les patients presentant une asplenie qui sont atteints d’un sepsis cause par des organismes encapsules ont un taux de deces de 50 % a 70 %, le plus eleve s’observant chez les enfants de moins de deux ans.(4) Chez les patients presentant une asplenie, la plupart des sepsis fulminants sont causes par des bacteries encapsulees par une capsule polysaccharidique. Le Streptococcus pneumoniae, l’organisme responsable du plus grand nombre de sepsis, est isole dans au moins 50 % des cas. L’Haemophilus influenzae de type b (Hib), le Neisseria meningitidis, les especes de Salmonella et l’Escherichia coli sont egalement frequents. Le Pseudomonas, la Klebsiella, les streptocoques et les staphylocoques sont aussi observes, mais moins souvent. Selon des donnees limitees, pendant les trois premiers mois de vie, le sepsis a coliformes (E coli ou Klebsiella) est plus courant.(5) Des morsures de chat ou de chien ont egalement cause un sepsis fulgurant, attribuable aux especes de Capnocytophaga.(6) Les patients presentant une asplenie sont egalement plus vulnerables a un paludisme grave ou fatal(7) et a une infection par le protozoaire Babesia,(8) transmis par des piqures de tiques. Les dispensateurs de soins qui soignent des enfants presentant une asplenie devraient s’assurer des meilleurs resultats cliniques possible grâce a des strategies preventives : l’education des parents et des patients, la vaccination, la prophylaxie antibiotique et la prise en charge vigoureuse d’une infection presumee.

Children with asplenia or hyposplenia are at risk of developing overwhelming sepsis. Health care providers caring for children with asplenia should ensure the best outcomes by using preventive strategies that focus on parent and patient education, immunization, antibiotic prophylaxis and aggressive management of suspected infection. The present position statement offers current guidance on each of these issues and replaces a previous CPS statement, 'Prevention and therapy of bacterial infections for children with asplenia or hyposplenia', published in 1999.Les enfants présentant une asplénie ou une hyposplénie sont vulnérables à un sepsis fulgurant. Les dispensateurs de soins qui s’occupent d’enfants présentant une asplénie devraient s’assurer des meilleurs résultats cliniques possible grâce à des stratégies préventives axées sur l’éducation des parents et des patients, la vaccination, la prophylaxie antibiotique et la prise en charge vigoureuse de l’infection présumée. Le présent document de principes, qui propose des conseils à jour sur chacun de ces sujets, remplace le document de la SCP intitulé « La prévention et le traitement des infections bactériennes chez les enfants aspléniques ou hypospléniques », publié en 1999.

Objectives To evaluate the frequency of central venous catheter (CVC)-related thrombi detected by routine surveillance ultrasound, and to assess whether positive findings had an impact on management or outcomes. Study design All neonates in a tertiary neonatal intensive care unit who had a CVC inserted for >14 days underwent routine surveillance ultrasound biweekly between January 2003 and December 2009. Data were reviewed retrospectively. Results Although all neonates were asymptomatic at time of surveillance ultrasound, 645 of the total 1333 CVCs inserted in 1012 neonates underwent surveillance ultrasound, and thrombi were detected in 69 (10.7%). The CVCs with thrombi were more likely to be removed for nonelective reasons compared with CVCs without thrombi (59% vs 38%; P = .001; OR, 2.4, 95% CI 1.4-3.9). A total of 955 surveillance ultrasounds were performed to detect and monitor 69 CVCs with thrombi. The majority of thrombi were nonocclusive and nonprogressive. A change in management occurred in 8 cases of CVC-related thrombi (12%), or 1% of all screened cases. An average of 14 ultrasounds were required to detect and monitor 1 CVC with thrombus, at a cost of $951 per CVC with thrombus and $8106 per case of CVC-related thrombi with a change in treatment. Conclusion Asymptomatic thrombi were detected in a significant proportion of CVCs by routine surveillance ultrasound. There were significant costs, but infrequent changes to patient management.

BACKGROUND The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI. METHOD We performed a multicenter, retrospective cohort study of children with de novo AML and evaluated CDI. Recurrence, sepsis and infection-related death were examined. Factors associated with CDI were also evaluated. RESULTS Forty-three CDI occurred in 37 of 341 (10.9%) patients during 42 of 1277 (3.3%) courses of chemotherapy. There were 6 children with multiple episodes of CDI. Three infections were associated with sepsis, and no children died of CDI. Only 2 children had an associated enterocolitis. Both days of broad-spectrum antibiotics (odds ratio 1.03, 95% confidence interval: 1.01 to 1.06; P = 0.003) and at least 1 microbiologically documented sterile site infection (odds ratio 10.81, 95% confidence interval: 5.88 to 19.89; P < 0.0001) were independently associated with CDI. CONCLUSIONS CDI occurred in 11% of children receiving intensive chemotherapy for AML, and outcomes were not severe. CDI is not a prominent issue in pediatric AML in terms of prevalence, incidence or associated outcomes.

Neonatal purpura fulminans is a rare, life-threatening condition, caused by congenital or acquired deficiencies of protein C or S. The condition is often fatal unless there is early recognition of the clinical symptoms, prompt diagnosis, and judicious replacement therapy is initiated. The clinical presentation is that of acute disseminated intravascular coagulation and hemorrhagic skin necrosis. The management includes an acute phase of replacement therapy with fresh frozen plasma or protein C concentrate and a maintenance therapy that includes anticoagulation with warfarin or low molecular weight heparin. This review focuses on the management of severe protein C deficiency.

Background As ultrasound (US) has become more widely available in sub-Saharan Africa, emerging evidence suggests that the prevalence of abdominal disease in endemic Burkitt lymphoma (eBL) is higher than previous estimates. This retrospective chart review was designed to assess: (1) abdominal US utilisation, (2) the incidence of abdominal disease at diagnosis, (3) correlation of extent of disease at diagnosis with overall and event-free survival (EFS). Procedure The charts of 95 consecutive children with eBL diagnosed between April 2006 and 2008 and treated according to the Malawi 2002/03 protocol at the Banso Baptist Hospital in Cameroon were examined for demographics, clinical presentation, diagnostic workup and outcome. Analysis was performed using descriptive statistics, Z-tests and Student's t-tests. Results Fifty of 95 presumptive eBL patients (52.7%) had fine needle aspirate (FNA) confirmation of their tumours. Ninety-four of 95 had an US at diagnosis. US was superior to clinical exam in demonstrating abdominal disease (P

Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG). Potential toxicities include central nervous system thrombosis (CNST) and hemorrhage. Historical practice at the Izaak Walton Killam Health Centre (IWK) involves measuring AT and FG levels after ASP administration and transfusing fresh-frozen plasma (FFP) or cryoprecipitate (CRY) to prevent thrombotic and hemorrhagic complications. To determine whether this reduced these complications in children with acute lymphoblastic leukemia (ALL), incidence, outcome, and clinical characteristics of ASP-related CNST in ALL patients at IWK were compared with a similar cohort from BC Children's Hospital (BCCH), where prophylaxis was not performed. Costs associated with preventative versus expectant management were estimated. From 1990 to 2005, 240 patients were treated at IWK and 479 at BCCH. Seven BCCH patients developed venous CNST (1.5%), compared with none at IWK. CNST occurred exclusively during induction. Six patients received anticoagulation and continued ASP. All 7 patients remain in remission. National Cancer Institute high-risk ALL predicted CNST risk (P = .02), whereas sex, age, race, and body mass index did not. Neither FFP nor CRY protected against CNST, suggesting prophylaxis is unwarranted for unselected ALL patients. However, prophylactic replacement for HR patients in induction may be cost-effective.

Summary Bone marrow examination (BME) in paediatric Hodgkin lymphoma (HL) was evaluated, as evidence from adult HL suggests it may be unnecessary. An internet-based survey was used to examine the practice of Canadian paediatric oncologists regarding BME in children and the impact of routine BME was evaluated in patients with HL treated at our institution. Sixteen of 17 paediatric oncology centres were represented. Forty-three percent of eligible doctors completed the survey. Routine BME for stages III and IV disease was consistent nationally. By contrast, 54% and 70% of respondents reported performing routine BME for stages I and II HL respectively. Respondents were more likely to report performing routine BME in low-stage HL if trained outside Canada (P =0 AE04, stage I; P =0 AE07, stage II) or practicing at smaller centres (P =0 AE05, stage I; P =0 AE03, stage II). At our institution, 62 patients were eligible for analysis. Only four patients (6AE5%) had a positive BME. Anaemia was the only significant risk factor (P =0 AE006). No patient with otherwise low stage was found to have marrow involvement. Comparison of staging with and without BME demonstrated no significant difference to final risk classification. BME in paediatric patients with low-stage HL has extremely low yield and may be unnecessary.

The advances in pediatric tertiary care have resulted in a decrease in the mortality of children with serious underlying conditions. Consequently, there has been an increase in previously rare complications of therapy in children, including venous thrombosis. Although there is a paucity of properly designed trials in the field of pediatric thrombosis, many advances have been made over the past 15 years. Venous thrombosis in children has been the subject of many reviews. This review is an update of the available evidence in the management of venous thrombosis in children, excluding thrombosis of the CNS.

Congenital sideroblastic anemia (CSA) is a hematological disorder characterized by the presence of ringed sideroblasts in bone marrow erythroid precursors. Mutations in the erythroid-specific glycine mitochondrial transporter gene SLC25A38 have been found in a subset of patients with transfusion-dependent congenital CSA. Further studies in a zebrafish model identified a promising ameliorative strategy with combined supplementation with glycine and folate. We tested this combination in three individuals with SLC25A38 CSA, with a primary objective to decrease red blood cell transfusion requirements. No significant impact was observed on transfusion requirements or any hematologic parameters.

This study evaluates our institution's target trough cyclosporine (CSA) concentrations as predictors of severe acute graft versus host disease (aGvHD) in children receiving either matched related or unrelated hematopoietic stem cell transplantation (HSCT). The outcomes of 87 consecutive children who underwent allogeneic HSCT and received CSA and methotrexate as prophylaxis against aGvHD between October 1, 1999 and September 30, 2002 were retrospectively evaluated. The proportion of time that each patient maintained a whole blood CSA concentration within or above the initial target range (105-155 ng/mL or 155-210 ng/mL) was calculated for each of the following time periods: in each week after HSCT from day 0 to +28; in the week preceding engraftment; and in the week preceding the onset of aGvHD. Patients were prospectively evaluated twice weekly for the presence and severity of aGvHD by senior attending physicians. The relationship between potential predictors and the development of severe aGvHD was examined using univariate logistic regression. The main variables of interest were the proportion of time that therapeutic or supratherapeutic CSA concentrations were maintained; median CSA concentrations; the number of methotrexate doses received; and the use of folinic acid rescue. Mean follow-up time was 3.0+/-1.9 years among children who survived beyond day +100. Three variables were significantly associated with the development of severe aGvHD on univariate analysis: initial CSA target concentration [odds ratio (OR), 0.24; P=0.03], proportion of time the target CSA concentration was achieved during the second week after transplant (OR, 0.16; P=0.02), and proportion of time the target CSA concentration was achieved during the week before engraftment (OR, 0.22; P=0.0489). Multivariable analysis demonstrated an inverse relationship between the median CSA concentration during the week before engraftment and the development of severe aGvHD (OR, 0.99; P=0.045). These results suggest that achievement of our CSA target concentrations is important to aGvHD outcomes.

Overwhelming sepsis remains a significant complication of asplenia and hyposplenia. The mainstays of prevention are education, immunization, and prophylactic antibiotics. Evidence to base recommendation and guidelines is lacking. Such decisions as the specific immunizations required, the timing of immunizations, the duration of antibiotic prophylaxis, and the prevention of overwhelming postsplenectomy sepsis in children undergoing splenectomy are often empiric. This article reviews the current literature on the prevention and management of severe infections in children with underlying asplenia or hyposplenia.

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.

Chronic immune thrombocytopenic purpura (ITP), defined as a platelet count of below 150 x 109/L persisting for more than 6 months from onset of illness, occurs in approximately 20% to 25% of children with acute-onset ITP. A small subset of these patients (approximately 5%) will manifest symptomatic, severe thrombocytopenia (platelet counts

Primary immune thrombocytopenia (ITP) in childhood, typically presents as an acute self-limiting illness. However, secondary ITP is often a chronic disorder due to an underlying disease. Combined cytopenias in childhood, that is, secondary ITP occurring with auto-immune hemolytic anemia and/or auto-immune neutropenia, are often associated with disorders characterized by immune dysregulation. Such disorders include systemic lupus erythematosus, auto-immune lymphoproliferative syndrome, and common variable immune deficiency. Evans syndrome describes the combination of ITP, autoimmune hemolytic anemia, and/or autoimmune neutropenia. However, it is now clear that some patients with Evans syndrome have an underlying immunodeficiency. This report focuses on combined auto-immune cytopenias and highlights the challenges in their diagnosis and management. Pediatr Blood Cancer 2012; 60: S12–S14. © 2012 Wiley Periodicals, Inc.

Hemophilia A and B are the most common of the severe bleeding disorders. The present article focuses on the practical aspects of the management of neonates and children diagnosed with hemophilia, and is based on questions frequently posed to paediatric hematologists. It highlights the importance of early diagnosis, the principle of early intervention and the role of comprehensive care hemophilia treatment centres.

Viridans group streptococci (VGS) cause significant morbidity in children treated for acute myeloid leukemia (AML). Our goals were to determine the occurrence and impact of these infections in children treated for AML and to understand the factors that increase the risk of VGS infections and viridans streptococcal shock syndrome (VSSS) in this population.We conducted a retrospective, population-based cohort study that included children ≤18 years of age with de novo AML treated at 15 Canadian centers. We evaluated factors related to VGS infection and VSSS.Among 341 children with AML, VGS occurred in 78 (22.9%) children over the entire course of therapy and 16 had recurrent episodes. VGS infection occurred in 97 of 1277 courses of chemotherapy (7.6%). VSSS occurred in 19.6% of these episodes and included 11 patients who required intensive care services with 2 VGS infections resulting in death. In multiple regression analysis, factors independently related to VGS included treatment on a Medical Research Council-based protocol (odds ratio (OR) 2.87, 95% confidence interval (CI) 1.53-5.39; P = 0.001), cytarabine dose per gram/m² (OR 1.04, 95% CI 1.01-1.07; P = 0.002) and prolonged neutropenia (OR 1.58, 95% CI: 0.97-2.56; P = 0.06). None of the evaluated factors were predictive of VSSS.VGS infections occur in 7.6% of chemotherapy courses and remain an important cause of morbidity and even mortality in children being treated for AML. Interventions to reduce VGS need to be identified.

Inherited platelet disorders encompass a heterogeneous group of bleeding disorders where a variety of molecular defects can affect platelet number, function or both. The defects involve deficiencies or dysfunction of platelet receptors, signaling pathways, cytoskeletal proteins, granule contents and abnormalities in procoagulant activity. These disorders can be difficult to distinguish clinically as they present with the common symptom of mucocutaneous bleeding. Inherited thrombocytopenia needs to be considered in all patients suspected of having primary immune thrombocytopenia, where platelets may also have functional defects. After a careful history and physical examination, initial investigations include a complete blood count with a peripheral smear, followed by appropriate specific investigations that often require specialized referral centers. This article is a summary of the current data on clinical presentation, pathogenesis, diagnosis and management of inherited platelet disorders.

A previously healthy 5-year-old girl presented with pica, emotional lability, and marked gait abnormalities. She had concurrent severe iron deficiency and polycythemia. Her magnetic resonance imaging (MRI) scan showed increased signal in the basal ganglia on T1-weighted images consistent with manganese neurotoxicity. Manganism was subsequently confirmed as her blood manganese levels were extremely elevated. Chelation therapy resulted in improvement in her mobility but she continues to have significant gait impairment. An epidemiological investigation identified well water as the potential source of manganese exposure for our patient, but to date, we have been unable to identify the nature of her neurotoxic susceptibility.

Background Disease-specific quality of life (QoL) measures have enhanced the capacity of outcome measures to evaluate subtle changes and differences between groups. However, when the specific disease is rare, the cohort of patients is small and international collaboration is often necessary to accomplish meaningful research. As many of the QoL measures have been developed in North American English, they require translation to ensure their usefulness in a multi-cultural and/or international society. Published guidelines provide formal methods to achieve cross-culturally comparable versions of a QoL tool. However, these guidelines describe a rigorous process that is not always feasible, particularly in rare disease groups. The objective of this manuscript is to describe the process that was developed to achieve accurate cross-cultural translations of a disease-specific QoL measure, to overcome the challenges of a small sample size, i.e. children with a rare disorder. Procedure A measurement study was conducted in the United Kingdom (UK), France, Germany and Uruguay, during which the validated measure was translated into the languages of the respective countries. Results This is a report of a modified, child-centric, cross-cultural translation and adaptation process in which culturally appropriate and methodologically valid translations of a disease-specific QoL measure, the Kids' ITP Tools (KIT), were performed in children with immune thrombocytopenic purpura (ITP). The KIT was translated from North American English into UK English, French, German, and Spanish. Conclusion This study was a successful international collaboration. The modified process through which culturally appropriate and methodologically valid translations of QoL measures may be achieved in a pediatric population with a relatively rare disorder is reported.

Arterial thromboembolism is rare in children. The frequency of arterial thromboembolisms has paralleled the advances in pediatric tertiary care with increasing numbers of children surviving life-threatening primary illnesses and, paradoxically, developing previously rare complications. The pathophysiology of thrombosis in children differs from that of adults, underscoring the need for a unique diagnostic and therapeutic approach in pediatrics. This review is a summary of the available data on the etiology, diagnosis and management of arterial thrombosis, occurring outside of the CNS, in children.